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Background: The utility of cardiac stress testing depends on the prevalence of myocardial ischemia within candidate populations. However, a comprehensive assessment of the factors influencing frequency of myocardial ischemia within contemporary populations referred for stress testing has not been performed., Methods: We assessed 19,690 patients undergoing nuclear stress testing from a multicenter registry. The chi-square test was used to assess the relative importance of features for predicting myocardial ischemia., Results: In the overall cohort, LVEF, male gender, and rest total perfusion deficit (TPD) were the top three predictors of ischemia, followed by CAD status, age, typical angina, and CAD risk factors. Myocardial ischemia was observed in 13.6 % of patients with LVEF > 55 %, in 26.2 % of patients with LVEF 45 %-54 %, and in 48.3% among patients with LVEF < 45 % (P < 0.001). A similar pattern was noted for rest TPD (P < 0.001). Men had a threefold higher frequency of ischemia versus women (25.8 % vs. 8.4%, P < 0.001). Although the relative ranking of ischemia predictors varied among centers, LVEF and/or rest TPD were among the two most potent predictors of myocardial ischemia within each center., Conclusion: The prevalence of myocardial ischemia varied markedly according to clinical and imaging characteristics. LVEF and rest TPD are robust predictors of myocardial ischemia., (© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Background: Phase analysis of single-photon emission computed tomography myocardial perfusion imaging provides dyssynchrony information which correlates well with assessments by echocardiography, but the independent prognostic significance is not well defined. This study assessed the independent prognostic value of single-photon emission computed tomography-myocardial perfusion imaging phase analysis in the largest multinational registry to date across all modalities., Methods: From the REFINE SPECT (Registry of Fast Myocardial Perfusion Imaging With Next Generation SPECT), a total of 19 210 patients were included (mean age 63.8±12.0 years and 56% males). Poststress total perfusion deficit, left ventricular ejection fraction, and phase variables (phase entropy, bandwidth, and SD) were obtained automatically. Cox proportional hazards analyses were performed to assess associations with major adverse cardiac events (MACE)., Results: During a follow-up of 4.5±1.7 years, 2673 (13.9%) patients experienced MACE. Annualized MACE rates increased with phase variables and were ≈4-fold higher between the second and highest decile group for entropy (1.7% versus 6.7%). Optimal phase variable cutoff values stratified MACE risk in patients with normal and abnormal total perfusion deficit and left ventricular ejection fraction. Only entropy was independently associated with MACE. The addition of phase entropy significantly improved the discriminatory power for MACE prediction when added to the model with total perfusion deficit and left ventricular ejection fraction ( P <0.0001)., Conclusions: In a largest to date imaging study, widely representative, international cohort, phase variables were independently associated with MACE and improved risk stratification for MACE beyond the prediction by perfusion and left ventricular ejection fraction assessment alone. Phase analysis can be obtained fully automatically, without additional radiation exposure or cost to improve MACE risk prediction and, therefore, should be routinely reported for single-photon emission computed tomography-myocardial perfusion imaging studies.

Objectives: Using a contemporary, multicenter international single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) registry, this study characterized the potential major adverse cardiovascular event(s) (MACE) benefit of early revascularization based on automatic quantification of ischemia., Background: Prior single-center data reported an association between moderate to severe ischemia SPECT-MPI and reduced cardiac death with early revascularization., Methods: Consecutive patients from a multicenter, international registry who underwent 99m Tc SPECT-MPI between 2009 and 2014 with solid-state scanners were included. Ischemia was quantified automatically as ischemic total perfusion deficit (TPD). Early revascularization was defined as within 90 days. The primary outcome was MACE (death, myocardial infarction, and unstable angina). A propensity score was developed to adjust for nonrandomization of revascularization; then, multivariable Cox modeling adjusted for propensity score and demographics was used to predict MACE., Results: In total, 19,088 patients were included, with a mean follow-up of 4.7 ± 1.6 years, during which MACE occurred in 1,836 (9.6%) patients. There was a significant interaction between ischemic TPD modeled as a continuous variable and early revascularization (interaction p value: 0.012). In this model, there was a trend toward reduced MACE in patients with >5.4% ischemic TPD and a significant association with reduced MACE in patients with >10.2% ischemic TPD., Conclusions: In this large, international, multicenter study reflecting contemporary cardiology practice, early revascularization of patients with >10.2% ischemia on SPECT-MPI, quantified automatically, was associated with reduced MACE., Competing Interests: Funding Support and Author Disclosures This research was supported in part by grant R01HL089765 from the National Heart, Lung, and Blood Institute/National Institutes of Health (principal investigator: Dr. Slomka). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The work was also supported in part by the Miriam and Sheldon Adelson Medical Research Foundation. Dr. R.J.H. Miller received funding support from the Arthur J E Child Fellowship grant. Dr. Einstein has served as a consultant for GE Healthcare, and his institution has received research support from Toshiba America Medical Systems and Roche Medical Systems. Dr. Ruddy has received research grant support from GE Healthcare and Advanced Accelerator Applications. Dr. E. Miller has served as a consultant for GE Healthcare and Bracco Inc.; and he and his institution have received grant support from Bracco Inc. Dr. Dorbala has served as a consultant for GE Healthcare and Bracco Diagnostics; and her institution has received grant support from Astellas. Dr. Di Carli has received research grant support from Spectrum Dynamics and consulting honoraria from Sanofi and GE Healthcare. Dr. Berman participates in software royalties for QPS software at Cedars-Sinai Medical Center; has served as a consultant for GE Healthcare; and his institution has received grant support from HeartFlow. Drs. Slomka participates in software royalties for QPS software at Cedars-Sinai Medical Center; and has received research grant support from Siemens Medical Systems. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Upper reference limits for transient ischemic dilation (TID) have not been rigorously established for cadmium-zinc-telluride (CZT) camera systems. We aimed to derive TID limits for common myocardial perfusion imaging protocols utilizing a large, multicenter registry (REFINE SPECT)., Methods: One thousand six hundred and seventy-two patients with low likelihood of coronary artery disease with normal perfusion findings were identified. Images were processed with Quantitative Perfusion SPECT software (Cedars-Sinai Medical Center, Los Angeles, CA). Non-attenuation-corrected, camera-, radiotracer-, and stress protocol-specific TID limits in supine position were derived from 97.5th percentile and mean + 2 standard deviations (SD). Reference limits were compared for different solid-state cameras (D-SPECT vs. Discovery), radiotracers (technetium-99m-sestamibi vs. tetrofosmin), different types of stress (exercise vs. four different vasodilator-based protocols), and different vasodilator-based protocols., Results: TID measurements did not follow Gaussian distribution in six out of eight subgroups. TID limits ranged from 1.18 to 1.52 (97.5th percentile) and 1.18 to 1.39 (mean + 2SD). No difference was noted between D-SPECT and Discovery cameras (P = 0.71) while differences between exercise and vasodilator-based protocols (adenosine, regadenoson, or regadenoson-walk) were noted (all P < 0.05)., Conclusions: We used a multicenter registry to establish camera-, radiotracer-, and protocol-specific upper reference limits of TID for supine position on CZT camera systems. Reference limits did not differ between D-SPECT and Discovery camera.

Aims: Ischaemia on single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is strongly associated with cardiovascular risk. Transient ischaemic dilation (TID) and post-stress wall motion abnormalities (WMA) are non-perfusion markers of ischaemia with incremental prognostic utility. Using a large, multicentre SPECT MPI registry, we assessed the degree to which these features increased the risk of major adverse cardiovascular events (MACE) in patients with less than moderate ischaemia., Methods and Results: Ischaemia was quantified with total perfusion deficit using semiautomated software and classified as: none (<1%), minimal (1 to <5%), mild (5 to <10%), moderate (10 to <15%), and severe (≥15%). Univariable and multivariable Cox proportional hazard analyses were used to assess associations between high-risk imaging features and MACE. We included 16 578 patients, mean age 64.2 and median follow-up 4.7 years. During follow-up, 1842 patients experienced at least one event. Patients with mild ischaemia and TID were more likely to experience MACE compared with patients without TID [adjusted hazard ratio (HR) 1.42, P = 0.023], with outcomes not significantly different from patients with moderate ischaemia without other high-risk features (unadjusted HR 1.15, P = 0.556). There were similar findings in patients with post-stress WMA. However, in multivariable analysis of patients with mild ischaemia, TID (adjusted HR 1.50, P = 0.037), but not WMA, was independently associated with increased MACE., Conclusion: In patients with mild ischaemia, TID or post-stress WMA identify groups of patients with outcomes similar to patients with moderate ischaemia. Whether these combinations identify patients who may derive benefit from revascularization deserves further investigation., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Objective: Prevalence and prognostic impact of cardiovascular disease differ between patients with or without diabetes. We aimed to explore differences in the prevalence and prognosis of myocardial ischemia by automated quantification of total perfusion deficit (TPD) among patients with and without diabetes., Research Design and Methods: Of 20,418 individuals who underwent single-photon emission computed tomography myocardial perfusion imaging, 2,951 patients with diabetes were matched to 2,951 patients without diabetes based on risk factors using propensity score. TPD was categorized as TPD = 0%, 0% < TPD < 1%, 1% ≤ TPD < 5%, 5% ≤ TPD ≤ 10%, and TPD >10%. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause mortality, myocardial infarction, unstable angina, or late revascularization., Results: MACE risk was increased in patients with diabetes compared with patients without diabetes at each level of TPD above 0 ( P < 0.001 for interaction). In patients with TPD >10%, patients with diabetes had greater than twice the MACE risk compared with patients without diabetes (annualized MACE rate 9.4 [95% CI 6.7-11.6] and 3.9 [95% CI 2.8-5.6], respectively, P < 0.001). Patients with diabetes with even very minimal TPD (0% < TPD < 1%) experienced a higher risk for MACE than those with 0% TPD (hazard ratio 2.05 [95% CI 1.21-3.47], P = 0.007). Patients with diabetes with a TPD of 0.5% had a similar MACE risk as patients without diabetes with a TPD of 8%., Conclusions: For every level of TPD >0%, even a very minimal deficit of 0% < TPD < 1%, the MACE risk was higher in the patients with diabetes compared with patients without diabetes. Patients with diabetes with minimal ischemia had comparable MACE risk as patients without diabetes with significant ischemia., (© 2019 by the American Diabetes Association.)

In the context of myocardial perfusion imaging (MPI) with cardiac magnetic resonance (CMR), there is ongoing debate on the merits of using technically complex acquisition methods to achieve whole-heart spatial coverage, rather than conventional 3-slice acquisition. An adequately powered comparative study is difficult to achieve given the requirement for two separate stress CMR studies in each patient. The aim of this work is to draw relevant conclusions from SPECT MPI by comparing whole-heart versus simulated 3-slice coverage in a large existing dataset. SPECT data from 651 patients with suspected coronary artery disease who underwent invasive angiography were analyzed. A computational approach was designed to model 3-slice MPI by retrospective subsampling of whole- heart data. For both whole-heart and 3-slice approaches, the diagnostic performance and the stress total perfusion deficit (TPD) score-a measure of ischemia extent/severity-were quantified and compared. Diagnostic accuracy for the 3-slice and whole-heart approaches were similar (area under the curve: 0.843 vs. 0.855, respectively; P = 0.07). The majority (54%) of cases missed by 3-slice imaging had primarily apical ischemia. Whole-heart and 3-slice TPD scores were strongly correlated (R2 = 0.93, P