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Objective: Data describing the prevalence, characteristics and management of coronary chronic total occlusions (CTOs) in patients undergoing coronary CT angiography (CCTA) have not been reported. The purpose of this study was to determine the prevalence, characteristics and treatment strategies of CTO identified by CCTA. Methods: We identified 23 745 patients who underwent CCTA for suspected coronary artery disease (CAD) from the prospective international CCTA registry. Baseline clinical data were collected, and allocation to early coronary revascularisation performed within 90 days of CCTA was determined. Multivariable hierarchical mixed-effects logistic regression reporting OR with 95% CI was performed. Results: The prevalence of CTO was 1.4% (342/23 745) in all patients and 6.2% in patients with obstructive CAD (≥50% stenosis). The presence of CTO was independently associated with male sex (OR 3.12, 95% CI 2.39 to 4.08, p

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 (

Background: Adopting artificial intelligence (AI) in medicine may improve speed and accuracy in patient diagnosis. We sought to develop an AI algorithm to interpret wide-complex tachycardia (WCT) electrocardiograms (ECGs) and compare its diagnostic accuracy with that of cardiologists., Methods: Using 3330 WCT ECGs (2906 supraventricular tachycardia [SVT] and 424 ventricular tachycardia [VT]), we created a training/validation (3131) and a test set (199 ECGs). A convolutional neural network structure using a modification of differentiable architecture search was developed to differentiate between SVT and VT., Results: The mean accuracy of electrophysiology (EP) cardiologists was 92.5% with sensitivity 91.7%, specificity 93.4%, positive predictive value 93.7%, and negative predictive value 91.7%. Non-EP cardiologists had an accuracy of 73.2 ± 14.4% with sensitivity, specificity, and positive and negative predictive values of 59.8 ± 18.2%, 93.8 ± 3.7%, 93.6 ± 2.3%, and 73.2 ± 14.4%, respectively. AI had superior sensitivity and accuracy (91.9% and 93.0%, respectively) than non-EP cardiologists and similar performance compared with EP cardiologists. Mean time to interpret each ECG varied from 10.1 to 13.8 seconds for EP cardiologists and from 3.1 to 16.6 seconds for non-EP cardiologists. AI required a mean of 0.0092 ± 0.0035 seconds for each ECG interpretation., Conclusions: AI appears to diagnose WCT with accuracy superior to non-EP cardiologists and similar to EP cardiologists. Using AI to assist with ECG interpretations may improve patient care., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Coronary CT angiography (CCTA) is now endorsed by all major cardiology guidelines for the investigation of chest pain and assessment for coronary artery disease (CAD) in appropriately selected patients. CAD is a leading cause of morbidity and mortality. There is extensive literature to support CCTA diagnostic and prognostic value both for stable and acute symptoms. It enables rapid and cost-effective rule-out of CAD, and permits quantification and characterization of coronary plaque and associated significance. In this comprehensive review, we detail the road traveled as CCTA evolved to include quantitative assessment of plaque stenosis and extent, characterization of plaque characteristics including high-risk features, functional assessment including fractional flow reserve-CT (FFR-CT), and CT perfusion techniques. The state of current guideline recommendations and clinical applications are reviewed, as well as future directions in the rapidly advancing field of CT technology, including photon counting and applications of artificial intelligence (AI).

Aims: Cardiovascular disease, primarily coronary artery disease (CAD), is the leading cause of mortality worldwide. Accurate diagnosis of CAD often requires pre-test probability (PTP) estimation, traditionally performed using scoring systems like the Diamond-Forrester (DF) and European Society of Cardiology (ESC) models. However, the applicability of such models in specific populations may vary. This study compares the performance of DF and PTP scores in the Brazilian context, using coronary computed tomography angiography (CCTA) as a reference standard., Methods and Results: PTP for obstructive CAD was calculated using DF and ESC scores in 409 symptomatic patients without known CAD who underwent CCTA between 2019 and 2022. Predicted PTP was compared with actual CAD prevalence. DF overestimated CAD prevalence across age and symptom categories, while ESC showed better alignment with actual prevalence., Conclusion: Our study confirms that the ESC PTP model is more appropriate than the DF model for determining PTP in the Brazilian population., Competing Interests: Conflict of interest: F.E.: Nothing to disclosure. R.L.: Nothing to disclosure. F.P.: Nothing to disclosure. R.G.: Nothing to disclosure. B.J.W.C. receives research support from TD Bank and Artrya. He is a consultant for and has an equity interest in Artrya., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: We sought to develop a novel deep learning (DL) workflow to interpret single-photon emission computed tomography (SPECT) wall motion., Background: Wall motion assessment with SPECT is limited by image temporal and spatial resolution. Visual interpretation of wall motion can be subjective and prone to error. Artificial intelligence (AI) may improve accuracy of wall motion assessment., Methods: A total of 1038 patients undergoing rest electrocardiogram (ECG)-gated SPECT and echocardiography were included. Using echocardiography as truth, a DL-model (DL-model 1) was trained to predict the probability of abnormal wall motion. Of the 1038 patients, 317 were used to train a DL-model (DL-model 2) to assess regional wall motion. A 10-fold cross-validation was adopted. Diagnostic performance of DL was compared with human readers and quantitative parameters., Results: The area under the receiver operating characteristic curve (AUC) and accuracy (ACC) of DL model (AUC: .82 [95% CI: .79-.85]; ACC: .88) were higher than human (AUC: .77 [95% CI: .73-.81]; ACC: .82; P < .001) and quantitative parameter (AUC: .74 [95% CI: .66-.81]; ACC: .78; P < .05). The net reclassification index (NRI) was 7.7%. The AUC and accuracy of DL model for per-segment and per-vessel territory diagnosis were also higher than human reader. The DL model generated results within 30 seconds with operable guided user interface (GUI) and therefore could provide preliminary interpretation., Conclusions: DL can be used to improve interpretation of rest SPECT wall motion as compared with current human readers and quantitative parameter diagnosis., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Coronary CT angiography (CCTA) has been gradually adopted into clinical practice over the last two decades. CCTA has high diagnostic accuracy, prognostic value, and unique features such as assessment of plaque composition. CCTA-derived functional assessment techniques such as fractional flow reserve and CT perfusion are also available and can increase the diagnostic specificity of the modality. These properties propound CCTA as a competitor of functional testing in diagnosis of obstructive CAD, however, utilizing CCTA in a concomitant fashion to potentiate the performance of the latter can lead to better patient care and may provide more accurate prognostic information. Although multiple diagnostic challenges such as evaluation of calcified segments, stents, and small distal vessels still exist, the technologic developments in hardware as well as growing incorporation of artificial intelligence to daily practice are all set to augment the diagnostic and prognostic role of CCTA in cardiovascular disorders., (Copyright © 2024. Published by Elsevier Inc.)

Background: Across medical specialties, including nuclear cardiology, competency based medical education (CBME) changes the emphasis of learning from a time or experiential emphasis to a proficiency focused approached. Plotted on a learning-curve graph the emphasis on learning has shifted from the duration/ volume-based x-axis to the performance-based y-axis., Current Status: It has proven difficult to establish y-axis-based standards within nuclear cardiology to assess learning. As such there is a paucity of data to verify current experiential training targets and only recently is data emerging that seeks to find CBME targets by which proficiency (y-axis units) can be evaluated. Initial reports from such CBME-oriented studies indicate that in current nuclear cardiology practice, the number of studies required to achieve competency is dependent upon the chosen measure of competency that is assessed (summed stress score versus % LV ischemia), the case mix, and the modality being learnt (PET versus SPECT). Recent findings have also suggested that prior levels of experiential training may be an underestimation of the number of supervised studies learners need to interpret before they achieve competency., Summary: Nuclear cardiology training has adopted the concept of CBME and is progressing toward a more modern approach to trainee assessment. This brief review provides the background, current requirements and insights into new developments in nuclear cardiology training., Competing Interests: Declaration of Competing Interest Dr Small has received honoraria and research funding from Pfizer. Dr Chow receives research support from TD Bank, Siemens Healthineers, and Artrya. He has an equity interest in Artrya., (Copyright © 2024. Published by Elsevier Inc.)

Background: Coronary computed tomography angiography (CCTA) has emerged as a reliable noninvasive modality to assess coronary artery stenosis and high-risk plaque (HRP). However, CCTA assessment of stenosis and HRP is time-consuming and requires specialized training, limiting its clinical translation., Objectives: The aim of this study is to develop and validate a fully automated deep learning system capable of characterizing stenosis severity and HRP on CCTA., Methods: A deep learning system was trained to assess stenosis and HRP on CCTA scans from 570 patients in multiple centers. Stenosis severity was categorized as >0%, 1 to 49%, ≥50%, and ≥70%. HRP was defined as low attenuation plaque (≤30 HU), positive remodeling (≥10% diameter), and spotty calcification (<3 mm). The model was then tested on 769 patients (3,012 vessels) for stenosis severity and 45 patients (325 vessels) for HRP., Results: Our deep learning system achieved 93.5% per-vessel agreement within 1 Coronary Artery Disease-Reporting and Data System (CAD-RADS) category for stenosis. Diagnostic performance for per-vessel stenosis was very good for sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve with: >0% stenosis: 90.6%, 88.8%, 83.4%, 93.9%, 89.7%, respectively; ≥50% stenosis: 87.1%, 92.3%, 60.9%, 98.1%, 89.7%, respectively. Similarly, the per-vessel HRP feature achieved very good diagnostic performance with an area under the curve of 0.80, 0.79, and 0.77 for low attenuation plaque, spotty calcification, and positive remodeling, respectively., Conclusions: A fully automated unsupervised deep learning system can rapidly evaluate stenosis severity and characterize HRP with very good diagnostic performance on CCTA., Competing Interests: Drs Ihdayhid and Dwivedi are consultants and have equity interest in Artrya Ltd. Drs Joyner, Flack, and Konstantopoulos have equity interest in Artrya Ltd, Drs Joyner and Konstantopoulos are employees of Artrya Ltd. Dr Ihdayhid has consulting honorarium from Boston Scientific and Abbott Medical. Dr Williams (FS/ICRF/20/26002) is supported by the 10.13039/501100000274British Heart Foundation. Dr Williams has given talks for Canon Medical Systems, Siemens Healthineers, and Novartis. Dr Dwivedi has speaker bureau for Janssen, Amgen, Pfizer, and AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

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: The Diamond-Forrester model was used extensively to predict obstructive coronary artery disease (CAD) but overestimates probability in current populations. Coronary artery calcium (CAC) is a useful marker of CAD, which is not routinely integrated with other features. We derived simple likelihood tables, integrating CAC with age, sex, and cardiac chest pain to predict obstructive CAD., Methods and Results: The training population included patients from 3 multinational sites (n=2055), with 2 sites for external testing (n=3321). We determined associations between age, sex, cardiac chest pain, and CAC with the presence of obstructive CAD, defined as any stenosis ≥50% on coronary computed tomography angiography. Prediction performance was assessed using area under the receiver-operating characteristic curves (AUCs) and compared with the CAD Consortium models with and without CAC, which require detailed calculations, and the updated Diamond-Forrester model. In external testing, the proposed likelihood tables had higher AUC (0.875 [95% CI, 0.862-0.889]) than the CAD Consortium clinical+CAC score (AUC, 0.868 [95% CI, 0.855-0.881]; P =0.030) and the updated Diamond-Forrester model (AUC, 0.679 [95% CI, 0.658-0.699]; P <0.001). The calibration for the likelihood tables was better than the CAD Consortium model (Brier score, 0.116 versus 0.121; P =0.005)., Conclusions: We have developed and externally validated simple likelihood tables to integrate CAC with age, sex, and cardiac chest pain, demonstrating improved prediction performance compared with other risk models. Our tool affords physicians with the opportunity to rapidly and easily integrate a small number of important features to estimate a patient's likelihood of obstructive CAD as an aid to clinical management.

Competing Interests: Conflict of interest. J.A., J.K., J.J., J.F., A.R.I., and G.D. have equity in Artrya Ltd. J.J., J.F., and S.K. are employees of Artrya Ltd. A.R.I. has speaker bureau from Boston Scientific, Abbott Medical, and Janssen. G.D. has speaker bureau for Janssen, Amgen, Pfizer, and AstraZeneca. For the remaining authors, none were declared.

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.)

Hypertrophic cardiomyopathy is a common inherited cardiac condition in which regional myocardial thickening and scarring can lead to a range of symptoms including breathlessness, dizziness, chest pain, and collapse with loss of consciousness. It is vital to be able to understand the mechanisms behind these epiphenomena and to be able to distinguish, for example, between syncope because of arrhythmia versus syncope because of mechanical outflow tract obstruction. Therefore, we require a technique that can characterize anatomy, physiology, and myocardial substrate. Traditionally, this role has been the preserve of cardiac magnetic resonance (CMR) imaging. This review makes the case for cardiac computed tomography (CT) as an alternative imaging method. We review the use of functional CT to identify the components of outflow tract obstruction (and obstruction at other levels, which may be simultaneous), and as an aid to interventional and surgical planning. We demonstrate the added value of multiplanar isotropic reformats in this condition, particularly in cases where the diagnosis may be more challenging or where complications (such as early apical aneurysm) may be difficult to recognize with 2-dimensional techniques. In conclusion, our aim is to convince readers that cardiac CT is a highly valuable and versatile tool, which deserves wider usage and greater recognition in those caring for patients with hypertrophic cardiomyopathy., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

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.)

Chest pain/discomfort (CP) is a common symptom and can be a diagnostic dilemma for many clinicians. The misdiagnosis of an acute or progressive chronic cardiac etiology may carry a significant risk of morbidity and mortality. This review summarizes the different options and modalities for establishing the diagnosis and severity of coronary artery disease. An effective test selection algorithm should be individually tailored to each patient to maximize diagnostic accuracy in a timely fashion, determine short- and long-term prognosis, and permit implementation of evidence-based treatments in a cost-effective manner. Through collaboration, a decision algorithm was developed (www.chowmd.ca/cadtesting) that could be adopted widely into clinical practice., (© 2023 The Authors.)

Background: Elevated coronary artery calcium (CAC) scores in subjects without prior atherosclerotic cardiovascular disease (ASCVD) have been shown to be associated with increased cardiovascular risk., Objectives: The authors sought to determine at what level individuals with elevated CAC scores who have not had an ASCVD event should be treated as aggressively for cardiovascular risk factors as patients who have already survived an ASCVD event., Methods: The authors performed a cohort study comparing event rates of patients with established ASVCD to event rates in persons with no history of ASCVD and known calcium scores to ascertain at what level elevated CAC scores equate to risk associated with existing ASCVD. In the multinational CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, the authors compared ASCVD event rates in persons without a history of myocardial infarction (MI) or revascularization (as categorized on CAC scores) to event rates in those with established ASCVD. They identified 4,511 individuals without known coronary artery disease (CAC) who were compared to 438 individuals with established ASCVD. CAC was categorized as 0, 1 to 100, 101 to 300, and >300. Cumulative major adverse cardiovascular events (MACE), MACE plus late revascularization, MI, and all-cause mortality incidence was assessed using the Kaplan-Meier method for persons with no ASCVD history by CAC level and persons with established ASCVD. Cox proportional hazards regression analysis was used to calculate HRs with 95% CIs, which were adjusted for traditional cardiovascular risk factors., Results: The mean age was 57.6 ± 12.4 years (56% male). In total, 442 of 4,949 (9%) patients experienced MACEs over a median follow-up of 4 years (IQR: 1.7-5.7 years). Incident MACEs increased with higher CAC scores, with the highest rates observed with CAC score >300 and in those with prior ASCVD. All-cause mortality, MACEs, MACE + late revascularization, and MI event rates were not statistically significantly different in those with CAC >300 compared with established ASCVD (all P > 0.05). Persons with a CAC score <300 had substantially lower event rates., Conclusions: Patients with CAC scores >300 are at an equivalent risk of MACE and its components as those treated for established ASCVD. This observation, that those with CAC >300 have event rates comparable to those with established ASCVD, supplies important background for further study related to secondary prevention treatment targets in subjects without prior ASCVD with elevated CAC. Understanding the CAC scores that are associated with ASCVD risk equivalent to stable secondary prevention populations may be important for guiding the intensity of preventive approaches more broadly., Competing Interests: Funding Support and Author Disclosures Dr Budoff has received grant support from the National Institute of Health and General Electric. Dr Al-Mallah has received support from the American Heart Association, BCBS Foundation of Michigan, and Astellas. Dr Cademartiri has received grant support from GE Healthcare; and has served on the Speakers Bureau of Bracco and as a consultant for Servier. Dr Chow holds the Saul and Edna Goldfarb Chair in Cardiac Imaging Research; and has received research support from TD Bank, AusculSciences, Siemens Healthineers, and Artrya. Dr Hausleiter has received a research grant from Siemens Medical Systems. Dr Kaufmann has received institutional research support from GE Healthcare; and has received grant support from Swiss National Science Foundation. Dr Berman has a consultant agreement with General Electric. Dr Min has served as an employee and retains equity from Cleerly, Inc; has served on the medical advisory board for Arineta; and has received grant support from the National Institutes of Health. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: The totality of atherosclerotic plaque derived from coronary computed tomography angiography (CCTA) emerges as a comprehensive measure to assess the intensity of medical treatment that patients need. This study examines the differences in age onset and prognostic significance of atherosclerotic plaque burden between sexes., Methods and Results: From a large multi-center CCTA registry the Leiden CCTA score was calculated in 24 950 individuals. A total of 11 678 women (58.5 ± 12.4 years) and 13 272 men (55.6 ± 12.5 years) were followed for 3.7 years for major adverse cardiovascular events (MACE) (death or myocardial infarction). The age where the median risk score was above zero was 12 years higher in women vs. men (64-68 years vs. 52-56 years, respectively, P < 0.001). The Leiden CCTA risk score was independently associated with MACE: score 6-20: HR 2.29 (1.69-3.10); score > 20: HR 6.71 (4.36-10.32) in women, and score 6-20: HR 1.64 (1.29-2.08); score > 20: HR 2.38 (1.73-3.29) in men. The risk was significantly higher for women within the highest score group (adjusted P-interaction = 0.003). In pre-menopausal women, the risk score was equally predictive and comparable with men. In post-menopausal women, the prognostic value was higher for women [score 6-20: HR 2.21 (1.57-3.11); score > 20: HR 6.11 (3.84-9.70) in women; score 6-20: HR 1.57 (1.19-2.09); score > 20: HR 2.25 (1.58-3.22) in men], with a significant interaction for the highest risk group (adjusted P-interaction = 0.004)., Conclusion: Women developed coronary atherosclerosis approximately 12 years later than men. Post-menopausal women within the highest atherosclerotic burden group were at significantly higher risk for MACE than their male counterparts, which may have implications for the medical treatment intensity., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose of Review: The goal of this article is to review the data supporting the use of fractional flow reserve derived from coronary computed tomography angiography (FFR CT ) in patients with chest pain., Review Findings: Numerous clinical trials have demonstrated that the diagnostic accuracy of coronary computed tomography angiography (CCTA) can be improved with the use of FFR CT , primarily due to its superior specificity when compared to CCTA alone. This promising development may help reduce the need for invasive angiography in patients presenting with chest pain. Furthermore, some studies have indicated that incorporating FFR CT into decision-making is safe, with an FFR CT value of ≥ 0.8 being associated with favorable outcomes. While FFR CT has been shown to be feasible in patients with acute chest pain, further large-scale studies are warranted to confirm its utility. The emergence of FFR CT as a tool for the management of patients with chest pain is promising. However, potential limitations require the interpretation of FFR CT in conjunction with clinical context., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Whether initial invasive management in older vs younger adults with chronic coronary disease and moderate or severe ischemia improves health status or clinical outcomes is unknown., Objectives: The goal of this study was to examine the impact of age on health status and clinical outcomes with invasive vs conservative management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial., Methods: One-year angina-specific health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ) (score range 0-100; higher scores indicate better health status). Cox proportional hazards models estimated the treatment effect of invasive vs conservative management as a function of age on the composite clinical outcome of cardiovascular death, myocardial infarction, or hospitalization for resuscitated cardiac arrest, unstable angina, or heart failure., Results: Among 4,617 participants, 2,239 (48.5%) were aged <65 years, 1,713 (37.1%) were aged 65 to 74 years, and 665 (14.4%) were aged ≥75 years. Baseline SAQ summary scores were lower in participants aged <65 years. Fully adjusted differences in 1-year SAQ summary scores (invasive minus conservative) were 4.90 (95% CI: 3.56-6.24) at age 55 years, 3.48 (95% CI: 2.40-4.57) at age 65 years, and 2.13 (95% CI: 0.75-3.51) at age 75 years (P interaction  = 0.008). Improvement in SAQ Angina Frequency was less dependent on age (P interaction  = 0.08). There were no age differences between invasive vs conservative management on the composite clinical outcome (P interaction  = 0.29)., Conclusions: Older patients with chronic coronary disease and moderate or severe ischemia had consistent improvement in angina frequency but less improvement in angina-related health status with invasive management compared with younger patients. Invasive management was not associated with improved clinical outcomes in older or younger patients. (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches [ISCHEMIA]; NCT01471522)., Competing Interests: Funding Support and Author Disclosures This project was supported in part by National Institutes of Health grants U01HL105907, U01HL105462, U01HL105561, and U01HL105565; and in part by Clinical Translational Science Award numbers 11UL1 TR001445 and UL1 TR002243 from the National Center for Advancing Translational Sciences. The contents of this project are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the Department of Health and Human Services. Dr Nguyen is currently supported by the National Heart, Lung, and Blood Institute under Award Number T32HL110837. Dr Spertus has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; has received personal fees from Bayer, Novartis, AstraZeneca, Amgen, Janssen, and United Healthcare; has received grants from the American College of Cardiology, outside the submitted work; has a patent copyright to SAQ with royalties paid; is on the Board of Directors for Blue Cross Blue Shield of Kansas City; and has equity in Health Outcomes Sciences. Dr Newman, Dr Alexander, Mrs Stevens, Dr O'Brien, Dr Gamma, Dr Perna, Dr Garg, Dr Vertes, Dr Smanio, Dr Senior, Dr Held, and Dr Maron have received grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Mr Jones reports employment by the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Chow holds the Saul and Edna Goldfarb Chair in Cardiac Imaging Research; receives research support from TD Bank, CV Diagnostix, AusculSciences, and Siemens Healthineers; and has equity interest in General Electric. Dr White has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; has received grant support paid to the institution and fees for serving on a steering committee for the ODYSSEY OUTCOMES trial from Sanofi and Regeneron Pharmaceuticals, for the ACCELERATE study from Eli Lilly, for the STRENGTH trial from Omthera Pharmaceuticals, for the HEART-FID study from American Regent, for the CAMELLIA-TIMI study from Eisai Inc, for the dal-GenE study from DalCor Pharma UK Inc, for the AEGIS-II study from CSL Behring, for the SCORED trial and the SOLOIST-WHF trial from Sanofi Australia Pty Ltd, and for the CLEAR Outcomes Study from Esperion Therapeutics Inc. Dr White was on the Advisory Board for Genentech, Inc; and has received lecture fees from AstraZeneca. Dr Boden has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; has received grants from AbbVie, Amarin, and Amgen; and has received personal fees from Amgen, the Cleveland Clinic Clinical Coordinating Center, and Janssen, outside the submitted work. Dr Mark has received grants from the National Heart, Lung, and Blood Institute during the conduct of the study; and has received grants from HeartFlow and Merck, outside the submitted work. Dr Reynolds has received funding for this research from the National Heart, Lung, and Blood Institute; and has received in-kind donations for unrelated research from Abbott Vascular, Siemens, and Philips. Dr Bangalore has received grants from the National Heart, Lung, and Blood Institute and Abbott Vascular; and serves on the advisory board for Abbott Vascular, Pfizer, Amgen, Biotronik, Meril, and Reata. Dr Chan has received funding from the American Heart Association; and is a consultant for Optum Rx. Dr Stone has received grants and personal fees from the National Heart, Lung, and Blood Institute during the conduct of the study; has received personal fees from Terumo, Amaranth, Shockwave, TherOx, Reva, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Matrizyme, Miracor, Neovasc, V-Wave, Abiomed, Claret, Sirtex, MAIA Pharmaceuticals, and Vectorious; has received personal fees and has equity/options from VALFIX, Ancora, Qool Therapeutics, SpectraWave, and Orchestra Biomed; has equity/options from Cagent, Applied Therapeutics, BioStar family of funds, MedFocus family of funds, and Aria; and has equity/options from Cardiac Success, outside the submitted work. Dr Hochman is Principal Investigator for the ISCHEMIA trial for which, in addition to support by a National Heart, Lung, and Blood Institute grant, devices and medications were provided by Abbott Vascular, Medtronic, Inc, Abbott Laboratories (formerly St Jude Medical, Inc), Royal Philips NV (formerly Volcano Corporation), Arbor Pharmaceuticals, LLC, AstraZeneca Pharmaceuticals, LP, Merck Sharp & Dohme Corp, Omron Healthcare, Inc, Sunovion Pharmaceuticals, Inc, Espero BioPharma, and Amgen, Inc, as well as financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac sarcoidosis (CS) is a rare form of arrhythmogenic cardiomyopathy; a delayed diagnosis can lead to significant consequences. Patients with clinically manifest CS often have minimal extracardiac involvement and thus frequently present initially to cardiology. Indeed, certain specific arrhythmic scenarios should trigger investigations for undiagnosed CS. Atrial fibrillation (AF) has been described as one of the presenting features of CS; however, the incidence of this presentation is not known., Methods: At our institution, cardiac computerized tomography is routinely performed prior to catheter ablation for AF. Noncardiac incidental findings are described by radiologists and are followed-up by interval investigations. We systematically reviewed noncardiac reports from 1574 consecutive patients in our prospective AF ablation registry. Specifically, we used text-scraping techniques to search on the following keywords: "adenopathy" and "sarcoidosis." Detailed chart review of identified cases was then performed to evaluate results of interval investigations and assess long-term outcomes., Results: Twenty of 1574 patients (1.3%) had noncardiac reports containing "adenopathy" and/or "sarcoidosis." After interval imaging and a follow-up period averaging 60 ± 35 months, only 2 patients of 1574 (0.13%) were diagnosed with CS. Four of 20 (20%) had a previous history of extracardiac sarcoidosis, and another 1 of 20 (5%) was subsequently diagnosed with extracardiac sarcoidosis. However, none of these 5 patients had evidence of cardiac involvement., Conclusions: CS is a rare finding among patients undergoing a first-time AF ablation. Our findings suggest that AF is an uncommon initial presentation of CS. Thus, investigations for CS in patients with AF are not warranted routinely, unless additional suggestive clinical features are present., (© 2023 The Authors.)

Background & Aims: Hepatic steatosis has been associated with increased risk of coronary artery disease. Individuals with familial hypercholesterolaemia have accelerated but variable progression of coronary artery disease. We investigated whether hepatic steatosis is associated with novel coronary atherosclerosis biomarkers in adults with heterozygous familial hypercholesterolaemia, using comprehensive coronary computed tomographic angiography., Methods: We conducted a cross-sectional study of 213 asymptomatic patients with familial hypercholesterolaemia (median age 54.0 years, 59 % female) who underwent coronary computed tomographic angiography for cardiovascular risk assessment in an outpatient clinic. High-risk plaque features, plaque volume and pericoronary adipose tissue attenuation were assessed. From concurrently captured upper abdominal images, severity of hepatic steatosis was computed, as liver minus spleen computed tomography attenuation and stratified into quartiles., Results: Of 213 familial hypercholesterolaemia patients, 59 % had coronary artery calcium, 36 % obstructive coronary artery disease (≥50 % stenosis) and 77 % high-risk plaque features. Increasing hepatic steatosis was associated with higher calcium scores, more high-risk plaque features and presence of obstructive coronary artery disease. Hepatic steatosis was associated with the presence of high-risk plaque features (OR: 1.48; 95 % CI: 1.09-2.00; p = 0.01), particularly in the proximal coronary segments (OR: 1.52; 95 % CI: 1.18-1.96; p = 0.001). Associations persisted on multivariable logistic regression analysis adjusting for cardiometabolic factors, obstructive coronary artery disease and calcium score. Hepatic steatosis was associated with higher plaque volumes (Q4: 499 mm 3 vs Q1: 414 mm 3 , p = 0.02), involving mainly low attenuation and noncalcified plaques (both p = 0.03). No differences in pericoronary adipose tissue attenuation were observed., Conclusions: Hepatic steatosis is associated with multiple indices of advanced coronary atherosclerosis in familial hypercholesterolaemia patients, particularly high-risk plaque features, independent of conventional cardiovascular risk factors and markers. This may involve specific mechanisms related to hepatic steatosis., Clinical Trial Number: N/A., Competing Interests: Declaration of competing interest GD reports paid lectures from AstraZeneca, Pfizer and Amgen not related to the topic in the manuscript, received conference support from Boehringer Ingelheim and provides consultancy services and has equity interest in Artrya Ltd. NSRL has received research funding and speaker honoraria from Sanofi and conference support from Boehringer Ingelheim. GFW has received financial support for lectures, advisory boards or research from Arrowhead, Amgen, Pfizer, Sanofi, Regeneron, Novartis, AstraZeneca, Silence Therapeutics and Esperion. GFW is a member of the editorial board for Metabolism: Clinical and Experimental. OTA provides consultancy services to Resonance Health and Sun Pharmaceuticals. Khurram Nasir and Raul Santos are colleagues within the field and represent conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Prognostic significance of non-obstructive left main (LM) disease was recently reported. However, the influence of diabetes mellitus (DM) on event rates in patients with and without non-obstructive LM disease is not well-known., Methods: We evaluated 27,252 patients undergoing coronary computed tomographic angiography from the COroNary CT Angiography Evaluation For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) Registry. Cumulative long-term incidence of all-cause mortality (ACM) was assessed between DM and non-DM patients by normal or non-obstructive LM disease (1-49% stenosis)., Results: The mean age of the study population was 57.6±12.6 years. Of the 27,252 patients, 4,434 (16%) patients had DM. A total of 899 (3%) deaths occurred during the follow-up of 3.6±1.9. years. Compared to patients with normal LM, those with non-obstructive LM had more pronounced overall coronary atherosclerosis and more cardiovascular risk factors. After clinical risk factors, segment involvement score, and stenosis severity adjustment, compared to patients without DM and normal LM, patients with DM were associated with increased ACM regardless of normal (HR 1.48, 95% CI 1.22-1.78, p<0.001) or non-obstructive LM (HR 1.46, 95% CI 1.04-2.04, p=0.029), while nonobstructive LM disease was not associated with increased ACM in patients without DM (HR 0.85, 95% CI 0.67-1.07, p=0.165) and there was no significant interaction between DM and LM status (HR 1.03, 95% CI 0.69-1.54, p=0.879)., Conclusion: From the CONFIRM registry, we demonstrated that DM was associated with increased ACM. However, the presence of non-obstructive LM was not an independent risk marker of ACM, and there was no significant interaction between DM and non-obstructive LM disease for ACM., (Copyright © 2022 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Objectives: Coronary artery calcium (CAC) scores derived from computed tomography (CT) scans are used for cardiovascular risk stratification. Artificial intelligence (AI) can assist in CAC quantification and potentially reduce the time required for human analysis. This study aimed to develop and evaluate a fully automated model that identifies and quantifies CAC., Methods: Fully convolutional neural networks for automated CAC scoring were developed and trained on 2439 cardiac CT scans and validated using 771 scans. The model was tested on an independent set of 1849 cardiac CT scans. Agatston CAC scores were further categorised into five risk categories (0, 1-10, 11-100, 101-400, and > 400). Automated scores were compared to the manual reference standard (level 3 expert readers)., Results: Of 1849 scans used for model testing (mean age 55.7 ± 10.5 years, 49% males), the automated model detected the presence of CAC in 867 (47%) scans compared with 815 (44%) by human readers (p = 0.09). CAC scores from the model correlated very strongly with the manual score (Spearman's r = 0.90, 95% confidence interval [CI] 0.89-0.91, p < 0.001 and intraclass correlation coefficient = 0.98, 95% CI 0.98-0.99, p < 0.001). The model classified 1646 (89%) into the same risk category as human observers. The Bland-Altman analysis demonstrated little difference (1.69, 95% limits of agreement: -41.22, 44.60) and there was almost excellent agreement (Cohen's κ = 0.90, 95% CI 0.88-0.91, p < 0.001). Model analysis time was 13.1 ± 3.2 s/scan., Conclusions: This artificial intelligence-based fully automated CAC scoring model shows high accuracy and low analysis times. Its potential to optimise clinical workflow efficiency and patient outcomes requires evaluation., Key Points: • Coronary artery calcium (CAC) scores are traditionally assessed using cardiac computed tomography and require manual input by human operators to identify calcified lesions. • A novel artificial intelligence (AI)-based model for fully automated CAC scoring was developed and tested on an independent dataset of computed tomography scans, showing very high levels of correlation and agreement with manual measurements as a reference standard. • AI has the potential to assist in the identification and quantification of CAC, thereby reducing the time required for human analysis., (© 2022. The Author(s).)

Background: Ischemia with nonobstructive coronary arteries (INOCA) is common clinically, particularly among women, but its prevalence among patients with at least moderate ischemia and the relationship between ischemia severity and non-obstructive atherosclerosis severity are unknown., Objectives: The authors investigated predictors of INOCA in enrolled, nonrandomized participants in ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), sex differences, and the relationship between ischemia and atherosclerosis in patients with INOCA., Methods: Core laboratories independently reviewed screening noninvasive stress test results (nuclear imaging, echocardiography, magnetic resonance imaging or nonimaging exercise tolerance testing), and coronary computed tomography angiography (CCTA), blinded to results of the screening test. INOCA was defined as all stenoses <50% on CCTA in a patient with moderate or severe ischemia on stress testing. INOCA patients, who were excluded from randomization, were compared with randomized participants with ≥50% stenosis in ≥1 vessel and moderate or severe ischemia., Results: Among 3,612 participants with core laboratory-confirmed moderate or severe ischemia and interpretable CCTA, 476 (13%) had INOCA. Patients with INOCA were younger, were predominantly female, and had fewer atherosclerosis risk factors. For each stress testing modality, the extent of ischemia tended to be less among patients with INOCA, particularly with nuclear imaging. There was no significant relationship between severity of ischemia and extent or severity of nonobstructive atherosclerosis on CCTA. On multivariable analysis, female sex was independently associated with INOCA (odds ratio: 4.2 [95% CI: 3.4-5.2])., Conclusions: Among participants enrolled in ISCHEMIA with core laboratory-confirmed moderate or severe ischemia, the prevalence of INOCA was 13%. Severity of ischemia was not associated with severity of nonobstructive atherosclerosis. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522)., Competing Interests: Funding Support and Author Disclosures This project was supported by National Institutes of Health grants (U01HL105907, U01HL105462, U01HL105561, and U01HL105565) and supported in part by Clinical Translational Science Award (11UL1 TR001445 and UL1 TR002243) from the National Center for Advancing Translational Sciences and by grants from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. The manuscript contents are solely the responsibility of the authors and do not necessarily represent official views of the National Center for Advancing Translational Sciences, the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the Department of Health and Human Services. Devices or medications were provided by Abbott Vascular (previously St. Jude Medical, Inc); Medtronic, Inc; Phillips (previously Volcano Corporation); and Omron Healthcare, Inc; medications were provided by Amgen Inc; Arbor Pharmaceuticals, LLC; AstraZeneca Pharmaceuticals, LP; Espero Pharmaceuticals; Merck, Sharp & Dohme Corp; and Sunovion Pharmaceuticals. All authors have received funding from the National Heart, Lung and Blood Institute for the study. Dr Reynolds has received nonfinancial support from Abbott Vascular, Siemens, BioTelemetry, and Leipsic; is a consultant and holder of stock options from Circle CVI and HeartFlow; is the recipient of research grants from GE Healthcare and Edwards; and serves on speakers bureaus for Philips and GE Healthcare. Dr Budoff has received grant support from General Electric; has been on the Medical Advisory Board of Arineta; and has received salary from and has ownership interest in Cleerly, Inc. Dr Berman has received software royalties from Cedars-Sinai Medical Center. Dr Lopes has received grants and other support from Bayer, Boehringer Ingleheim, Bristol-Myers Squibb, Daiichi Sankyo, and Glaxo Smith Kline; and has received grants from Medtronic, Merck, Pfizer, Portola, and Sanofi. Dr Chow holds the Saul and Edna Goldfarb Chair in Cardiac Imaging Research; has received research support from TD Bank, CV Diagnostix and AusculSciences, and Siemens Healthineers; and has equity interest in General Electric. Dr Stone has received personal fees from Terumo, Amaranth, Shockwave, Valfix, TherOx, Reva, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Matrizyme, Miracor, Neovasc, V-wave, SpectreWave, MAIA Pharmaceuticals, Orchestra Biomed, Vectorious Abiomed, Claret, Sirtex, Ancora, and Qool Therapeutics; other considerations from Cagent, Applied Therapeutics, Biostar family of funds; support from MedFocus family of funds, Aria; and personal fees from Cardiac Success work. Dr Boden has received support from Abbvie and Amarin; grants from Amgen; and personal fees from Amgen, Cleveland Clinic Clinical Coordinating Center, and Janssen. Dr Bangalore has received grants and personal fees from Abbott Vascular; and personal fees from Biotronik, Pfizer, and Amgen. Dr Hochman is principal investigator for the ISCHEMIA trial, for which grant, devices, and medications were provided by Abbott Vascular; Medtronic, Inc; St. Jude Medical, Inc; Volcano Corporation; Arbor Pharmaceuticals, LLC; AstraZeneca Pharmaceuticals, LP; Merck Sharp & Dohme Corp; Omron Healthcare, Inc; and financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale and Objectives: Determine in cardiac amyloid (CA) patients, whether cardiac CT derived extracellular volume (ECV) correlates with that obtained by MRI. Perform this correlation with single (SECT) versus dual energy (DECT) CT and evaluate whether a single sample volume ECV-measure was as reliable as a global (16 segment) assessment., Materials and Methods: CA patients who had undergone a clinical cardiac MRI (CMR) were recruited prospectively. SECT and DECT cardiac scans were performed. Three ECG-triggered prospective SECT scans were acquired: non-contrast, arterial-phase contrast and 5-minute delayed images. A DECT scan was performed at 7 min. Post processing was used to determine ECV. Analyses of SECT or DECT global ECV versus CMR were performed using the Pearson correlation coefficient, Bland Altman analysis and Intraclass correlation coefficient (ICC). Similar analyses were performed to examine the performance of single-segment sampling by SECT or DECT versus CMR., Results: 25 patients were recruited, mean age was 80.0 ± 7.1 years, 80 % were male, 21 patients had transthyretin- CA, 4 had light chain- CA. Correlations were close with both SECT or DECT global ECV versus CMR (r = 0.79 and 0.88 respectively, p < 0.001 for both). Reliability of both SECT and DECT to assess global ECV in comparison to CMR was good: ICC for SECT was 0.88 (95 % CI 0.73-0.95) and 0.93 (95 % CI 0.82-0.97) for DECT. For single volume sampling techniques: correlations were close with both SECT or DECT versus CMR (r = 0.60 and 0.72 respectively, p < 0.01 for both) There was no difference in ICC for SECT (0.74, 95 %CI 0.41-0.88) versus DECT (0.84, 95 % CI 0.63-0.93). Wider confidence intervals were noted for ICC with single versus global CT derived ECV assessment. Mean effective radiation dose was for SECT was 5.49 ± 8.04 mSv and 6.90 ± 3.01 mSv for DECT dual energy CT (p = 0.75)., Conclusions: Global ECV values derived by both DECT or SECT correlated with those obtained by CMR and demonstrated good reliability by ICC in a population of CA patients. DECT and SECT single sampling derived ECV values also demonstrated close correlation and good reliability but the ICCs for single sampling had wider confidence intervals than global ECV assessment., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr Gary R Small reports a relationship with Pfizer Global Research and Development that includes: funding grants and speaking and lecture fees. Dr Benjamin JW Chow reports a relationship with Siemens Medical Solutions USA Inc that includes: funding grants.]., (© 2022 The Author(s).)

Inflammation is a key determinant of cardiovascular outcomes, but its role in heart failure is uncertain. In patients with cardiometabolic disease enrolled in the prospective, multicenter ancillary study of CIRT (Cardiovascular Inflammation Reduction Trial), CIRT-CFR (Coronary Flow Reserve to Assess Cardiovascular Inflammation), impaired coronary flow reserve was independently associated with increased inflammation and myocardial strain despite well-controlled lipid, glycemic, and hemodynamic profiles. Inflammation modified the relationship between CFR and myocardial strain, disrupting the association between cardiac blood flow and function. Future studies are needed to investigate whether an early inflammation-mediated reduction in CFR capturing microvascular ischemia may lead to heart failure in patients with cardiometabolic disease. (Cardiovascular Inflammation Reduction Trial [CIRT]; NCT01594333; Coronary Flow Reserve to Assess Cardiovascular Inflammation [CIRT-CFR]; NCT02786134)., Competing Interests: This research was supported by National Institutes of Health (NIH) R01HL132021 (to Drs Di Carli and Taqueti) and K23HL135438 (to Dr Taqueti). Dr Shah was supported by NIH R01HL135008, R01HL143224, R01HL150342, R01HL14818, and K24HL152008. Dr Libby was supported by R01HL134892. Dr Shah has received research support from Novartis; and consulting fees from Philips Ultrasound and Edwards Lifesciences. Dr Dorbala has received research support from Pfizer, GE Healthcare, and Attralus; and consulting honoraria from Pfizer and GE Healthcare. Dr Chow holds the Saul and Edna Goldfarb Chair in Cardiac Imaging Research; has received research support from TD Bank, AusculSciences, Siemens Healthineers, and Artrya; and has equity interest in General Electric. Dr Hage has received grant support from GE Healthcare, Novartis, and Idorsia Pharmaceuticals. Dr Beanlands holds the Chair in Cardiology at the University of Ottawa Heart Institute; is a University of Ottawa Distinguished Research Chair in Cardiovascular Imaging; and is a consultant for and has received grant funding from GE Healthcare, Lantheus Medical Imaging, and Jubilant DraxImage. Dr Libby is an unpaid consultant to or involved in clinical trials for Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Medimmune, Merck, Norvo Nordisk, Novartis, Pfizer, Sanofi-Regeneron; is on the Scientific Advisory Board for Amgen, Caristo, Cartesian, Corvidia Therapeutics, CSL Behring, DalCor Pharmaceuticals, Dewpoint, Kowa Pharmaceuticals, Olatec Therapeutics, Medimmune, Novartis, PlaqueTec, and XBiotech, Inc; is on the Board of Directors and has a financial interest in XBiotech, Inc; and has received research funding from Novartis, the American Heart Association, the RRM Charitable Fund, and the Simard Fund. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 Published by Elsevier on behalf of the American College of Cardiology Foundation.)

Background: Absence of subclinical atherosclerosis is considered safe to defer statin therapy in general population. However, impact of statins on atherosclerotic cardiovascular disease in patients with diabetes stratified by coronary artery calcium (CAC) scores and extent of non-obstructive CAD on coronary computed tomography angiography (CCTA) has not been evaluated., Methods: CONFIRM (Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multi-center Registry) study enrolled consecutive adults 18 years of age between 2005 and 2009 who underwent 3 64-detector row CCTA for suspected CAD. The long-term registry includes data on 12,086 subjects who underwent CCTA at 17 centers in 9 countries. In this sub-study of CONFIRM registry, patients with diabetes mellitus (DM) and without diabetes mellitus with normal CCTA or non-obstructive plaque (<50 % diameter stenosis) for whom data on baseline statin use was available were included. CAC score was calculated using Agatston score. The magnitude of non-obstructive coronary artery disease on CCTA was quantified using segment involvement score (SIS). Primary outcome was major cardiovascular events (MACE) which included all-cause mortality, myocardial infarction, and target vessel re-vascularization., Results: A total of 7247 patients (Mean age 56.8 years) with a median follow up of 5 years were included. For DM patients, baseline statin therapy significantly reduced MACE for patients with CAC ≥100 (HR: 0.24; 95 % CI 0.07-0.87; p = 0.03) and SIS≥3 (HR: 0.23; 95 % CI 0.06-0.83; p = 0.024) compared to those not on statin therapy. Among Diabetics with lower CAC (<100) and SIS (≤3) scores, MACE was similar in statin and non-statin groups. In contrast, among non-DM patients, MACE was similar in statin and no statin groups irrespective of baseline CAC (1-99 or ≥100) and SIS., Conclusion: In this large multicenter cohort of patients, the presence and extent of subclinical atherosclerosis as assessed by CAC and SIS identified patients most likely to derive benefit from statin therapy., (Copyright © 2022. Published by Elsevier Inc.)

Background: We examined age differences in whole-heart volumes of non-calcified and calcified atherosclerosis by coronary computed tomography angiography (CCTA) of patients with future ACS., Methods: A total of 234 patients with core-lab adjudicated ACS after baseline CCTA were enrolled. Atherosclerotic plaque was quantified and characterized from the main epicardial vessels and side branches on a 0.5 ​mm cross-sectional basis. Calcified plaque and non-calcified plaque were defined by above or below 350 Hounsfield units. Patients were categorized according to their age by deciles. Also, coronary artery calcium scores (CACS) were evaluated when available., Results: Patients were on average 62.2 ​± ​11.5 years old. On the pre-ACS CCTA, patients showed diffuse, multi-site, predominantly non-obstructive atherosclerosis across all age categories, with plaque being detected in 93.5% of all ACS cases. The proportion calcified plaque from the total plaque burden increased significantly with older presentation (10% calcification in those <50 years, and 50% calcification in those >80 years old). Patients with ACS <50 years had remarkably lower atherosclerotic burden compared with older patients, but a high proportion of high risk markers such as low-attenuation plaque. CACS was >0 in 85% of the patients older than 50 years, and in 57% of patients younger than 50 years., Conclusion: The proportion of calcified plaque varied depending on patient age at the time of ACS. Only a small proportion of plaque was calcified when ACS occurred at <50 years old, while this increased gradually with older age. Purely non-calcified atherosclerotic plaque was not uncommon in patients <50 years., Competing Interests: Declaration of competing interest Dr. Chinnaiyan is a non-compensated medical advisory board member of Heartflow Inc. Dr. Chow holds the Saul and Edna Goldfarb Chair in Cardiac Imaging Research, receives support from CV Diagnostix and Ausculsciences, receives educational support from TeraRecon Inc., and has equity interest in General Electric. Dr. Min is an employee of Cleerly, Inc. Dr. Samady serves on the scientific advisory board of Philips, has equity interest in Covanos Inc., and has a research grant from Medtronic, Abbott Vascular, and Philips. Dr. Shaw is on the scientific advisory board for Covanos, Inc. The remaining authors have no relevant conflicts to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Aims: The temporal instability of coronary atherosclerotic plaque preceding an incident acute coronary syndrome (ACS) is not well defined. We sought to examine differences in the volume and composition of coronary atherosclerosis between patients experiencing an early (≤90 days) versus late ACS (>90 days) after baseline coronary computed tomography angiography (CCTA)., Methods and Results: From a multicenter study, we enrolled patients who underwent a clinically indicated baseline CCTA and experienced ACS during follow-up. Separate core laboratories performed blinded adjudication of ACS events and quantification of CCTA including compositional plaque volumes by Hounsfield units (HU): calcified plaque >350 HU, fibrous plaque 131-350 HU, fibrofatty plaque 31-130 HU and necrotic core <30 HU. In 234 patients (mean age 62 ± 12 years, 36% women), early and late ACS occurred in 129 and 105 patients after a mean of 395 ± 622 days, respectively. Patients with early ACS had a greater maximal diameter stenosis and maximal cross-sectional plaque burden as compared to patients with late ACS (P < 0.05). Larger total, fibrous, fibrofatty, and necrotic core volumes were observed in the early ACS group (P < 0.05). Findings for total, fibrous, fibrofatty, and necrotic core volumes were reproduced in an external validation cohort (P < 0.05)., Conclusions: Volumetric differences in composition of coronary atherosclerosis exist between ACS patients according to their timing antecedent to the acute event. These data support that a large burden of non-calcified plaque on CCTA is strongly associated with near-term plaque instability and ACS risk., Competing Interests: Conflict of interest: Dr Chow receives support from CV Diagnostix and Ausculsciences, educational support from TeraRecon Inc., and has equity interest in General Electric. Dr Leipsic is a consultant and has stock options in Circle CVI and HeartFlow and receives research support from GE Healthcare. Dr Min is an employee of Cleerly, Inc. Dr Shaw serves on the scientific advisory board for Covanos, Inc. Dr Samady serves on the scientific advisory board of Philips, has equity interest in Covanos Inc., and has a research grant from Medtronic, Abbott Vascular, and Philips. The remaining authors have no relevant conflicts to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aim: Obstructive coronary artery disease (CAD) in proximal coronary segments is associated with a poor prognosis. However, the relative importance of plaque location regarding the risk for major adverse cardiovascular events (MACE) in patients with non-obstructive CAD has not been well defined., Methods and Results: From the Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter (CONFIRM) registry, 4644 patients without obstructive CAD were included in this study. The degree of stenosis was classified as 0 (no) and 1-49% (non-obstructive). Proximal involvement was defined as any plaque present in the left main or the proximal segment of the left anterior descending artery, left circumflex artery, and right coronary artery. Extensive CAD was defined as segment involvement score of >4. During a median follow-up of 5.2 years (interquartile range 4.1-6.0), 340 (7.3%) MACE occurred. Within the non-obstructive CAD group (n = 2065), proximal involvement was observed in 1767 (85.6%) cases. When compared to non-obstructive CAD patients without proximal involvement, those with proximal involvement had an increased MACE risk (log-rank P = 0.033). Multivariate Cox analysis showed when compared to patients with no CAD, proximal non-obstructive CAD was associated with increased MACE risk [hazard ratio (HR) 1.90, 95% confidence interval (CI) 1.47-2.45, P < 0.001] after adjusting for extensive CAD and conventional cardiovascular risk factors; however, non-proximal non-obstructive CAD did not increase MACE risk (HR 1.26, 95% CI 0.79-2.01, P = 0.339)., Conclusions: Independent of plaque extent, proximal coronary involvement was associated with increased MACE risk in patients with non-obstructive CAD. The plaque location information by coronary computed tomography angiography may provide additional risk prediction over CAD extent in patients with non-obstructive CAD., Competing Interests: Conflict of interest: J.K.M. receives funding from the Dalio Foundation, National Institutes of Health, and GE Healthcare; has serves on the scientific advisory board of Arineta and GE Healthcare; and has an equity interest in Cleerly. B.J.W.C. receives research grant support from TD Bank, Artrya, Siemens, and AusculSciences and has an equity interest in GE healthcare. P.A.K.’s nuclear department at the University Hospital Zurich holds research agreement with GE Healthcare. G.P. receives honorarium as speaker and research institutional grant from GE, Bracco, Boehringer, and HeartFlow. All other authors declared no conflict of interest., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Purpose: In this cohort study, 5-year data from the Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry (ie, CONFIRM) were examined to identify associations of baseline aspirin and statin use with mortality, major adverse cardiovascular events (MACE), and myocardial infarction (MI) in individuals without substantial (≥50%) stenosis., Materials and Methods: In this prospective cohort study, all participants in the registry underwent coronary CT angiography and were classified as having no detectable coronary plaque or having nonobstructive coronary artery disease (CAD) (1%-49% stenosis). Participants with obstructive (≥50%) stenosis were excluded from analysis. The study commenced in June 2003 and was completed in March 2016. All unadjusted and risk-adjusted analyses utilized the Cox proportional hazard model with hospital sites modeled using shared frailty., Results: A total of 6386 participants with no detectable plaque or with nonobstructive CAD were included (mean age, 56.0 years ± 13.3 [SD], 52% men). The mean follow-up period was 5.66 years ± 1.10. Nonobstructive CAD ( n = 2815, 44% of all participants included in the study) was associated with a greater risk of all-cause mortality (10.6% [298 of 2815] vs 4.8% [170 of 3571], P < .001) compared to those without CAD ( n = 3571, 56%). Baseline aspirin and statin use was documented for 1415 and 1429 participants, respectively, with nonobstructive CAD, and for 1560 and 1565 participants without detectable plaque, respectively. In individuals with nonobstructive CAD, baseline aspirin use was not associated with a reduction in MACE (10.9% [102 of 936] vs 14.7% [52 of 355], P = .06), all-cause mortality (9.6% [95 of 991] vs 10.9% [46 of 424], P = .468), or MI (4.4% [41 of 936] vs 6.2% [22 of 355], P = .18). On multivariate risk-adjusted analysis, baseline statin use was associated with a lower rate of MACE (hazard ratio, 0.59; 95% CI: 0.40, 0.87; P = .007). Neither therapy improved clinical outcomes for participants with no detectable plaque., Conclusion: In participants with nonobstructive CAD, baseline use of statins, but not of aspirin, was associated with improved clinical outcomes. Neither therapy was associated with benefit in participants without plaque. Keywords: Aspirin, Statin, Coronary Artery Disease, CT Angiography, Nonobstructive Coronary Artery DiseaseClinical trial registration no. NCT01443637 Supplemental material is available for this article. © RSNA, 2022See also the commentary by Canan and Navar in this issue., Competing Interests: Disclosures of conflicts of interest: P.I. No relevant relationships. C.N. No relevant relationships. S.B.Z. No relevant relationships. H.G. No relevant relationships. P.B. Consulting fees from Edwards Lifesciences, Neovasc, and Boston Scientific. S.S. No relevant relationships. S.A. No relevant relationships. M.H.A. Grant/contract from Siemens; consulting fees from Philips. D.A. No relevant relationships. D.S.B. Software royalties from Cedars-Sinai Medical Center. M.J.B. No relevant relationships. F.C. No relevant relationships. T.Q.C. No relevant relationships. H.J.C. No relevant relationships. K.C. Executive Committee and Board of Directors, Society for Cardiovascular Computed Tomography (SCCT), unpaid. B.J.W.C. Saul and Edna Goldfarb Chair in Cardiac Imaging; research grants from TD Bank, AusculSciences, Artrya, and CV Diagnostix; board member of SCCT (ended in 2021); stock in GE (equity sold in 2021). R.C.C. Consults for Covera Health, GE Healthcare, and Cleerly (not related to the topic of this article). A.D. No relevant relationships. G.F. No relevant relationships. M.H. No relevant relationships. J.H. Grant/contract from Edwards Lifesciences, payment or honoraria from Abbott Vascular and Edwards Lifesciences, support for meetings and travel from Abbott Vascular and Edwards Lifesciences. P.A.K. University Hospital Zurich holds a research grant with GE Healthcare (unrelated to the present study), Advisory Board for GE Healthcare on the myocardial perfusion tracer Flurpiridaz (unrelated to present study), Vice Chair of the Swiss Society of Nuclear Medicine (unpaid). Y.J.K. No relevant relationships. E.M. No relevant relationships. H.M. No relevant relationships. P.d.A.G. No relevant relationships. G.P. No relevant relationships. G.L.R. No relevant relationships. R.R. Board member of SCCT. T.C.V. No relevant relationships. F.Y.L. Research grant from GE. L.J.S. No relevant relationships. J.N. No relevant relationships. J.J.B. The department of cardiology, Leiden University Medical Center has received unrestricted research grants from Abbott, Edwards Lifesciences, Bayer, Novartis, Boston Scientific, Medtronic, Biotronik, GE Healthcare; payment or honoraria from Speaker Bureau Abbott and Edwards Lifesciences. J.A.L. Unrestricted research grant from GE Healthcare, stock options and consulting fees from HeartFlow and Circle CVI, payment or honoraria from Philips, board of directors of SCCT, deputy editor for Radiology: Cardiothoracic Imaging., (© 2022 by the Radiological Society of North America, Inc.)

Importance: Distinct plaque locations and vessel geometric features predispose to altered coronary flow hemodynamics. The association between these lesion-level characteristics assessed by coronary computed tomographic angiography (CCTA) and risk of future acute coronary syndrome (ACS) is unknown., Objective: To examine whether CCTA-derived adverse geometric characteristics (AGCs) of coronary lesions describing location and vessel geometry add to plaque morphology and burden for identifying culprit lesion precursors associated with future ACS., Design, Setting, and Participants: This substudy of ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a multicenter nested case-control cohort study, included patients with ACS and a culprit lesion precursor identified on baseline CCTA (n = 116) and propensity score-matched non-ACS controls (n = 116). Data were collected from July 20, 2012, to April 30, 2017, and analyzed from October 1, 2020, to October 31, 2021., Exposures: Coronary lesions were evaluated for the following 3 AGCs: (1) distance from the coronary ostium to lesion; (2) location at vessel bifurcations; and (3) vessel tortuosity, defined as the presence of 1 bend of greater than 90° or 3 curves of 45° to 90° using a 3-point angle within the lesion., Main Outcomes and Measures: Association between lesion-level AGCs and risk of future ACS-causing culprit lesions., Results: Of 548 lesions, 116 culprit lesion precursors were identified in 116 patients (80 [69.0%] men; mean [SD], age 62.7 [11.5] years). Compared with nonculprit lesions, culprit lesion precursors had a shorter distance from the ostium (median, 35.1 [IQR, 23.6-48.4] mm vs 44.5 [IQR, 28.2-70.8] mm), more frequently localized to bifurcations (85 [73.3%] vs 168 [38.9%]), and had more tortuous vessel segments (5 [4.3%] vs 6 [1.4%]; all P < .05). In multivariable Cox regression analysis, an increasing number of AGCs was associated with a greater risk of future culprit lesions (hazard ratio [HR] for 1 AGC, 2.90 [95% CI, 1.38-6.08]; P = .005; HR for ≥2 AGCs, 6.84 [95% CI, 3.33-14.04]; P < .001). Adverse geometric characteristics provided incremental discriminatory value for culprit lesion precursors when added to a model containing stenosis severity, adverse morphological plaque characteristics, and quantitative plaque characteristics (area under the curve, 0.766 [95% CI, 0.718-0.814] vs 0.733 [95% CI, 0.685-0.782]). In per-patient comparison, patients with ACS had a higher frequency of lesions with adverse plaque characteristics, AGCs, or both compared with control patients (≥2 adverse plaque characteristics, 70 [60.3%] vs 50 [43.1%]; ≥2 AGCs, 92 [79.3%] vs 60 [51.7%]; ≥2 of both, 37 [31.9%] vs 20 [17.2%]; all P < .05)., Conclusions and Relevance: These findings support the concept that CCTA-derived AGCs capturing lesion location and vessel geometry are associated with risk of future ACS-causing culprit lesions. Adverse geometric characteristics may provide additive prognostic information beyond plaque assessment in CCTA.

We assessed the left atrial-left ventricular (LA-LV) long axis angulation value as a new measure of LA remodeling, and studied its predictors, its effect on two-dimensional LA volume (2D LAVol) estimation, and optimization techniques for 2D LAVol values. Retrospective electrocardiogram-gated coronary computed tomographic angiograms of 164 consecutive patients were reviewed. The LA-LV angle was measured in reconstructed 3-chamber views, and its predictors were determined. The LAVol measured by the area-length method after image optimization along the LV long axis (AL) and the LA long axis (AC-AL), was compared with that measured by the three-dimensional (3D)-volumetric method. LAVol calculation was modified to minimize differences from the 3D values. LA-LV angles ranged from 0° to 63°. In the univariate analysis, decreasing angulation was significantly associated with increasing LV end-diastolic volume (LVEDV), mitral regurgitation grade, LV and LA anteroposterior dimensions, and decreasing LV ejection fraction (LVEF). On multivariate analysis, increasing LVEDV, MR, and LA anteroposterior dimension inversely correlated with angulation; LVEF was positively correlated. The AL and 3D methods significantly differed only for patients with angles ≤ 29.9°. Conversely, LAVol was overestimated for all angules by AC-AL. Modification of AL LAVol using a regression equation, or by substituting the shortest with the longest and average LA lengths in patients with angles ≤ 29.9° and 30-39.9°, respectively neutralized the difference. The LA-LV angle is a new measure of LA and LV remodeling predicted by LV size and function, MR, and LA-anteroposterior dimension. AL formula modifications based on angulation in LV-optimized views better correlate with the 3D method than LA-view modification., (© 2021. The Author(s).)

Research in artificial intelligence (AI) has progressed over the past decade. The field of cardiac imaging has seen significant developments using newly developed deep learning methods for automated image analysis and AI tools for disease detection and prognostication. This review is aimed at those without special background in AI. We review AI concepts and survey the growing contemporary applications of AI for image analysis in echocardiography, nuclear cardiology, cardiac computed tomography, cardiac magnetic resonance, and invasive angiography., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)