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Background: Disparities exist in medicine and can affect patient care. We sought to understand influences of racial biases in diagnostic testing within a Cardiac CT (CCT) population., Methods: Race of CCT patients, referring physicians and the population in the catchment area were captured between February 2006 and November 2021. The frequency of CCT referrals for each race was indexed to the catchment population., Results: Of 21,241 CCT patients, 17,514 (82.5 ​%) patients were White. The Non-White population was comprised of 467(2.2 ​%) Indigenous, 656(3.1 ​%) Black, 932(4.4 ​%) Asian, 276(1.3 ​%) South Asian, 1100(5.2 ​%) Middle Eastern and 296(1.4 ​%) Latin American races. The catchment population was 907,675, with 619,514 individuals of whom 69.7 ​% identified as White. Compared to the catchment population, there was a disproportionately higher referral rate for Whites than Non-Whites. The referral index for Whites was higher than Non-Whites (1.2 versus 0.6, p ​< ​0.001)). This pattern was consistent across all racial minorities and age categories. A total of 356 physicians (236(66.3 ​%) White, 4(1.2 ​%) Black, 39(12.0 ​%) Asian, 30(9.2 ​%) South Asian, 43(13.2 ​%), Middle Eastern and 4 (1.2 ​%) Latin American) made referrals to CCT. The racial difference in referral patterns was independent of physician race and was independent of their years in practice., Conclusions: Racial differences exist in CCT referrals. These differences are independent of prevalence of disease, physician race or years in practice. This study supports the need to better understand reasons for disparity and strategies to mitigate potential bias., Competing Interests: Declaration of competing interest Benjamin Chow receives research support from TD Bank, Artrya, and Siemens Healthineers. He is also a consultant for Artrya and has equity interest. No other authors have conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Prospective ECG-triggered cardiac computed tomography (CT) imaging limits the ability to assess left ventricular (LV) ejection fraction (EF). We previously developed a new index derived from LV volume changes over 100 ​ms during systole (LVEF 100msec ) as a surrogate of LV function in patients undergoing prospective ECG-triggered cardiac CT. We sought to evaluate the prognostic value of LVEF 100msec ., Methods: Patients undergoing prospective systolic ECG-triggered cardiac CT were enrolled between January 2015 and September 2022. Each CT was analyzed for LVEF 100msec . Area under the curve analysis and Cox proportional hazards models were used to define the best LVEF 100msec cut-off and to predict major adverse cardiovascular events (MACE), defined as a composite of all-cause death, cardiac death/arrest, non-fatal myocardial infarction, and stroke., Results: The study enrolled 313 patients (median age ​= ​58 years, male ​= ​52.4 ​%). During a median follow-up of 924 (660-1365) days, 24 (7.7 ​%) patients had MACE. LVEF 100msec was significantly lower in the MACE group compared to the non-MACE group (4.8 ​% vs. 8.3 ​%, p ​= ​0.002). Optimal LVEF 100msec cut-off for predicting MACE was 6.3 ​%. MACE-free survival rate was significantly lower in patients with LVEF 100msec ≤6.3 ​% than those with >6.3 ​% (p ​< ​0.001). LVEF 100msec ≤6.3 ​% was an independent predictor of MACE, with an adjusted hazard ratio of 3.758 (95 ​% CI, 1.543-9.148; p ​= ​0.004). The prognostic value of LVEF 100msec was consistent across the various severities of coronary artery disease., Conclusion: LVEF 100msec was an independent predictor of adverse events. The implementation of LVEF 100msec may improve the prognostic value of prospective ECG-triggered cardiac CT., Competing Interests: Declaration of competing interest Gary R. Small receives grant funding from Pfizer for amyloid research. Benjamin Chow receives research support from TD Bank, Siemens Healthineers, and Artrya. He is a consultant for and has equity interest in Artrya., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Coronary computed tomography angiography (CCTA) is an important non-invasive tool for the assessment of coronary artery disease and the delivery of information incremental to coronary anatomy. CCTA measured left ventricular (LV) mid-diastolic volume (LV MDV ) and LV mass (LV Mass ) have important prognostic information but the utility of prospectively ECG-triggered CCTA to predict reduced left ventricular ejection fraction (LVEF) is unknown. The objective of this study was to determine if indexed LV MDV (LV MDVi ) and the LV MDV :LV Mass ratio on CCTA can identify patients with reduced LVEF., Materials/methods: 8179 patients with prospectively ECG-triggered CCTA between November 2014 and December 2019 were reviewed. A subset derivation cohort of 4352 healthy patients was used to define normal LV MDVi and LV MDV :LV Mass . Sex-specific thresholds were tested in a validation cohort of 1783 patients, excluded from the derivation cohort, with cardiac disease and known LVEF. The operating characteristics for 1 SD above the mean were tested for the identification of abnormal LVEF, LVEF≤35 ​% and ≤30 ​%., Results: The derivation cohort had a mean LV MDVi of 61.0 ​± ​13.7 ​mL/m 2 and LV MDV :LV Mass of 1.11 ​± ​0.24 ​mL/g. LV MDVi and LV MDV :LV Mass were both higher in patients with reduced LVEF than those with normal LVEF (98.8 ​± ​40.8 ​mL/m 2 vs. 63.3 ​± ​19.7 ​mL/m 2 , p ​< ​0.001, and 1.32 ​± ​0.44 ​mL/g vs. 1.05 ​± ​0.28 ​mL/g, p ​< ​0.001). Both mean LV MDVi and LV MDV :LV Mass increased with the severity of LVEF reduction. Sex-specific LV MDVi thresholds were 79 ​% and 80 ​% specific for identifying abnormal LVEF in females (LV MDVi  ​≥ ​69.9 ​mL/m 2 ) and males (LV MDVi  ​≥ ​78.8 ​mL/m 2 ), respectively. LV MDV :LV Mass thresholds had high specificity (87 ​%) in both females (LV MDVi :LV Mass  ​≥ ​1.39 ​mL/g) and males (LV MDVi :LV Mass  ​≥ ​1.30 ​mL/g)., Conclusion: Our study provides reference thresholds for LV MDVi and LV MDV :LV Mass on prospectively ECG-triggered CCTA, which may identify patients who require further LV function assessment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Benjamin Chow reports a relationship with TD Bank that includes: funding grants. Benjamin Chow reports a relationship with SIEMENS that includes: funding grants. Benjamin Chow reports a relationship with Artrya that includes: equity or stocks and funding grants. Daniel Juneau reports a relationship with Advanced Accelerator Applications that includes: consulting or advisory. Daniel Juneau reports a relationship with Pfizer Inc that includes: consulting or advisory. Daniel Juneau reports a relationship with AbbVie Inc that includes: consulting or advisory., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Coronary computed tomography angiography (CCTA) is vital for diagnosing coronary artery disease; however, prospective ECG-triggered acquisition, minimizing radiation exposure, limits left ventricular (LV) ejection fraction (EF) evaluation. We aimed to assess the feasibility and utility of LVEF 100msec , a new index for estimating LV function using volumetric changes during 100 msec within systole., Methods: This retrospective study analyzed patients who underwent prospective ECG-triggered CCTA with systolic acquisition between January 2015 and June 2022. The LVEF 100msec was calculated using the maximum and minimum LV volumes among the three phases (300, 350, and 400 msec post-QRS) and expressed as a percentage. Patients were classified into normal, mild-moderately reduced, or severely reduced LV function categories based on the reference test. The LVEF 100msec was compared among groups, and the optimal cutoff value of LVEF 100msec for predicting severe LV dysfunction was investigated., Results: The study included 271 patients (median age ​= ​58 years, 52% male). LVEF was normal in 188 (69.4%), mild-moderately reduced in 57 (21.0%), and severely reduced in 26 (9.6%) patients. Median LVEF 100msec value was 9.0 (6.7-12.6) for normal LV function, 4.7 (3.1-8.8) for mild-moderately reduced, and 2.9 (1.5-3.8) for severely reduced LV function. LVEF 100msec values significantly differed among categories (p ​< ​0.001). The optimal LVEF 100msec cutoff for severe LV dysfunction was 4.3%, with an AUC of 0.924, sensitivity of 88%, and specificity of 89%., Conclusion: The LVEF 100msec may serve as a valuable indicator of severe LV dysfunction., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gary S. Small receives grant funding from Pfizer for amyloid research. Benjamin J.W. Chow receives research support from TD Bank, Siemens Healthineers, and Artrya. He is a consultant for and has equity interest in Artrya., (Copyright © 2023 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Recent advancements in artificial intelligence have witnessed human-level performance; however, AI-enabled cognitive assistance for therapeutic procedures has not been fully explored nor pre-clinically validated. Here we propose AI-Endo, an intelligent surgical workflow recognition suit, for endoscopic submucosal dissection (ESD). Our AI-Endo is trained on high-quality ESD cases from an expert endoscopist, covering a decade time expansion and consisting of 201,026 labeled frames. The learned model demonstrates outstanding performance on validation data, including cases from relatively junior endoscopists with various skill levels, procedures conducted with different endoscopy systems and therapeutic skills, and cohorts from international multi-centers. Furthermore, we integrate our AI-Endo with the Olympus endoscopic system and validate the AI-enabled cognitive assistance system with animal studies in live ESD training sessions. Dedicated data analysis from surgical phase recognition results is summarized in an automatically generated report for skill assessment., (© 2023. Springer Nature Limited.)

Aims: Indiscriminate coronary computed tomography angiography (CCTA) referrals for suspected coronary artery disease could result in a higher rate of equivocal and non-diagnostic studies, leading to inappropriate downstream resource utilization or delayed time to diagnosis. We sought to develop a simple clinical tool for predicting the likelihood of a non-diagnostic CCTA to help identify patients who might be better served with a different test., Methods and Results: We developed a clinical scoring system from a cohort of 21 492 consecutive patients who underwent CCTA between February 2006 and May 2021. Coronary computed tomography angiography study results were categorized as normal, abnormal, or non-diagnostic. Multivariable logistic regression analysis was conducted to produce a model that predicted the likelihood of a non-diagnostic test. Machine learning (ML) models were utilized to validate the predictor selection and prediction performance. Both logistic regression and ML models achieved fair discriminate ability with an area under the curve of 0.630 [95% confidence interval (CI) 0.618-0.641] and 0.634 (95% CI 0.612-0.656), respectively. The presence of a cardiac implant and weight >100 kg were among the most influential predictors of a non-diagnostic study., Conclusion: We developed a model that could be implemented at the 'point-of-scheduling' to identify patients who would be best served by another non-invasive diagnostic test., Competing Interests: Conflicts of interest: Benjamin Chow holds the Saul and Edna Goldfarb Chair in Cardiac Imaging Research. He receives research support from TD Bank, AusculSciences, Siemens Healthineers, and Artrya. The remaining authors have nothing to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: This study sought to assess training volumes and its relationship to learning and identify potential new thresholds for determining expertise., Background: Competency-based medical education (CBME) is being rapidly adopted and therefore training programs will need to adapt and identify new and novel methods of defining, measuring, and assessing clinical skills., Methods: Consecutive cardiac computed tomography (CT) studies were interpreted independently by trainees and expert readers, and their interpretations (Agatston score, coronary artery disease severity, and Coronary Artery Disease Reporting and Data System) were collected. Kappa agreements were measured between trainees and experts for every 50 consecutive cases. Agreements between trainees and experts were tracked and compared with the agreement between expert readers., Results: A total of 36 trainees interpreted 14,432 cardiac CT studies. Agreement between trainees and experts increased with CT case volumes, but trainees learned at different rates. Using a threshold for expertise, skill of measuring coronary calcification was achieved within 50 cases, but expertise for coronary CT angiography appeared to require a mean case volume of 750, comprising 400 abnormal cases., Conclusions: Current volume-based training guidelines may be insufficient and higher case volumes may be required. We demonstrate that tracking cardiac CT learners is feasible and that CBME could be incorporated into CT training programs., Competing Interests: Funding Support and Author Disclosures This study was supported in part by the University of Ottawa Heart Institute AMO Alternate Funding Plan: Innovations Funding. Dr. Chow has received research support from TD Bank, CV Diagnostix, AusculSciences, and Siemens and has equity interest in General Electric. 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: Left ventricular mass (LVM) is a predictor for adverse cardiovascular outcomes. Coronary atherosclerosis (coronary artery disease [CAD]) and concentric left ventricular (LV) remodeling are linked pathophysiologically by endothelial dysfunction., Aim: This study sought to determine the potential association between coronary atherosclerosis and LVM., Methods: A total of 2384 consecutive patients, without structural heart disease or a medical history of CAD, undergoing prospective mid-diastolic electrocardiogram-gated computed tomography coronary angiography were enrolled in the study. LVM and LV mid-diastolic volume were measured using semiautomated software and indexed to body surface area. The average LV mid-diastolic wall thickness and concentricity index (LVM/LV mid-diastolic volume) were calculated. According to the Agatston Score, the patients were divided into 3 groups (Agatston=0, 0.1 to 399.9, ≥400). Similarly, patients were also divided into 4 groups on the basis of the Total Plaque Score (TPS) (0, 1 to 4, 5 to 8, and ≥9). In addition, patients were categorized according to CAD (normal coronaries, nonobstructive CAD, and obstructive stenosis [obstruction >50%]). The association between the different categories of CAD and LV measures was assessed., Results: Both left ventricular mass index (LVMi) and the LV concentricity index increased with TPS categories from 55.3±12.1, 57.4±11.7, 60.9±13.6, and 63.7±15.3 g/m2 (P<0.05), and 0.935±0.424, 0.975±0.3273, 1.046±0.431, and 1.138±0.443 mL/g (P<0.01), respectively. A similar trend of increasing LVMi was observed with increasing Agatston Score (P<0.001) and CAD category (P<0.05)., Conclusion: In patients without known structural heart disease, LVMi is independently associated with measures of CAD., Competing Interests: B.J.W.C. holds the Saul and Edna Goldfarb Chair in Cardiac Imaging Research. He receives research support from CV Diagnostix and AusculSciences, Siemens Healthineers, and educational support from TeraRecon Inc. He has equity interest in General Electric. F.J.R. is the Medical Director of Imagia Cybernetics. The remaining authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We sought to determine the prognostic value of coronary computed tomography angiography (CCTA) in patients with a history of percutaneous coronary intervention (PCI)., Background: Although the prognostic value of CCTA has been well studied, its incremental value in patients with previous PCI has not been robustly investigated., Methods: Consecutive patients with previous PCI were prospectively enrolled and CCTA images were evaluated for coronary artery disease (CAD) severity. Patients were followed for major adverse cardiovascular events (MACE) which was a composite of cardiac death and non-fatal myocardial infarction. All-cause death was assessed as a secondary endpoint., Results: A total of 501 patients were analyzed with a mean follow-up time of 59.5 ± 32.0 months and 52 patients (10.4%) experienced MACE. Multivariable Cox regression analysis showed that CAD severity was a predictor of MACE with 0, 1, 2, and 3 vessel disease having annual rates of 1.3%, 2.2%, 2.2%, and 5.3%, respectively. All-cause death was similar in all categories of CAD., Conclusions: In patients with previous PCI, CAD severity as measured with CCTA has independent and incremental prognostic value., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Coronary CT angiography (CCTA) is increasing seen as a first line investigation in patients with suspected coronary artery disease. Heart-rate control improves the image quality and diagnostic accuracy of CCTA. Typically, beta-blockers are administered to induce sinus bradycardia. Sinus bradycardia may also be induced by ivabradine. We hypothesized that in a real-world population ivabradine would be an effective alternative to metoprolol at heart rate lowering for CCTA., Methods: This was a retrospective analysis of consecutive patients who were exposed to an ivabradine-based (IB) versus a metoprolol-only (MO) protocol to achieve a target heart rate 65 and received heart-rate lowering medication: 1958 patients had MO, and 718 received IB protocol. Target heart rate of

Aims: This large prospective cohort study sought to confirm the incremental prognostic value of coronary computed tomographic angiography (CCTA) measured over a prolonged follow-up duration. CCTA has diagnostic and prognostic value but data supporting its long-term prognostic value in a large prospectively recruited cohort with suspected coronary artery disease (CAD) has been limited., Methods and Results: Consecutive patients (without history of myocardial infarction, revascularization, cardiac transplantation, and congenital heart disease) were prospectively enrolled. CCTA was evaluated for CAD severity, total plaque score (TPS), and left ventricular ejection fraction. Patients were followed for major adverse events (MAE) and major adverse cardiac events (MACE).Over a total of 99 months, 8667 consecutive CCTA patients (mean age = 57.1 ± 11.1 years, 52.9% men) were prospectively enrolled and followed for a mean duration of 7.0 ± 2.6 years. At follow-up, there were a total of 723 MAE, 278 MACE, 547 all-cause deaths, 110 cardiac deaths, and 104 non-fatal myocardial infarction. Patients without coronary atherosclerosis at the time of CCTA had a very low annual event rate for both MAE and MACE (0.45%/year and 0.19%/year, respectively). Both MAE and MACE increased with increasing TPS and severity of CAD. In patients with non-obstructive CAD and who were statin-naive, TPS ≥5 had MACE rates >0.75%/year. Patients with high-risk CAD had an annual MAE and MACE rates of 3.52%/year and 2.58%/year, respectively. Adjusted hazard ratio of the severity of CAD based on multivariable analyses indicated that the prognostic values were incremental., Conclusion: CCTA has independent and incremental prognostic value that is durable over time. The absence of coronary atherosclerosis portends an excellent prognosis. Patients with increasing non-obstructive plaque burden have worse prognosis and a TPS threshold ≥5 may identify a population that may benefit from statin therapy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study sought to develop a clinical model that identifies a lower-risk population for coronary artery disease that could benefit from stress-first myocardial perfusion imaging (MPI) protocols and that can be used at point of care to risk stratify patients., Background: There is an increasing interest in stress-first and stress-only imaging to reduce patient radiation exposure and improve patient workflow and experience., Methods: A secondary analysis was conducted on a single-center cohort of patients undergoing single-photon emission computed tomography (SPECT) and positron emission tomography (PET) studies. Normal MPI was defined by the absence of perfusion abnormalities and other ischemic markers and the presence of normal left ventricular wall motion and left ventricular ejection fraction. A model was derived using a cohort of 18,389 consecutive patients who underwent SPECT and was validated in a separate cohort of patients who underwent SPECT (n = 5,819), 1 internal cohort of patients who underwent PET (n=4,631), and 1 external PET cohort (n = 7,028)., Results: Final models were made for men and women and consisted of 9 variables including age, smoking, hypertension, diabetes, dyslipidemia, typical angina, prior percutaneous coronary intervention, prior coronary artery bypass graft, and prior myocardial infarction. Patients with a score ≤1 were stratified as low risk. The model was robust with areas under the curve of 0.684 (95% confidence interval [CI]: 0.674 to 0.694) and 0.681 (95% CI: 0.666 to 0.696) in the derivation cohort, 0.745 (95% CI: 0.728 to 0.762) and 0.701 (95% CI: 0.673 to 0.728) in the SPECT validation cohort, 0.672 (95% CI: 0.649 to 0.696) and 0.686 (95% CI: 0.663 to 0.710) in the internal PET validation cohort, and 0.756 (95% CI: 0.740 to 0.772) and 0.737 (95% CI: 0.716 to 0.757) in the external PET validation cohort in men and women, respectively. Men and women who scored ≤1 had negative likelihood ratios of 0.48 and 0.52, respectively., Conclusions: A novel model, based on easily obtained clinical variables, is proposed to identify patients with low probability of having abnormal MPI results. This point-of-care tool may be used to identify a population that might qualify for stress-first MPI protocols., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: There is conflicting data on early left ventricle (LV) remodeling in diabetes mellitus (DM) and hypertension (HTN). This study examines the feasibility of cardiac computed tomography angiography (CCTA) to detect early LV geometric changes in patients with DM and HTN., Methods: Consecutive patients (n = 5,992) who underwent prospective electrocardiography (ECG)-triggered (mid-diastolic) CCTA were screened. Patients with known structural heart disease or known LV dysfunction were excluded. Left ventricular mass (LVM), left ventricular mid-diastolic volume (LVMDV), and LV concentricity (LVM/LVMDV) were measured and indexed to body surface area., Results: A total of 4,283 patients were analyzed (mean age 57 ± 10.69 years, female 46.7%). DM, HTN, and HTN + DM were present in 4.1%, 35.8% and 10.6% of patients, respectively. Compared to normal patients, HTN and HTN + DM patients had increased LVM indexed to body surface area (LVMi) (56.87 ± 17.24, 59.26 ± 13.62, and 58.56 ± 13.09, respectively; P < 0.05). There was no difference in LVMi between normal subjects and patients with DM (56.39 ± 11.50, P = 0.617).Concentricity indices were higher in patient with HTN (1.0456 ± 0.417; P < 0.001), DM (1.109 ± 0.638; P = 0.004), and HTN + DM (1.083 ± 0.311, P < 0.001) than normal individuals (0.9671 ± 0.361). There was no overlap of the 95% confidence intervals in the composite of concentricity indices and LVMi between the different groups., Conclusions: CCTA measures of LVM and concentricity index may discriminate patients with HTN and DM before overt structural heart disease., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aims: The impact of anatomical versus functional testing in patients with prior coronary artery bypass surgery (CABG) is poorly defined. We therefore sought to determine the rates of downstream investigations and the attendant healthcare costs in CABG patients undergoing CCTA versus SPECT., Methods and Results: 2754 consecutive CABG patients were imaged by SPECT (2163) or CCTA (591). 425 patients (15.4%) underwent downstream testing which was more common in those imaged with CCTA versus SPECT (23.18% vs 13.31% respectively, p < 0.01). When a propensity score adjustment was made for differences in baseline characteristics, the findings in downstream testing persisted (p < 0.01). When patients who subsequently underwent repeat revascularization (arguably the highest risk patients) were removed from the analysis, downstream testing remained more frequent in CCTA (12.7%) versus SPECT imaged patients (8.8%) (p = 0.01). Costs of downstream tests per patient were two-fold greater in the CCTA group in comparison to the SPECT group ($366.79 ± 29.59 vs $167.35 ± 10.12 respectively, p < 0.01). Conversely, total costs which included the index costs were less in the CCTA group, $764.66 ± 29.59 versus $1396.73 ± 1012 for the SPECT cohort, p < 0.0001)., Conclusions: Index imaging with SPECT versus CCTA in CABG patients was associated with fewer downstream tests, less ICA, less repeat revascularization but greater expense. Cost however is only part of the decision making process that determines an optimal index test. Until CCTA demonstrates improved risk stratification over SPECT in CABG patients it is likely SPECT will remain the preferred first imaging test., (© 2020 The Authors.)

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Objectives: This study sought to: 1) determine if the current training volume guidelines are reasonable for attaining competence for interpreting myocardial perfusion imaging (MPI); and if not, 2) identify potential thresholds for training volumes and competence., Background: There is a growing desire to adopt competency-based medical education (CBME). As such, the implementation of CBME will require new and novel methods of defining, measuring, and assessing clinical competence. The potential use of CBME in cardiac imaging has not been well studied., Methods: Consecutive MPI studies were interpreted independently by trainees, and expert readers reviewed the same studies. Studies were quantified using summed scores and % left ventricular (LV) ischemia and the kappa agreement between trainee and expert were measured every 50 cases. Agreement for all MPI and abnormal MPI cases was calculated., Results: A total of 24 trainees interpreted 9,668 MPI studies over 37 months. Agreement between trainees and expert readers increased with MPI case volumes but at different rates. The threshold for competence was set at 2 SDs below expert interobserver agreement. The average trainee surpassed this threshold for both summed stress score and %LV ischemia after 800 studies and after 400 abnormal MPI studies. Trainees learned at different rates and surpassed the competence threshold after different case volumes., Conclusions: The use of CBME within nuclear cardiology appears to be feasible. Our results suggest that current guidelines may be insufficient to ensure competence and would support the need to increase the MPI case volumes. The use of CBME principles would suggest that trainees may achieve competence at different rates and our results suggest a shift in focus from volume-based learning toward target agreement thresholds., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Thermal discomfort is one of the main triggers for occupants' interactions with components of the built environment such as adjustments of thermostats and/or opening windows and strongly related to the energy use in buildings. Understanding causes for thermal (dis-)comfort is crucial for design and operation of any type of building. The assessment of human thermal perception through rating scales, for example in post-occupancy studies, has been applied for several decades; however, long-existing assumptions related to these rating scales had been questioned by several researchers. The aim of this study was to gain deeper knowledge on contextual influences on the interpretation of thermal perception scales and their verbal anchors by survey participants. A questionnaire was designed and consequently applied in 21 language versions. These surveys were conducted in 57 cities in 30 countries resulting in a dataset containing responses from 8225 participants. The database offers potential for further analysis in the areas of building design and operation, psycho-physical relationships between human perception and the built environment, and linguistic analyses.

Background: Obesity is an in independent risk factor for cardiovascular disease., Goal: To describe the early LV remodelling pattern in patients with overweight and obesity and structurally normal hearts., Methods: Consecutive patients (n = 2374), with structurally normal hearts and BMI ≥ 18.5 kg/m 2 , undergoing prospective mid-diastolic ECG gated CTCA were selected. Left ventricular mass (LVM) and Left ventricular mid-diastolic volume (LVMDV) were measured. The concentricity index (LVM/LVMDV) were calculated. According to the definitions of the World Health Organization (WHO), the patients were divided into weight categories., Results: The mean LVM ± Std. deviation in the subgroups according to WHO classification was 101.68 ± 28.99 g (normal weight), 115.79 ± 29.14 g (overweight), 123.8 ± 33.44 g (class I obesity), 125.85 ± 32.89 g (class II obesity) and 132.45 ± 37.85 g (class III obesity). (p < 0.001) The mean LVMDV progressed with increasing WHO weight category from 112.37 ± 36.46 in patients with normal BMI to 140.26 ± 43.78 in patients with class III obesity. (p < 0.001) The concentricity index was 0.935 ± 0.216 g/ml in patients with normal BMI, 0.979 ± 0.253 g/ml, 1.058 ± 0.635 g/ml, 0.996 ± 0.284 g/ml and 0.9768 ± 0.244 g/ml in patients with BMI categories 25-29.99, 30-34.99, 35-39.99 and ≥40 kg/m 2 , respectively., Conclusions: Our study demonstrates a non-linear (inverse U-shape) relationship between increasing BMI class and concentricity index, reaching its maximum at a BMI of 30-34.99 kg/m 2 . Further increase in BMI results in LV dilation., (Copyright © 2019 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background: Coronary computed tomography angiography (CCTA) left ventricle (LV) volumes have prognostic value. LV measurements however can differ depending on post-processing software. Two common methods are the contour (CON) or attenuation (ATT) based methods. This study aims to determine differences in LV volume measurements using the 2 methods., Methods: LV mid-diastolic volumes (LVMDV) were measured using both ATT and CON from 2 vendors in 750 consecutive patients undergoing CCTA. 500 were measured in a derivation cohort to establish a linear regression equation that would correct for any detected differences between the two methods. The equation was then assessed in 250 cases in the validation cohort. Comparisons were made between intra-vendor LVMDV CON and LVMDV ATT as well as inter-vendor LVMDV ATT ., Results: In the derivation cohort, the correlation between the two methods and vendors were very good (0.98 and 0.97 respectively). LVMDV CON was 20.4 ± 7.4% greater than LVMDV ATT . LVMDV ATT was 9.2 ± 6.6% greater with one vendor compared to the other. Validation cohort corrected LVMDV ATT was not statistically different to measured LVMDV ATT (p = 0.45)., Conclusion: A systematic difference was found between ATT and CON measuring methods. Using a derived linear regression equation, we were able to correct for differences in measurement techniques. The method of LVMDV measurement requires careful consideration when establishing reference values and extrapolating published study results., (Copyright © 2019 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

The surface plasmon resonance (SPR) sensor is an important tool widely used for studying binding kinetics between biomolecular species. The SPR approach offers unique advantages in light of its real-time and label-free sensing capabilities. Until now, nearly all established SPR instrumentation schemes are based on single- or several-channel configurations. With the emergence of drug screening and investigation of biomolecular interactions on a massive scale these days for finding more effective treatments of diseases, there is a growing demand for the development of high-throughput 2-D SPR sensor arrays based on imaging. The so-called SPR imaging (SPRi) approach has been explored intensively in recent years. This review aims to provide an up-to-date and concise summary of recent advances in SPRi. The specific focuses are on practical instrumentation designs and their respective biosensing applications in relation to molecular sensing, healthcare testing, and environmental screening.

Extent of coronary atherosclerotic disease (CAD) burden on coronary computed tomography angiography (CCTA) as measured by segment involvement score (SIS) has a prognostic value. We sought to investigate the incremental prognostic value of 'age adjusted SIS' (aSIS), which may be a marker of premature atherosclerosis and vascular age. Consecutive patients were prospectively enrolled into the CONFIRM (Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicentre) multinational observational study. Patients were followed for the outcome of all-cause death. aSIS was calculated on CCTA for each patient, and its incremental prognostic value was evaluated. A total of 22,211 patients [mean age 58.5 ± 12.7 years, 55.8% male) with a median follow-up of 27.3 months (IQR 17.8, 35.4)] were identified. After adjustment for clinical factors and presence of obstructive CAD, higher aSIS was associated with increased death on multivariable analysis, with hazard ratio (HR) 2.40 (1.83-3.16, p < 0.001), C-statistic 0.723 (0.700-0.756), net reclassification improvement (NRI) 0.36 (0.26-0.47, p < 0.001), and relative integrated discrimination improvement (IDI) 0.33 (p = 0.009). aSIS had HR 3.48 (2.33-5.18, p < 0.001) for mortality in those without obstructive CAD, compared to HR 1.79 (1.25-2.58, p = 0.02) in those with obstructive CAD. In conclusion, aSIS has an incremental prognostic value to traditional risk factors and obstructive CAD, and may enhance CCTA risk stratification.

This paper reports a digital micro-mirror device (DMD)-enabled real-time multi-channel biosensing system based on angular interrogation surface plasmon resonance (SPR). In the experiments, angular scanning is achieved by a DMD that facilitates SPR measurements using a single-point photodetector. In the four-channel measurement setup, real-time monitoring of bovine serum albumin (BSA) and anti-BSA binding interactions is performed at various concentration levels. The experimental results have verified that the system has a resolution of 3.54 × 10 -6 RIU (refractive index unit); and a detection limit of 9 ng/mL. The new DMD-based SPR interrogation system presents a new design route for practical solid-state SPR biosensing with a user-selectable range of interrogation, enhanced signal-to-noise ratio, and fast data throughput.

Background: Prognostic value of positron emission tomography (PET) myocardial perfusion imaging (MPI) is well established. There is paucity of data on how the prognostic value of PET relates to the hemodynamic response to vasodilator stress. We hypothesize that inadequate hemodynamic response will affect the prognostic value of PET MPI., Methods and Results: Using a multicenter rubidium (Rb)-82 PET registry, 3406 patients who underwent a clinically indicated rest/stress PET MPI with a vasodilator agent were analyzed. Patients were categorized as, "responders" [increase in heart rate ≥ 10 beats per minute (bpm) and decrease in systolic blood pressure (SBP) ≥10 mmHg], "partial responders" (either a change in HR or SBP), and "non-responders" (no change in HR or SBP). Primary outcome was all-cause death (ACD), and secondary outcome was cardiac death (CD). Ischemic burden was measured using summed stress score (SSS) and % left ventricular (LV) ischemia. After a median follow-up of 1.68 years (interquartile range = 1.17- 2.55), there were 7.9% (n = 270) ACD and 2.6% (n = 54) CD. Responders with a normal PET MPI had an annualized event rate (AER) of 1.22% (SSS of 0-3) and 1.58% (% LV ischemia = 0). Partial and non-responders had higher AER with worsening levels of ischemic burden. In the presence of severe SSS ≥12 and LV ischemia of ≥10%, partial responders had an AER of 10.79% and 10.36%, compared to non-responders with an AER of 19.4% and 12.43%, respectively. Patient classification was improved when SSS was added to a model containing clinical variables (NRI: 42%, p < 0.001) and responder category was added (NRI: 61%, p < 0.001). The model including clinical variables, SSS and hemodynamic response has good discrimination ability (Harrell C statistics: 0.77 [0.74-0.80])., Conclusion: Hemodynamic response during a vasodilator Rb-82 PET MPI is predictive of ACD. Partial and non-responders may require additional risk stratification leading to altered patient management.

Purpose: Cardiac imaging expenditures have come under scrutiny, and a focus on appropriate use criteria (AUC) has arisen to ensure cost-effective resource utilization. Although AUC has been developed by clinical experts, it has not undergone rigorous quality assurance testing to ensure that inappropriate indications for testing yield little clinical benefit. The objective of the study was to evaluate the potential incremental prognostic value of coronary computed tomographic angiography (CCTA) in the different AUC categories., Materials and Methods: Consecutive patients enrolled into a cardiac CT Registry were collated. Patient indications were reviewed and based on the 2010 AUC (appropriate, uncertain, and inappropriate). Patients were followed-up for death, myocardial infarction (MI), and late revascularization, with the primary composite endpoint being cardiac death, nonfatal MI, and late revascularization. The prognostic value of CCTA over clinical variables in each of the AUC categories was assessed., Results: Indications for CCTA were appropriate, uncertain, and inappropriate in 1284 (66.5%), 312 (16.2%), and 334 (17.3%) patients, respectively. Rates of all-cause of death, cardiac death, nonfatal MI, and late revascularization were similar across patients with appropriate, uncertain, and inappropriate indications for CCTA. Moreover, in each AUC category, CCTA had incremental prognostic value over a routine clinical risk score (National Cholesterol Education Program) with hazard ratios of 9.98, 7.39, and 5.61., Conclusions: CCTA has incremental prognostic value in all AUC categories, even when the reason for the study was deemed "inappropriate." This suggests that CCTA may still have clinical value in "inappropriate" indications and that further quality assurance AUC studies are needed.

This paper presents the design of a sliding mode controller for networked control systems subject to successive Markovian packet dropouts. This paper adopts the Gilbert-Elliott channel model to describe the temporal correlation among packet losses, and proposes an update scheme to select the assumed available states for use in a sliding mode control law. A technique used in the theory of discrete-time Markov jump linear systems is applied to tackle the effect of the packet losses. This involves introducing a couple of Lyapunov functions dependent on the indicator functions of the instantaneous packet loss, and proving that the sliding mode controller is able to drive the system state trajectories into the neighborhood of the designed integral sliding surface in mean-square sense given that the corresponding Lyapunov inequalities are satisfied. The system is guaranteed thereafter to remain inside the neighborhood of the sliding surface. Simulated case studies are presented to illustrate the effectiveness of the control law.

Background: Appropriate Use Criteria (AUC) guidelines for cardiac computed tomography (CCT) were developed to limit testing to reasonable clinical settings. However, significant testing is still done for inappropriate indications. This study investigates the impact of AUC on evaluability of CCT to determine if inappropriate tests result in a greater proportion of nondiagnostic results., Methods: Investigators reviewed the medical records of 2417 consecutive patients who underwent CCT at the University of Ottawa Heart Institute. We applied the 2010 AUC and classified them as appropriate, inappropriate, or uncertain. Unclassifiable tests, as well as those with uncertain appropriateness, were excluded from the final analysis. Cardiac computed tomography results were classified as diagnostic if (1) all coronary segments were visualized, evaluable, and without obstructive stenosis; or (2) obstructive coronary artery disease with greater than 50% diameter stenosis in at least 1 coronary artery. All other test results were considered nondiagnostic., Results: Of the 1984 patients included in the final analysis, 1522 patients (76.7%) had indications that were appropriate, whereas the remaining 462 (23.3%) were inappropriate. Inappropriate tests resulted in a higher rate of nondiagnostic results compared with appropriate CCT (9.0% vs 6.2%, P = 0.034). Inappropriate tests also had significantly more studies with nonevaluable segments than appropriate tests (24.5% vs 16.4%, P < 0.001) and were more likely to reveal obstructive coronary disease than appropriate CCT (50.5% vs 32.7%, P < 0.001)., Conclusions: Cardiac computed tomography done for inappropriate indications may be associated with lower diagnostic yield and could impact future downstream resource utilization and health care costs.

Background: Coronary artery disease is a leading killer of women. Arterial stiffness predicts myocardial infarction, and postmenopausal women have lower arterial compliance (AC) than men. We hypothesized that lower AC would be associated with greater burden of coronary artery plaque and calcification, and that these associations would be stronger in women than men., Methods and Results: We evaluated 3639 consecutive adults without coronary artery disease history who had coronary computed tomography between 2006 and 2014. Coronary artery calcification was calculated using the Agatston method. Plaque extent was assessed by the number of arterial segments with visible plaque divided by the number of visualized segments ×100 (percent plaque score). Indexed AC was calculated as stroke volume index/central pulse pressure. We used step-wise multivariable linear regression to assess associations of log indexed AC with log (percent plaque score+1) and log (coronary artery calcification+1). Sex-specific models were performed if the interaction sex×AC was significant. Mean age was 57±11 years, 53% were men, and 71% were hypertensive. Interaction term sex×AC was significant for both models ( P =0.008 for percent plaque score and 0.022 for coronary artery calcification). Lower indexed AC was associated with higher percent plaque score and coronary artery calcification in women (β±SE: -0.231±0.113, P =0.042 and -0.334±0.166, P =0.044, respectively), but not in men (β±SE: -0.062±0.104, P =0.551 and 0.114±0.173, P =0.510, respectively)., Conclusions: Lower AC is associated with greater burden of coronary artery plaque and calcification in women, but not in men. Our findings highlight low AC as a correlate of more-advanced coronary artery disease and as a potential link to the worse cardiovascular outcomes in women., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Preliminary data suggests the absence of coronary artery calcification (CAC) excludes ischemic etiologies of cardiomyopathy. We prospectively validate and perform a systematic review to determine the utility of an Agatston score=0 to exclude the diagnosis of ischemic cardiomyopathy., Methods and Results: Patients with newly diagnosed LV dysfunction were prospectively enrolled. Patients underwent CAC imaging and were followed until an etiologic diagnosis of cardiomyopathy was made. Eighty-two patients were enrolled in the study and underwent CAC imaging with 81.7% patients having non-ischemic cardiomyopathy. An Agatston score=0 successfully excluded an ischemic etiology for cardiomyopathy with a specificity of 100% (CI: 74.7-100%) and a positive predictive value of 100% (CI: 85.0%-100%). A systematic literature review was performed and studies were deemed suitable for inclusion if: 1) patients with CHF, cardiomyopathy or LV dysfunction were enrolled, 2) underwent CAC imaging and patients were assessed for an Agatston score=0 or the absence of CAC, and 3) the final etiologic diagnosis (ischemic or non-ischemic) was provided. Eight studies provided sufficient information to calculate operating characteristics for an Agatston score=0 and were combined with our validation cohort for a total of 754 patients. An Agatston score=0 excluded ischemic cardiomyopathy with specificity and positive predictive values of 98.4% (CI: 95.6-99.5%), and 98.3% (CI: 95.5-99.5%), respectively., Conclusions: In patients with cardiomyopathy of unknown etiology, an Agatston score=0 appears to rule out an ischemic etiology. A screening CAC may be a simple and cost-effective method of triaging patients, identifying those who do and do not need additional CAD investigations., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Downstream resource utilization and its impact on outcomes after a canceled CCTA have not been well studied. We sought to understand downstream resource utilization and patient outcomes after canceled CCTA., Methods and Results: Consecutive patients were prospectively enrolled into an institutional cardiac CT registry. Patients who had the CCTA study canceled because of severe coronary calcification were followed for downstream resource utilization and the composite of all-cause mortality and non-fatal myocardial infarction (MI). 463 patients had their CCTA canceled due to severe coronary calcification and follow-up was available for 453 (97.8%) patients (median follow-up=36.0months). There were a total of 62 events (41 all-cause deaths and 21 non-fatal MI) with an annualized event rate of 4%. Three hundred and twenty patients underwent downstream CAD (ICA or MPI or EST) investigations. Age, NCEP/ATP III risk, beta-blocker use, Agatston and downstream CAD testing were associated with the primary outcome. There were fewer events in those that received downstream CAD testing (30 (9.7%) versus 32 (22.4%)). The annualized event rates for those who did and did not receive downstream CAD testing were 2.8% and 6.2%, respectively. Multivariable analysis confirmed that downstream CAD testing was an independent predictor of event-free survival and that the absence of additional CAD testing was associated with worse outcome (HR: 2.58 (95% CI: 1.54-4.31))., Conclusions: Patients with canceled CCTA due to severe and/or extensive CAC have high rates of death and non-fatal MI. The use of additional CAD testing appears to be associated with improved outcomes., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aims: To determine the influence of cardiac motion on measurements of left ventricular (LV) mass obtained with 64-slice computed tomography (CT) and to elucidate the prognostic value of LV mass on major adverse cardiac events (MACE) and all-cause mortality. Increased LV mass has been linked with MACE. Although Cardiac CT allows measurement of LV anatomy, it is susceptible to motion artefacts often requiring image acquisition during diastasis. There is a need to understand variability in LV mass measurements across phases of the cardiac cycle, and whether mid-diastolic measurements have prognostic value., Methods and Results: The study comprised two equally sized cohorts of patients that had undergone retrospectively gated cardiac CT: patients who had MACE and/or all-cause death at follow-up and a matched (age, sex, and risk factors) event-free cohort. LV mass was measured at mid-diastole, end-diastole, and end-systole. Correlation and agreement between phases were determined. The incremental value of mid-diastolic hypertrophy (LVH) over the National Cholesterol Education Programme (NCEP) risk was performed for LV mass indices normalized to body surface area (LVMI BSA ) or weight (LVMI Weight ). Of 166 patients, 31.3% experienced MACE and 28.9% died of any cause (follow-up 22.9 ± 13.4 months). LV mass at all cardiac phases were strongly correlated (r > 0.94). Mean mid-diastolic LVMI BSA was higher in the cohort with events (93.7 vs. 80.7 g/m 2 , P= 0.008) as was LVMI Weight (2.26 vs. 1.88 g/kg, P = 0.001). LVMI BSA and LVMI Weight had prognostic value incremental to NCEP with 1.85 and 2.47 hazard ratios, respectively., Conclusions: Measurement of LV mass can be obtained by cardiac CT images obtained at mid-diastasis. LV mass measurements obtained at mid-diastasis have prognostic value., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: Total plaque score (TPS) on coronary computed tomography angiography (CCTA) has been validated as a surrogate measure of coronary artery disease (CAD) burden and is prognostic. We propose a novel measure, percentage TPS adjusted to age (%TPS/age), that may reflect vascular age and potentially more rapidly progressive atherosclerosis and evaluate its potential prognostic value., Methods: %TPS/age was calculated for consecutive patients prospectively enrolled into our institutional CCTA registry and evaluated for primary composite outcome of cardiac death, nonfatal myocardial infarction, and late revascularization., Results: Of 1896 patients identified (mean age 57.7 ± 11.4 years, 50.1% male, median follow-up 18.6 months [interquartile range: 15.3, 32.4]), 552 (29%) had %TPS/age = 0 (no atherosclerosis), with 1 (0.2%) primary outcome observed (annual event rate [AER] = 0.1%). Two events (0.4%, AER = 0.3%) were observed in %TPS/age < 0.314 category, 22 (5.0%, AER = 2.2%) in %TPS/age 0.314 to 0.699 category, and 54 (12.0%, AER = 5.7%) in %TPS/age ≥ 0.700 category. After adjusting for clinical predictors and obstructive CAD, higher %TPS/age category was associated with hazard ratio 1.95 (1.31-2.88, P < .001) for primary outcome on multivariable analysis, Harrell-C-Statistic 0.87 (confidence interval 95%: 0.84-0.90), and net reclassification improvement of 0.71 ( P < .001)., Conclusion: %TPS/Age has incremental prognostic value to traditional risk factors and CCTA measures of CAD and improves evaluation of burden of coronary atherosclerosis and clinical risk.

Background: Cardiac CT is a non-invasive modality with the ability to estimate LVEF. However, given its limited temporal resolution and radiation, there has been initial resistance to use CT to measure LVEF. Developing an accurate, fast, low radiation dose protocol is desirable., Objective: The objective of this study is to demonstrate that a 'low radiation dose' 64 slice cardiac computed tomography (CT) protocol is feasible and can accurately measure left ventricular ejection fraction (LVEF) while delivering a radiation dose lower than radionuclide angiography (RNA)., Methods: Patients undergoing RNA were prospectively screened and enrolled to undergo a 'low-dose' 64 slice CT LVEF protocol. LVEF measures, duration of each study and radiation dose between CT and RNA were compared., Results: A total of 77 patients (mean age = 61.8 ± 12.2 years and 58 men) were analyzed. The mean LVEF measured by CT and RNA were 41.9 ± 15.2% and 39.4 ± 13.9%, respectively, (P = 0.154) with a good correlation (r = 0.863). Bland-Altman plot revealed a good agreement between the CT and RNA LVEF (mean difference of -2.4). There was good agreement between CT LVEF and RNA for identifying patients with LVEF ≤30% (kappa = 0.693) and LVEF ≥50% (kappa = 0.749). The mean dose estimated effective dose for CT and RNA were 4.7 ± 1.6 and 9.5 ± 1.0 mSv, respectively. The mean CT LVEF imaging duration (4:32 ± 3:05 minutes) was significantly shorter than the RNA image acquisition time (9:05 ± 2:36 minutes; p < 0.001)., Conclusion: The results of our study suggest that low-dose CT LVEF protocol is feasible, accurate, and fast while delivering a lower radiation dose than traditional RNA.

The inverse relationship between obesity and adverse cardiovascular outcomes has been coined the 'obesity-paradox'. We sought to determine the relationship between measures of obesity [body mass index (BMI), body surface area (BSA) and body fat percentage (BF%)] and coronary artery calcification (CAC). We retrospectively analyzed patients who underwent CAC using the Agatston score. Baseline demographics were collected and BMI, BSA and BF% were calculated. A two-stage regression modeling approach was used to evaluate the association between BMI, BSA, BF% and Agatston score. Of the 6661 patients [mean age = 57.1 ± 10.8 years, men = 54.3%, median Agatston score = 14 (0, 163)], 0.1% were underweight, 21.3% had normal BMI, 39.1% were overweight and 39.4% were obese. The mean BMI, BSA and BF% were 29.6 ± 6.1 kg/m(2), 1.97 ± 0.25 m(2) and 37 ± 10 %, respectively. There was an independent association between the presence of CAC and BMI (5 kg/m(2) increments) (OR 1.05, CI 1.00-1.11, P = 0.038) and BF% (OR 2.38, CI 1.05-5.41, P = 0.038). Neither BMI categories nor large BSA independently predicted the presence of CAC. BF% predicted the extent of CAC in men but not in women, and higher BF% was associated with higher category of CAC severity in men only. BMI and BF% were independent predictors of the presence of CAC. BF% was associated with the extent of CAC and higher BF% was associated with higher category of CAC severity in men only. These results suggest that further study is needed to better understand the obesity-paradox.

Objectives: This study sought to develop a clinical model that identifies patients with and without high-risk coronary artery disease (CAD)., Background: Although current clinical models help to estimate a patient's pre-test probability of obstructive CAD, they do not accurately identify those patients with and without high-risk coronary anatomy., Methods: Retrospective analysis of a prospectively collected multinational coronary computed tomographic angiography (CTA) cohort was conducted. High-risk anatomy was defined as left main diameter stenosis ≥50%, 3-vessel disease with diameter stenosis ≥70%, or 2-vessel disease involving the proximal left anterior descending artery. Using a cohort of 27,125, patients with a history of CAD, cardiac transplantation, and congenital heart disease were excluded. The model was derived from 24,251 consecutive patients in the derivation cohort and an additional 7,333 nonoverlapping patients in the validation cohort., Results: The risk score consisted of 9 variables: age, sex, diabetes, hypertension, current smoking, hyperlipidemia, family history of CAD, history of peripheral vascular disease, and chest pain symptoms. Patients were divided into 3 risk categories: low (≤7 points), intermediate (8 to 17 points) and high (≥18 points). The model was statistically robust with area under the curve of 0.76 (95% confidence interval [CI]: 0.75 to 0.78) in the derivation cohort and 0.71 (95% CI: 0.69 to 0.74) in the validation cohort. Patients who scored ≤7 points had a low negative likelihood ratio (<0.1), whereas patients who scored ≥18 points had a high specificity of 99.3% and a positive likelihood ratio (8.48). In the validation group, the prevalence of high-risk CAD was 1% in patients with ≤7 points and 16.7% in those with ≥18 points., Conclusions: We propose a scoring system, based on clinical variables, that can be used to identify patients at high and low pre-test probability of having high-risk CAD. Identification of these populations may detect those who may benefit from a trial of medical therapy and those who may benefit most from an invasive strategy., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: We sought to examine the risk of mortality associated with nonobstructive coronary artery disease (CAD) and to determine the impact of baseline statin and aspirin use on mortality., Approach and Results: Coronary computed tomographic angiography permits direct visualization of nonobstructive CAD. To date, the prognostic implications of nonobstructive CAD and the potential benefit of directing therapy based on nonobstructive CAD have not been carefully examined. A total of 27 125 consecutive patients who underwent computed tomographic angiography (12 enrolling centers and 6 countries) were prospectively entered into the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry. Patients, without history of previous CAD or obstructive CAD, for whom baseline statin and aspirin use was available were analyzed. Each coronary segment was classified as normal or nonobstructive CAD (1%-49% stenosis). Patients were followed up for a median of 27.2 months for all-cause mortality. The study comprised 10 418 patients (5712 normal and 4706 with nonobstructive CAD). In multivariable analyses, patients with nonobstructive CAD had a 6% (95% confidence interval, 1%-12%) higher risk of mortality for each additional segment with nonobstructive plaque (P=0.021). Baseline statin use was associated with a reduced risk of mortality (hazard ratio, 0.44; 95% confidence interval, 0.28-0.68; P=0.0003), a benefit that was present for individuals with nonobstructive CAD (hazard ratio, 0.32; 95% confidence interval, 0.19-0.55; P<0.001) but not for those without plaque (hazard ratio, 0.66; 95% confidence interval, 0.30-1.43; P=0.287). When stratified by National Cholesterol Education Program/Adult Treatment Program III, no mortality benefit was observed in individuals without plaque. Aspirin use was not associated with mortality benefit, irrespective of the status of plaque., Conclusions: The presence and extent of nonobstructive CAD predicted mortality. Baseline statin therapy was associated with a significant reduction in mortality for individuals with nonobstructive CAD but not for individuals without CAD., Clinical Trial Registration: URL: http://clinicaltrials.gov/. Unique identifier NCT01443637., (© 2015 American Heart Association, Inc.)

Background: Cardiac allograft vasculopathy is a key prognostic determinant after heart transplant. Detection and risk stratification of patients with cardiac allograft vasculopathy are problematic. Positron emission tomography using rubidium-82 allows quantification of absolute myocardial blood flow and may have utility for risk stratification in this population., Methods and Results: Patients with a history of heart transplant undergoing dipyridamole rubidium-82 positron emission tomography were prospectively enrolled. Myocardial perfusion and left ventricular ejection fraction were recorded. Absolute flow quantification at rest and after dipyridamole stress as well as the ratio of mean global flow at stress and at rest, termed myocardial flow reserve, were calculated. Patients were followed for all-cause death, acute coronary syndrome, and heart failure hospitalization. A total of 140 patients (81% men; median age, 62 years; median follow-up, 18.2 months) were included. There were 14 events during follow-up (9 deaths, 1 acute coronary syndrome, and 4 heart failure admissions). In addition to baseline clinical variables (estimated glomerular filtration rate, previously documented cardiac allograft vasculopathy), relative perfusion defects, mean myocardial flow reserve, and mean stress myocardial blood flow were significant predictors of adverse outcome., Conclusions: Abnormalities on rubidium-82 positron emission tomography were predictors of adverse events in heart transplant patients. Larger prospective studies are required to confirm these findings., (© 2014 American Heart Association, Inc.)

Aims: We sought to determine the prognostic value of positron emission tomography (PET) myocardial perfusion imaging (MPI) in patients with prior coronary artery bypass graft (CABG) surgery. PET MPI has recently been shown to provide incremental risk stratification for patients with suspected coronary artery disease (CAD), but the prognostic utility of PET MPI in CABG patients has not been well studied., Methods and Results: A multi-centre PET registry of 7061 patients who underwent Rb-82 PET MPI from four participating centres was screened. Nine hundred and fifty-three CABG patients were identified and their images were analysed. Outcomes of all-cause mortality and cardiac death were collected. With a mean follow-up of 2.4 ± 1.4 years, 128 (13.4%) all-cause deaths and 44 (4.6%) cardiac deaths were observed. Multivariable analyses, adjusted for clinical variables, demonstrated that the summed stress score (SSS) was a significant independent predictor of both all-cause mortality [HR: 1.60 (per 1 category increase in SSS); 95% CI: 1.34-1.92; P < 0.001] and cardiac death (HR: 1.80; 95% CI: 1.33, 2.44; P < 0.001). The receiver-operator characteristic (ROC) curves showed that the addition of SSS increased the area under the curve (AUC) from 0.645 to 0.693 (P = 0.014) for all-cause mortality, and from 0.612 to 0.704 (P = 0.027) for cardiac death. SSS also improved the net reclassification improvement (NRI) for all-cause mortality (category-free NRI = 0.422; 95% CI: 0.240-0.603; P < 0.001) and cardiac death (category-free NRI = 0.552; 95% CI: 0.268-0.836; P < 0.001)., Conclusions: PET MPI provides independent and incremental prognostic value to clinical variables in predicting all-cause mortality and cardiac death in CABG patients., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Aims: To evaluate the practical use of the single slice measurement of epicardial adipose tissue (EAT) at the level of the left main coronary artery (EATLM) in predicting the presence of obstructive coronary artery disease (CAD)., Methods and Results: Quantification of EATTotal and EATLM was performed on non-contrast CT scans of consecutive patients (without history of revascularization, cardiac transplantation, device implantation, and congenital heart disease) who underwent coronary artery calcium (CAC) scoring and computed tomographic coronary angiography (CTA) between May 2011 and July 2011. One hundred and ninety-two patients were evaluated, of which 47 had obstructive CAD (>50% stenosis). EATLM (3.8 ± 2.2 cm(3)) and EATTotal (126.2 ± 56.3 cm(3)) are highly correlated (r = 0.89, P < 0.001). Multivariate analysis revealed that both EATLM (OR: 1.204 per 1 cm(3), 95% CI: 1.028-1.411, P = 0.021) and EATTotal (OR: 1.007 per 10 cm(3), 95% CI: 1.000-1.013, P = 0.038) are associated with obstructive CAD. However, when the CAC score was added to multivariate analysis, both failed to show statistical significance. (EATTotal, OR 1.004 per 1 cm(3), 95% CI: 0.996-1.011, P = 0.328 and EATLM, OR: 1.136 per 10 cm(3), 95% CI: 0.948-1.362) ROC curve analysis revealed that both EATTotal and EATLM are of incremental value in detecting CAD, when compared with clinical risk scores (NCEP plus EATTotal plus BMI and NCEP plus EATLM plus BMI vs. NCEP alone; AUC 0.7090, P = 0.009 and 0.7167, P = 0.003 vs. 0.6069, respectively)., Conclusion: Measuring epicardial adipose tissue on a single slice at the level of the left main coronary artery may serve as an indirect measure of total epicardial adipose tissue burden. EATLM and EATTotal are independently associated with obstructive coronary artery disease and are incremental to traditional risk factors for predicting its presence.

Objectives: This study sought to determine and compare the prognostic and incremental value of positron emission tomography (PET) in normal, overweight, and obese patients., Background: Cardiac rubidium 82 (Rb-82) PET is increasingly being used for myocardial perfusion imaging (MPI). A strength of PET is its accurate attenuation correction, thereby potentially improving its diagnostic accuracy in obese patients. The prognostic value of PET in obese patients has not been well studied., Methods: A total of 7,061 patients who had undergone Rb-82 PET MPI were entered into a multicenter observational registry. All patients underwent pharmacologic Rb-82 PET and were followed for cardiac death and all-cause mortality. Based on body mass index (BMI), patients were categorized as normal (<25 kg/m(2)), overweight (25 to 29.9 kg/m(2)), or obese (≥30 kg/m(2)). Using a 17-segment model and 5-point scoring system, the percentage of abnormal myocardium was calculated for stress and rest patients categorized as normal (0%), mild (0.1% to 9.9%), moderate (10% to 19.9%), and severe (≥20%)., Results: A total of 6,037 patients were followed for cardiac death (median: 2.2 years) and the mean BMI was 30.5 ± 7.4 kg/m(2). A total of 169 cardiac deaths were observed. PET MPI demonstrated independent and incremental prognostic value over BMI. Normal PET MPI conferred an excellent prognosis with very low annual cardiac death rates in normal (0.38%), overweight (0.43%), and obese (0.15%) patients. As well, both moderately and severe obese patients with a normal PET MPI had excellent prognosis (0.20% and 0.10%, respectively). The net reclassification improvement of PET was 0.46 (95% confidence interval [CI]: 0.31 to 0.61), and appeared similar in the moderately and severe obese patients which were 0.44 (95% CI: 0.12 to 0.76) and 0.63 (95% CI: 0.27 to 0.98), respectively., Conclusions: Rb-82 PET has incremental prognostic value in all patients irrespective of BMI. In the obese population, where other modalities may have reduced diagnostic accuracy, cardiac PET appears to be a promising noninvasive modality with prognostic value., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: We sought to quantify coronary artery calcium (CAC) using a single contrast-enhanced cardiac computed tomography angiography (CCTA) study. CCTA has been successfully used for the assessment of coronary artery stenoses, whereas non-contrast ECG-gated computed tomography (Standard-CAC) is commonly performed to quantify CAC. Thus each scan individually contributes to the total radiation dose., Methods Results: Patients who underwent both Standard-CAC and CCTA scans were identified. Standard-CAC images were scored using the Agatston method. CCTA scans were scored for CAC (CCTA-CAC), whereby CAC was defined as plaque with attenuation 2 SD above the mean attenuation value of the ascending aorta (HU(aorta)). The correlation between Standard-CAC and CCTA-CAC was determined with the slope used to derive a correction factor for the conversion of CCTA-CAC results to a Standard-CAC Agatston score (AS). To test applicability, the correction factor was assessed in a separate validation cohort of similar demographics. From April 2011 to June 2012, a derivation cohort of 92 patients was identified and analysed. An additional 47 patients were identified for the validation cohort. Correlation between Standard-CAC and CCTA-CAC was excellent (r = 0.96). The slope (y = 2.74 × CCTA-CAC score) derived correction factor from the derivation cohort was used to adjust CCTA-CAC derived scores to an AS (CCTA-CAC(corrected) = 2.74 × CCTA-CAC). The correction factor was applied to the validation cohort CCTA-CAC results with excellent agreement between CCTA-CAC(corrected) and Standard-CAC (kappa = 0.93)., Conclusions: Quantification of CAC from a single contrast-enhanced CCTA scan is feasible and correlates well with Standard-CAC. Larger, multicentre studies are needed to validate the universal applicability of CAC quantified using CCTA.

Patients with chronic kidney disease have a worse cardiovascular prognosis than those without. The aim of this study was to determine the incremental prognostic value of coronary computed tomographic angiography in predicting mortality across the entire spectrum of renal function in patients with known or suspected coronary artery disease (CAD). A large international multicenter registry was queried, and patients with left ventricular ejection fraction (LVEF) and creatinine data were screened. National Cholesterol Education Program Adult Treatment Panel III risk was calculated. Coronary computed tomographic angiographic results were evaluated for CAD severity (normal, nonobstructive, or obstructive) and an LVEF <50%. Patients were followed for the end point of all-cause mortality. Among 5,655 patients meeting the study criteria, follow-up was available for 5,572 (98.9%; median follow-up duration 18.6 months). All-cause mortality (66 deaths) significantly increased with every 10-unit decrease in renal function (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.07 to 1.41). All-cause mortality occurred in 0.33% of patients without coronary atherosclerosis, 1.82% of patients with nonobstructive CAD, and 2.43% of patients with obstructive CAD. Multivariate Cox proportional-hazards models revealed that impaired renal function (HR 2.29, 95% CI 1.65 to 3.18), CAD severity (HR 1.81, 95% CI 1.31 to 2.51), and an abnormal LVEF (HR 4.16, 95% CI 2.45 to 7.08) were independent predictors of all-cause mortality. In conclusion, coronary computed tomographic angiographic measures of CAD severity and the LVEF provide effective risk stratification across a wide spectrum of renal function. Furthermore, renal dysfunction, CAD severity, and the LVEF have additive value for predicting all-cause death in patients with suspected obstructive CAD., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aim: Clinical predictors are routinely used to identify individuals who may benefit from aggressive risk factor modification. However, clinical predictors cannot account for all genetic and environmental variables. The objective of this study is to investigate the association of Framingham Risk Score (FRS) with computed tomography angiography (CTA) measures of coronary atherosclerosis., Methods and Results: Consecutive patients who underwent CTA were prospectively enrolled and categorized according to clinical predictors such as FRS and pre-test probability for obstructive coronary artery disease (CAD). Atherosclerotic calcific and non-calcific plaques were assessed. Of the 1507 patients without a history of diabetes mellitus, myocardial infarction, and not on statin therapy, coronary atherosclerosis was present in 63.5% of the patients. Of the 1173 patients with low and intermediate FRS, atherosclerotic plaque was visually present in 47.6 and 72.7% of the patients, respectively. A higher proportion of low FRS patients had isolated non-calcific plaque (14.8%) compared with patients in the intermediate (10.1%) or high (7.2%) FRS groups, and 11.7% of high FRS patients had no visual evidence of plaque. The correlation between FRS and plaque was fair (r = 0.48; P < 0.001)., Conclusion: Although clinical variables are predictive of CAD events, CTA identified coronary atherosclerosis in a significant proportion of patients with low to intermediate FRS, and a small minority of patients with high FRS had no evidence of atherosclerosis. Prospective studies are required to determine the potential value of identifying coronary atherosclerosis using CTA and to assess whether modifying therapies based on these results are warranted.

Aims: Cardiac computed tomography (CT) measured coronary artery calcium (CAC-CT) is a well-validated and accurate tool for estimating atherosclerotic burden and prognosis. Computed tomography attenuation correction (ACCT) obtained during cardiac positron emission tomography (PET) has been used to visually estimate CAC; however, quantification using a non-gated ACCT images has not been described. We sought to understand the relationship between CAC measured using cardiac computed tomography (CT) and CAC using ACCT images obtained during cardiac PET perfusion imaging., Methods and Results: Patients with both CAC-CT and cardiac PET within 6 months of each other were identified. CAC-CT images were scored using the Agatston scoring method, while ACCT images were scored using different attenuation thresholds for calcium. CAC-CT and ACCT scores were compared. Between August 2007 and October 2010, 91 patients were included in the analysis. Interobserver reliability was excellent at all thresholds of detection tested. Pearson correlation was strongest between CAC-CT and ACCT at 50 HU threshold of detection (ACCT(50)). Implementing CAC categories (0, 1-100, 101-400, >400), there was a high degree of agreement between observers as well as between CAC-CT and ACCT(50). Correlation was best for lower CAC scores; however, as CAC-CT increased, ACCT(50) underestimated CAC., Conclusion: Quantifying CAC using ACCT images appears to be feasible and accurate. In a single cardiac PET examination, information regarding perfusion, LV function, flow quantification, and CAC can be obtained without additional radiation.

A single imaging modality that can accurately assess both coronary anatomy and mitral valve (MV) anatomy prior to surgery may be desirable. We sought to determine the diagnostic accuracy of cardiac computed tomography (CT) to detect and characterize mitral valve prolapse (MVP) compared to echocardiography. Consecutive patients referred for 'single-source' cardiac CT for investigation prior to non-coronary cardiac sugery were identified. MV anatomy was assessed for MVP and results were compared to echocardiography and to intra-operative visual assessment of the MV. Comparison between the three modalities was performed at the per-patient, per-leaflet and per-scallop levels. A total of 67 consecutive patients that were referred for Cardiac CT prior to non-coronary cardiac surgery and were prospectively recruited into a Cardiac CT registry. Of these, 65 patients underwent cardiac surgery. 63 patients had echocardiography and 32 patients had intra-operative visual assessment of the mitral valve. Compared to echocardiography, cardiac CT had excellent sensitivity (92.6%) and specificity (97.1%) for the detection of any MVP, but had poor sensitivity (68.5%) for the detection of individual prolapsing scallop. Compared to intra-operative visual assessment of the prolapsing scallop, both cardiac CT and echocardiography had low sensitivity (58.1 and 78.1%, respectively). Cardiac CT was able to identify patients with MVP but had difficulty identifying the prolapsed scallops compared to echocardiography. Single-source CT may not be ready for characterization of individual mitral valve scallops.

Aims: Computed tomographic coronary angiography (CTA) appears to be a useful modality for the detection of obstructive coronary artery disease (CAD). Recent data suggest that CTA may reduce the frequency of normal invasive coronary angiograms. However, there remains concern that the implementation of CTA could increase referrals to invasive coronary angiography (ICA). To further support the clinical acceptance of CTA, it is important to compare CTA to another accepted modality such as single photon emission computed tomography (SPECT). We followed a cohort of 64-slice CTA patients and a matched cohort of Tc-99m SPECT patients to determine downstream referrals for ICA and revascularization., Methods and Results: Consecutive CTA patients (without history of revascularization or cardiac transplantation) were prospectively enrolled and compared with a Tc-99m SPECT cohort (matched for age, gender, and Morise score). Each CTA and SPECT was evaluated for obstructive CAD and patients were followed for downstream ICA and revascularization. Of the 1221 patients in each cohort, 129 (10.6%) CTA patients and 125 (10.2%) SPECT patients were referred to ICA. Of those referred to ICA, obstructive CAD was confirmed in 105 (81.4%) CTA patients and in 88 (70.4%) SPECT patients. Differences in false positive rates were significantly lower in the CTA than the SPECT cohort (9.7 and 25.8%, respectively, P = 0.009). Rates of revascularization were similar in the CTA and SPECT cohorts (6.2 vs. 5.9%, respectively)., Conclusion: Compared with SPECT, CTA had similar referrals for ICA and revascularization rates but lower false positive rates. Computed tomographic coronary angiography appears to be a viable non-invasive diagnostic modality and does not appear to negatively impact upon ICA resources.

Background: With the goal of minimizing patient radiation exposure, many centres have adopted prospective ECG-gated computed tomographic coronary angiography. Since image acquisition occurs only during ventricular diastasis, the ability to measure left ventricular (LV) ejection fraction (EF) and LV volumes has been lost. Given that LV volumes have prognostic value, the ability to estimate LV end diastolic volume (EDV) may be clinically desirable., Objective: We sought to predict LV EDV using CT coronary angiography (CTA) images obtained during ventricular diastasis., Methods: Consecutive patients who underwent retrospective ECG-gated CTA were enrolled. Images were reconstructed at the 75% phase and at end-diastole. LV and left atrial (LA) volumes were measured., Results: A total of 153 consecutive patients were analyzed (mean age = 56.7 ± 11.2 years; men = 56.2%). The mean LV EDV and EF were 144.4 ± 40.2 mL and 63.4 ± 9.9%, respectively. There appeared to be a very strong linear relationship between the 75% phase LV volume and LV EDV with an R(2) of 0.993. Using LV and LA volumes at the 75% phase, a prediction model of LV EDV was developed (LV EDV = (1.021 × 75% phase LV volume)+(0.259 × 75% phase LA volume), adjusted R(2) = 0.995)., Conclusion: LV EDV can be estimated using CTA data obtained during ventricular diastasis. Further studies are needed to demonstrate that such estimates of LV EDV have incremental prognostic value over coronary artery disease severity assessment with prospective ECG-gated CTA., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objectives: We sought to determine the incremental prognostic value of 64 multi-slice coronary computed tomography angiography (CCTA) in coronary artery bypass graft (CABG) patients., Background: Prognostication in CABG patients can be difficult. Anatomical assessment of native coronary artery disease and graft patency might provide useful information, but the utility of CCTA in the assessment of CABG patients is unknown., Methods: Six hundred fifty-seven CABG patients with all-cause mortality follow-up were identified from a multicenter CCTA registry, of 10,628 patients from 5 CCTA centers. Clinical risk was profiled with modified logistic and additive EuroSCOREs (European Systems for Cardiac Operative Risk Evaluations). The CCTA defined coronary anatomy. Patients were classified by unprotected coronary territory (UCT) or a summary of native vessel disease and graft patency: the coronary artery protection score (CAPS)., Results: Forty-four deaths occurred during a mean follow-up of 20 months. Left ventricular ejection fraction, creatinine, age, severity of native vessel disease, UCT, CAPS, and EuroSCOREs were univariate predictors of mortality (p < 0.001). In multivariate analysis with additive EuroSCORE, UCT (p = 0.004) and CAPS were predictive of events (p < 0.001). In comparison with additive EuroSCORE, CAPS score was associated with a 27% net reclassification index., Conclusions: Coronary computed tomography angiography provides incremental anatomical data to clinical risk assessment to help determine the prognosis of patients after CABG. The CAPS evaluation with CCTA might help identify those patients at highest risk., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)