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Quantitative myocardial perfusion positron emission tomography and caffeine revisited with new insights on major adverse cardiovascular events and coronary flow capacity.
Kitkungvan, D, Bui, L, Johnson, NP, Patel, MB, Roby, AE, Vejpongsa, P, Babar, AK, Madjid, M, Nacimbene, A, Kumar, S, et al
European heart journal. Cardiovascular Imaging. 2019;(7):751-762
Abstract
AIMS: To evaluate effects of caffeine on quantitative myocardial perfusion by positron emission tomography (PET) and associated major adverse cardiovascular events (MACE). METHODS AND RESULTS Serum caffeine was measured for all 6087 PETs with 328 positive results (5.4%). Paired caffeine positive/negative PETs (84 patients for dipyridamole with median caffeine 1.6 mg/L, and additional 25 volunteers for regadenoson with median caffeine 7.4 mg/L) were compared for quantitative perfusion. Multivariate regression analysis for associations among caffeine, clinical/imaging variables, predicted caffeine probability was performed. MACEs were followed up to 9 years after PETs. For caffeine vs. no caffeine, respectively, stress flow was 1.74 ± 0.55 vs. 2.14 ± 0.53 for dipyridamole and 1.82 ± 0.61 vs. 2.33 ± 0.49 mL/min/g for regadenoson, and coronary flow reserve (CFR) was 2.26 ± 0.67 vs. 2.67 ± 0.72 for dipyridamole and 1.84 ± 0.33 vs. 2.31 ± 0.41 for regadenoson (all P < 0.001). Subjects were reclassified from high-risk CFR ≤2.0 with caffeine to low-risk CFR >2.0 without caffeine in 66.7% and 80% of dipyridamole and regadenoson caffeine-no-caffeine pairs, respectively. While relative images showed no differences, caffeine significantly altered coronary flow capacity (CFC) to false negative and false positive severity in 2.1% and 5.5% of the 328 caffeine positives, respectively (0.1% and 0.3% of 6087 PETs) but without change in severity guided management in most patients (92.4% of 328 caffeine or 99.6% of total 6087 PETs). CONCLUSION Even low serum caffeine levels reduce quantitative perfusion during vasodilatory stress with false positive or false negative results minimized by empathic instruction, CFC analysis or repeat PET after strict caffeine abstention for definitive individualized risk stratification and management.
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Late sodium channel blockade improves angina and myocardial perfusion in patients with severe coronary microvascular dysfunction: Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction ancillary study.
Rambarat, CA, Elgendy, IY, Handberg, EM, Bairey Merz, CN, Wei, J, Minissian, MB, Nelson, MD, Thomson, LEJ, Berman, DS, Shaw, LJ, et al
International journal of cardiology. 2019;:8-13
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BACKGROUND In a prior trial of late sodium channel inhibition (ranolazine) among symptomatic subjects without obstructive coronary artery disease (CAD) and limited myocardial perfusion reserve index (MPRI), we observed no improvement in angina or MPRI, overall. Here we describe the clinical characteristics and myocardial perfusion responses of a pre-defined subgroup who had coronary flow reserve (CFR) assessed invasively. METHODS Symptomatic patients without obstructive CAD and limited MPRI in a randomized, double-blind, crossover trial of ranolazine vs. placebo were subjects of this prespecified substudy. Because we had previously observed that adverse outcomes and beneficial treatment responses occurred in those with lower CFR, patients were subgrouped by CFR <2.5 vs ≥2.5. Symptoms were assessed using the Seattle Angina Questionnaire and the SAQ-7, and left-ventricular volume and MPRI were assessed by magnetic resonance imaging (MRI). Coronary angiograms, CFR, and MRI data were analyzed by core labs masked to treatment and patient characteristics. RESULTS During qualifying coronary angiography, 81 patients (mean age 55 years, 98% women) had invasively determined CFR 2.69 ± 0.65 (mean ± SD; range 1.4-5.5); 43% (n = 35) had CFR <2.5. Demographic and symptomatic findings did not differ comparing CFR subgroups. Those with low CFR had improved angina (p = 0.04) and midventricular MPRI (p = 0.03) with ranolazine vs placebo. Among patients with low CFR, reduced left-ventricular end-diastolic volume predicted a beneficial angina response. CONCLUSIONS Symptomatic patients with CFR <2.5 and no obstructive CAD had improved angina and myocardial perfusion with ranolazine, supporting the hypothesis that the late sodium channel is important in management of coronary microvascular dysfunction. TRIAL REGISTRATION clinicaltrials.gov Identifier NCT01342029.
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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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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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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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Development and validation of a patient-tailored dose regime in myocardial perfusion imaging using CZT-SPECT.
van Dijk, JD, Jager, PL, Mouden, M, Slump, CH, Ottervanger, JP, de Boer, J, Oostdijk, AH, van Dalen, JA
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2014;(6):1158-67
Abstract
BACKGROUND Guidelines for SPECT myocardial perfusion imaging (MPI) traditionally recommend a fixed tracer dose. Yet, clinical practice shows degraded image quality in heavier patients. The aim was to optimize and validate the tracer dose and scan time to obtain a constant image quality less dependent on patients' physical characteristics. METHODS 125 patients underwent Cadmium Zinc Telluride (CZT)-SPECT stress MPI using a fixed Tc-99m-tetrofosmin tracer dose. Image quality was scored by three physicians on a 4-point grading scale and related to the number of photon counts normalized to tracer dose and scan time. Counts were correlated with various patient-specific parameters dealing with patient size and weight to find the best predicting parameter. From these data, a formula to provide constant image quality was derived, and subsequently tested in 92 new patients. RESULTS Degradation in image quality and photon counts was observed for heavier patients for all patients' specific parameters (P < .01). We found body weight to be the best-predicting parameter for image quality and derived a new dose formula. After applying this new body weight-depended tracer dose and scan time in a new group, image quality was found to be constant (P > .19) in all patients. CONCLUSIONS Also in CZT SPECT image quality decreases with weight. The use of a tracer dose and scan time that depends linearly on patient's body weight corrected for the varying image quality in CZT-SPECT MPI. This leads to better radiation exposure justification.
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Effect of caffeine on adenosine-induced reversible perfusion defects assessed by automated analysis.
Lee, JC, Fraser, JF, Barnett, AG, Johnson, LP, Wilson, MG, McHenry, CM, Walters, DL, Warnholtz, CR, Khafagi, FA
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2012;(3):474-81
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OBJECTIVES This prospective study investigated the effects of caffeine ingestion on the extent of adenosine-induced perfusion abnormalities during myocardial perfusion imaging (MPI). METHODS Thirty patients with inducible perfusion abnormalities on standard (caffeineabstinent) adenosine MPI underwent repeat testing with supplementary coffee intake. Baseline and test MPIs were assessed for stress percent defect, rest percent defect, and percent defect reversibility. Plasma levels of caffeine and metabolites were assessed on both occasions and correlated with MPI findings. RESULTS Despite significant increases in caffeine [mean difference 3,106 μg/L (95% CI 2,460 to 3,752 μg/L; P < .001)] and metabolite concentrations over a wide range, there was no statistically significant change in stress percent defect and percent defect reversibility between the baseline and test scans. The increase in caffeine concentration between the baseline and the test phases did not affect percent defect reversibility (average change -0.003 for every 100 μg/L increase; 95% CI -0.17 to 0.16; P = .97). CONCLUSION There was no significant relationship between the extent of adenosine-induced coronary flow heterogeneity and the serum concentration of caffeine or its principal metabolites. Hence, the stringent requirements for prolonged abstinence from caffeine before adenosine MPI - based on limited studies - appear ill-founded.
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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).
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Incidence of caffeine in serum of patients undergoing dipyridamole myocardial perfusion stress test by an intensive versus routine caffeine history screening.
Banko, LT, Haq, SA, Rainaldi, DA, Klem, I, Siegler, J, Fogel, J, Sacchi, TJ, Heitner, JF
The American journal of cardiology. 2010;(10):1474-9
Abstract
The coronary vasodilatory effect of dipyridamole is competitively blocked by caffeine. The purposes of this study were to (1) assess the incidence of having detectable serum caffeine and (2) evaluate whether an intensive caffeine history screening strategy was superior to routine history screening before dipyridamole myocardial perfusion imaging. One hundred ninety-four patients who were randomized to an intensive or a routine screening history strategy were prospectively evaluated. Serum caffeine levels were determined in all patients. Outcomes data, including death, nonfatal myocardial infarction, and history of revascularization, were obtained at 24 months. Nearly 1 in 5 patients (19%) who screened negative by history had detectable serum caffeine. In patients who screened negative by history, there was no statistically significant difference in the percentage of caffeine seropositivity between the intensive and routine arms (16% vs 22%, respectively, p = 0.31). The incidence of combined end points of death, myocardial infarction, or revascularization was 22.9% and 7.3% in patients with and without detectable serum caffeine, respectively (p = 0.01). In conclusion, despite initial negative results on screening by history, a considerably high percentage of patients had positive serum caffeine levels. These results do not support the use of an intensive screening strategy. Detectable serum caffeine was associated with a higher incidence of adverse outcomes.
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Erythromycin as an alternative to reduce interfering extra-cardiac activity in myocardial perfusion imaging.
Vorster, M, Sathekge, MM, Rheeder, P
Cardiovascular journal of Africa. 2010;(3):142-7
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OBJECTIVES We sought to determine whether taking oral erythromycin prior to SPECT myocardial perfusion imaging with Tc99m-sestamibi would reduce the amount of interfering extra-cardiac activity and improve the image quality. METHODS A total of 96 patients who were routinely referred for myocardial perfusion imaging were randomly assigned to one of two groups. Patients in group A received 500 mg of non-enterically coated erythromycin orally one hour prior to image acquisition (45 patients). Patients in group B received diluted lemon juice which comprises the current standard of care in our department (51 patients). A two-day protocol was followed and study participants received the same intervention on both days. Planar images of both the stress and rest images were assessed visually by three experienced nuclear medicine physicians for the presence of interfering extracardiac activity. Physicians were blinded to the detail of the protocol and independently assessed the images. RESULTS The qualitative results favoured lemon juice in reducing the amount of interfering extra-cardiac activity. The overall incidence of interfering extra-cardiac activity was 46.15% in the lemon juice group vs 55.56% in the erythromycin group. However, this difference was not found to be statistically significant (p = 0.36). The use of a MYO:EXT ratio similar to the one described by Peace and Lloyd,11 appeared promising in quantifying interfering extra-cardiac activity. CONCLUSION The difference between the effect of erythromycin and lemon juice on interfering extra-cardiac activity appears statistically insignificant and erythromycin could therefore be considered as a suitable alternative to lemon juice.