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Mickaël Martin,1 Natalie Almeras,1 Jean-Pierre Després,1 Harvey O Coxson,2 George R Washko,3 Isabelle Vivodtzev,4 Emiel FM Wouters,5 Erica Rutten,6 Michelle C Williams,7 John T Murchison,8 William MacNee,7 Don D Sin,2 François Maltais1 On behalf of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Study Group 1Research Centre, Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, QC, 2Department of Radiology, University of British Columbia, Vancouver, BC, Canada; 3Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 4Hypoxia Pathophysiology Laboratory, Grenoble University Hospital, Grenoble, France; 5Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, 6Research and Development, CIRO, Horn, the Netherlands; 7Department of Respiratory Medicine, University of Edinburgh, 8Department of Radiology, Royal Infirmary of Edinburgh, Edinburgh, UK Background: Obesity is increasingly associated with COPD, but little is known about the prevalence of ectopic fat accumulation in COPD and whether this can possibly be associated with poor clinical outcomes and comorbidities. The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) substudy tested the hypothesis that COPD is associated with increased ectopic fat accumulation and that this would be associated with COPD-related outcomes and comorbidities.Methods: Computed tomography (CT) images of the thorax obtained in ECLIPSE were used to quantify ectopic fat accumulation at L2–L3 (eg, cross-sectional area [CSA] of visceral adipose tissue [VAT] and muscle tissue [MT] attenuation, a reflection of muscle fat infiltration) and CSA of MT. A dose–response relationship between CSA of VAT, MT attenuation and CSA of MT and COPD-related outcomes (6-minute walking distance [6MWD], exacerbation rate, quality of life, and forced expiratory volume in 1 second [FEV1] decline) was addressed with the Cochran–Armitage trend test. Regression models were used to investigate possible relationships between CT body composition indices and comorbidities.Results: From the entire ECLIPSE cohort, we identified 585 subjects with valid CT images at L2–L3 to assess body composition. CSA of VAT was increased (P

Background and aimsSmoking is associated with increased risk for brain aging/atrophy and dementia. Few studies have examined early associations with brain aging. This study aimed to measure whether adult men with a history of heavier smoking in early mid-life would have older than predicted brain age 16-28 years later.DesignProspective cohort observational study, utilizing smoking pack years data from average age 40 (early mid-life) predicting predicted brain age difference scores (PBAD) at average ages 56, 62 (later mid-life) and 68 years (early old age). Early mid-life alcohol use was also evaluated.SettingPopulation-based United States sample.Participants/casesParticipants were male twins of predominantly European ancestry who served in the United States military between 1965 and 1975. Structural magnetic resonance imaging (MRI) began at average age 56. Subsequent study waves included most baseline participants; attrition replacement subjects were added at later waves.MeasurementsSelf-reported smoking information was used to calculate pack years smoked at ages 40, 56, 62, and 68. MRIs were processed with the Brain-Age Regression Analysis and Computation Utility software (BARACUS) program to create PBAD scores (chronological age-predicted brain age) acquired at average ages 56 (n = 493; 2002-08), 62 (n = 408; 2009-14) and 68 (n = 499; 2016-19).FindingsIn structural equation modeling, age 40 pack years predicted more advanced age 56 PBAD [β = -0.144, P = 0.012, 95% confidence interval (CI) = -0.257, -0.032]. Age 40 pack years did not additionally predict PBAD at later ages. Age 40 alcohol consumption, but not a smoking × alcohol interaction, predicted more advanced PBAD at age 56 (β = -0.166, P = 0.001, 95% CI = -0.261, -0.070) with additional influences at age 62 (β = -0.115, P = 0.005, 95% CI = -0.195, -0.036). Age 40 alcohol did not predict age 68 PBAD. Within-twin-pair analyses suggested some genetic mechanism partially underlying effects of alcohol, but not smoking, on PBAD.ConclusionsHeavier smoking and alcohol consumption by age 40 appears to predict advanced brain aging by age 56 in men.

18 F-GP1 is a novel highly specific radiotracer that binds to activated platelets and thrombus. We aimed to establish the observer repeatability of coronary, carotid and cerebral 18 F-GP1 uptake in patients presenting with acute myocardial infarction or ischaemic stroke. Forty-three patients presenting with acute myocardial infarction or ischaemic stroke underwent hybrid positron emission tomography (PET) and computed tomography (CT) angiography. Qualitative and quantitative assessment of 18 F-GP1 uptake was performed on coronary arteries, carotid arteries and brain parenchyma. Qualitative uptake of 18 F-GP1 had excellent intraobserver and interobserver agreement, with complete agreement for the presence or absence of visual 18 F-GP1 uptake. For quantitative analysis, there were excellent intraclass correlation coefficients for intraobserver repeatability for coronary artery, carotid artery and brain parenchymal SUV max and TBR max measurements (all ≥ 0.92). Coronary artery and brain parenchymal analyses showed the strongest agreement in SUV max values with mean biases of - 0.04 (limits of agreement - 0.21 to 0.20) and 0.02 (limits of agreement - 0.29 to 0.32) respectively. There was good interclass correlation coefficients for interobserver repeatability for coronary artery, carotid artery and brain parenchymal SUV max and TBR max measurements (all ≥ 0.89). The strongest interobserver agreement was seen with brain parenchymal SUV max (mean SUV max 1.95 ± 0.94) and TBR max (mean TBR max 9.55 ± 6.56) with mean biases of - 0.05 (limits of agreement - 0.37 to 0.27) and 0.04 (limits of agreement - 0.59 to 0.52) respectively. Visual qualitative and quantitative 18 F-GP1 PET-CT image analyses provide robust and repeatable measurements of activated platelets and thrombi within the coronary arteries, carotid arteries and brain parenchyma., (© 2024. The Author(s).)

Background: Aortic stenosis (AS) is characterized by calcification and fibrosis. The ability to quantify these processes simultaneously has been limited with previous imaging methods., Objectives: The purpose of this study was to evaluate the aortic valve fibrocalcific volume by computed tomography (CT) angiography in patients with AS, in particular, to assess its reproducibility, association with histology and disease severity, and ability to predict/track progression., Methods: In 136 patients with AS, fibrocalcific volume was calculated on CT angiograms at baseline and after 1 year. CT attenuation distributions were analyzed using Gaussian-mixture-modeling to derive thresholds for tissue types enabling the quantification of calcific, noncalcific, and fibrocalcific volumes. Scan-rescan reproducibility was assessed and validation provided against histology and in an external cohort., Results: Fibrocalcific volume measurements took 5.8 ± 1.0 min/scan, demonstrating good correlation with ex vivo valve weight (r = 0.51; P < 0.001) and excellent scan-rescan reproducibility (mean difference -1%, limits of agreement -4.5% to 2.8%). Baseline fibrocalcific volumes correlated with mean gradient on echocardiography in both male and female participants (rho = 0.64 and 0.69, respectively; both P < 0.001) and in the external validation cohort (n = 66, rho = 0.58; P < 0.001). The relationship was driven principally by calcific volume in men and fibrotic volume in women. After 1 year, fibrocalcific volume increased by 17% and correlated with progression in mean gradient (rho = 0.32; P = 0.003). Baseline fibrocalcific volume was the strongest predictor of subsequent mean gradient progression, with a particularly strong association in female patients (rho = 0.75; P < 0.001)., Conclusions: The aortic valve fibrocalcific volume provides an anatomic assessment of AS severity that can track disease progression precisely. It correlates with disease severity and hemodynamic progression in both male and female patients., Competing Interests: Funding Support and Author Disclosures The SALTIRE 2 trial was funded by the British Heart Foundation (FS/14/78/31020). This work was partially supported by a grant from the Korea Health Technology R and D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (grant number HI22C0154 to Dr Lee). Dr Joshi has received funding from the British Heart Foundation through a Clinical Research Training Fellowship and Research Excellence Award (FS/CRTF/20/24087 and RE/18/5/34216). Dr Williams is supported by the British Heart Foundation (FS/ICRF/20/26002); and has given talks for Canon Medical Systems, Siemens Healthineers and Novartis. Dr Newby is supported by the British Heart Foundation (CH/09/002, RG/20/10/34966, RE/18/5/34216, CH/F/21/90010); and is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr Dweck is supported by the British Heart Foundation (FS/SCRF/21/32010); is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA); has received speaker fees from Pfizer, Radcliffe Cardiology, Bristol Myers Squibb, Edwards, and Novartis; has received consultancy fees from Novartis, Jupiter Bioventures, Beren, and Silence therapeutics; and is Director of the Imaging Corelab at the University of Edinburgh. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: There are sex differences in the extent, severity, and outcomes of coronary artery disease. We aimed to assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18 F-sodium fluoride ( 18 F-NaF) positron emission tomography (PET), and to determine whether 18 F-NaF PET has prognostic value in both women and men., Methods: In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18 F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men., Results: Baseline 18 F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27-434] versus 205 [51-571] Agatston units; p = 0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p = 0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p = 0.21) and similar proportions of women and men had no 18 F-NaF uptake (53.0% (n = 80) and 48.3% (n = 73); p = 0.42), or CMA values > 1.56 (21.8% (n = 33) and 21.8% (n = 33); p = 1.00). Over a median follow-up of 4.5 [4.0-6.0] years, myocardial infarction occurred in 6.6% of women (n = 10) and 7.8% of men (n = 66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p = 0.04) and men (HR: 5.29; 95% CI:2.28-12.28; p < 0.001)., Conclusion: Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: Whether index testing using coronary computed tomography angiography (CTA) improves outcomes in stable chest pain is debated. The risk factor weighted clinical likelihood (RF-CL) model provides likelihood estimation of obstructive coronary artery disease. This study investigated the prognostic effect of coronary CTA vs. usual care by RF-CL estimates., Methods: Large-scale studies randomized patients (N = 13 748) with stable chest pain to coronary CTA as part of the initial work-up in addition to or instead of usual care including functional testing. Patients were stratified according to RF-CL estimates [RF-CL: very-low (≤5%), low (>5%-15%), and moderate/high (>15%)]. The primary endpoint was myocardial infarction or death at 3 years., Results: The primary endpoint occurred in 313 (2.3%) patients. Event rates were similar in patients allocated to coronary CTA vs. usual care [risk difference (RD) 0.3%, hazard ratio (HR) 0.84 (95% CI 0.67-1.05)]. Overall, 33%, 44%, and 23% patients had very-low, low, and moderate/high RF-CL. Risk was similar in patients with very low and moderate/high RF-CL allocated to coronary CTA vs. usual care [very low: RD 0.3%, HR 1.27 (0.74-2.16); moderate/high: RD 0.5%, HR 0.88 (0.63-1.23)]. Conversely, patients with low RF-CL undergoing coronary CTA had lower event rates [RD 0.7%, HR 0.67 (95% CI 0.47-0.97)]. The number needed to test using coronary CTA to prevent one event within 3 years was 143., Conclusions: Despite an overall good prognosis, low RF-CL patients have reduced risk of myocardial infarction or death when allocated to coronary CTA vs. usual care. Risk is similar in patients with very-low and moderate/high likelihood., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: To develop and evaluate a multi-task deep-learning (DL) model for automated segment-level coronary artery calcium (CAC) scoring on non-contrast computed tomography (CT) for precise localization and quantification of calcifications in the coronary artery tree., Methods: This study included 1514 patients (mean age, 60.0 ± 10.2 years; 56.0% female) with stable chest pain from 26 centers participating in the multicenter DISCHARGE trial (NCT02400229). The patients were randomly assigned to a training/validation set (1059) and a test set (455). We developed a multi-task neural network for performing the segmentation of calcifications on the segment level as the main task and the segmentation of coronary artery segment regions with weak annotations as an auxiliary task. Model performance was evaluated using (micro-average) sensitivity, specificity, F1-score, and weighted Cohen's κ for segment-level agreement based on the Agatston score and performing interobserver variability analysis., Results: In the test set of 455 patients with 1797 calcifications, the model assigned 73.2% (1316/1797) to the correct coronary artery segment. The model achieved a micro-average sensitivity of 0.732 (95% CI: 0.710-0.754), a micro-average specificity of 0.978 (95% CI: 0.976-0.980), and a micro-average F1-score of 0.717 (95% CI: 0.695-0.739). The segment-level agreement was good with a weighted Cohen's κ of 0.808 (95% CI: 0.790-0.824), which was only slightly lower than the agreement between the first and second observer (0.809 (95% CI: 0.798-0.845))., Conclusion: Automated segment-level CAC scoring using a multi-task neural network approach showed good agreement on the segment level, indicating that DL has the potential for automated coronary artery calcification classification., Critical Relevance Statement: Multi-task deep learning can perform automated coronary calcium scoring on the segment level with good agreement and may contribute to the development of new and improved calcium scoring methods., Key Points: Segment-level coronary artery calcium scoring is a tedious and error-prone task. The proposed multi-task model achieved good agreement with a human observer on the segment level. Deep learning can contribute to the automation of segment-level coronary artery calcium scoring., (© 2024. The Author(s).)

Background: Plaque quantification from coronary computed tomography angiography has emerged as a valuable predictor of cardiovascular risk. Deep learning can provide automated quantification of coronary plaque from computed tomography angiography. We determined per-patient age- and sex-specific distributions of deep learning-based plaque measurements and further evaluated their risk prediction for myocardial infarction in external samples., Methods: In this international, multicenter study of 2803 patients, a previously validated deep learning system was used to quantify coronary plaque from computed tomography angiography. Age- and sex-specific distributions of coronary plaque volume were determined from 956 patients undergoing computed tomography angiography for stable coronary artery disease from 5 cohorts. Multicenter external samples were used to evaluate associations between coronary plaque percentiles and myocardial infarction., Results: Quantitative deep learning plaque volumes increased with age and were higher in male patients. In the combined external sample (n=1847), patients in the ≥75th percentile of total plaque volume (unadjusted hazard ratio, 2.65 [95% CI, 1.47-4.78]; P =0.001) were at increased risk of myocardial infarction compared with patients below the 50th percentile. Similar relationships were seen for most plaque volumes and persisted in multivariable analyses adjusting for clinical characteristics, coronary artery calcium, stenosis, and plaque volume, with adjusted hazard ratios ranging from 2.38 to 2.50 for patients in the ≥75th percentile of total plaque volume., Conclusions: Per-patient age- and sex-specific distributions for deep learning-based coronary plaque volumes are strongly predictive of myocardial infarction, with the highest risk seen in patients with coronary plaque volumes in the ≥75th percentile., Competing Interests: Dr Miller has received consulting fees and research support from Pfizer. S. Cadet, Dr Slomka, Dr Dey, and Dr Berman received software royalties from Cedars-Sinai Medical Center and report equity in APQ Health Inc. outside of the current work. Dr Berman, Dr Slomka, and Dr Dey hold a patent (US8885905B2/WO2011069120A1, Method and System for Plaque Characterization). Dr Grodecki reports grants or contracts from the Foundation for Polish Science and Polish Society of Cardiology. Dr Kwan reports partial effort support from the Doris Duke Charitable Foundation Grant. Dr Kuronuma is supported by grants from The Society of Nuclear Medicine and Molecular Imaging Wagner-Torizuka Fellowship and Nihon University School of Medicine Alumni Association. S. Cadet reports financial support from the Miriam and Sheldon G Adelson Medical Research Foundation Grant. Dr Nicholls reports grants or contracts from AstraZeneca, New Amsterdam Pharma, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, and LipoScience; and consulting fees from AstraZeneca, Amarin, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, and Boehringer Ingelheim. Dr Dweck reports consulting fees from Novartis, Jupiter Bioventures, and Silence Therapeutics; and payment or honoraria from Pfizer and Novartis. Dr Newby reports a grant from the British Heart Foundation (RE/24/130012, CH/09/002, and RG/F/22/110093) and Wellcome Trust. Dr Williams has given talks for Canon Medical Systems, Siemens Healthineers and Novartis. The other authors report no conflicts.

Purpose To determine the prevalence of clinically relevant extracardiac findings at cardiac CT and MRI examinations from a multicenter, multinational MR/CT registry and the relationship of prevalence with examination indications and patient characteristics. Materials and Methods This was a retrospective analysis of data from the European Society of Cardiovascular Radiology MR/CT Registry. Data from 208 506 cardiac CT examinations (median patient age, 66 years [IQR, 55-77]; 121 617 [58.33%] male patients) and 228 462 cardiac MRI examinations (median patient age, 57 years [IQR, 42-69]; 145 792 [63.81%] male patients) entered into the registry between January 2011 and November 2023 were analyzed. Clinically relevant extracardiac findings were defined as findings requiring follow-up examinations or influencing clinical management. The association of examination indication and patient characteristics, including age, with prevalence of extracardiac findings was evaluated using incidence rate ratios (IRRs) derived from multivariable Poisson regression models. Results The prevalence of clinically relevant extracardiac findings was 3.28% (6832 of 208 506) at cardiac CT and 1.50% (3421 of 228 462) at cardiac MRI examinations. Extracardiac findings were more common at CT examinations performed for transcatheter aortic valve replacement (IRR, 2.07; P < .001) and structural heart disease (IRR, 1.44; P < .001) compared with CT performed for coronary artery disease (IRR, 1; reference). Extracardiac findings were more common at MRI examinations performed for myocarditis (IRR, 1.36; P < .001) and structural heart disease (IRR, 1.16; P < .001) than for coronary artery disease. Older patient age was also significantly associated with higher prevalence of extracardiac findings, with an IRR for both CT and MRI examinations of 1.02 ( P < .001). Conclusion Data from the multicenter, multinational MR/CT registry indicate that clinically relevant extracardiac findings are present at cardiovascular CT and MRI examinations, and the prevalence of these findings is associated with examination indication and patient age. Keywords: Cardiac Imaging Techniques, Incidental Findings, MRI, CT Angiography, CT, Heart Disease Supplemental material is available for this article. © RSNA, 2024.

Background: In patients with coronary artery disease, coronary plaques with high-risk features and low-attenuation plaque burden are independent measures associated with major adverse cardiovascular events (MACEs). Patients with chronic kidney failure may have different coronary artery disease characteristics. The aim was to assess the association of coronary plaque characteristics and coronary artery disease extent with MACE and all-cause mortality in patients with chronic kidney failure., Methods: Potential kidney transplant candidates who underwent coronary computed tomography angiography as part of the cardiac screening program before kidney transplantation were included. We evaluated high-risk plaques and diameter stenosis semiqualitatively and quantified coronary artery calcium score and plaque burden (percentage atheroma volume)., Results: In 484 patients with chronic kidney failure and few or no symptoms of coronary artery disease (mean age, 53±12 years; 62% men; 32% on dialysis), 56 (12%) patients suffered MACE and 69 (14%) patients died during a median follow-up of 4.9 years. High-risk plaques were present in 39 (70%) patients with MACE. Median calcified plaque burden was 3.7% in patients with MACE versus 0.2% in patients without MACE. The median low-attenuation plaque burden was 0.3% versus 0.03%, respectively. In semiqualitative analyses, the presence of high-risk plaque and a higher coronary artery calcium score were associated with increased risk of MACE (hazard ratio (HR), 2.0 [95% CI, 1.0-3.7]; P =0.040; HR, 1.2 [95% CI, 1.0-1.3]; P =0.014), respectively. Neither were associated with all-cause mortality. In quantified analysis, increasing levels of both calcified and low-attenuation plaque burdens were associated with risk of MACE (HR, 2.6 [95% CI, 1.8-3.7]; P <0.001; HR, 2.6 [95% CI, 1.5-4.5]; P =0.001 [per variable doubling, respectively]) and all-cause mortality (HR, 1.6 [95% CI, 1.2-2.1]; P =0.002; HR, 1.8 [95% CI, 1.1-3.0]; P =0.028, respectively)., Conclusions: In patients with chronic kidney failure, calcified and low-attenuation plaque burdens were independently associated with MACE and all-cause mortality, while high-risk plaques and coronary artery calcium score were only associated with MACE., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01344434., Competing Interests: Dr Winther had a nonfinancial collaboration agreement with Medis, the Netherlands, which sponsored the QAngio software. The provider had no role in the collection or the analysis of data nor in the interpretation of the results or writing of the article. Aside from this, the authors’ disclosures are unrelated to the present study. Dr Winther acknowledges support from the Novo Nordisk Foundation Clinical Emerging Investigator grant (NNF21OC0066981). Dr Rasmussen acknowledges support in terms of a research grant (PD5Y-2023001-DCA) from the Danish Cardiovascular Academy, which is funded by the Novo Nordisk Foundation (grant NNF20SA0067242) and the Danish Heart Foundation. Dr Ivarsen discloses consultancy/advisory board participation for CSL Vifor Pharma, Otsuka, and Novartis, speaker’s honorarium from Otsuka, and research grants from the Augustinus Foundation and CSL Vifor Pharma. Dr Svensson discloses funding from Novo Nordisk and the Augustinus Foundation. Dr Birn discloses consultancy and advisory board participation for NOVO Nordisk, AstraZeneca, Boehringer Ingelheim, Bayer, Alexion, Vifor Pharma, Otsuka, and Galapagos; speaker’s honorarium from AstraZeneca, Astellas, Novartis, and MSD; and research grants from Vifor Pharma, GSK, the NOVO Foundation, the Karen Elise Jensen Foundation, and the Augustinus Foundation. Dr Bøttcher discloses advisory board participation for NOVO Nordisk, AstraZeneca, Pfizer, Boehringer Ingelheim, Bayer, Sanofi, Novartis, Amgen, CSL Behring, and Acarix. The other authors report no conflicts.

Prokaryotic CRISPR-Cas immunity is subverted by anti-CRISPRs (Acrs), which inhibit Cas protein activities when expressed during the phage lytic cycle or from resident prophages or plasmids 1 . Acrs often bind to specific cognate Cas proteins, and hence inhibition is typically limited to a single CRISPR-Cas subtype 2 . Furthermore, although acr genes are frequently organized together in phage-associated gene clusters 3 , how such inhibitors initially evolve has remained unclear. Here we investigated the Acr content and inhibition specificity of diverse Listeria isolates, which naturally harbour four CRISPR-Cas systems (types I-B, II-A, II-C and VI-A). We observed widespread antagonism of CRISPR, which we traced to 11 previously unknown and 4 known acr gene families encoded by endogenous mobile elements. Among these were two Acrs that possess sequence homology to type I-B Cas proteins, one of which assembles into a defective interference complex. Surprisingly, an additional type I-B Cas homologue did not affect type I immunity, but instead inhibited the RNA-targeting type VI CRISPR system by means of CRISPR RNA (crRNA) degradation. By probing viral sequence databases, we detected abundant orphan cas genes located within putative anti-defence gene clusters. Among them, we verified the activity of a particularly broad-spectrum cas3 homologue that inhibits type I-B, II-A and VI-A CRISPR immunity. Our observations provide direct evidence of Acr evolution by cas gene co-option, and new genes with potential for broad-spectrum control of genome editing technologies., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Stable chest pain is a common symptom with multiple potential causes. Non-invasive imaging has an important role in diagnosis and guiding management through the assessment of coronary stenoses, atherosclerotic plaque, myocardial ischaemia or infarction, and cardiac function. Computed tomography (CT) provides the anatomical evaluation of coronary artery disease (CAD) with the assessment of stenosis, plaque type and plaque burden, with additional functional information available from CT fractional flow reserve (FFR) or CT myocardial perfusion imaging. Stress magnetic resonance imaging, nuclear stress myocardial perfusion imaging, and stress echocardiography can assess myocardial ischaemia and other cardiac functional parameters. Coronary CT angiography can be used as a first-line test for many patients with stable chest pain, particularly those with low to intermediate pre-test probability. Functional testing may be considered for patients with known CAD, where the clinical significance is uncertain based on anatomical testing, or in patients with high pre-test probability. This practice recommendations document can be used to guide the selection of non-invasive imaging for patients with stable chest pain and provides brief recommendations on how to perform and report these diagnostic tests. KEY POINTS: The selection of non-invasive imaging tests for patients with stable chest pain should be based on symptoms, pre-test probability, and previous history. Coronary CT angiography can be used as a first-line test for many patients with stable chest pain, particularly those with low to intermediate pre-test probability. Functional testing can be considered for patients with known CAD, where the clinical significance of CAD is uncertain based on anatomical testing, or in patients with high pre-test probability. KEY RECOMMENDATIONS: Non-invasive imaging is an important part of the assessment of patients with stable chest pain. The selection of non-invasive imaging test should be based on symptoms, pre-test probability, and previous history. (Level of evidence: High). Coronary CT angiography can be used as a first line test for many patients with stable chest pain, particularly those with low to intermediate pre-test probability. CT provides information on stenoses, plaque type, plaque volume, and if required functional information with CT fractional flow reserve or CT perfusion. (Level of evidence: High). Functional testing can be considered for patients with known CAD, where the clinical significance of CAD is uncertain based on anatomical testing, or in patients with high pre-test probability. Stress MRI, SPECT, PET, and echocardiography can provide information on myocardial ischemia, along with cardiac functional and other information. (Level of evidence: Medium)., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Competing Interests: Conflict of interest: None declared.

Background: Patients with osteoporosis demonstrate increased vascular calcification but the effect of osteoporosis treatments on vascular calcification remains unclear. The present study aimed to examine whether coronary or aortic calcification are influenced by denosumab and alendronic acid treatment., Methods and Results: In a double-blind randomized controlled SALTIRE2 (Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis) trial, patients with aortic stenosis were randomized 2:1:2:1 to denosumab, placebo injection, alendronic acid, or placebo capsule. Participants underwent serial imaging with computed tomography and 18F-sodium fluoride positron emission tomography for the assessment of vascular calcium burden and calcification activity, respectively. We report the prespecified secondary analyses of 24-month change in coronary calcium score, and 12-month changes in thoracic aorta calcium score, coronary and aortic 18F-sodium fluoride activity. One hundred fifty patients with aortic stenosis (72±8 years; 21% female) were randomized to denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25). There were no differences in change in coronary calcium scores between placebo (16 [-64 to 148] Agatston units) and either denosumab (94 [0-212] Agatston units, P =0.24) or alendronic acid (34 [-62 to 134], P =0.99). There were no differences in change in thoracic aorta calcium scores between placebo (132 [22-512] Agatston units) and either denosumab (118 [11-340], P =0.75) or alendronic acid (116 [26-498] Agatston units, P =0.62). There were no differences in changes in coronary or aortic 18F-sodium fluoride activity between treatment groups., Conclusions: Neither alendronic acid nor denosumab are associated with changes in the activity or progression of coronary or aortic calcification. Osteoporosis treatments do not appear to have major impact on vascular calcification of atherosclerosis., Registration: https://www.clinicaltrials.gov; Unique identifier: NCT02132026.

Rationale: To provide an overview of the current status of cardiac multimodality imaging practices in Europe and radiologist involvement using data from the European Society of Cardiovascular Radiology (ESCR) MRCT-registry., Materials and Methods: Numbers on cardiac CT and MRI examinations were extracted from the MRCT-registry of the ESCR, entered between January 2011 and October 2023 (n = 432,265). Data collection included the total/annual numbers of examinations, indications, complications, and reporting habits., Results: Thirty-two countries contributed to the MRCT-registry, including 29 European countries. Between 2011 and 2022, there was a 4.5-fold increase in annually submitted CT examinations, from 3368 to 15,267, and a 3.8-fold increase in MRI examinations, from 3445 to 13,183. The main indications for cardiac CT were suspected coronary artery disease (CAD) (59%) and transcatheter aortic valve replacement planning (21%). The number of patients with intermediate pretest probability who underwent CT for suspected CAD showed an increase from 61% in 2012 to 82% in 2022. The main MRI indications were suspected myocarditis (26%), CAD (21%), and suspected cardiomyopathy (19%). Adverse event rates were very low for CT (0.3%) and MRI (0.7%) examinations. Reporting of CT and MRI examinations was performed mainly by radiologists (respectively 76% and 71%) and, to a lesser degree, in consensus with non-radiologists (19% and 27%, respectively). The remaining examinations (4.9% CT and 1.7% MRI) were reported by non-radiological specialties or in separate readings of radiologists and non-radiologists., Conclusions: Real-life data on cardiac imaging in Europe using the largest available MRCT-registry demonstrate a considerable increase in examinations over the past years, the vast majority of which are read by radiologists. These findings indicate that radiologists contribute to meeting the increasing demands of competent and effective care in cardiac imaging to a relevant extent., Clinical Relevance Statement: The number of cardiac CT and MRI examinations has risen over the past years, and radiologists read the vast majority of these studies as recorded in the MRCT-registry., Key Points: • The number of cardiac imaging examinations is constantly increasing. • Radiologists play a central role in providing cardiac CT and MR imaging services to a large volume of patients. • Cardiac CT and MR imaging examinations performed and read by radiologists show a good safety profile., (© 2024. The Author(s).)

In current clinical practice, qualitative or semi-quantitative measures are primarily used to report coronary artery disease on cardiac CT. With advancements in cardiac CT technology and automated post-processing tools, quantitative measures of coronary disease severity have become more broadly available. Quantitative coronary CT angiography has great potential value for clinical management of patients, but also for research. This document aims to provide definitions and standards for the performance and reporting of quantitative measures of coronary artery disease by cardiac CT., Competing Interests: Declaration of competing interest Héctor M. García-García reports the following Institutional grant support: Biotronik, Boston Scientific, Medtronic, Abbott, Neovasc, Shockwave, Phillips and Corflow; Consultancy fee from Boston Scientific, Abbott and Amgen. Koen Nieman acknowledges support from the NIH (NIH R01- HL141712; NIH R01 - HL146754), and reports unrestricted institutional research support from Siemens Healthineers, Bayer, HeartFlow Inc, Novartis unrelated to this work, consulting for Novartis and Siemens Medical Solutions USA, Artrya, Cleerly, Elucid, and equity in Lumen Therapeutics. Maksymilian P. Opolski reports institutional grant support from B. Braun; consulting for Boston Scientific and proctorship for Boston Scientific, Terumo and Biotronik. Michelle Williams has given talks for Canon Medical Systems, Siemens Healthineers and Novartis. Damini Dey has received software royalties from Cedars-Sinai Medical Center and is supported by grants from the NIH/NHLBI (1R01HL148787-01A1 and 1R01HL151266). Jonathon Leipsic is a consultant and holds stock options in HeartFlow Inc., is a consultant to Circle CVI and has received modest corelab personal fees from Arineta and has received modest speaking fees from GE Healthcare and Philips HealthCare. Michael T Lu reports institutional research support from the American Heart Association (18UNPG34030172; 810,966), AstraZeneca, Ionis, Johnson & Johnson Innovation, Kowa, the National Academy of Medicine, and the NIH (U01HL123339; U24HL164284; R33HL141047; R01HL164629). Maros Ferencik received grant support from the American Heart Association and National Institutes of Health. Maros Ferencik received consulting fees HeartFlow, Elucid, Siemens Healthineers., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Coronary artery disease continues to be the leading cause of death globally. Identifying patients who are at risk of coronary artery disease remains a public health priority. At present, the focus of cardiovascular disease prevention relies heavily on probabilistic risk scoring despite no randomized controlled trials demonstrating their efficacy. The concept of using imaging to guide preventative therapy is not new, but has previously focused on indirect measures such as carotid intima-media thickening or coronary artery calcification. In recent trials, patients found to have coronary artery disease on computed tomography (CT) coronary angiography were more likely to be started on preventative therapy and had lower rates of cardiac events. This led to the design of the SCOT-HEART 2 (Scottish Computed Tomography of the Heart 2) trial, which aims to determine whether screening with the use of CT coronary angiography is more clinically effective than cardiovascular risk scoring to guide the use of primary preventative therapies and reduce the risk of myocardial infarction., Competing Interests: Funding Support and Author Disclosures Dr McDermott is supported by a British Heart Foundation Clinical Research Training Fellowship (FS/CRTF/23/24491). Drs Mills and Newby are supported by a Chair Award, Programme Grant, and Research Excellence Award (CH/F/21/90010, CH/09/002/26360, RG/20/10/34966, RG/F/22/110093, RE/24/130012) from the British Heart Foundation. The SCOT-HEART 2 trial is funded by the British Heart Foundation (CS/18/4/34074). Dr Williams is supported by the British Heart Foundation (FS/ICRF/20/26002); and has given talks for Canon Medical Systems, Siemens Healthineers, and Novartis. Dr Mills has received research grants, honoraria, or consultancy fees from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, LumiraDx, and Pyros Laboratories. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A key focus of cardiovascular medicine is the detection, treatment, and prevention of disease, with a move towards more personalized and patient-centred treatments. To achieve this goal, novel imaging approaches that allow for early and accurate detection of disease and risk stratification are needed. At present, the diagnosis, monitoring, and prognostication of thrombotic cardiovascular diseases are based on imaging techniques that measure changes in structural anatomy and biological function. Molecular imaging is emerging as a new tool for the non-invasive detection of biological processes, such as thrombosis, that can improve identification of these events above and beyond current imaging modalities. At the forefront of these evolving techniques is the use of high-sensitivity radiotracers in conjunction with positron emission tomography imaging that could revolutionise current diagnostic paradigms by improving our understanding of the role and origin of thrombosis in a range of cardiovascular diseases., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

The evolution of complete blood count (CBC) methodology from manual calculations to sophisticated high throughput hematology analyzers is the focus of this article. In recent years, hematology testing has greatly benefitted from the combination of various technologies with automated neural networks. In addition to an increasing complexity of the laboratory instrumentation, there is a demand on point of care CBC testing with its benefits and drawbacks. This article highlights exciting advancements of hematology testing from the past to the present and into the future., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest Conflict of interest information will be provided by Stacy De La O, CAE, Consultant, SCCT Guidelines sdelao@scct.org.

Cardiac computed tomography (CT) is an important diagnostic tool in the management of cardiovascular disease. Various factors influence the overall financial viability of a cardiac CT program, including hardware, software, personnel, billing, and practice type. This review offers a comprehensive analysis of these different cardiac CT costs, and how programs across various practice types manage them., Competing Interests: Declaration of competing interest Monvadi B. Srichai – Dr. Srichai has served as consultant for Clario, AstraZeneca, and Artrya. Ron Blankstein - Dr. Blankstein has received research support from Amgen Inc and Novartis Inc, and has served as a consultant for Caristo Inc, Hearflow Inc, an Nanox AI. Sylvia Lesic - None. Michelle C. Williams - Dr. Williams has given talks for Canon Medical Systems, Siemens Healthineers, GE Healthcare, and Novartis and performed consultancy for FEOPS and Canon Medical Systems., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Introduction: Colitis is an inflammatory bowel disease (IBD) characterized by immune cell dysregulation and alterations in the gut microbiome. In our previous report, we showed a natural product in cruciferous vegetables and ligand of the aryl hydrocarbon receptor (AhR), indole-3-carbinol (I3C), was able to reduce colitis-induced disease severity and microbial dysbiosis in an interleukin-22 (IL-22) dependent manner., Methods: In the current study, we performed single-cell RNA sequencing (scRNAseq) from colonocytes during colitis induction and supplementation with I3C and show how this treatment alters expression of genes involved in IL-22 signaling. To further define the role of IL-22 signaling in I3C-mediated protection during colitis and disease-associated microbial dysbiosis, we generated mice with AhR deficiency in RAR-related orphan receptor c (Rorc)-expressing cells (AhR ΔRorc ) which depletes this receptor in immune cells involved in production of IL-22. Colitis was induced in wildtype (WT), AhR ΔRorc , and littermate (LM) mice with or without I3C treatment., Results: Results showed AhR ΔRorc mice lost the efficacy effects of I3C treatment which correlated with a loss of ability to increase IL-22 by innate lymphoid type 3 (ILC3s), not T helper 22 (Th22) cells. 16S rRNA microbiome profiling studies showed AhR ΔRorc mice were unable to regulate disease-associated increases in Bacteroides, which differed between males and females. Lastly, inoculation with a specific disease-associated Bacteroides species, Bacteroides acidifaciens ( B. acidifaciens ), was shown to exacerbate colitis in females, but not males., Discussion: Collectively, this report highlights the cell and sex-specific role of AhR in regulating microbes that can impact colitis disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mitchell, Staley, Williams, Saxena, Bogdon, Roark, Hailey, Miranda, Becker, Dopkins, Pena, Hogan, Baird, Wilson, Nagarkatti, Nagarkatti and Busbee.)

Cardiovascular imaging is exponentially increasing in the diagnosis, risk stratification, and therapeutic management of patients with cardiovascular disease. The European Society of Cardiovascular Radiology (ESCR) is a non-profit scientific medical society dedicated to promoting and coordinating activities in cardiovascular imaging. The purpose of this paper, written by ESCR committees and Executive board members and approved by the ESCR Executive Board and Guidelines committee, is to codify a standardized approach to creating ESCR scientific documents. Indeed, consensus development methods must be adopted to ensure transparent decision-making that optimizes national and global health and reaches a certain scientific credibility. ESCR consensus documents developed based on a rigorous methodology will improve their scientific impact on the management of patients with cardiac involvement. CRITICAL RELEVANCE STATEMENT: This document aims to codify the methodology for producing consensus documents of the ESCR. These ESCR indications will broaden the scientific quality and credibility of further publications and, consequently, the impact on the diagnostic management of patients with cardiac involvement. KEY POINTS: Cardiovascular imaging is exponentially increasing for diagnosis, risk stratification, and therapeutic management. The ESCR is committed to promoting cardiovascular imaging. A rigorous methodology for ESCR consensus documents will improve their scientific impact., (© 2024. The Author(s).)

Background: Guidelines recommend the use of risk scores to select patients for further investigation after myocardial infarction has been ruled out but their utility to identify those with coronary artery disease is uncertain., Methods: In a prospective cohort study, patients with intermediate high-sensitivity cardiac troponin I concentrations (5 ng/L to sex-specific 99th percentile) in whom myocardial infarction was ruled out were enrolled and underwent coronary CT angiography (CCTA) after hospital discharge. History, ECG, Age, Risk factors, Troponin (HEART), Emergency Department Assessment of Chest Pain Score (EDACS), Global Registry of Acute Coronary Event (GRACE), Thrombolysis In Myocardial Infarction (TIMI), Systematic COronary Risk Evaluation 2 and Pooled Cohort Equation risk scores were calculated and the odds ratio (OR) and diagnostic performance for obstructive coronary artery disease were determined using established thresholds., Results: Of 167 patients enrolled (64±12 years, 28% female), 29.9% (50/167) had obstructive coronary artery disease. The odds of having obstructive disease were increased for all scores with the lowest and highest increase observed for an EDACS score ≥16 (OR 2.2 (1.1-4.6)) and a TIMI risk score ≥1 (OR 12.9 (3.0-56.0)), respectively. The positive predictive value (PPV) was low for all scores but was highest for a GRACE score >88 identifying 39% as high risk with a PPV of 41.9% (30.4-54.2%). The negative predictive value (NPV) varied from 77.3% to 95.2% but was highest for a TIMI score of 0 identifying 26% as low risk with an NPV of 95.2% (87.2-100%)., Conclusions: In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been excluded, clinical risk scores can help identify patients with and without coronary artery disease, although the performance of established risk thresholds is suboptimal for utilisation in clinical practice., Trial Registration Number: NCT04549805., Competing Interests: Competing interests: MCW has received speaker fees from Cannon Medical Systems, Siemens Healthineers and Novartis. NLM reports research grants awarded to the University of Edinburgh from Abbott Diagnostics, Siemens Healthineers and Roche Diagnostics outside the submitted work, and honoraria from Abbott Diagnostics, Siemens Healthineers, Roche Diagnostics, LumiraDx and Psyros Diagnostics. All other authors have no interests to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Rationale and Objectives: Evidence is building in support of the clinical utility of atherosclerotic plaque imaging by computed tomography angiography (CTA). There is increasing organized activity to embrace non-calcified plaque (NCP) as a formally defined biomarker for clinical trials, and high-risk plaque (HRP) for clinical care, as the most relevant measures for the field to advance and worthy of community efforts to validate. Yet the ability to assess the quantitative performance of any given specific solution to make these measurements or classifications is not available. Vendors use differing definitions, assessment metrics, and validation data sets to describe their offerings without clinician users having the capability to make objective assessments of accuracy and precision and how this affects diagnostic confidence., Materials and Methods: The QIBA Profile for Atherosclerosis Biomarkers by CTA was created by the Quantitative Imaging Biomarkers Alliance (QIBA) to improve objectivity and decrease the variability of noninvasive plaque phenotyping. The Profile provides claims on the accuracy and precision of plaque measures individually and when combined., Results: Individual plaque morphology measurements are evaluated in terms of bias (accuracy), slope (consistency of the bias across the measurement range, needed for measurements of change), and variability. The multiparametric plaque stability phenotype is evaluated in terms of agreement with expert pathologists. The Profile is intended for a broad audience, including those engaged in discovery science, clinical trials, and patient care., Conclusion: This report provides a rationale and overview of the Profile claims and how to comply with the Profile in research and clinical practice., Summary Statement: This article summarizes objective means to validate the analytical performance of non-calcified plaque (NCP), other emerging plaque morphology measurements, and multiparametric histology-defined high-risk plaque (HRP), as outlined in the QIBA Profile for Atherosclerosis Biomarkers by CTA., Competing Interests: Declaration of Competing Interest The nature of the work is a standards-based activity undertaken by a cross-section of academic, practicing, and industry professionals. The RSNA maintains a comprehensive vetting and representation of conflict statements, but in short, no conflicts are noted that undermine the integrity and openness of the work. The first author Andrew J. Buckler is a founder and shareholder of Elucid Bioimaging Inc., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Background: Quality assessment of modified or processed red blood cell (RBC) components, such as pathogen-reduced RBCs, using only in vitro testing may not always be predictive of in vivo performance. Mouse or rat in vivo models are limited by a lack of applicability to certain aspects of human RBC biology. Here, we used a guinea pig model to study the effects of riboflavin combined with UV light on the integrity of RBCs in vitro and following transfusion in vivo., Materials and Methods: Guinea pig RBCs were collected from whole blood (WB) treated with varying UV doses (10, 20, 40 or 80 J/mL) in the presence of riboflavin (UVR-RBCs). In vitro tests for UVR-RBCs included hemolysis, osmotic fragility, and cellular morphology by scanning electron microscopy. Guinea pigs transfused with one-day post-treatment UVR-RBCs were evaluated for plasma hemoglobin (Hb), non-transferrin bound iron (NTBI), total iron and Perls-detectable hemosiderin deposition in the spleen and kidney, and renal uptake of Hb., Results: Acute RBC injury was dose dependently accelerated after treatment with UV light in the presence of riboflavin. Aberrant RBC morphology was evident at 20, 40, and 80 J/mL, and membrane lysis with Hb release was prominent at 80 J/mL. Guinea pigs transfused with 40 and 80 J/mL UVR-RBCs showed increased plasma Hb levels, and plasma NTBI was elevated in all UVR-RBC groups (10-80 J/mL). Total iron levels and Perls-hemosiderin staining in spleen and kidney as well as Hb uptake in renal proximal tubules were increased 8 hours post-transfusion with 40 and 80 J/mL UVR-RBCs., Discussion: UVR-RBCs administered to guinea pigs increased markers of intravascular and extravascular hemolysis in a UV dose-dependent manner. This model may allow for the discrimination of RBC injury during testing of extensively processed RBCs intended for transfusion.

Background: Most pretest probability (PTP) tools for obstructive coronary artery disease (CAD) were Western -developed. The most appropriate PTP models and the contribution of coronary artery calcium score (CACS) in Asian populations remain unknown. In a mixed Asian cohort, we compare 5 PTP models: local assessment of the heart (LAH), CAD Consortium (CAD2), risk factor-weighted clinical likelihood, the American Heart Association/American College of Cardiology and the European Society of Cardiology PTP and 3 extended versions of these models that incorporated CACS: LAH (CACS) , CAD2 (CACS) , and the CACS-clinical likelihood., Methods and Results: The study cohort included 771 patients referred for stable chest pain. Obstructive CAD prevalence was 27.5%. Calibration, area under the receiver-operating characteristic curves (AUC) and net reclassification index were evaluated. LAH clinical had the best calibration (χ 2 5.8; P =0.12). For CACS models, LAH (CACS) showed least deviation between observed and expected cases (χ 2 37.5; P <0.001). There was no difference in AUCs between the LAH clinical (AUC, 0.73 [95% CI, 0.69-0.77]), CAD2 clinical (AUC, 0.72 [95% CI, 0.68-0.76]), risk factor-weighted clinical likelihood (AUC, 0.73 [95% CI: 0.69-0.76) and European Society of Cardiology PTP (AUC, 0.71 [95% CI, 0.67-0.75]). CACS improved discrimination and reclassification of the LAH (CACS) (AUC, 0.88; net reclassification index, 0.46), CAD2 (CACS) (AUC, 0.87; net reclassification index, 0.29) and CACS-CL (AUC, 0.87; net reclassification index, 0.25)., Conclusions: In a mixed Asian cohort, Asian-derived LAH models had similar discriminatory performance but better calibration and risk categorization for clinically relevant PTP cutoffs. Incorporating CACS improved discrimination and reclassification. These results support the use of population-matched, CACS-inclusive PTP tools for the prediction of obstructive CAD.

Objectives: Coronary artery calcifications (CACs) indicate the presence of coronary artery disease. CAC can be found on thoracic computed tomography (CT) conducted for non-cardiac reasons. This systematic review and meta-analysis of non-gated thoracic CT aims to assess the clinical impact and prevalence of CAC., Methods: Online databases were searched for articles assessing prevalence, demographic characteristics, accuracy and prognosis of incidental CAC on non-gated thoracic CT. Meta-analysis was performed using a random effects model., Results: A total of 108 studies (113,406 patients) were included (38% female). Prevalence of CAC ranged from 2.7 to 100% (pooled prevalence 52%, 95% confidence interval [CI] 46-58%). Patients with CAC were older (pooled standardised mean difference 0.88, 95% CI 0.65-1.11, p < 0.001), and more likely to be male (pooled odds ratio [OR] 1.95, 95% CI 1.55-2.45, p < 0.001), with diabetes (pooled OR 2.63, 95% CI 1.95-3.54, p < 0.001), hypercholesterolaemia (pooled OR 2.28, 95% CI 1.33-3.93, p < 0.01) and hypertension (pooled OR 3.89, 95% CI 2.26-6.70, p < 0.001), but not higher body mass index or smoking. Non-gated CT assessment of CAC had excellent agreement with electrocardiogram-gated CT (pooled correlation coefficient 0.96, 95% CI 0.92-0.98, p < 0.001). In 51,582 patients, followed-up for 51.6 ± 27.4 months, patients with CAC had increased all cause mortality (pooled relative risk [RR] 2.13, 95% CI 1.57-2.90, p = 0.004) and major adverse cardiovascular events (pooled RR 2.91, 95% CI 2.26-3.93, p < 0.001). When CAC was present on CT, it was reported in between 18.6% and 93% of reports., Conclusion: CAC is a common, but underreported, finding on non-gated CT with important prognostic implications., Clinical Relevance Statement: Coronary artery calcium is an important prognostic indicator of cardiovascular disease. It can be assessed on non-gated thoracic CT and is a commonly underreported finding. This represents a significant population where there is a potential missed opportunity for lifestyle modification recommendations and preventative therapies. This study aims to highlight the importance of reporting incidental coronary artery calcium on non-gated thoracic CT., Key Points: • Coronary artery calcification is a common finding on non-gated thoracic CT and can be reliably identified compared to gated-CT. • Coronary artery calcification on thoracic CT is associated with an increased risk of all cause mortality and major adverse cardiovascsular events. • Coronary artery calcification is frequently not reported on non-gated thoracic CT., (© 2023. The Author(s).)

Introduction: Non-invasive detection of pathological changes in thoracic aortic disease remains an unmet clinical need particularly for patients with congenital heart disease. Positron emission tomography combined with magnetic resonance imaging (PET-MRI) could provide a valuable low-radiation method of aortic surveillance in high-risk groups. Quantification of aortic microcalcification activity using sodium [ 18 F]fluoride holds promise in the assessment of thoracic aortopathies. We sought to evaluate aortic sodium [ 18 F]fluoride uptake in PET-MRI using three methods of attenuation correction compared to positron emission tomography computed tomography (PET-CT) in patients with bicuspid aortic valve, METHODS: Thirty asymptomatic patients under surveillance for bicuspid aortic valve disease underwent sodium [ 18 F]fluoride PET-CT and PET-MRI of the ascending thoracic aorta during a single visit. PET-MRI data were reconstructed using three iterations of attenuation correction (Dixon, radial gradient recalled echo with two [RadialVIBE-2] or four [RadialVIBE-4] tissue segmentation). Images were qualitatively and quantitatively analysed for aortic sodium [ 18 F]fluoride uptake on PET-CT and PET-MRI., Results: Aortic sodium [ 18 F]fluoride uptake on PET-MRI was visually comparable with PET-CT using each reconstruction and total aortic standardised uptake values on PET-CT strongly correlated with each PET-MRI attenuation correction method (Dixon R = 0.70; RadialVIBE-2 R = 0.63; RadialVIBE-4 R = 0.64; p < 0.001 for all). Breathing related artefact between soft tissue and lung were detected using Dixon and RadialVIBE-4 but not RadialVIBE-2 reconstructions, with the presence of this artefact adjacent to the atria leading to variations in blood pool activity estimates. Consequently, quantitative agreements between radiotracer activity on PET-CT and PET-MRI were most consistent with RadialVIBE-2., Conclusion: Ascending aortic microcalcification analysis in PET-MRI is feasible with comparable findings to PET-CT. RadialVIBE-2 tissue attenuation correction correlates best with the reference standard of PET-CT and is less susceptible to artefact. There remain challenges in segmenting tissue types in PET-MRI reconstructions, and improved attenuation correction methods are required., (© 2024. The Author(s).)

Purpose of Review: Despite recent advances, coronary artery disease remains one of the leading causes of mortality worldwide. Noninvasive imaging allows atherosclerotic phenotyping by measurement of plaque burden, morphology, activity and inflammation, which has the potential to refine patient risk stratification and guide personalized therapy. This review describes the current and emerging roles of advanced noninvasive cardiovascular imaging methods for the assessment of coronary artery disease., Recent Findings: Cardiac computed tomography enables comprehensive, noninvasive imaging of the coronary vasculature, and is used to assess luminal stenoses, coronary calcifications, and distinct adverse plaque characteristics, helping to identify patients prone to future events. Novel software tools, implementing artificial intelligence solutions, can automatically quantify and characterize atherosclerotic plaque from standard computed tomography datasets. These quantitative imaging biomarkers have been shown to improve patient risk stratification beyond clinical risk scores and current clinical interpretation of cardiac computed tomography. In addition, noninvasive molecular imaging in higher risk patients can be used to assess plaque activity and plaque thrombosis. Noninvasive imaging allows unique insight into the burden, morphology and activity of atherosclerotic coronary plaques. Such phenotyping of atherosclerosis can potentially improve individual patient risk prediction, and in the near future has the potential for clinical implementation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Vessel-specific coronary artery calcification (CAC) is additive to global CAC for prognostic assessment. We assessed accuracy and prognostic implications of vessel-specific automated deep learning (DL) CAC analysis on electrocardiogram (ECG) gated and attenuation correction (AC) computed tomography (CT) in a large multi-centre registry., Methods and Results: Vessel-specific CAC was assessed in the left main/left anterior descending (LM/LAD), left circumflex (LCX), and right coronary artery (RCA) using a DL model trained on 3000 gated CT and tested on 2094 gated CT and 5969 non-gated AC CT. Vessel-specific agreement was assessed with linear weighted Cohen's Kappa for CAC zero, 1-100, 101-400, and >400 Agatston units (AU). Risk of major adverse cardiovascular events (MACE) was assessed during 2.4 ± 1.4 years follow-up, with hazard ratios (HR) and 95% confidence intervals (CI). There was strong to excellent agreement between DL and expert ground truth for CAC in LM/LAD, LCX and RCA on gated CT [0.90 (95% CI 0.89 to 0.92); 0.70 (0.68 to 0.73); 0.79 (0.77 to 0.81)] and AC CT [0.78 (0.77 to 0.80); 0.60 (0.58 to 0.62); 0.70 (0.68 to 0.71)]. MACE occurred in 242 (12%) undergoing gated CT and 841(14%) of undergoing AC CT. LM/LAD CAC >400 AU was associated with the highest risk of MACE on gated (HR 12.0, 95% CI 7.96, 18.0, P < 0.001) and AC CT (HR 4.21, 95% CI 3.48, 5.08, P < 0.001)., Conclusion: Vessel-specific CAC assessment with DL can be performed accurately and rapidly on gated CT and AC CT and provides important prognostic information., Competing Interests: Conflict of interest: M.C.W. has given talks for Canon Medical Systems and Siemens Healthineers. Dr. Robert Miller has received consulting fees and research support from Pfizer. Drs. Berman and Slomka and Mr. Kavanagh participate in software royalties for QPS software at Cedars-Sinai Medical Center. Dr. Berman is a consultant for GE Healthcare and Dr. Edward Miller has served as Pfizer, Eidos, CSL Behring, Anylam, and GE Healthcare consultant with grant support from Eidos, Pfizer, and Anylam. Dr. Slomka has received research grant support from Siemens Medical Systems. The remaining authors have no relevant disclosures., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Aims: Recovery of cardiovascular diagnostic testing in Italy after the coronavirus disease-2019 (COVID-19) pandemic has not been quantified. The study aims to describe cardiac diagnostic procedure volumes, centres practice and protocols, and staff members' well-being 1 year after COVID-19 outbreak in Italy., Methods and Results: A global survey was conducted by the International Atomic Energy Agency to evaluate changes in cardiac diagnostic procedure volumes in April 2021. Evaluated procedures were transoesophageal echocardiogram, coronary computed tomography angiography, coronary artery calcium scanning, nuclear medicine infection studies, invasive coronary angiography, rest and stress transthoracic echocardiogram, cardiac magnetic resonance, single-photon emission computed tomography and positron emission tomography, and stress electrocardiogram. Data were compared with April 2020 and March 2019. Forty-two Italian centres took part in the survey. In April 2020, there was a 72% decrease of median volumes of cardiac diagnostic procedures compared with March 2019. In April 2021, volumes of cardiac diagnostic procedures remained decreased by 3% when compared with March 2019. Stress electrocardiogram, coronary computed tomography angiography, and stress cardiac magnetic resonance volumes increased in April 2021 compared with baseline (29%, 6%, and 16%, respectively). The majority of centres had adopted physical distancing measures (93%), COVID-19 screening through questionnaires (76%), or temperature checks (93%). Twenty-five per cent of physicians at Italian responding sites reported excessive levels of psychological stress., Conclusion: In April 2021, volumes of cardiac diagnostic procedures at Italian responding sites were still recovering. Centres had implemented several adaptations to ensure the provision of care to their patients. Even 1 year after the pandemic, a substantial minority of Italian healthcare providers were still experiencing excessive psychological stress., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Total coronary atherosclerotic plaque activity across the entire coronary arterial tree is associated with patient-level clinical outcomes., Objectives: We aimed to investigate whether vessel-level coronary atherosclerotic plaque activity is associated with vessel-level myocardial infarction., Methods: In this secondary analysis of an international multicenter study of patients with recent myocardial infarction and multivessel coronary artery disease, we assessed vessel-level coronary atherosclerotic plaque activity using coronary 18 F-sodium fluoride positron emission tomography to identify vessel-level myocardial infarction., Results: Increased 18 F-sodium fluoride uptake was found in 679 of 2,094 coronary arteries and 414 of 691 patients. Myocardial infarction occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (HR: 2.08; 95% CI: 1.16-3.72; P = 0.013). This association was not demonstrable in those treated with coronary revascularization (HR: 1.02; 95% CI: 0.47-2.25) but was notable in untreated vessels (HR: 3.86; 95% CI: 1.63-9.10; P interaction  = 0.024). Increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk of cardiac death or myocardial infarction (HR: 2.43; 95% CI: 1.37-4.30; P = 0.002) as well as first (HR: 2.19; 95% CI: 1.18-4.06; P = 0.013) and total (HR: 2.50; 95% CI: 1.42-4.39; P = 0.002) myocardial infarctions., Conclusions: In patients with recent myocardial infarction and multivessel coronary artery disease, coronary atherosclerotic plaque activity prognosticates individual coronary arteries and patients at risk for myocardial infarction., Competing Interests: Funding Support and Author Disclosures The PRE(18)FFIR study was funded by the Wellcome Trust (WT103782AIA). The funder played no roles in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and any decisions to submit the manuscript for publication. The University of Edinburgh and the National Health Service Lothian Health Board were cosponsors. Dr Rudd is part-supported by the National Institute for Health and Care Research Cambridge Biomedical Research Centre, the British Heart Foundation, the Higher Education Funding Council for England, the Engineering and Physical Sciences Research Council, and the Wellcome Trust. Dr Piotr is supported by the National Heart, Lung, and Blood Institute at the National Institutes of Health (R35HL161195). Dr Mills is supported by the British Heart Foundation (CH/F/21/90010, RE/18/5/34216, and RG/20/10/34966). Dr van Beek is supported by the Scottish Imaging Network. Dr Williams is supported by the British Heart Foundation (FS/ICRF/20/26002). Dr Dweck is supported by the British Heart Foundation (FS/SCRF/21/32010). Dr Newby is supported by the British Heart Foundation (CH/09/002, RE/18/5/34216, and RG/F/22/110093). Dr Moss is a current employee of AstraZeneca. Dr Williams has given talks for Canon Medical Systems, Novartis, and Siemens Healthineers. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Here, we report on the process of a highly impactful and successful creative, collaborative, and multi-partner public engagement project, Radiation Reveal. It brought together ten young adults aged 17-25-year-olds with experience of radiotherapy with researchers at Cancer Research UK RadNet City of London across three 2-hour online workshops. Our aims were to 1) initiate discussions between young adults and radiation researchers, and 2) identify what people wish they had known about radiotherapy before or during treatment. These aims were surpassed; other benefits included peer support, participants' continued involvement in subsequent engagement projects, lasting friendships, creation of support groups for others, and creation and national dissemination of top ten tips for medical professionals and social media resources. A key learning was that this project required a dedicated and (com)passionate person with connections to national cancer charities. When designing the project, constant feedback is also needed from charities and young adults with and without radiotherapy experience. Finally, visually capturing discussions and keeping the door open beyond workshops further enhanced impact. Here, we hope to inform and inspire people to help project the patient voice in all we do., (© 2024. The Author(s).)

Background: Coronary artery calcium scoring (CACS) improves management of chest pain patients. However, it is unknown whether the benefit of CACS is dependent on the clinical likelihood (CL)., Objectives: This study aims to investigate for which patients CACS has the greatest benefit when added to a CL model., Methods: Based on data from a clinical database, the CL of obstructive coronary artery disease (CAD) was calculated for 39,837 patients referred for cardiac imaging due to symptoms suggestive of obstructive CAD. Patients were categorized according to the risk factor-weighted (RF-CL) model (very low, ≤5%; low, >5 to ≤15%; moderate >15 to ≤50%; high, >50%). CL was then recalculated incorporating the CACS result (CACS-CL). Reclassification rates and the number needed to test with CACS to reclassify patients were calculated and validated in 3 independent cohorts (n = 9,635)., Results: In total, 15,358 (39%) patients were down- or upclassified after including CACS. Reclassification rates were 8%, 75%, 53%, and 30% in the very low, low, moderate, and high RF-CL categories, respectively. Reclassification to very low CACS-CL occurred in 48% of reclassified patients. The number needed to test to reclassify 1 patient from low RF-CL to very low CACS-CL was 2.1 with consistency across age, sex, and cohorts. CACS-CL correlated better to obstructive CAD prevalence than RF-CL., Conclusions: Added to an RF-CL model for obstructive CAD, CACS identifies more patients unlikely to benefit from further testing. The number needed to test with CACS to reclassify patients depends on the pretest RF-CL and is lowest in patients with low (>5% to ≤15%) likelihood of CAD., Competing Interests: Funding Support and Author Disclosures Drs Newby and Williams have received support from the British Heart Foundation (FS/ICRF/20/26002, CH/09/002, RG/16/10/32375, RE/18/5/34216). The PROMISE study was supported by grants from the National Heart, Lung, and Blood Institute (R01HL098237, R01HL098236, R01HL098305, and R01HL098235). Dr Winther has received support from the Novo Nordisk Foundation Clinical Emerging Investigator grant (NNF21OC0066981). Dr Williams has been a speaker for Canon Medical Systems, Siemens Healthineers, and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The HIV-1 nucleocapsid protein (NC) is a multifunctional viral protein necessary for HIV-1 replication. Recent studies have demonstrated that reverse transcription (RT) completes in the intact viral capsid, and the timing of RT and uncoating are correlated. How the small viral core stably contains the ~10 kbp double stranded (ds) DNA product of RT, and the role of NC in this process, are not well understood. We showed previously that NC binds and saturates dsDNA in a non-specific electrostatic binding mode that triggers uniform DNA self-attraction, condensing dsDNA into a tight globule against extending forces up to 10 pN. In this study, we use optical tweezers and atomic force microscopy to characterize the role of NC's basic residues in dsDNA condensation. Basic residue mutations of NC lead to defective interaction with the dsDNA substrate, with the constant force plateau condensation observed with wild-type (WT) NC missing or diminished. These results suggest that NC's high positive charge is essential to its dsDNA condensing activity, and electrostatic interactions involving NC's basic residues are responsible in large part for the conformation, size, and stability of the dsDNA-protein complex inside the viral core. We observe DNA re-solubilization and charge reversal in the presence of excess NC, consistent with the electrostatic nature of NC-induced DNA condensation. Previous studies of HIV-1 replication in the presence of the same cationic residue mutations in NC showed significant defects in both single- and multiple-round viral infectivity. Although NC participates in many stages of viral replication, our results are consistent with the hypothesis that cationic residue mutations inhibit genomic DNA condensation, resulting in increased premature capsid uncoating and contributing to viral replication defects.

In this review, the authors summarize the role of coronary computed tomography angiography and coronary artery calcium scoring in different clinical presentations of chest pain and preventative care and discuss future directions and new technologies such as pericoronary fat inflammation and the growing footprint of artificial intelligence in cardiovascular medicine., Competing Interests: Disclosure M.C. Williams has given talks for Canon Medical Systems, Siemens Healthineers, and Novartis. The work of M.C. Williams is supported by the British Heart Foundation, United Kingdom (FS/ICRF/20/26002)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Bacteriophage T4 gene 32 protein (gp32) is a single-stranded DNA (ssDNA) binding protein essential for DNA replication. gp32 forms stable protein filaments on ssDNA through cooperative interactions between its core and N-terminal domain. gp32's C-terminal domain (CTD) is believed to primarily help coordinate DNA replication via direct interactions with constituents of the replisome. However, the exact mechanisms of these interactions are not known, and it is unclear how tightly-bound gp32 filaments are readily displaced from ssDNA as required for genomic processing. Here, we utilized truncated gp32 variants to demonstrate a key role of the CTD in regulating gp32 dissociation. Using optical tweezers, we probed the binding and dissociation dynamics of CTD-truncated gp32, *I, to an 8.1 knt ssDNA molecule and compared these measurements with those for full-length gp32. The *I-ssDNA helical filament becomes progressively unwound with increased protein concentration but remains significantly more stable than that of full-length, wild-type gp32. Protein oversaturation, concomitant with filament unwinding, facilitates rapid dissociation of full-length gp32 from across the entire ssDNA segment. In contrast, *I primarily unbinds slowly from only the ends of the cooperative clusters, regardless of the protein density and degree of DNA unwinding. Our results suggest that the CTD may constrain the relative twist angle of proteins within the ssDNA filament such that upon critical unwinding the cooperative interprotein interactions largely vanish, facilitating prompt removal of gp32. We propose a model of CTD-mediated gp32 displacement via internal restructuring of its filament, providing a mechanism for rapid ssDNA clearing during genomic processing., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

HIV-1 cores, which contain the viral genome and replication machinery, must disassemble (uncoat) during viral replication. However, the viral and host factors that trigger uncoating remain unidentified. Recent studies show that infectious cores enter the nucleus and uncoat near the site of integration. Here, we show that efficient uncoating of nuclear cores requires synthesis of a double-stranded DNA (dsDNA) genome >3.5 kb and that the efficiency of uncoating correlates with genome size. Core disruption by capsid inhibitors releases viral DNA, some of which integrates. However, most of the viral DNA is degraded, indicating that the intact core safeguards viral DNA. Atomic force microscopy and core content estimation reveal that synthesis of full-length genomic dsDNA induces substantial internal strain on the core to promote uncoating. We conclude that HIV-1 cores protect viral DNA from degradation by host factors and that synthesis of long double-stranded reverse transcription products is required to trigger efficient HIV-1 uncoating.

Objective: Aortic stenosis (AS) shares pathophysiological similarities with atherosclerosis including active inflammation. CT attenuation of perivascular adipose tissue provides a measure of vascular inflammation that is linked to prognosis and has the potential to be applied to the aortic valve. We investigated perivascular adipose tissue attenuation around the aortic valve in patients with AS., Methods: CT attenuation was measured in the perivascular adipose tissue extending 3 mm radially and 10 mm longitudinally around the aortic valve in patients with and without AS. Associations between perivascular adipose tissue attenuation and AS disease severity, activity and progression were investigated., Results: Perivascular adipose tissue attenuation around the aortic valve demonstrated good intraobserver and interobserver repeatability (interobserver: intraclass correlation coefficient 0.977 (95% CI: 0.94, 0.99)) but was similar between patients with AS (n=120) and control subjects (n=80) (-62.4 (-68.7, -56.5) Hounsfield units (HU) vs -61.2 (-65.3, -55.6) HU, p=0.099). There were no differences between perivascular adipose tissue attenuation in patients with mild (-60.2 (-66.9, -55.1) HU), moderate (-62.8 (-69.6, -56.80) HU) or severe (-62.3 (-69.3, -55.4) HU) AS (all p>0.05), and perivascular adipose tissue attenuation did not demonstrate an association with AS severity as assessed by echocardiography or CT calcium scoring, nor with disease activity assessed by 18 F-sodium fluoride positron emission tomography. Moreover, there was no association between baseline aortic valve perivascular adipose tissue attenuation and subsequent AS progression (annualised change in peak velocity: r=0.072, p=0.458). Similar results were found using five other image analysis methods., Conclusions: CT-derived aortic valve perivascular adipose tissue attenuation is not associated with AS disease severity, activity or progression suggesting that it has no value in the investigation and management of patients with AS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The COVID-19 pandemic disproportionately impacted Latin America (LATAM), significantly disrupting cardiovascular testing. This study evaluated cardiac procedure recovery in LATAM one year after the outbreak., Methods: The International Atomic Energy Agency (IAEA) surveyed 669 centers in 107 countries worldwide, including 135 facilities in 19 LATAM countries, to assess cardiovascular procedure volumes in March 2019, April 2020, and April 2021, and changes in center practices and staffing conditions one year into the COVID-19 pandemic., Findings: LATAM centers reported a 21 % decrease in procedure volumes in April 2021 from pre-pandemic-baseline, vs. a 0 % change in the rest of the world (RoW), and greater volume reductions for almost all procedure types. Centers in Central America and Mexico reported the largest procedure reductions (47 % reduction) compared to the Caribbean (15 %), and South America (14 %, p = 0.01), and this LATAM region was a significant predictor of lower procedure recovery in multivariable regression. More LATAM centers reported reduced salaries and increased layoffs of clinical staff compared to RoW, and LATAM respondents estimated that half of physician and non-physician staff experienced excess psychological stress related to the pandemic, compared to 25 % and 30 % in RoW (p < 0.001)., Conclusions: Cardiovascular testing recovery in LATAM trailed behind RoW for most procedure types, with centers in Central America and Mexico reporting the greatest volume reductions. This study found lasting impacts of COVID-19 on cardiovascular care in LATAM and the need for mental health support for LATAM healthcare workers in current and future pandemics., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr. Massardo has been supported by Pfizer for educational activities related to ATTR amyloidosis and has participated in two multicenter research projects supported by Pfizer. Dr. Williams has given talks for Canon Medical Systems, Siemens Healthineers and Novartis and is supported by the British Heart Foundation (FS/ICRF/20/26002). Dr. Villines is a current employee of Elucid Biomining, Inc that is unrelated to this work. Dr. Dorbala has received honoraria from Pfizer and GE Healthcare; and has received grants to her institution from Pfizer and GE Healthcare. Dr. Einstein has received fees for speaking from Ionetix, consulting from W. L. Gore & Associates, serving on a scientific advisory committee for Canon Medical Systems USA, and authorship from Wolters Kluwer Healthcare – UpToDate; has grants/grants pending from Attralus, Canon Medical Systems USA, Eidos Therapeutics, GE Healthcare, Pfizer, Roche Medical Systems, W. L. Gore & Associates, XyloCor Therapeutics, Neovasc, Intellia Therapeutics, Ionis Pharmaceuticals, the National Institutes of Health, and the IAEA. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose]., (Published by Elsevier B.V.)

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.)

The COVID-19 pandemic disrupted the delivery of cardiovascular care, including noninvasive testing protocols and test selection for the evaluation of coronary artery disease (CAD). Trends in test selection in traditional versus advanced noninvasive tests for CAD during the pandemic and in countries of varying income status have not been well studied. The International Atomic Energy Agency conducted a global survey to assess the pandemic-related changes in the practice of cardiovascular diagnostic testing. Site procedural volumes for noninvasive tests to evaluate CAD from March 2019 (prepandemic), April 2020 (onset), and April 2021 (initial recovery) were collected. We considered traditional testing modalities, such as exercise electrocardiography, stress echocardiography, and stress single-photon emission computed tomography, and advanced testing modalities, such as stress cardiac magnetic resonance, coronary computed tomography angiography, and stress positron emission tomography. Survey data were obtained from 669 centers in 107 countries, reporting the performance of 367,933 studies for CAD during the study period. Compared with 2019, traditional tests were performed 14% less frequently (recovery rate 82%) in 2021 versus advanced tests, which were performed 15% more frequently (128% recovery rate). Coronary computed tomography angiography, stress cardiac magnetic resonance, and stress positron emission tomography showed 14%, 25%, and 25% increases in volumes from 2019 to 2021, respectively. The increase in advanced testing was isolated to high- and upper middle-income countries, with 132% recovery in advanced tests by 2021 compared with 55% in lower income nations. The COVID-19 pandemic exacerbated economic disparities in CAD testing practice between wealthy and poorer countries. Greater recovery rates and even new growth were observed for advanced imaging modalities; however, this growth was restricted to wealthy countries. Efforts to reduce practice variations in CAD testing because of economic status are warranted., Competing Interests: Declaration of competing interest Dr. Villines was an employee of Elucid Bioimaging and has separately received authorship fees from Wolters Kluwer Healthcare-UpToDate. Dr. Williams has given talks for Canon Medical Systems, Siemens Healthineers and Novartis. Dr. Einstein reports receiving speaker's fee from Ionetix, consulting fees from W. L. Gore & Associates and authorship fees from Wolters Kluwer Healthcare—UpToDate and serving on a scientific advisory board for Canon Medical Systems USA; his institution has grants/grants pending from Attralus, Bruker, Canon Medical Systems USA, Eidos Therapeutics, GE Healthcare, Intellia Therapeutics, Ionis Pharmaceuticals, Neovasc, Pfizer, Roche Medical Systems, and W. L. Gore & Associates. The remaining authors have no competing interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)