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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: 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.)

Background: Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known., Objectives: To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors., Methods: In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health., Results: From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86)., Conclusion: Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need., Trail Registration Number: ISRCTN10980107., Competing Interests: Competing interests: KK is chair of the ethnicity subgroup of the UK Scientific Advisory Group for Emergencies (SAGE) and is a member of SAGE. KK (Chair) and RE are members of the Long COVID Epidemiological Research Group that reports to the CMO. CB is an author of the COVID-19 rapid guideline: managing the long-term effects of COVID-19 NICE guideline (NG188) https://www.nice.org.uk/guidance/ng188/history. CB is a member of the NHS National Services Scotland Long COVID group and his employer, the University of Glasgow, holds a research agreement with AstraZeneca and Somalogic for research in COVID-19. AJM is an employee of AstraZeneca., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Dysregulated epicardial adipose tissue (EAT) may contribute to the development of heart failure in Type 2 diabetes (T2D). This study aimed to evaluate the associations between EAT volume and composition with imaging markers of subclinical cardiac dysfunction in people with T2D and no prevalent cardiovascular disease., Methods: Prospective case-control study enrolling participants with and without T2D and no known cardiovascular disease. Two hundred and fifteen people with T2D (median age 63 years, 60 % male) and thirty-nine non-diabetics (median age 59 years, 62 % male) were included. Using computed tomography (CT), total EAT volume and mean CT attenuation, as well as, low attenuation (Hounsfield unit range -190 to -90) EAT volume were quantified by a deep learning method and volumes indexed to body surface area. Associations with cardiac magnetic resonance-derived left ventricular (LV) volumes and strain indices were assessed using linear regression., Results: T2D participants had higher LV mass/volume ratio (median 0.89 g/mL [0.82-0.99] vs 0.79 g/mL [0.75-0.89]) and lower global longitudinal strain (GLS; 16.1 ± 2.3 % vs 17.2 ± 2.2 %). Total indexed EAT volume correlated inversely with mean CT attenuation. Low attenuation indexed EAT volume was 2-fold higher (18.8 cm 3 /m 2 vs. 9.4 cm 3 /m 2 , p < 0.001) in T2D and independently associated with LV mass/volume ratio (ß = 0.002, p = 0.01) and GLS (ß = -0.03, p = 0.03)., Conclusions: Higher EAT volumes seen in T2D are associated with a lower mean CT attenuation. Low attenuation indexed EAT volume is independently, but only weakly, associated with markers of subclinical cardiac dysfunction in T2D., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alastair J Moss reports a relationship with AstraZeneca UK Limited that includes: employment. If there are other authors, they 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 Authors. Published by Elsevier B.V. All rights reserved.)

Background: Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) frequently co-exist. There is a limited understanding on whether this coexistence is associated with distinct alterations in myocardial remodelling and mechanics. We aimed to determine if patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) represent a distinct phenotype., Methods: In this secondary analysis of adults with HFpEF (NCT03050593), participants were comprehensively phenotyped with stress cardiac MRI, echocardiography and plasma fibroinflammatory biomarkers, and were followed for the composite endpoint (HF hospitalisation or death) at a median of 8.5 years. Those with AF were compared to sinus rhythm (SR) and unsupervised cluster analysis was performed to explore possible phenotypes., Results: 136 subjects were included (SR = 75, AF = 61). The AF group was older (76 ± 8 vs. 70 ± 10 years) with less diabetes (36% vs. 61%) compared to the SR group and had higher left atrial (LA) volumes (61 ± 30 vs. 39 ± 15 mL/m 2 , p < 0.001), lower LA ejection fraction (EF) (31 ± 15 vs. 51 ± 12%, p < 0.001), worse left ventricular (LV) systolic function (LVEF 63 ± 8 vs. 68 ± 8%, p = 0.002; global longitudinal strain 13.6 ± 2.9 vs. 14.7 ± 2.4%, p = 0.003) but higher LV peak early diastolic strain rates (0.73 ± 0.28 vs. 0.53 ± 0.17 1/s, p < 0.001). The AF group had higher levels of syndecan-1, matrix metalloproteinase-2, proBNP, angiopoietin-2 and pentraxin-3, but lower level of interleukin-8. No difference in clinical outcomes was observed between the groups. Three distinct clusters were identified with the poorest outcomes (Log-rank p = 0.029) in cluster 2 (hypertensive and fibroinflammatory) which had equal representation of SR and AF., Conclusions: Presence of AF in HFpEF is associated with cardiac structural and functional changes together with altered expression of several fibro-inflammatory biomarkers. Distinct phenotypes exist in HFpEF which may have differing clinical outcomes., (© 2024. The Author(s).)

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous multi-system syndrome with limited efficacious treatment options. The prevalence of Type 2 diabetes (T2D) continues to rise and predisposes patients to HFpEF, and HFpEF remains one of the biggest challenges in cardiovascular medicine today. Novel therapeutic targets are required to meet this important clinical need. Deep phenotyping studies including -OMIC analyses can provide important pathogenic information to aid the identification of such targets. The aims of this study were to determine; 1) the impact of a low-energy diet on plasma sphingolipid/ceramide profiles in people with T2D compared to healthy controls and, 2) if the change in sphingolipid/ceramide profile is associated with reverse cardiovascular remodelling., Methods: Post-hoc analysis of a randomised controlled trial (NCT02590822) including adults with T2D with no cardiovascular disease who completed a 12-week low-energy (∼810 kcal/day) meal-replacement plan (MRP) and matched healthy controls (HC). Echocardiography, cardiac MRI and a fasting blood for lipidomics were undertaken pre/post-intervention. Candidate biomarkers were identified from case-control comparison (fold change > 1.5 and statistical significance p < 0.05) and their response to the MRP reported. Association between change in biomarkers and change indices of cardiac remodelling were explored., Results: Twenty-four people with T2D (15 males, age 51.1 ± 5.7 years), and 25 HC (15 male, 48.3 ± 6.6 years) were included. Subjects with T2D had increased left ventricular (LV) mass:volume ratio (0.84 ± 0.13 vs. 0.70 ± 0.08, p < 0.001), increased systolic function but impaired diastolic function compared to HC. Twelve long-chain polyunsaturated sphingolipids, including four ceramides, were downregulated in subjects with T2D at baseline. Three sphingomyelin species and all ceramides were inversely associated with LV mass:volume. There was a significant increase in all species and shift towards HC following the MRP, however, none of these changes were associated with reverse cardiac remodelling., Conclusion: The lack of association between change in sphingolipids/ceramides and reverse cardiac remodelling following the MRP casts doubt on a causative role of sphingolipids/ceramides in the progression of heart failure in T2D., Trial Registration: NCT02590822., (© 2023. The Author(s).)

Maintaining data quality on Amazon Mechanical Turk (MTurk) has always been a concern for researchers. These concerns have grown recently due to the bot crisis of 2018 and observations that past safeguards of data quality (e.g., approval ratings of 95%) no longer work. To address data quality concerns, CloudResearch, a third-party website that interfaces with MTurk, has assessed ~165,000 MTurkers and categorized them into those that provide high- (~100,000, Approved) and low- (~65,000, Blocked) quality data. Here, we examined the predictive validity of CloudResearch's vetting. In a pre-registered study, participants (N = 900) from the Approved and Blocked groups, along with a Standard MTurk sample (95% HIT acceptance ratio, 100+ completed HITs), completed an array of data-quality measures. Across several indices, Approved participants (i) identified the content of images more accurately, (ii) answered more reading comprehension questions correctly, (iii) responded to reversed coded items more consistently, (iv) passed a greater number of attention checks, (v) self-reported less cheating and actually left the survey window less often on easily Googleable questions, (vi) replicated classic psychology experimental effects more reliably, and (vii) answered AI-stumping questions more accurately than Blocked participants, who performed at chance on multiple outcomes. Data quality of the Standard sample was generally in between the Approved and Blocked groups. We discuss how MTurk's Approval Rating system is no longer an effective data-quality control, and we discuss the advantages afforded by using the Approved group for scientific studies on MTurk., (© 2022. The Author(s).)

To understand human behavior, social scientists need people and data. In the last decade, Amazon's Mechanical Turk (MTurk) emerged as a flexible, affordable, and reliable source of human participants and was widely adopted by academics. Yet despite MTurk's utility, some have questioned whether researchers should continue using the platform on ethical grounds. The brunt of their concern is that people on MTurk are financially insecure, subject to abuse, and earn inhumane wages. We investigated these issues with two representative probability surveys of the U.S. MTurk population (N = 4094). The surveys revealed: (1) the financial situation of people on MTurk mirrors the general population, (2) most participants do not find MTurk stressful or requesters abusive, and (3) MTurk offers flexibility and benefits that most people value above other options for work. People reported it is possible to earn more than $10 per hour and said they would not trade the flexibility of MTurk for less than $25 per hour. Altogether, our data are important for assessing whether MTurk is an ethical place for research., (© 2022. The Psychonomic Society, Inc.)

People in online studies sometimes misrepresent themselves. Regardless of their motive for doing so, participant misrepresentation threatens the validity of research. Here, we propose and evaluate a way to verify the age of online respondents: a test of era-based knowledge. Across six studies (N = 1543), participants of various ages completed an age verification instrument. The instrument assessed familiarity with cultural phenomena (e.g., songs and TV shows) from decades past and present. We consistently found that our instrument discriminated between people of different ages. In Studies 1a and 1b, self-reported age correlated strongly with performance on the instrument (mean r = .8). In Study 2, the instrument reliably detected imposters who we knew were misrepresenting their age. For impostors, self-reported age did not correlate with performance on the instrument (r = .077). Finally, in Studies 3a, 3b, and 3c, the instrument remained robust with African Americans, people from low educational backgrounds, and recent immigrants to the United States. Thus, our instrument shows promise for verifying the age of online respondents, and, as we discuss, our approach of assessing "insider knowledge" holds great promise for verifying other identities within online studies., (© 2022. The Psychonomic Society, Inc.)

Background: Recently, deep learning via convolutional neural networks (CNNs) has largely superseded conventional methods for proton ( 1 H)-MRI lung segmentation. However, previous deep learning studies have utilized single-center data and limited acquisition parameters., Purpose: Develop a generalizable CNN for lung segmentation in 1 H-MRI, robust to pathology, acquisition protocol, vendor, and center., Study Type: Retrospective., Population: A total of 809 1 H-MRI scans from 258 participants with various pulmonary pathologies (median age (range): 57 (6-85); 42% females) and 31 healthy participants (median age (range): 34 (23-76); 34% females) that were split into training (593 scans (74%); 157 participants (55%)), testing (50 scans (6%); 50 participants (17%)) and external validation (164 scans (20%); 82 participants (28%)) sets., Field Strength/sequence: 1.5-T and 3-T/3D spoiled-gradient recalled and ultrashort echo-time 1 H-MRI., Assessment: 2D and 3D CNNs, trained on single-center, multi-sequence data, and the conventional spatial fuzzy c-means (SFCM) method were compared to manually delineated expert segmentations. Each method was validated on external data originating from several centers. Dice similarity coefficient (DSC), average boundary Hausdorff distance (Average HD), and relative error (XOR) metrics to assess segmentation performance., Statistical Tests: Kruskal-Wallis tests assessed significances of differences between acquisitions in the testing set. Friedman tests with post hoc multiple comparisons assessed differences between the 2D CNN, 3D CNN, and SFCM. Bland-Altman analyses assessed agreement with manually derived lung volumes. A P value of <0.05 was considered statistically significant., Results: The 3D CNN significantly outperformed its 2D analog and SFCM, yielding a median (range) DSC of 0.961 (0.880-0.987), Average HD of 1.63 mm (0.65-5.45) and XOR of 0.079 (0.025-0.240) on the testing set and a DSC of 0.973 (0.866-0.987), Average HD of 1.11 mm (0.47-8.13) and XOR of 0.054 (0.026-0.255) on external validation data., Data Conclusion: The 3D CNN generated accurate 1 H-MRI lung segmentations on a heterogenous dataset, demonstrating robustness to disease pathology, sequence, vendor, and center., Evidence Level: 4., Technical Efficacy: Stage 1., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Coronary 18 F-sodium fluoride ( 18 F-fluoride) uptake is a marker of both atherosclerotic disease activity and disease progression. It is currently unknown whether there are rapid temporal changes in coronary 18 F-fluoride uptake and whether these are more marked in those with clinically unstable coronary artery disease. This study aimed to determine the natural history of coronary 18 F-fluoride uptake over 12 mo in patients with either advanced chronic coronary artery disease or a recent myocardial infarction. Methods: Patients with established multivessel coronary artery disease and either chronic disease or a recent acute myocardial infarction underwent coronary 18 F-fluoride PET and CT angiography, which was repeated at 3, 6, or 12 mo. Coronary 18 F-fluoride uptake was assessed in each vessel by measuring the coronary microcalcification activity (CMA). Coronary calcification was quantified by measuring calcium score, mass, and volume. Results: Fifty-nine patients had chronic coronary artery disease (median age, 68 y; 93% male), and 52 patients had a recent myocardial infarction (median age, 65 y; 83% male). Reflecting the greater burden of coronary artery disease, baseline CMA values were higher in those with chronic coronary artery disease. Coronary 18 F-fluoride uptake (CMA > 0) was associated with higher baseline calcium scores (294 Agatston units [AU] [interquartile range, 116-483 AU] vs. 72 AU [interquartile range, 8-222 AU]; P < 0.001) and more rapid progression of coronary calcification scores (39 AU [interquartile range, 10-82 AU] vs. 12 AU [interquartile range, 1-36 AU]; P < 0.001) than was the absence of uptake (CMA = 0). Coronary 18 F-fluoride uptake did not markedly alter over the course of 3, 6, or 12 mo in patients with either chronic coronary artery disease or a recent myocardial infarction. Conclusion: Coronary 18 F-fluoride uptake is associated with the severity and progression of coronary artery disease but does not undergo a rapid dynamic change in patients with chronic or unstable coronary artery disease. This finding suggests that coronary 18 F-fluoride uptake is a temporally stable marker of established and progressive disease., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Survey respondents who are non-attentive, respond randomly, or misrepresent who they are can impact the outcomes of surveys. Prior findings reported by the CDC have suggested that people engaged in highly dangerous cleaning practices during the COVID-19 pandemic, including ingesting household cleaners such as bleach. In our attempts to replicate the CDC's results, we found that 100% of reported ingestion of household cleaners are made by problematic respondents. Once inattentive, acquiescent, and careless respondents are removed from the sample, we find no evidence that people ingested cleaning products to prevent a COVID-19 infection. These findings have important implications for public health and medical survey research, as well as for best practices for avoiding problematic respondents in all survey research conducted online., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Litman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Left ventricular (LV) strain measurements can be derived using cardiac MRI from routinely acquired balanced steady-state free precession (bSSFP) cine images., Purpose: To compare the interfield strength agreement of global systolic strain, peak strain rates and artificial intelligence (AI) landmark-based global longitudinal shortening at 1.5 T and 3 T., Study Type: Prospective., Subjects: A total of 22 healthy individuals (mean age 36 ± 12 years; 45% male) completed two cardiac MRI scans at 1.5 T and 3 T in a randomized order within 30 minutes. FIELD STRENGTH/SEQUENCE: bSSFP cine images at 1.5 T and 3 T., Assessment: Two software packages, Tissue Tracking (cvi42, Circle Cardiovascular Imaging) and QStrain (Medis Suite, Medis Medical Imaging Systems), were used to derive LV global systolic strain in the longitudinal, circumferential and radial directions and peak (systolic, early diastolic, and late diastolic) strain rates. Global longitudinal shortening and mitral annular plane systolic excursion (MAPSE) were measured using an AI deep neural network model., Statistical Tests: Comparisons between field strengths were performed using Wilcoxon signed-rank test (P value < 0.05 considered statistically significant). Agreement was determined using intraclass correlation coefficients (ICCs) and Bland-Altman plots., Results: Minimal bias was seen in all strain and strain rate measurements between field strengths. Using Tissue Tracking, strain and strain rate values derived from long-axis images showed poor to fair agreement (ICC range 0.39-0.71), whereas global longitudinal shortening and MAPSE showed good agreement (ICC = 0.81 and 0.80, respectively). Measures derived from short-axis images showed good to excellent agreement (ICC range 0.78-0.91). Similar results for the agreement of strain and strain rate measurements were observed with QStrain., Conclusion: The interfield strength agreement of short-axis derived LV strain and strain rate measurements at 1.5 T and 3 T was better than those derived from long-axis images; however, the agreement of global longitudinal shortening and MAPSE was good., Evidence Level: 2 TECHNICAL EFFICACY: Stage 2., (© 2022 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Aims: Coronary artery calcification is a marker of cardiovascular risk, but its association with qualitatively and quantitatively assessed plaque subtypes is unknown., Methods and Results: In this post-hoc analysis, computed tomography (CT) images and 5-year clinical outcomes were assessed in SCOT-HEART trial participants. Agatston coronary artery calcium score (CACS) was measured on non-contrast CT and was stratified as zero (0 Agatston units, AU), minimal (1-9 AU), low (10-99 AU), moderate (100-399 AU), high (400-999 AU), and very high (≥1000 AU). Adverse plaques were investigated by qualitative (visual categorization of positive remodelling, low-attenuation plaque, spotty calcification, and napkin ring sign) and quantitative (calcified, non-calcified, low-attenuation, and total plaque burden; Autoplaque) assessments. Of 1769 patients, 36% had a zero, 9% minimal, 20% low, 17% moderate, 10% high, and 8% very high CACS. Amongst patients with a zero CACS, 14% had non-obstructive disease, 2% had obstructive disease, 2% had visually assessed adverse plaques, and 13% had low-attenuation plaque burden >4%. Non-calcified and low-attenuation plaque burden increased between patients with zero, minimal, and low CACS (P < 0.001), but there was no statistically significant difference between those with medium, high, and very high CACS. Myocardial infarction occurred in 41 patients, 10% of whom had zero CACS. CACS >1000 AU and low-attenuation plaque burden were the only predictors of myocardial infarction, independent of obstructive disease, and 10-year cardiovascular risk score., Conclusion: In patients with stable chest pain, zero CACS is associated with a good but not perfect prognosis, and CACS cannot rule out obstructive coronary artery disease, non-obstructive plaque, or adverse plaque phenotypes, including low-attenuation plaque., Competing Interests: Conflict of interest: D.D., P.S., S.C., and D.S.B. may receive software royalties from Cedars-Sinai Medical Center, and D.D., P.S., and D.S.B. have a patent. Outside the submitted work, E.v.B. reports personal fees from Aidence NV, Mentholatum, grants from Siemens Healthineers, and other from QCTIS, Astra Zeneca, and Roche Diagnostics. D.E.N. reports grants from Chief Scientist Office, British Heart Foundation, and Royal Bank of Scotland and personal fees from Toshiba during the conduct of the study. Outside the submitted work, P.J.S. reports grants from NIH, Siemens Medical Systems, and Amazon Web Services. The remaining authors have nothing to disclose., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Long COVID refers to a multitude of symptoms that persist long after SARS-CoV-2 infection. Fatigue and breathlessness are the most common symptoms of long COVID across a range of studies. They are also cardinal symptoms of chronic heart failure (CHF). In this review, we propose that fatigue and breathlessness in patients with long COVID may be explained by skeletal muscle abnormalities, in a manner similar to patients with CHF. The ergoreflex is a cardiorespiratory reflex activated by exercise, which couples ventilation and cardiovascular function to exercise intensity. At least part of the symptomatology of CHF is related to abnormal skeletal muscle and an enhanced ergoreflex, resulting in heightened sympathetic, vasoconstrictor and ventilator drives. Similarly, SARS-CoV-2 infection results in a hyperinflammatory and hypercatabolic state. This leads to reduction in skeletal muscle mass and altered function. We postulate that the ergoreflex is chronically overstimulated, resulting in fatigue and breathlessness. Exercise training preserves muscle mass and function as well as reduces ergoreflex activation; therefore may have a role in improving symptoms associated with long COVID. Should the ergoreflex be proven to be an important pathophysiological mechanism of long COVID, tailored exercise interventions should be trialed with the aim of improving both symptoms and perhaps outcomes in patients with long COVID., 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 © 2022 Sze, Pan, Moss, Ong, Pareek, Squire and Clark.)

Background: Aortic atherosclerosis represents an important contributor to ischemic stroke risk. Identifying patients with high-risk aortic atheroma could improve preventative treatment strategies for future ischemic stroke., Objectives: The purpose of this study was to investigate whether thoracic 18 F-sodium fluoride positron emission tomography (PET) could improve the identification of patients at the highest risk of ischemic stroke., Methods: In a post hoc observational cohort study, we quantified thoracic aortic and coronary 18 F-sodium fluoride activity in 461 patients with stable cardiovascular disease undergoing PET combined with computed tomography (CT). Progression of atherosclerosis was assessed by change in aortic and coronary CT calcium volume. Clinical outcomes were determined by the occurrence of ischemic stroke and myocardial infarction. We compared the prognostic utility of 18 F-sodium fluoride activity for predicting stroke to clinical risk scores and CT calcium quantification using survival analysis and multivariable Cox regression., Results: After 12.7 ± 2.7 months, progression of thoracic aortic calcium volume correlated with baseline thoracic aortic 18 F-sodium fluoride activity (n = 140; r = 0.31; P = 0.00016). In 461 patients, 23 (5%) patients experienced an ischemic stroke and 32 (7%) a myocardial infarction after 6.1 ± 2.3 years of follow-up. High thoracic aortic 18 F-sodium fluoride activity was strongly associated with ischemic stroke (HR: 10.3 [95% CI: 3.1-34.8]; P = 0.00017), but not myocardial infarction (P = 0.40). Conversely, high coronary 18 F-sodium fluoride activity was associated with myocardial infarction (HR: 4.8 [95% CI: 1.9-12.2]; P = 0.00095) but not ischemic stroke (P = 0.39). In a multivariable Cox regression model including imaging and clinical risk factors, thoracic aortic 18 F-sodium fluoride activity was the only variable associated with ischemic stroke (HR: 8.19 [95% CI: 2.33-28.7], P = 0.0010)., Conclusions: In patients with established cardiovascular disease, thoracic aortic 18 F-sodium fluoride activity is associated with the progression of atherosclerosis and future ischemic stroke. Arterial 18 F-sodium fluoride activity identifies localized areas of atherosclerotic disease activity that are directly linked to disease progression and downstream regional clinical atherothrombotic events. (DIAMOND-Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND], NCT02110303; Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis [SALTIRE II], NCT02132026; Novel Imaging Approaches To Identify Unstable Coronary Plaques, NCT01749254; and Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis, NCT01358513)., Competing Interests: Funding Support and Author Disclosures Drs Fletcher (FS/19/15/34155), Tzolos (FS/17/51/33096), Syed (FS/18/31/33676), Moss (AA/18/3/34220), Walker (FS/19/15/34155), Williams (FS/ICRF/20/26002), Newby (CH/09/002, RG/16/10/32375, RE/18/5/34216), and Dweck (FS/14/78/31020) are supported by the British Heart Foundation. Dr Lembo is supported by the International PhD programme in Cardiovascular Pathophysiology and Therapeutics (CardioPaTh). Dr van Beek is supported by SINAPSE. Dr Adamson is supported by a Heart Foundation of New Zealand Senior Fellowship (1844). Dr Wardlaw is supported by the UK Dementia Research Institute (funded by the MRC, Alzheimer Society and Alzheimer Research UK). Dr Slomka and FusionQuant Development are supported by the National Institute of Health Grant HL135557 (PI: Dr Slomka); and his laboratory is supported by National Institutes of Health R01HL135557. Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA); and holds investigator-initiated research grants from Siemens Healthineers. Dr Dweck is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA). The Edinburgh Imaging facility QMRI (Edinburgh) is supported by the National Health Service Research Scotland through National Health Service Lothian Health Board. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Standard methods for quantifying positron emission tomography (PET) uptake in the aorta are time consuming and may not reflect overall vessel activity. We describe aortic microcalcification activity (AMA), a novel method for quantifying 18 F-sodium fluoride (18F-NaF) uptake in the thoracic aorta., Methods: Twenty patients underwent two hybrid 18 F-NaF PET and computed tomography (CT) scans of the thoracic aorta less than three weeks apart. AMA, as well as maximum (TBRmax) and mean (TBRmean) tissue to background ratios, were calculated by two trained operators. Intra-observer repeatability, inter-observer repeatability and scan-rescan reproducibility were assessed. Each 18 F-NaF quantification method was compared to validated cardiovascular risk scores., Results: Aortic microcalcification activity demonstrated excellent intra-observer (intraclass correlation coefficient 0.98) and inter-observer (intraclass correlation coefficient 0.97) repeatability with very good scan-rescan reproducibility (intraclass correlation coefficient 0.86) which were similar to previously described TBRmean and TBRmax methods. AMA analysis was much quicker to perform than standard TBR assessment (3.4min versus 15.1min, P<0.0001). AMA was correlated with Framingham stroke risk scores and Framingham risk score for hard cononary heart disease., Conclusions: AMA is a simple, rapid and reproducible method of quantifying global 18 F-NaF uptake across the ascending aorta and aortic arch that correlates with cardiovascular risk scores., (© 2021. The Author(s).)

Background: Pericoronary adipose tissue (PCAT) attenuation and low-attenuation noncalcified plaque (LAP) burden can both predict outcomes., Objectives: This study sought to assess the relative and additive values of PCAT attenuation and LAP to predict future risk of myocardial infarction., Methods: In a post hoc analysis of the multicenter SCOT-HEART (Scottish Computed Tomography of the Heart) trial, the authors investigated the relationships between the future risk of fatal or nonfatal myocardial infarction and PCAT attenuation measured from coronary computed tomography angiography (CTA) using multivariable Cox regression models including plaque burden, obstructive coronary disease, and cardiac risk score (incorporating age, sex, diabetes, smoking, hypertension, hyperlipidemia, and family history)., Results: In 1,697 evaluable participants (age: 58 ± 10 years), there were 37 myocardial infarctions after a median follow-up of 4.7 years. Mean PCAT was -76 ± 8 HU and median LAP burden was 4.20% (IQR: 0%-6.86%). PCAT attenuation of the right coronary artery (RCA) was predictive of myocardial infarction (HR: 1.55; P = 0.017, per 1 SD increment) with an optimum threshold of -70.5 HU (HR: 2.45; P = 0.01). In multivariable analysis, adding PCAT-RCA of ≥-70.5 HU to an LAP burden of >4% (the optimum threshold for future myocardial infarction; HR: 4.87; P < 0.0001) led to improved prediction of future myocardial infarction (HR: 11.7; P < 0.0001). LAP burden showed higher area under the curve compared to PCAT attenuation for the prediction of myocardial infarction (AUC = 0.71 [95% CI: 0.62-0.80] vs AUC = 0.64 [95% CI: 0.54-0.74]; P < 0.001), with increased area under the curve when the 2 metrics are combined (AUC = 0.75 [95% CI: 0.65-0.85]; P = 0.037)., Conclusion: Coronary CTA-defined LAP burden and PCAT attenuation have marked and complementary predictive value for the risk of fatal or nonfatal myocardial infarction., Competing Interests: Funding Support and Author Disclosures This trial was funded by The Chief Scientist Office of the Scottish Government Health and Social Care Directorates (CZH/4/588), with supplementary awards from Edinburgh and Lothian’s Health Foundation Trust and the Heart Diseases Research Fund. Dr Williams, (FS/ICRF/20/26002, FS/11/014, CH/09/002), Dr Newby (CH/09/002, RG/16/10/32375, RE/18/5/34216), and Dr Dweck (FS/14/78/31020) are supported by the British Heart Foundation. Dr Williams was supported by The Chief Scientist Office of the Scottish Government Health (PCL/17/04). Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr van Beek is supported by the Scottish Imaging Network: A Platform of Scientific Excellence (SINAPSE). Dr Mills is supported by the British Heart Foundation through the award of the Butler Senior Clinical Research Fellowship and a Programme Grant (FS/16/14/32023, RG/20/10/34966). Dr Adamson is supported by a National Heart Foundation of New Zealand Senior Fellowship (1844). Dr Dweck is supported by the Sir Jules Thorn Biomedical Research Award 2015 (15/JTA). The Royal Bank of Scotland supported the provision of the 320-multidetector computed tomography for National Health Service Lothian and the University of Edinburgh. The Edinburgh Imaging Facility, The Queen's Medical Research Institute (Edinburgh) is supported by the National Health Service Research Scotland through the National Health Service Lothian Health Board. The Clinical Research Facility Glasgow and Clinical Research Facility Tayside are supported by National Health Service Research Scotland. This work is supported in part by the National Institutes of Health/National Heart, Lung, and Blood Institute grants 1R01HL148787-01A1 and 1R01HL151266. Drs Lin and Grodecki, Priscilla McElhinney, Sebastien Cadet, and Dr Dey are supported by National Institutes of Health/National Heart, Lung, and Blood Institute grant 1R01HL148787-01A1. This work is also supported in part by the Miriam and Sheldon G. Adelson Medical Research Foundation. Sebastien Cadet, and Drs Berman, Slomka, and Dey received software royalties from Cedars-Sinai Medical Center. Drs Slomka, Berman, and Dey hold a patent (US8885905B2 in the United States and World Intellectual Property Organization patent WO2011069120A1, “Method and System for Plaque Characterization”). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the association between nonalcoholic fatty liver disease (NAFLD) and quantitative atherosclerotic plaque at CT., Materials and Methods: In this post hoc analysis of the prospective Scottish Computed Tomography of the HEART trial (November 2010 to September 2014), hepatosteatosis and coronary artery calcium score were measured at noncontrast CT. Presence of stenoses, visually assessed high-risk plaque, and quantitative plaque burden were assessed at coronary CT angiography. Multivariable models were constructed to assess the impact of hepatosteatosis and cardiovascular risk factors on coronary artery disease., Results: Images from 1726 participants (mean age, 58 years ± 9 [SD]; 974 men) were included. Participants with hepatosteatosis (155 of 1726, 9%) had a higher body mass index, more hypertension and diabetes mellitus, and higher cardiovascular risk scores ( P < .001 for all) compared with those without hepatosteatosis. They had increased coronary artery calcium scores (median, 43 Agatston units [AU] [interquartile range, 0-273] vs 19 AU [0-225], P = .046), more nonobstructive disease (48% vs 37%, P = .02), and higher low-attenuation plaque burden (5.11% [0-7.16] vs 4.07% [0-6.84], P = .04). However, these associations were not independent of cardiovascular risk factors. Over a median of 4.7 years, there was no evidence of a difference in myocardial infarction between those with and without hepatosteatosis (1.9% vs 2.4%, P = .92)., Conclusion: Hepatosteatosis at CT was associated with an increased prevalence of coronary artery disease at CT, but this was not independent of the presence of cardiovascular risk factors. Keywords: CT, Cardiac, Nonalcoholic Fatty Liver Disease, Coronary Artery Disease, Hepatosteatosis, Plaque QuantificationClinical trial registration no. NCT01149590 Supplemental material is available for this article. © RSNA, 2022See also commentary by Abohashem and Blankstein in this issue., Competing Interests: Disclosures of conflicts of interest: J.C. No relevant relationships. T.D.H. Investigator-sponsored research grant from Gilead Sciences paid to the University of Liverpool to conduct pilot study 2017; payment or honoraria for lectures from Janssen (2019), Gilead Sciences (2018), and Merck (2020) for speaking at an educational event. M.N.M. No relevant relationships. E.T. British Heart Foundation grant (FS/CRTF/20/24086). J.K. No relevant relationships. M.D. No relevant relationships. P.M. No relevant relationships. A.J.M. No relevant relationships. P.D.A. National Heart Foundation of New Zealand Senior Fellowship and Health Research Council of New Zealand Research grants; support from Abbott Vascular for travel provided to attend educational meetings. A.H. BHF Funded Clinical Research Fellowship. S.A. No relevant relationships. A.S.V.S. No relevant relationships. T.P. No relevant relationships. C.W. No relevant relationships. J.R.W.M. Editorial board of Radiology: Cardiothoracic Imaging. G.R. No relevant relationships. E.J.R.v.B. Consulting fee from Contextflow (not related to this work); QCTIS founder/owner (not related to this work); payment or honoraria from AstraZeneca (presentation) and Roche Diagnostics (presentation) (not related to this work); medical advisory board for Aidence and steering committee clinical study for AstraZeneca (not related to this work). E.D.N. Consulting fees from Medneo Diagnostics, Caristo, and Terarecon; secretary of SCCT. L.J.S. No relevant relationships. D.S.B. No relevant relationships. P.J.S. NIH (5R01HL135557); royalties or license from Cedar-Sinai software; consulting fees from IBA; patent (method and system for plaque characterization) US8885905B2; ASNC 2021 meeting chair; SNMMI CVC council vice president. N.L.M. No relevant relationships. M.R.D. No relevant relationships. D.E.N. British Heart Foundation (CH/09/002, RG/16/10/32375, RE/18/5/34216); Wellcome Trust Senior Investigator Award (WT103782AIA); National Institutes of Health (1R01HL148787); Siemens Healthineers educational grant; Toshiba consultancy. S.W.M. No relevant relationships. D.D. Supported in part by the National Institutes of Health/National Heart, Lung, and Blood Institute grant 1R01HL148787-01A1. M.C.W. British Heart Foundation grant (FS/ICRF/20/26002); speakers bureau for Canon Medical Systems; member of board of directors for SCCT; president elect of British Society of Cardiovascular Imaging; editorial board member of Radiology: Cardiothoracic Imaging., (© 2022 by the Radiological Society of North America, Inc.)

Non-ST-elevation acute coronary syndrome (NSTE-ACS) comprises a broad spectrum of disease ranging from unstable angina to myocardial infarction. International guidelines recommend a routine invasive strategy for managing patients with NSTE-ACS at high to very high-risk, supported by evidence of improved composite ischaemic outcomes as compared with a selective invasive strategy. However, accurate diagnosis of NSTE-ACS in the acute setting is challenging due to the spectrum of non-coronary disease that can manifest with similar symptoms. Heterogeneous clinical presentations and limited uptake of risk prediction tools can confound physician decision-making regarding the use and timing of invasive coronary angiography (ICA). Large proportions of patients with suspected NSTE-ACS do not require revascularisation but may unnecessarily undergo ICA with its attendant risks and associated costs. Advances in coronary CT angiography and cardiac MRI have prompted evaluation of whether non-invasive strategies may improve patient selection, or whether tailored approaches are better suited to specific subgroups. Future directions include (1) better understanding of risk stratification as a guide to investigation and therapy in suspected NSTE-ACS, (2) randomised clinical trials of non-invasive imaging versus standard of care approaches prior to ICA and (3) defining the optimal timing of very early ICA in high-risk NSTE-ACS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Cardiac MR is widely used to diagnose cardiac amyloid, but cannot differentiate AL and ATTR subtypes: an important distinction given their differing treatments and prognoses. We used PET/MR imaging to quantify myocardial uptake of 18F-fluoride in ATTR and AL amyloid patients, as well as participants with aortic stenosis and age/sex-matched controls., Methods: In this prospective multicenter study, patients were recruited in Edinburgh and New York and underwent 18F-fluoride PET/MR imaging. Standardized volumes of interest were drawn in the septum and areas of late gadolinium enhancement to derive myocardial standardized uptake values (SUV) and tissue-to-background ratio (TBR MEAN ) after correction for blood pool activity in the right atrium., Results: 53 patients were scanned: 18 with cardiac amyloid (10 ATTR and 8 AL), 13 controls, and 22 with aortic stenosis. No differences in myocardial TBR values were observed between participants scanned in Edinburgh and New York. Mean myocardial TBR MEAN values in ATTR amyloid (1.13 ± 0.16) were higher than controls (0.84 ± 0.11, P = .0006), aortic stenosis (0.73 ± 0.12, P < .0001), and those with AL amyloid (0.96 ± 0.08, P = .01). TBR MEAN values within areas of late gadolinium enhancement provided discrimination between patients with ATTR (1.36 ± 0.23) and all other groups (e.g., AL [1.06 ± 0.07, P = .003]). A TBR MEAN threshold >1.14 in areas of LGE demonstrated 100% sensitivity (CI 72.25 to 100%) and 100% specificity (CI 67.56 to 100%) for ATTR compared to AL amyloid (AUC 1, P = .0004)., Conclusion: Quantitative 18F-fluoride PET/MR imaging can distinguish ATTR amyloid from other similar phenotypes and holds promise in improving the diagnosis of this condition., (© 2020. The Author(s).)

Objectives: Coronary and cardiac calcification are frequent incidental findings on non-gated thoracic computed tomography (CT). However, radiologist opinions and practices regarding the reporting of incidental calcification are poorly understood., Methods: UK radiologists were invited to complete this online survey, organised by the British Society of Cardiovascular Imaging (BSCI). Questions included anonymous information on subspecialty, level of training and reporting practices for incidental coronary artery, aortic valve, mitral and thoracic aorta calcification., Results: The survey was completed by 200 respondents: 10% trainees and 90% consultants. Calcification was not reported by 11% for the coronary arteries, 22% for the aortic valve, 35% for the mitral valve and 37% for the thoracic aorta. Those who did not subspecialise in cardiac imaging were less likely to report coronary artery calcification ( p = 0.005), aortic valve calcification ( p = 0.001) or mitral valve calcification ( p = 0.008), but there was no difference in the reporting of thoracic aorta calcification. Those who did not subspecialise in cardiac imaging were also less likely to provide management recommendations for coronary artery calcification ( p < 0.001) or recommend echocardiography for aortic valve calcification ( p < 0.001), but there was no difference for mitral valve or thoracic aorta recommendations., Conclusion: Incidental coronary artery, valvular and aorta calcification are frequently not reported on thoracic CT and there are differences in reporting practices based on subspeciality., Advances in Knowledge: On routine thoracic CT, 11% of radiologists do not report coronary artery calcification. Radiologist reporting practices vary depending on subspeciality but not level of training., (© 2022 The Authors. Published by the British Institute of Radiology.)

Obesity is associated with the development of heart failure and is a major risk factor for heart failure with preserved ejection fraction (HFpEF). Epicardial adipose tissue (EAT) is a unique visceral fat in close proximity to the heart and is of particular interest to the study of cardiac disease. Small poorly differentiated adipocytes with altered lipid:water content are associated with a proinflammatory secretome and may contribute to the pathophysiology observed in HFpEF. Multimodality imaging approaches can be used to quantify EAT volume and characterise EAT composition. Current research studies remain unclear as to the magnitude of effect that EAT plays on myocardial dysfunction and further work using multimodality imaging techniques is ongoing. Pharmacological interventions, including glucagon-like peptide 1 receptor agonists and sodium-dependent glucose linked transporter 2 inhibitors have shown promise in attenuating the deleterious metabolic and inflammatory changes seen in EAT. Clinical studies are ongoing to explore whether these therapies exert their beneficial effects by modifying this unique adipose deposit., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We aimed to establish the observer repeatability and interscan reproducibility of coronary 18 F-sodium-fluoride positron emission tomography (PET) uptake using a novel semi-automated approach, coronary microcalcification activity (CMA)., Methods: Patients with multivessel coronary artery disease underwent repeated hybrid PET and computed tomography angiography (CTA) imaging (PET/CTA). CMA was defined as the integrated standardized uptake values (SUV) in the entire coronary tree exceeding 2 standard deviations above the background SUV. Coefficients of repeatability between the same observer (intraobserver repeatability), between 2 observers (interobserver repeatability) and coefficient of reproducibility between 2 scans (interscan reproducibility), were determined at vessel and patient level., Results: In 19 patients, CMA was assessed twice in 43 coronary vessels on two PET/CT scans performed 12 ± 5 days apart. There was excellent intraclass correlation for intraobserver and interobserver repeatability as well as interscan reproducibility (all ≥ 0.991). There was 100% intraobserver, interobserver and interscan agreement for the presence (CMA > 0) or absence (CMA = 0) of coronary 18 F-NaF uptake. Mean CMA was 3.12 ± 0.62 with coefficients of repeatability of ≤ 10% for all measures: intraobserver 0.24 and 0.22, interobserver 0.30 and 0.29 and interscan 0.33 and 0.32 at a per-vessel and per-patient level, respectively., Conclusions: CMA is a repeatable and reproducible global measure of coronary atherosclerotic activity., (© 2020. American Society of Nuclear Cardiology.)

Background: Lipoprotein(a) [Lp(a)] is associated with increased risk of myocardial infarction, although the mechanism for this observation remains uncertain., Objectives: This study aims to investigate whether Lp(a) is associated with adverse plaque progression., Methods: Lp(a) was measured in patients with advanced stable coronary artery disease undergoing coronary computed tomography angiography at baseline and 12 months to assess progression of total, calcific, noncalcific, and low-attenuation plaque (necrotic core) in particular. High Lp(a) was defined as Lp(a) ≥ 70 mg/dL. The relationship of Lp(a) with plaque progression was assessed using linear regression analysis, adjusting for body mass index, segment involvement score, and ASSIGN score (a Scottish cardiovascular risk score comprised of age, sex, smoking, blood pressure, total and high-density lipoprotein [HDL]-cholesterol, diabetes, rheumatoid arthritis, and deprivation index)., Results: A total of 191 patients (65.9 ± 8.3 years of age; 152 [80%] male) were included in the analysis, with median Lp(a) values of 100 (range: 82 to 115) mg/dL and 10 (range: 5 to 24) mg/dL in the high and low Lp(a) groups, respectively. At baseline, there was no difference in coronary artery disease severity or plaque burden. Patients with high Lp(a) showed accelerated progression of low-attenuation plaque compared with low Lp(a) patients (26.2 ± 88.4 mm 3 vs -0.7 ± 50.1 mm 3 ; P = 0.020). Multivariable linear regression analysis confirmed the relation between Lp(a) and low-attenuation plaque volume progression (β = 10.5% increase for each 50 mg/dL Lp(a), 95% CI: 0.7%-20.3%). There was no difference in total, calcific, and noncalcific plaque volume progression., Conclusions: Among patients with advanced stable coronary artery disease, Lp(a) is associated with accelerated progression of coronary low-attenuation plaque (necrotic core). This may explain the association between Lp(a) and the high residual risk of myocardial infarction, providing support for Lp(a) as a treatment target in atherosclerosis., Competing Interests: Funding Support and Author Disclosures Drs Kaiser and Stroes were supported by the Netherlands Heart Foundation CVON 2017-20: generating the best evidence-based pharmaceutical targets for atherosclerosis [GENIUS II]). Dr Dey is supported by the National Institute of Health/National Heart, Lung, and Blood Institute grants (1R01HL148787-01A1 and 1R01HL151266). Dr Dweek is supported by the British Heart Foundation (FS/14/78/31020) and is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA); has received speaker fees from Pfizer and Novartis; and has received consultancy fees from Novartis, Jupiter Bioventures, and Silence therapeutics. Dr Stroes has received research grants/support to his institution from Amgen, Sanofi, Resverlogix, and Athera; and has served as a consultant for Amgen, Sanofi, Esperion, Novartis, and Ionis Pharmaceuticals. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine the contribution of comorbidities on the reported widespread myocardial abnormalities in patients with recent COVID-19., Methods: In a prospective two-centre observational study, patients hospitalised with confirmed COVID-19 underwent gadolinium and manganese-enhanced MRI and CT coronary angiography (CTCA). They were compared with healthy and comorbidity-matched volunteers after blinded analysis., Results: In 52 patients (median age: 54 (IQR 51-57) years, 39 males) who recovered from COVID-19, one-third (n=15, 29%) were admitted to intensive care and a fifth (n=11, 21%) were ventilated. Twenty-three patients underwent CTCA, with one-third having underlying coronary artery disease (n=8, 35%). Compared with younger healthy volunteers (n=10), patients demonstrated reduced left (ejection fraction (EF): 57.4±11.1 (95% CI 54.0 to 60.1) versus 66.3±5 (95 CI 62.4 to 69.8)%; p=0.02) and right (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 60.5±4.9 (95% CI 57.1 to 63.2)%; p≤0.0001) ventricular systolic function with elevated native T1 values (1225±46 (95% CI 1205 to 1240) vs 1197±30 (95% CI 1178 to 1216) ms;p=0.04) and extracellular volume fraction (ECV) (31±4 (95% CI 29.6 to 32.1) vs 24±3 (95% CI 22.4 to 26.4)%; p<0.0003) but reduced myocardial manganese uptake (6.9±0.9 (95% CI 6.5 to 7.3) vs 7.9±1.2 (95% CI 7.4 to 8.5) mL/100 g/min; p=0.01). Compared with comorbidity-matched volunteers (n=26), patients had preserved left ventricular function but reduced right ventricular systolic function (EF: 51.7±9.1 (95% CI 53.9 to 60.1) vs 59.3±4.9 (95% CI 51.0 to 66.5)%; p=0.0005) with comparable native T1 values (1225±46 (95% CI 1205 to 1240) vs 1227±51 (95% CI 1208 to 1246) ms; p=0.99), ECV (31±4 (95% CI 29.6 to 32.1) vs 29±5 (95% CI 27.0 to 31.2)%; p=0.35), presence of late gadolinium enhancement and manganese uptake. These findings remained irrespective of COVID-19 disease severity, presence of myocardial injury or ongoing symptoms., Conclusions: Patients demonstrate right but not left ventricular dysfunction. Previous reports of left ventricular myocardial abnormalities following COVID-19 may reflect pre-existing comorbidities., Trial Registration Number: NCT04625075., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Coronary 18 F-sodium fluoride ( 18 F-NaF) PET and CT angiography-based quantitative plaque analysis have shown promise in refining risk stratification in patients with coronary artery disease. We combined both of these novel imaging approaches to develop an optimal machine-learning model for the future risk of myocardial infarction in patients with stable coronary disease. Methods: Patients with known coronary artery disease underwent coronary 18 F-NaF PET and CT angiography on a hybrid PET/CT scanner. Machine-learning by extreme gradient boosting was trained using clinical data, CT quantitative plaque analysis, measures and 18 F-NaF PET, and it was tested using repeated 10-fold hold-out testing. Results: Among 293 study participants (65 ± 9 y; 84% male), 22 subjects experienced a myocardial infarction over the 53 (40-59) months of follow-up. On univariable receiver-operator-curve analysis, only 18 F-NaF coronary uptake emerged as a predictor of myocardial infarction (c-statistic 0.76, 95% CI 0.68-0.83). When incorporated into machine-learning models, clinical characteristics showed limited predictive performance (c-statistic 0.64, 95% CI 0.53-0.76) and were outperformed by a quantitative plaque analysis-based machine-learning model (c-statistic 0.72, 95% CI 0.60-0.84). After inclusion of all available data (clinical, quantitative plaque and 18 F-NaF PET), we achieved a substantial improvement ( P = 0.008 versus 18 F-NaF PET alone) in the model performance (c-statistic 0.85, 95% CI 0.79-0.91). Conclusion: Both 18 F-NaF uptake and quantitative plaque analysis measures are additive and strong predictors of outcome in patients with established coronary artery disease. Optimal risk stratification can be achieved by combining clinical data with these approaches in a machine-learning model., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: 18 F-Fluoride uptake denotes calcification activity in aortic stenosis and atherosclerosis. While PET/MR has several advantages over PET/CT, attenuation correction of PET/MR data is challenging, limiting cardiovascular application. We compared PET/MR and PET/CT assessments of 18 F-fluoride uptake in the aortic valve and coronary arteries., Methods and Results: 18 patients with aortic stenosis or recent myocardial infarction underwent 18 F-fluoride PET/CT followed immediately by PET/MR. Valve and coronary 18 F-fluoride uptake were evaluated independently. Both standard (Dixon) and novel radial GRE) MR attenuation correction (AC) maps were validated against PET/CT with results expressed as tissue-to-background ratios (TBRs). Visually, aortic valve 18 F-fluoride uptake was similar on PET/CT and PET/MR. TBR MAX values were comparable with radial GRE AC (PET/CT 1.55±0.33 vs. PET/MR 1.58 ± 0.34, P = 0.66; 95% limits of agreement - 27% to + 25%) but performed less well with Dixon AC (1.38 ± 0.44, P = 0.06; bias (-)14%; 95% limits of agreement - 25% to + 53%). In native coronaries, 18 F-fluoride uptake was similar on PET/MR to PET/CT regardless of AC approach. PET/MR identified 28/29 plaques identified on PET/CT; however, stents caused artifact on PET/MR making assessment of 18 F-fluoride uptake challenging., Conclusion: Cardiovascular PET/MR demonstrates good visual and quantitative agreement with PET/CT. However, PET/MR is hampered by stent-related artifacts currently limiting clinical application., (© 2019. The Author(s).)

Objectives: This study was designed to investigate whether coronary computed tomography angiography assessments of coronary plaque might explain differences in the prognosis of men and women presenting with chest pain., Background: Important sex differences exist in coronary artery disease. Women presenting with chest pain have different risk factors, symptoms, prevalence of coronary artery disease and prognosis compared to men., Methods: Within a multicenter randomized controlled trial, we explored sex differences in stenosis, adverse plaque characteristics (positive remodeling, low-attenuation plaque, spotty calcification, or napkin ring sign) and quantitative assessment of total, calcified, noncalcified and low-attenuation plaque burden., Results: Of the 1,769 participants who underwent coronary computed tomography angiography, 772 (43%) were female. Women were more likely to have normal coronary arteries and less likely to have adverse plaque characteristics (p < 0.001 for all). They had lower total, calcified, noncalcified, and low-attenuation plaque burdens (p < 0.001 for all) and were less likely to have a low-attenuation plaque burden >4% (41% vs. 59%; p < 0.001). Over a median follow-up of 4.7 years, myocardial infarction (MI) occurred in 11 women (1.4%) and 30 men (3%). In those who had MI, women had similar total, noncalcified, and low-attenuation plaque burdens as men, but men had higher calcified plaque burden. Low-attenuation plaque burden predicted MI (hazard ratio: 1.60; 95% confidence interval: 1.10 to 2.34; p = 0.015), independent of calcium score, obstructive disease, cardiovascular risk score, and sex., Conclusions: Women presenting with stable chest pain have less atherosclerotic plaque of all subtypes compared to men and a lower risk of subsequent MI. However, quantitative low-attenuation plaque is as strong a predictor of subsequent MI in women as in men. (Scottish Computed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590)., Competing Interests: Funding Support and Author Disclosures Drs. Dey, Slomka, and Berman and Mr. Cadet may receive software royalties from Cedars-Sinai Medical Center; and Drs. Dey, Slomka, and Berman have a patent. This trial was funded by The Chief Scientist Office of the Scottish Government Health and Social Care Directorates (CZH/4/588), with supplementary awards from Edinburgh and Lothian’s Health Foundation Trust and the Heart Diseases Research Fund. Drs. Williams, Mills, Newby, and Dweck are supported by the British Heart Foundation (FS/ICRF/20/26002, CH/09/002, FS/11/014, FS/16/14/32023, RG/20/10/34966, RE/18/5/34216, RG/16/10/32375, FS/14/78/31020). Dr. Williams was supported by The Chief Scientist Office of the Scottish Government Health (PCL/17/04). Dr. Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr. van Beek is supported by Scottish Imaging Network: A Platform of Scientific Excellence (SINAPSE). Dr. Adamson is supported by a National Heart Foundation of New Zealand Senior Fellowship (1844). Dr. Dweck is supported by the Sir Jules Thorn Biomedical Research Award 2015 (15/JTA). The Royal Bank of Scotland supported the provision of 320-multidetector CT for NHS Lothian and the University of Edinburgh. The Edinburgh Imaging facility QMRI (Edinburgh) is supported by the National Health Service Research Scotland (NRS) through National Health Service Lothian Health Board. The Clinical Research Facility Glasgow and Clinical Research Facility Tayside are supported by National Health Service Research Scotland (NRS). Ms. McElhinney and Dr. Dey are supported by National Institute of Health/National Heart, Lung, and Blood Institute grants (1R01HL148787-01A1 and 1R01HL151266). Mr. Cadet is supported by the Miriam and Sheldon G. Adelson Medical Research Foundation. All other authors have no reported that they have norelationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The COVID-19 pandemic has made the world seem less predictable. Such crises can lead people to feel that others are a threat. Here, we show that the initial phase of the pandemic in 2020 increased individuals' paranoia and made their belief updating more erratic. A proactive lockdown made people's belief updating less capricious. However, state-mandated mask-wearing increased paranoia and induced more erratic behaviour. This was most evident in states where adherence to mask-wearing rules was poor but where rule following is typically more common. Computational analyses of participant behaviour suggested that people with higher paranoia expected the task to be more unstable. People who were more paranoid endorsed conspiracies about mask-wearing and potential vaccines and the QAnon conspiracy theories. These beliefs were associated with erratic task behaviour and changed priors. Taken together, we found that real-world uncertainty increases paranoia and influences laboratory task behaviour., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Spontaneous coronary artery dissection (SCAD) is a pathophysiologically distinct cause of acute coronary syndromes (ACS). It is increasingly recognized that optimal management is different from that for atherosclerotic ACS and that a SCAD diagnosis has specific long-term prognostic and therapeutic implications. Accurate diagnosis is therefore essential to ensure the best treatment of patients. At present this relies on the recognition of typical features of SCAD identified on invasive coronary angiography. Although most SCAD can be readily distinguished angiographically from alternative causes of ACS, false positive and false negative diagnoses remain common. In particular, sometimes non-SCAD presentations, including atherothrombosis, takotsubo cardiomyopathy, coronary embolism, coronary vasospasm, contrast streaming, and myocardial infarction with nonobstructive coronary arteries, can mimic angiographic features usually associated with SCAD. The authors present the combined experience from European and US SCAD referral centers reviewing the classical angiographic appearances of SCAD, presenting potential diagnostic pitfalls and exemplars of SCAD mimickers. The authors further review the benefits and limitations of intracoronary imaging in the context of SCAD. Finally, the authors discuss the investigation of ambiguous cases and an approach to minimize misdiagnosis in difficult cases., Competing Interests: Funding Support and Author Disclosures This SCAD research study was supported by BeatSCAD, the British Heart Foundation (PG/13/96/30608), the National Institute for Health Research rare disease translational collaboration, the Leicester NIHR Biomedical Research Centre, and SCAD Research. Dr Moss receives funding support from the British Heart Foundation (AA/18/3/34220). Dr Adlam has received research funding from Abbott Vascular for a clinical research fellow and from AstraZeneca for SCAD genetics research and unrelated research; and has undertaken consultancy with General Electric to support general research funds. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The ability to characterize and to quantify the extent of coronary artery disease has the potential to improve the prognostic capability of coronary computed tomography angiography. Although reproducible techniques have been described in those with mild coronary disease, this has yet to be assessed in patients with advanced disease., Methods: Twenty patients with known multivessel disease underwent repeated computed tomography coronary angiography, 2 weeks apart. Coronary artery segments were analysed using semi-automated software by two trained observers to determine intraobserver, interobserver and interscan reproducibility., Results: Overall, 149 coronary arterial segments were analysed. There was excellent intraobserver and interobserver agreement for all plaque volume measurements (Lin's coefficient 0.95 to 1.0). There were no substantial interscan differences (P ​> ​0.05 for all) for total (2063 ​± ​1246 ​mm 3 , mean of differences -35.6 ​mm 3 ), non-calcified (1795 ​± ​910 ​mm 3 , mean of differences -4.3 ​mm 3 ), calcified (298 ​± ​425 ​mm 3 , mean of differences -31.3 ​mm 3 ) and low-attenuation (13 ​± ​13 ​mm 3 , mean of differences -2.6 ​mm 3 ) plaque volumes. Interscan agreement was highest for total and noncalcified plaque volumes. Calcified and low-attenuation plaque (-236.6 to 174 ​mm 3 and -15.8 to 10.5 ​mm 3 respectively) had relatively wider 95% limits of agreement reflecting the lower absolute plaque volumes., Conclusion: In the presence of advanced coronary disease, semi-automated plaque quantification provides excellent reproducibility, particularly for total and non-calcified plaque volumes. This approach has major potential to assess change in disease over time and optimize risk stratification in patients with established coronary artery disease., Competing Interests: Declaration of competing interest Drs. Dey and Slomka received software royalties from Cedars-Sinai Medical Center and have a patent. The remaining authors have no disclosures to report., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Ticagrelor is a potent and orally active P2Y 12 inhibitor. Ticagrelor has been extensively tested in Phase II and Phase III trials in patients with coronary artery disease. The pharmacokinetics and pharmacodynamics of ticagrelor result in more rapid and effective inhibition of platelet activation compared with other P2Y 12 inhibitors. This has resulted in a reduction in recurrent major cardiovascular events in initial randomized controls trials comparing ticagrelor with clopidogrel. More recently, clinical trials have investigated the use of ticagrelor in patients with stable coronary artery disease and a high residual risk of coronary thrombotic events. In patients with stable coronary artery disease, the potent antiplatelet effect of ticagrelor is counterbalanced by an increased risk of major bleeding. Further research is ongoing to determine the optimal duration of ticagrelor therapy.

Aims: Valvular heart disease can be identified by calcification on coronary computed tomography angiography (CCTA) and has been associated with adverse clinical outcomes. We assessed aortic and mitral valve calcification in patients presenting with stable chest pain and their association with cardiovascular risk factors, coronary artery disease, and cardiovascular outcomes., Methods and Results: In 1769 patients (58 ± 9 years, 56% male) undergoing CCTA for stable chest pain, aortic and mitral valve calcification were quantified using Agatston score. Aortic valve calcification was present in 241 (14%) and mitral calcification in 64 (4%). Independent predictors of aortic valve calcification were age, male sex, hypertension, diabetes mellitus, and cerebrovascular disease, whereas the only predictor of mitral valve calcification was age. Patients with aortic and mitral valve calcification had higher coronary artery calcium scores and more obstructive coronary artery disease. The composite endpoint of cardiovascular mortality, non-fatal myocardial infarction, or non-fatal stroke was higher in those with aortic [hazard ratio (HR) 2.87; 95% confidence interval (CI) 1.60-5.17; P < 0.001] or mitral (HR 3.50; 95% CI 1.47-8.07; P = 0.004) valve calcification, but this was not independent of coronary artery calcification or obstructive coronary artery disease., Conclusion: Aortic and mitral valve calcification occurs in one in six patients with stable chest pain undergoing CCTA and is associated with concomitant coronary atherosclerosis. Whilst valvular calcification is associated with a higher risk of cardiovascular events, this was not independent of the burden of coronary artery disease., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background Positron emission tomography (PET) using 18 F-sodium fluoride ( 18 F-fluoride) to detect microcalcification may provide insight into disease activity in coronary atherosclerosis. This study aimed to investigate the relationship between 18 F-fluoride uptake and progression of coronary calcification in patients with clinically stable coronary artery disease. Methods Patients with established multivessel coronary atherosclerosis underwent 18 F-fluoride PET-computed tomography angiography and computed tomography calcium scoring, with repeat computed tomography angiography and calcium scoring at one year. Coronary PET uptake was analyzed qualitatively and semiquantitatively in diseased vessels by measuring maximum tissue-to-background ratio. Coronary calcification was quantified by measuring calcium score, mass, and volume. Results In a total of 183 participants (median age 66 years, 80% male), 116 (63%) patients had increased 18 F-fluoride uptake in at least one vessel. Individuals with increased 18 F-fluoride uptake demonstrated more rapid progression of calcification compared with those without uptake (change in calcium score, 97 [39-166] versus 35 [7-93] AU; P <0.0001). Indeed, the calcium score only increased in coronary segments with 18 F-fluoride uptake (from 95 [30-209] to 148 [61-289] AU; P <0.001) and remained unchanged in segments without 18 F-fluoride uptake (from 46 [16-113] to 49 [20-115] AU; P =0.329). Baseline coronary 18 F-fluoride maximum tissue-to-background ratio correlated with 1-year change in calcium score, calcium volume, and calcium mass (Spearman ρ=0.37, 0.38, and 0.46, respectively; P <0.0001 for all). At the segmental level, baseline 18 F-fluoride activity was an independent predictor of calcium score at 12 months ( P <0.001). However, at the patient level, this was not independent of age, sex, and baseline calcium score ( P =0.50). Conclusions Coronary 18 F-fluoride uptake identifies both patients and individual coronary segments with more rapid progression of coronary calcification, providing important insights into disease activity within the coronary circulation. At the individual patient level, total calcium score remains an important marker of disease burden and progression. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02110303.

Early microcalcification is a feature of coronary plaques with an increased propensity to rupture and to cause acute coronary syndromes. In this ex vivo imaging study of coronary artery specimens, the non-invasive imaging radiotracer, 18 F-fluoride, was highly selective for hydroxyapatite deposition in atherosclerotic coronary plaque. Specifically, coronary 18 F-fluoride uptake had a high signal to noise ratio compared with surrounding myocardium that makes it feasible to identify coronary mineralisation activity. Areas of 18 F-fluoride uptake are associated with osteopontin, an inflammation-associated glycophosphoprotein that mediates tissue mineralisation, and Runt-related transcription factor 2, a nuclear protein involved in osteoblastic differentiation. These results suggest that 18 F-fluoride is a non-invasive imaging biomarker of active coronary atherosclerotic mineralisation.

Objectives: The goal of this study was to determine whether ticagrelor reduces high-sensitivity troponin I concentrations in patients with established coronary artery disease and high-risk coronary plaque., Background: High-risk coronary atherosclerotic plaque is associated with higher plasma troponin concentrations suggesting ongoing myocardial injury that may be a target for dual antiplatelet therapy., Methods: In a randomized, double-blind, placebo-controlled trial, patients with multivessel coronary artery disease underwent coronary 18 F-fluoride positron emission tomography/coronary computed tomography scanning and measurement of high-sensitivity cardiac troponin I. Patients were randomized (1:1) to receive ticagrelor 90 mg twice daily or matched placebo. The primary endpoint was troponin I concentration at 30 days in patients with increased coronary 18 F-fluoride uptake., Results: In total, 202 patients were randomized to treatment, and 191 met the pre-specified criteria for inclusion in the primary analysis. In patients with increased coronary 18 F-fluoride uptake (120 of 191), there was no evidence that ticagrelor had an effect on plasma troponin concentrations at 30 days (ratio of geometric means for ticagrelor vs. placebo: 1.11; 95% confidence interval: 0.90 to 1.36; p = 0.32). Over 1 year, ticagrelor had no effect on troponin concentrations in patients with increased coronary 18 F-fluoride uptake (ratio of geometric means: 0.86; 95% confidence interval: 0.63 to 1.17; p = 0.33)., Conclusions: Dual antiplatelet therapy with ticagrelor did not reduce plasma troponin concentrations in patients with high-risk coronary plaque, suggesting that subclinical plaque thrombosis does not contribute to ongoing myocardial injury in this setting. (Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND]; NCT02110303)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Reliable methods for predicting myocardial infarction in patients with established coronary artery disease are lacking. Coronary 18 F-sodium fluoride ( 18 F-NaF) positron emission tomography (PET) provides an assessment of atherosclerosis activity., Objectives: This study assessed whether 18 F-NaF PET predicts myocardial infarction and provides additional prognostic information to current methods of risk stratification., Methods: Patients with known coronary artery disease underwent 18 F-NaF PET computed tomography and were followed up for fatal or nonfatal myocardial infarction over 42 months (interquartile range: 31 to 49 months). Total coronary 18 F-NaF uptake was determined by the coronary microcalcification activity (CMA)., Results: In a post hoc analysis of data collected for prospective observational studies, the authors studied 293 study participants (age: 65 ± 9 years; 84% men), of whom 203 (69%) showed increased coronary 18 F-NaF activity (CMA >0). Fatal or nonfatal myocardial infarction occurred only in patients with increased coronary 18 F-NaF activity (20 of 203 with a CMA >0 vs. 0 of 90 with a CMA of 0; p < 0.001). On receiver operator curve analysis, fatal or nonfatal myocardial infarction prediction was highest for 18 F-NaF CMA, outperforming coronary calcium scoring, modified Duke coronary artery disease index and Reduction of Atherothrombosis for Continued Health (REACH) and Secondary Manifestations of Arterial Disease (SMART) risk scores (area under the curve: 0.76 vs. 0.54, 0.62, 0.52, and 0.54, respectively; p < 0.001 for all). Patients with CMA >1.56 had a >7-fold increase in fatal or nonfatal myocardial infarction (hazard ratio: 7.1; 95% confidence interval: 2.2 to 25.1; p = 0.003) independent of age, sex, risk factors, segment involvement and coronary calcium scores, presence of coronary stents, coronary stenosis, REACH and SMART scores, the Duke coronary artery disease index, and recent myocardial infarction., Conclusions: In patients with established coronary artery disease, 18 F-NaF PET provides powerful independent prediction of fatal or nonfatal myocardial infarction., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The future risk of myocardial infarction is commonly assessed using cardiovascular risk scores, coronary artery calcium score, or coronary artery stenosis severity. We assessed whether noncalcified low-attenuation plaque burden on coronary CT angiography (CCTA) might be a better predictor of the future risk of myocardial infarction., Methods: In a post hoc analysis of a multicenter randomized controlled trial of CCTA in patients with stable chest pain, we investigated the association between the future risk of fatal or nonfatal myocardial infarction and low-attenuation plaque burden (% plaque to vessel volume), cardiovascular risk score, coronary artery calcium score or obstructive coronary artery stenoses., Results: In 1769 patients (56% male; 58±10 years) followed up for a median 4.7 (interquartile interval, 4.0-5.7) years, low-attenuation plaque burden correlated weakly with cardiovascular risk score ( r =0.34; P <0.001), strongly with coronary artery calcium score ( r =0.62; P <0.001), and very strongly with the severity of luminal coronary stenosis (area stenosis, r =0.83; P <0.001). Low-attenuation plaque burden (7.5% [4.8-9.2] versus 4.1% [0-6.8]; P <0.001), coronary artery calcium score (336 [62-1064] versus 19 [0-217] Agatston units; P <0.001), and the presence of obstructive coronary artery disease (54% versus 25%; P <0.001) were all higher in the 41 patients who had fatal or nonfatal myocardial infarction. Low-attenuation plaque burden was the strongest predictor of myocardial infarction (adjusted hazard ratio, 1.60 (95% CI, 1.10-2.34) per doubling; P =0.014), irrespective of cardiovascular risk score, coronary artery calcium score, or coronary artery area stenosis. Patients with low-attenuation plaque burden greater than 4% were nearly 5 times more likely to have subsequent myocardial infarction (hazard ratio, 4.65; 95% CI, 2.06-10.5; P <0.001)., Conclusions: In patients presenting with stable chest pain, low-attenuation plaque burden is the strongest predictor of fatal or nonfatal myocardial infarction. These findings challenge the current perception of the supremacy of current classical risk predictors for myocardial infarction, including stenosis severity. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01149590.

Objective: This cross-sectional observational study sought to describe variations in CT in the context of transcatheter aortic valve implantation (CT-TAVI) as currently performed in the UK., Methods: 408 members of the British Society of Cardiovascular Imaging were invited to complete a 27-item online CT-TAVI survey., Results: 47 responses (12% response rate) were received from 40 cardiac centres, 23 (58%) of which performed TAVI on-site (TAVI centres). Only six respondents (13%) performed high-volume activity (>200 scans per year) compared with 13 (28%) performing moderate (100-200 scans per year) and 27 (59%) performing low (0-99 scans per year) volume activity. Acquisition protocols varied (41% retrospective, 12% prospective with wide padding, 47% prospective with narrow padding), as did the phase of reporting (45% systolic, 37% diastolic, 11% both, 6% unreported). Median dose length product was 675 mGy.cm (IQR 477-954 mGy.cm). Compared with non-TAVI centres, TAVI centres were more likely to report minimum iliofemoral luminal diameter (n=25, 96% vs n=7, 58%, p=0.003) and optimal tube angulation for intervention (n=12, 46% vs n=1, 8%, p=0.02)., Conclusions: This national survey formally describes current CT-TAVI practice in the UK. High-volume activity was only present at one in seven cardiac CT centres. There is wide variation in scan acquisition, scan reporting and radiation dose exposure in cardiac CT centres., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)