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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.)

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.)

Hypertrophic cardiomyopathy is a common inherited cardiac condition where the myocardium progressively thickens in the absence of abnormal loading conditions. Left ventricular hypertrophy often leads to outflow tract obstruction, and this confers significant mortality and morbidity implications. Septal reduction therapies aim to relieve the obstruction in an attempt to reduce the burden of symptoms and potentially improve prognosis. However, both surgical and catheter-based approaches to septal reduction carry risks. At present, international guidelines and expert consensus statements suggest surgical myomectomy is the gold-standard treatment. In this point-counterpoint review, we discuss why in our opinion this recommendation should be reconsidered. We hope to cover the history of catheter based septal reduction therapies and the significant advances made over the last two decades. We also hope to show why we believe the current evidence shows catheter-based alcohol septal ablation is superior to surgical myomectomy., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Obstructive hypertrophic cardiomyopathy is the most common genetically transmitted cardiomyopathy that is associated with significant morbidity and mortality. Despite contemporary treatments and interventions, the management of patients with obstructive hypertrophic cardiomyopathy remains poorly defined compared with other branches of cardiology. In this review, we discuss established and novel therapeutic interventions in patients with obstructive hypertrophic cardiomyopathy with a focus on percutaneous and surgical strategies including surgical myectomy, mitral valve repair or replacement, percutaneous alcohol septal ablation, pacemaker and cardioverter-defibrillator implantation, septal embolization, radiofrequency endocardial catheter ablation, and percutaneous intramyocardial septal radiofrequency ablation., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

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: BMS-986141 is a novel potent highly selective antagonist of PAR (protease-activated receptor) type 4. PAR4 antagonism has been demonstrated to reduce thrombus formation in isolation and in combination with factor Xa inhibition in high shear conditions in healthy people. We sought to determine whether PAR4 antagonism had additive antithrombotic effects in patients with coronary artery disease who were receiving antiplatelet therapy., Methods: Forty-five patients with stable coronary heart disease and 10 healthy volunteers completed a phase 2a open-label 4-arm single-center study. Patients were allocated to 1 of 3 treatment arms for 7 days: (1) ticagrelor (90 mg BID), (2) aspirin (75 mg QD), or (3) the combination of ticagrelor and aspirin. Agonist-induced platelet aggregation, platelet activation, and ex vivo thrombus formation were measured before and 2 and 24 hours after a single oral 4-mg dose of BMS-986141 on the first study visit day in all participants., Results: BMS-986141 demonstrated highly selective inhibition of PAR4-AP (agonist peptide)-induced platelet aggregation, P-selectin expression, and platelet-monocyte aggregate expression ( P ≤0.001 for all), which were unaffected by concomitant antiplatelet therapies. PAR4 antagonism reduced ex vivo thrombus area in high shear conditions in healthy volunteers (-21%; P =0.001) and in patients receiving ticagrelor alone (-28%; P =0.001), aspirin alone (-23%; P =0.018), or both in combination (-24%; P ≤0.001). Plasma concentration of BMS-986141 correlated with PAR4-AP-induced platelet responses ( P ≤0.001 for all) and total thrombus area under high shear stress conditions ( P ≤0.01 for all)., Conclusions: PAR4 antagonism has additive antithrombotic effects when used in addition to ticagrelor, aspirin, or their combination, in patients with stable coronary heart disease., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05093790., Competing Interests: Disclosures D.E. Newby and J. Nash are employed by the University of Edinburgh but were supported by, or received consultancy from, Bristol Myers Squibb. L. Chao, S. Merali, M. Kim, Z. Wang, Y. Zhang, S. Jin, B. Wang, and M. Kozinn are employed by Bristol Myers Squibb. N.L. Mills has received honoraria from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, LumiraDx, and Psyros Diagnostics and is employed by the University of Edinburgh, which has received research funding from Abbott Diagnostics, Siemens Healthineers, and Roche Diagnostics unrelated to the current work. The other authors report no conflicts.

Background: Computed tomography coronary angiography (CTCA) offers detailed assessment of the presence of coronary atherosclerosis and helps guide patient management. We investigated influences of early CTCA on the subsequent use of preventative treatment in patients with suspected acute coronary syndrome., Methods: In this secondary analysis of a multicenter randomized controlled trial of early CTCA in intermediate-risk patients with suspected acute coronary syndrome, prescription of aspirin, P2Y 12 receptor antagonist, statin, renin-angiotensin system blocker, and beta-blocker therapies from randomization to discharge were compared within then between those randomized to early CTCA or to standard of care only. Effects of CTCA findings on adjustment of these therapies were further examined., Results: In 1,743 patients (874 randomized to early CTCA and 869 to standard of care only), prescription of P2Y 12 receptor antagonist, dual antiplatelet, and statin therapies increased more in the early CTCA group (between-group difference: 4.6% [95% confidence interval, 0.3-8.9], 4.5% [95% confidence interval, 0.2-8.7], and 4.3% [95% confidence interval, 0.2-8.5], respectively), whereas prescription of other preventative therapies increased by similar extent in both study groups. Among patients randomized to early CTCA, there were additional increments of preventative treatment in those with obstructive coronary artery disease and higher rates of reductions in antiplatelet and beta-blocker therapies in those with normal coronary arteries., Conclusions: Prescription patterns of preventative treatment varied during index hospitalization in patients with suspected acute coronary syndrome. Early CTCA facilitated targeted individualization of these therapies based on the extent of coronary artery disease., Competing Interests: Disclosure We have no competing interests related to this manuscript to disclose. Katherine Oatey reports research grants from the British Heart Foundation, the Jon Moulton Charity Trust, and University of Edinburgh. Nick Curzen reports research grants from Beckman Coulter, Boston Scientific, HeartFlow, and Haemonetics; consulting fees and/or honoraria from Abbott, Boston Scientific, and Edwards Lifesciences; travel sponsorship from Abbott, Biosensors, and Edwards Lifesciences. Attila Kardos reports honoraria from the TomTec Imaging Systems. Liza Keating reports research grants from the Medical Research Council Developmental Pathway Funding Scheme and the Royal College of Emergency Medicine. Robert F Storey reports research grants from AstraZeneca, Cytosorbents, and GlyCardial Diagnostics; consulting fees and/or honoraria from Alfasigma, Alnylam Pharmaceuticals, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Chiesi, CSL Behring, Cytosorbents, Daiichi-Sankyo, GlyCardial Diagnostics, Hengrui, Idorsia, Intas Pharmaceuticals, Novartis, Pfizer, PhaseBio, Sanofi, and Thromboserin. Carl Roobottom reports honoraria from GE HealthCare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: Recurrent coronary events in patients with recent myocardial infarction remain a major clinical problem. Noninvasive measures of coronary atherosclerotic disease activity have the potential to identify individuals at greatest risk., Objective: To assess whether coronary atherosclerotic plaque activity as assessed by noninvasive imaging is associated with recurrent coronary events in patients with myocardial infarction., Design, Setting, and Participants: This prospective, longitudinal, international multicenter cohort study recruited participants aged 50 years or older with multivessel coronary artery disease and recent (within 21 days) myocardial infarction between September 2015 and February 2020, with a minimum 2 years' follow-up., Intervention: Coronary 18F-sodium fluoride positron emission tomography and coronary computed tomography angiography., Main Outcomes and Measures: Total coronary atherosclerotic plaque activity was assessed by 18F-sodium fluoride uptake. The primary end point was cardiac death or nonfatal myocardial infarction but was expanded during study conduct to include unscheduled coronary revascularization due to lower than anticipated primary event rates., Results: Among 2684 patients screened, 995 were eligible, 712 attended for imaging, and 704 completed an interpretable scan and comprised the study population. The mean (SD) age of participants was 63.8 (8.2) years, and most were male (601 [85%]). Total coronary atherosclerotic plaque activity was identified in 421 participants (60%). After a median follow-up of 4 years (IQR, 3-5 years), 141 participants (20%) experienced the primary end point: 9 had cardiac death, 49 had nonfatal myocardial infarction, and 83 had unscheduled coronary revascularizations. Increased coronary plaque activity was not associated with the primary end point (hazard ratio [HR], 1.25; 95% CI, 0.89-1.76; P = .20) or unscheduled revascularization (HR, 0.98; 95% CI, 0.64-1.49; P = .91) but was associated with the secondary end point of cardiac death or nonfatal myocardial infarction (47 of 421 patients with high plaque activity [11.2%] vs 19 of 283 with low plaque activity [6.7%]; HR, 1.82; 95% CI, 1.07-3.10; P = .03) and all-cause mortality (30 of 421 patients with high plaque activity [7.1%] vs 9 of 283 with low plaque activity [3.2%]; HR, 2.43; 95% CI, 1.15-5.12; P = .02). After adjustment for differences in baseline clinical characteristics, coronary angiography findings, and Global Registry of Acute Coronary Events score, high coronary plaque activity was associated with cardiac death or nonfatal myocardial infarction (HR, 1.76; 95% CI, 1.00-3.10; P = .05) but not with all-cause mortality (HR, 2.01; 95% CI, 0.90-4.49; P = .09)., Conclusions and Relevance: In this cohort study of patients with recent myocardial infarction, coronary atherosclerotic plaque activity was not associated with the primary composite end point. The findings suggest that risk of cardiovascular death or myocardial infarction in patients with elevated plaque activity warrants further research to explore its incremental prognostic implications.

Background: Assessments of coronary disease activity with 18 F-sodium fluoride positron emission tomography and radiomics-based precision coronary plaque phenotyping derived from coronary computed tomography angiography may enhance risk stratification in patients with coronary artery disease. We sought to investigate whether the prognostic information provided by these 2 approaches is complementary in the prediction of myocardial infarction., Methods: Patients with known coronary artery disease underwent coronary 18 F-sodium fluoride positron emission tomography and coronary computed tomography angiography on a hybrid positron emission tomography/computed tomography scanner. Coronary 18 F-NaF uptake was determined by the coronary microcalcification activity. We performed quantitative plaque analysis of coronary computed tomography angiography datasets and extracted 1103 radiomic features for each plaque. Using weighted correlation network analysis, we derived latent morphological features of coronary lesions which were aggregated to patient-level radiomics nomograms to predict myocardial infarction., Results: Among 260 patients with established coronary artery disease (age, 65±9 years; 83% men), 179 (69%) participants showed increased coronary 18 F-NaF activity (coronary microcalcification activity>0). Over 53 (40-59) months of follow-up, 18 patients had a myocardial infarction. Using weighted correlation network analysis, we derived 15 distinct eigen radiomic features representing latent morphological coronary plaque patterns in an unsupervised fashion. Following adjustments for calcified, noncalcified, and low-density noncalcified plaque volumes and 18 F-NaF coronary microcalcification activity, 4 radiomic features remained independent predictors of myocardial infarction (hazard ratio, 1.46 [95% CI, 1.03-2.08]; P =0.03; hazard ratio, 1.62 [95% CI, 1.04-2.54]; P =0.02; hazard ratio, 1.49 [95% CI, 1.07-2.06]; P =0.01; and hazard ratio, 1.50 (95% CI, 1.05-2.13); P =0.02)., Conclusions: In patients with established coronary artery disease, latent coronary plaque morphological features, quantitative plaque volumes, and disease activity on 18 F-sodium fluoride positron emission tomography are additive predictors of myocardial infarction., Competing Interests: Disclosures None.

Objective: In patients with acute chest pain who have had myocardial infarction excluded, plasma cardiac troponin I concentrations ≥5 ng/L are associated with risk of future adverse cardiovascular events. We aim to evaluate the association between cardiac troponin and coronary plaque composition in such patients., Methods: In a prespecified secondary analysis of a prospective cohort study, blinded quantitative plaque analysis was performed on 242 CT coronary angiograms of patients with acute chest pain in whom myocardial infarction was excluded. Patients were stratified by peak plasma cardiac troponin I concentration ≥5 ng/L or <5 ng/L. Associations were assessed using univariable and multivariable logistic regression analyses., Results: The cohort was predominantly middle-aged (62±12 years) men (69%). Patients with plasma cardiac troponin I concentration ≥5 ng/L (n=161) had a higher total (median 33% (IQR 0-47) vs 0% (IQR 0-33)), non-calcified (27% (IQR 0-37) vs 0% (IQR 0-28)), calcified (2% (IQR 0-8) vs 0% (IQR 0-3)) and low-attenuation (1% (IQR 0-3) vs 0% (IQR 0-1)) coronary plaque burden compared with those with concentrations <5 ng/L (n=81; p≤0.001 for all). Low-attenuation plaque burden was independently associated with plasma cardiac troponin I concentration ≥5 ng/L after adjustment for clinical characteristics (adjusted OR per doubling 1.62 (95% CI 1.17 to 2.32), p=0.005) or presence of any visible coronary artery disease (adjusted OR per doubling 1.57 (95% CI 1.07 to 2.37), p=0.026)., Conclusion: In patients with acute chest pain but without myocardial infarction, plasma cardiac troponin I concentrations ≥5 ng/L are associated with greater burden of low-attenuation coronary plaque., Competing Interests: Competing interests: Outside the current study, DD received software royalties from Cedars-Sinai Medical Center and has a patent. MCW has spoken at meetings sponsored by Canon Medical Systems and Siemens Healthineers. DEN is on the Editorial Board of Heart. MRD, MCW and KKL are members of Heart’s Editorial Board., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Manganese-enhanced magnetic resonance imaging can provide a surrogate measure of myocardial calcium handling. Its repeatability and reproducibility are currently unknown. Sixty-eight participants: 20 healthy volunteers, 20 with acute myocardial infarction, 18 with hypertrophic and 10 with non-ischemic dilated cardiomyopathy underwent manganese-enhanced magnetic resonance imaging. Ten healthy volunteers were re-scanned at 3 months. Native T1 values and myocardial manganese uptake were assessed for intra and inter-observer repeatability. Scan-rescan reproducibility was assessed in ten healthy volunteers. Intra-observer and inter-observer correlation was excellent in healthy volunteers for mean native T1 mapping [Lin's correlation coefficient (LCC) 0.97 and 0.97 respectively] and myocardial manganese uptake (LCC: 0.99 and 0.96 respectively). Scan-rescan correlation for native T1 and myocardial manganese uptake was also excellent. Similarly, intra-observer correlations for native T1 and myocardial manganese uptake in patients with acute myocardial infarction (LCC: 0.97 and 0.97 respectively), hypertrophic (LCC: 0.98 and 0.97 respectively) and dilated cardiomyopathy (LCC: 0.99 and 0.95 respectively) were excellent. Limits of agreement were broader in patients with dilated cardiomyopathy. Manganese-enhanced magnetic resonance imaging has high repeatability and reproducibility in healthy myocardium and high repeatability in diseased myocardium. However, further study is needed to establish robustness in pathologies with diffuse myocardial fibrosis., (© 2023. The Author(s).)

Electrocardiography and high-sensitivity cardiac troponin testing are routinely applied as the initial step for clinical evaluation of patients with suspected non-ST-segment elevation myocardial infarction. Once diagnosed, patients with non-ST-segment elevation myocardial infarction are commenced on antithrombotic and secondary preventative therapies before undergoing invasive coronary angiography to determine the strategy of coronary revascularisation. However, this clinical pathway is imperfect and can lead to challenges in the diagnosis, management, and clinical outcomes of these patients. Computed tomography coronary angiography (CTCA) has increasingly been utilised in the setting of patients with suspected non-ST-segment elevation myocardial infarction, where it has an important role in avoiding unnecessary invasive coronary angiography and reducing downstream non-invasive functional testing for myocardial ischaemia. CTCA is an excellent gatekeeper for the cardiac catheterisation laboratory. In addition, CTCA provides complementary information for patients with myocardial infarction in the absence of obstructive coronary artery disease and highlights alternative or incidental diagnoses for those with cardiac troponin elevation. However, the routine application of CTCA has yet to demonstrate an impact on subsequent major adverse cardiovascular events. There are several ongoing studies evaluating CTCA and its associated technologies that will define and potentially expand its application in patients with suspected or diagnosed non-ST-segment elevation myocardial infarction. We here review the current evidence relating to the clinical application of CTCA in patients with non-ST-segment elevation myocardial infarction and highlight the areas where CTCA is likely to have an increasing important role and impact for our patients.

Background: In patients with stable chest pain, computed tomography (CT) plaque burden is an independent predictor of future coronary events., Objectives: The purpose of this study was to determine whether plaque burden and characteristics can predict subsequent death or myocardial infarction in patients with acute chest pain., Methods: In a post hoc analysis of a multicenter trial of early coronary CT angiography, the authors performed quantitative plaque analysis to assess the association between primary endpoint of 1-year all-cause death or nonfatal myocardial infarction and the GRACE (Global Registry of Acute Coronary Events) score, presence of obstructive coronary artery disease, and plaque burden in 404 patients with suspected acute coronary syndrome., Results: Following the index event, 25 patients had a primary event that was associated with a higher GRACE score (134 ± 44 vs 113 ± 35; P = 0.012), larger burdens of total (46% [IQR: 43%-50%] vs 36% [IQR: 21%-46%]; P < 0.001), noncalcified (41% [IQR: 37%-%47] vs 33% [IQR: 20%-41%]; P < 0.001), and low-attenuation plaque (4.22% [IQR: 3.3%-5.68%] vs 2.14% [IQR: 0.5%-4.88%]; P < 0.001), but not obstructive coronary artery disease (P = 0.065). Total, noncalcified, and low-attenuation plaque burden were the strongest predictors of future events independent of GRACE score and obstructive coronary artery disease (P ≤ 0.002 for all). Patients with a low-attenuation burden above the median had nearly an 8-fold increased risk of the primary endpoint (HR: 7.80 [95% CI: 2.33-26.0]; P < 0.001), outperforming either a GRACE score of >140 (HR: 3.80 [95% CI :1.45-6.98]; P = 0.004) or obstructive coronary artery disease (HR: 2.07 [95% CI: 0.94-4.53]; P = 0.07)., Conclusions: In patients with suspected acute coronary syndrome, low-attenuation plaque burden is a major predictor of 1-year death or recurrent myocardial infarction. (Rapid Assessment of Potential Ischaemic Heart Disease With CTCA [RAPID-CTCA]; NCT02284191)., Competing Interests: Funding Support and Author Disclosures The National Institute for Health Research HTA Programme funded the RAPID-CTCA trial study (13/04/108). Dr Meah is supported by the British Heart Foundation (FS/19/46/34445). Dr Tzolos is supported by a British Heart Foundation grant (FS/CRTF/20/24086). Dr Bularga is supported by a clinical research training fellowship (MR/V007254/1). Dr Curzen has received unrestricted research grants from Boston Scientific, HeartFlow, and Beckmann Coulter. Drs Mills, Newby, and Williams are supported by the British Heart Foundation (FS/ICRF/20/26002, CH/09/002, RG/20/10/34966, RE/18/5/34216, CH/F/21/90010). Drs Slomka and Dey have received software royalties from Cedars-Sinai Medical Center and have a patent, outside of the current study. Dr Dey is supported by National Institute of Health/National Heart, Lung, and Blood Institute grant 1R01HL148787-01A1 and 1R01HL151266. Dr Newby is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). 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 determine whether quantitative plaque characterization by using CT coronary angiography (CTCA) can discriminate between type 1 and type 2 myocardial infarction., Materials and Methods: This was a secondary analysis of two prospective studies (ClinicalTrials.gov registration nos. NCT03338504 [2014-2019] and NCT02284191 [2018-2020]) that performed blinded quantitative plaque analysis on findings from CTCA in participants with type 1 myocardial infarction, type 2 myocardial infarction, and chest pain without myocardial infarction. Logistic regression analyses were performed to identify predictors of type 1 myocardial infarction., Results: Overall, 155 participants (mean age, 64 years ± 12 [SD]; 114 men) and 36 participants (mean age, 67 years ± 12; 19 men) had type 1 and type 2 myocardial infarction, respectively, and 136 participants (62 years ± 12; 78 men) had chest pain without myocardial infarction. Participants with type 1 myocardial infarction had greater total (median, 44% [IQR: 35%-50%] vs 35% [IQR: 29%-46%]), noncalcified (39% [IQR: 31%-46%] vs 34% [IQR: 29%-40%]), and low-attenuation (4.15% [IQR: 1.88%-5.79%] vs 1.64% [IQR: 0.89%-2.28%]) plaque burdens ( P < .05 for all) than those with type 2. Participants with type 2 myocardial infarction had similar low-attenuation plaque burden to those with chest pain without myocardial infarction (P = .4). Low-attenuation plaque was an independent predictor of type 1 myocardial infarction (adjusted odds ratio, 3.44 [95% CI: 1.84, 6.96]; P < .001), with better discrimination than noncalcified plaque burden and maximal area of coronary stenosis (C statistic, 0.75 [95% CI: 0.67, 0.83] vs 0.62 [95% CI: 0.53, 0.71] and 0.61 [95% CI: 0.51, 0.70] respectively; P ≤ .001 for both)., Conclusion: Higher low-attenuation coronary plaque burden in patients with type 1 myocardial infarction may help distinguish these patients from those with type 2 myocardial infarction. Keywords: Ischemia/Infarction, CT Angiography, Quantitative CTClinical trial registration nos. NCT03338504 and NCT02284191 Supplemental material is available for this article. © RSNA, 2022., Competing Interests: Disclosures of conflicts of interest: M.M. Author is a British Heart Foundation (BHF) clinical research fellow at the University of Edinburgh, a BHF grant (grant no. FS/19/46/34445) has supported author’s work since November 2019. A.B. Support for the present manuscript from the BHF (grant no. FS/16/75/32533). E.T. No relevant relationships. A.R.C. No relevant relationships. M.D. No relevant relationships. J.D.H. No relevant relationships. J.C. No relevant relationships. C.T. No relevant relationships. R.W. Clinical training research fellowship from the Medical Research Council UK (no. MR/V007017/1). A.G. Participation on advisory board for Abbott for brain and cardiac biomarkers, fees paid to author’s institution. M.R.D. No relevant relationships. C.R. No relevant relationships. N.C. Unrestricted research grants from Boston Scientific, Haemonetics, Beckmann Coulter, and HeartFlow; speakers fees from Abbott and Boston Scientific; travel sponsorship from Biosensors, Abbott, Edwards, and Medtronic. A.K. No relevant relationships. D.F. No relevant relationships. N.L.M. BHF grants (grant nos. CH/F/21/90010, RG/20/10/34966, and RE/18/5/34216) paid to author’s institution; payment or honoraria for lectures from Abbott Diagnostics and Siemens Healthineers; payment for participation on advisory boards for LumiraDX, Roche Diagnostics, and Siemens Healthineers; receipt of reagent from Siemens Healthineers to support research. P.J.S. Grants from Siemens Medical Systems and National Institutes of Health, paid to author’s institution; royalties or licenses from Cedars-Sinai Medical Systems, paid to author and author’s institution; consulting fees from IBA; several patents planned and pending, not related to this field of work, via Cedars-Sinai; vice-president of Society of Nuclear Medicine. D.E.N. Supported by the BHF (grant nos. CH/09/002, RG/16/10/32375, and RE/18/5/34216) and is the recipient of a Wellcome Trust Senior Investigator award (no. WT103782AIA); author is a co-applicant and co-author on the RAPID-CTA trial funded by the National Institute for Health (NIH) Research Health Technology Assessment Programme (no. 13/04/108) and the DEMAND-MI study funded by the BHF (FS/16/75/32533). D.D. NIH/National Heart, Lung, and Blood Institute grants (nos. 1R01HL148787-01A1 and 1R01HL151266); software royalties from Cedars-Sinai Medical Center, outside the current work. M.C.W. Supported by the BHF (grant no. FS/ICRF/20/26002); author has given talks for Canon Medical Systems and Siemens Healthineers; member of the board of directors of Society of Cardiovascular Computed Tomography; president-elect of the education committee of the British Society of Cardiovascular Imaging; president-elect of the European Society of Cardiovascular Radiology; Radiology: Cardiothoracic Imaging editorial board member., (© 2022 by the Radiological Society of North America, Inc.)

Cardiovascular disease remains a major cause of mortality, accounting for a third of all global deaths annually. Although there have been major improvements in our ability to detect and to treat patients with coronary heart disease, most myocardial infarctions occur in previously asymptomatic individuals. Identification of individuals at risk of myocardial infarction remains challenging and primary prevention guidelines rely on the use of cardiovascular risk scores that can be supplemented by coronary artery calcium scores. Coronary artery calcium scores provide a simple surrogate late marker of atherosclerosis but is unable to identify the early high risk non-calcified plaque which can be particularly problematic in younger individuals. Coronary computed tomography angiography is increasingly being used as the imaging strategy of choice in patients with symptoms of coronary heart disease. As an anatomical test, it can non-invasively detect the presence of coronary atherosclerosis, providing clinicians with a strong mandate to commence symptom relieving and preventative therapies. For asymptomatic individuals, it allows precise targeting of therapies to those with coronary heart disease rather than those "at risk" of disease. Moreover, our ability to calculate risk using coronary computed tomography angiography is rapidly improving with the use of techniques, such as plaque quantification and characterisation. These techniques have the potential to provide clinicians with tools to target cardiovascular disease prevention in a precision medicine approach. We here debate the ways in which coronary computed tomography angiography could improve the selection of asymptomatic individuals for preventative therapies over and above risk calculators and calcium scoring., Competing Interests: Declaration of competing interest None., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to describe the potential of 18 F-sodium fluoride ( 18 F-NaF) positron emission tomography (PET) to identify graft vasculopathy and to investigate the influence of coronary artery bypass graft (CABG) surgery on native coronary artery disease activity and progression., Background: As well as developing graft vasculopathy, CABGs have been proposed to accelerate native coronary atherosclerosis., Methods: Patients with established coronary artery disease underwent baseline 18 F-NaF PET, coronary artery calcium scoring, coronary computed tomographic angiography, and 1-year repeat coronary artery calcium scoring. Whole-vessel coronary microcalcification activity (CMA) on 18 F-NaF PET and change in calcium scores were quantified in patients with and without CABG surgery., Results: Among 293 participants (mean age 65 ± 9 years, 84% men), 48 (16%) underwent CABG surgery 2.7 years [IQR: 1.4-10.4 years] previously. Although all arterial and the majority (120 of 128 [94%]) of vein grafts showed no 18 F-NaF uptake, 8 saphenous vein grafts in 7 subjects had detectable CMA. Bypassed native coronary arteries had 3 times higher CMA values (2.1 [IQR: 0.4-7.5] vs 0.6 [IQR: 0-2.7]; P < 0.001) and greater progression of 1-year calcium scores (118 Agatston unit [IQR: 48-194 Agatston unit] vs 69 [IQR: 21-142 Agatston unit]; P = 0.01) compared with patients who had not undergone CABG, an effect confined largely to native coronary plaques proximal to the graft anastomosis. In sensitivity analysis, bypassed native coronary arteries had higher CMA (2.0 [IQR: 0.4-7.5] vs 0.8 [IQR: 0.3-3.2]; P < 0.001) and faster disease progression (24% [IQR: 16%-43%] vs 8% [IQR: 0%-24%]; P = 0.002) than matched patients (n = 48) with comparable burdens of coronary artery disease and cardiovascular comorbidities in the absence of bypass grafting., Conclusions: Native coronary arteries that have been bypassed demonstrate increased disease activity and more rapid disease progression than nonbypassed arteries, an observation that appears independent of baseline atherosclerotic plaque burden. Microcalcification activity is not a dominant feature of graft vasculopathy., Competing Interests: Funding Support and Author Disclosures This research was supported in part by grant R01HL135557 from the National Heart, Lung, and Blood Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr Newby (CH/09/002, RE/18/5/34216, RG/16/10/32375), Dr Tzolos (FS/CRTF/20/24086), Dr Fletcher (FS/19/15/34155), Dr Baker (RG/20/5/34796), Dr Dweck (FS/14/78/31020), and Dr Williams (FS/ICRF/20/26002) are supported by the British Heart Foundation. Dr Adamson is supported by a Heart Foundation of New Zealand Senior Fellowship (1844). Dr van Beek is supported by the Scottish Imaging Network. Dr Tzolos was supported by a grant from the Dr Miriam and Sheldon G. Adelson Medical Research Foundation. Dr Newby is a recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr Dweck is a recipient of the Sir Jules Thorn Award for Biomedical Research Award (2015). Dr Sellers is supported by fellowships from the Canadian Institutes of Health Research and the Michael Smith Foundation for Health Research. 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.)

Background: Type 2 myocardial infarction is caused by myocardial oxygen supply-demand imbalance, and its diagnosis is increasingly common with the advent of high-sensitivity cardiac troponin assays. Although this diagnosis is associated with poor outcomes, widespread uncertainty and confusion remain among clinicians as to how to investigate and manage this heterogeneous group of patients with type 2 myocardial infarction., Methods: In a prospective cohort study, 8064 consecutive patients with increased cardiac troponin concentrations were screened to identify patients with type 2 myocardial infarction. We excluded patients with frailty or renal or hepatic failure. All study participants underwent coronary (invasive or computed tomography angiography) and cardiac (magnetic resonance or echocardiography) imaging, and the underlying causes of infarction were independently adjudicated. The primary outcome was the prevalence of coronary artery disease., Results: In 100 patients with a provisional diagnosis of type 2 myocardial infarction (median age, 65 years [interquartile range, 55-74 years]; 43% women), coronary and cardiac imaging reclassified the diagnosis in 7 patients: type 1 or 4b myocardial infarction in 5 and acute myocardial injury in 2 patients. In those with type 2 myocardial infarction, median cardiac troponin I concentrations were 195 ng/L (interquartile range, 62-760 ng/L) at presentation and 1165 ng/L (interquartile range, 277-3782 ng/L) on repeat testing. The prevalence of coronary artery disease was 68% (63 of 93), which was obstructive in 30% (28 of 93). Infarct-pattern late gadolinium enhancement or regional wall motion abnormalities were observed in 42% (39 of 93), and left ventricular systolic dysfunction was seen in 34% (32 of 93). Only 10 patients had both normal coronary and normal cardiac imaging. Coronary artery disease and left ventricular systolic dysfunction were previously unrecognized in 60% (38 of 63) and 84% (27 of 32), respectively, with only 33% (21 of 63) and 19% (6 of 32) on evidence-based treatments., Conclusions: Systematic coronary and cardiac imaging of patients with type 2 myocardial infarction identified coronary artery disease in two-thirds and left ventricular systolic dysfunction in one-third of patients. Unrecognized and untreated coronary or cardiac disease is seen in most patients with type 2 myocardial infarction, presenting opportunities for initiation of evidence-based treatments with major potential to improve clinical outcomes., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT03338504.

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.)

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:  The capabilities of coronary computed tomography angiography (CCTA) have advanced significantly in the past decade. Its capacity to detect stenotic coronary arteries safely and consistently has led to a marked decline in invasive diagnostic angiography. However, CCTA can do much more than identify coronary artery stenoses., Method:  This review discusses applications of CCTA beyond coronary stenosis assessment, focusing in particular on the visual and quantitative analysis of atherosclerotic plaque., Results:  Established signs of visually assessed high-risk plaque on CT include positive remodeling, low-attenuation plaque, spotty calcification, and the napkin-ring sign, which correlate with the histological thin-cap fibroatheroma. Recently, quantification of plaque subtypes has further improved the assessment of coronary plaque on CT. Quantitatively assessed low-attenuation plaque, which correlates with the necrotic core of the thin-cap fibroatheroma, has demonstrated superiority over stenosis severity and coronary calcium score in predicting subsequent myocardial infarction. Current research aims to use radiomic and machine learning methods to further improve our understanding of high-risk atherosclerotic plaque subtypes identified on CCTA., Conclusion:  Despite rapid technological advances in the field of coronary computed tomography angiography, there remains a significant lag in routine clinical practice where use is often limited to lumenography. We summarize some of the most promising techniques that significantly improve the diagnostic and prognostic potential of CCTA., Key Points:   · In addition to its ability to determine severity of luminal stenoses, CCTA provides important prognostic information by evaluating atherosclerotic plaque.. · Simple scoring systems such as the segment involved score or the CT-adapted Leaman score can provide more prognostic information on major adverse coronary events compared to traditional risk factors such as presence of hypertension or diabetes.. · CT signs of high-risk plaque, including positive remodeling, low-attenuation plaque, spotty calcification, and the napkin-ring sign, are significantly more likely to predict acute coronary syndromes.. · Quantitative plaque assessment can provide precise description of volume and burden of plaque subtypes and have been found to predict subsequent myocardial infarction better than cardiovascular risk scores, calcium scoring and severity of coronary artery stenoses.. · Machine learning techniques have the potential to automate risk stratification and enhance health economy, even though present clinical applications are limited. In this era of "big data" they are an exciting avenue for future research.., Citation Format: · Meah MN, Williams MC. Clinical Relevance of Coronary Computed Tomography Angiography Beyond Coronary Artery Stenosis. Fortschr Röntgenstr 2021; 193: 1162 - 1170., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. 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.)

Background: Dual antiplatelet therapy (DAPT) has important implications for clinical outcomes in coronary disease. However, the optimal DAPT duration remains uncertain., Methods and Results: We searched four major databases for randomised controlled trials comparing long-term (≥12 months) with short-term (≤6 months) or shorter (≤3 months) DAPT in patients with coronary syndromes. The primary outcome was all-cause mortality. Secondary outcomes were any bleeding and major bleeding (safety), cardiac death, myocardial infarction, stent thrombosis, revascularisation and stroke (efficacy). Nineteen randomised controlled trials (n=60 111) satisfied inclusion criteria, 8 assessed ≤3 months DAPT. Compared with long-term (≥12 months), short-term DAPT (≤6 months) was associated with a trend towards reduced all-cause mortality (RR: 0.90, 95% CI: 0.80 to 1.01) and significant bleeding reduction (RR: 0.68, 95% CI: 0.55 to 0.83 and RR: 0.66, 95% CI: 0.56 to 0.77 for major and any bleeding, respectively). There were no significant differences in efficacy outcomes. These associations persisted in sensitivity analysis comparing shorter duration DAPT (≤3 months) to long-term DAPT (≥12 months) for all-cause mortality (RR: 0.91, 95% CI: 0.79 to 1.05). In subgroup analysis, short-term DAPT was associated with lower risk of bleeding in patients with acute or chronic coronary syndromes (RR: 0.66, 95% CI: 0.54 to 0.81 and RR: 0.53, 95% CI: 0.33 to 0.65, respectively), but higher risk of stent thrombosis in acute coronary syndrome (RR: 1.49, 95% CI: 1.02 to 2.17 vs RR: 1.25, 95% CI 0.44 to 3.58)., Conclusion: Our meta-analysis suggests that short (≤6 months) and shorter (≤3 months) durations DAPT are associated with lower risk of bleeding, equivalent efficacy and a trend towards lower all-cause mortality irrespective of coronary artery disease stability., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background Major bleeding after acute coronary syndrome predicts a poor outcome but is challenging to define. The choice of antiplatelet influences bleeding risk. Methods and Results Major bleeding, subsequent myocardial infarction (MI), and all-cause mortality to 1 year were compared in consecutive patients with acute coronary syndrome treated with clopidogrel (n=2491 between 2011 and 2013) and ticagrelor (n=2625 between 2012 and 2015) in 5 English hospitals. Clinical outcomes were identified from national hospital episode statistics. Bleeding and MI events were independently adjudicated by 2 experienced clinicians, blinded to drug, sequence, and year. Bleeding events were categorized using Bleeding Academic Research Consortium 3 to 5 and PLATO (Platelet Inhibition and Patient Outcomes) criteria and MI by the Third Universal Definition. Multivariable regression analysis was used to adjust outcomes for case mix. The median age was 68 years and 34% were women. 39% underwent percutaneous coronary intervention and 13% coronary artery bypass graft surgery. Clinical outcome data were 100% complete for bleeding and 99.7% for MI. No statistically significant difference was seen in crude or adjusted major bleeding for ticagrelor compared with clopidogrel (Bleeding Academic Research Consortium 3-5, hazard ratio [HR], 1.23; 95% CI, 0.90-1.68; P =0.2, PLATO major adjusted HR, 1.30; 95% CI, 0.98-1.74; P =0.07) except in the non-coronary artery bypass graft cohort (n=4464), where bleeding was more frequent with ticagrelor (Bleeding Academic Research Consortium 3-5, adjusted HR, 1.58; 95% CI, 1.09-2.31; P =0.017; and PLATO major HR, 1.67; 95% CI, 1.18-2.37; P =0.004). There was no difference in crude or adjusted subsequent MI (adjusted HR, 1.20; 95% CI, 0.87-1.64; P =0.27). Crude mortality was higher in the clopidogrel group but not after adjustment, using either Cox proportional hazards or propensity matched population (HR, 0.90; 95% CI, 0.76-1.10; P =0.21) as was the case for stroke (HR, 0.82; 95% CI, 0.52-1.32; P =0.42). Conclusions This observational study indicates that the apparent benefit of ticagrelor demonstrated in a clinical trial population may not be observed in the broader population encountered in clinical practice. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02484924.

Background: Complex chronic total occlusion (CTO) cases often require dual access. Evidence suggests that radial access is associated with lower success rates in complex CTOs. Our primary outcome was to determine efficacy of biradial access compared with femoral access., Methods: This was a retrospective, single-center, observational study. Patients who underwent dual-access CTO percutaneous coronary intervention (PCI) between January 2014 and January 2018 were enrolled. They were separated into biradial and femoral access groups. Data on demographics, comorbidities, complications, lesion characteristics, radiation, and contrast dose were collected. Standard univariate analyses were performed to identify predictors for revascularization failure., Results: There were 150 cases identified, 109 biradial and 41 femoral access. There was no significant difference in success rate between the radial and femoral groups (87% vs 78%, respectively; P=.17). The average J-CTO score was 3 vs 4 (P=.04). Matched cohort analysis showed equivalent success rates (80.6% vs 75.0%, respectively; P=.53). Elevated body mass index, poor renal function, previous coronary artery bypass grafting, higher J-CTO, CTO >20 mm, presence of >45° bend within the diseased segment, and absence of collaterals were associated with CTO-PCI failure. Biradial access had shorter procedures (111 minutes vs 147 minutes; P<.01), reduced radiation exposure (dose-area product, 17,452 cGy•cm² vs 23,651 cGy•cm²; P<.01), less contrast (237 mL vs 315 mL; P=.11) and reduced hospital stay (0.38 ± 1.3 days vs 0.61 ± 1.1 days; P=.02)., Conclusion: With shorter length of stay, fewer complications, and less radiation used in radial cases, we suggest biradial access is an effective and safe alternative in CTO-PCI. Prospective studies are needed to determine superiority.

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.

Objective: PAR (protease-activated receptor)-4 antagonism has antiplatelet effects under conditions of high shear stress. We aimed to establish whether PAR4 antagonism had additive antithrombotic activity in the presence of factor Xa inhibition in an ex vivo model of acute arterial injury. Approach and Results: Fifteen healthy volunteers (29±6 years, 7 women) completed a phase zero double-blind randomized controlled crossover trial. Ex vivo platelet activation, platelet aggregation, and thrombus formation were measured following blood perfusion of low shear and high shear stress chambers. Upstream of the chambers, extracorporeal blood was admixed with (1) vehicle, (2) low-dose apixaban (20 ng/mL), (3) high-dose apixaban (80 ng/mL), (4) BMS-986141 (400 ng/mL), (5) BMS-968141 and low-dose apixaban, or (6) BMS-968141 and high-dose apixaban in 6 sequential studies performed in random order. Compared with vehicle, BMS-986141 demonstrated selective inhibition of PAR4-AP (agonist peptide)-stimulated platelet aggregation, platelet-monocyte aggregates, and P-selectin expression ( P ≤0.01 for all). Total thrombus area was reduced under both low shear and high shear stress conditions for all drug infusions ( P <0.0001 for all versus vehicle). BMS-968141 reduced total (≤44.4%) and platelet-rich (≤39.3%) thrombus area, whereas apixaban reduced total (≤42.9%) and fibrin-rich (≤31.6%) thrombus area. Combination of BMS-986141 with apixaban caused a further modest reduction in total thrombus area (9.6%-12.4%), especially under conditions of high shear stress ( P ≤0.027)., Conclusions: In the presence of factor Xa inhibition, PAR4 antagonism with BMS-986141 further reduces thrombus formation, especially under conditions of high shear stress. This suggests the potential for additive efficacy of combination PAR4 antagonism and factor Xa inhibition in the prevention of atherothrombotic events.

Competing Interests: Competing interests: None declared.

Concentrations of nitrate and nitrite have been determined in a range of foods and the dietary intake estimated from the MAFF Total Diet Study. The estimated dietary intake of nitrate ion for the UK population was 54 mg/day and the estimated dietary intake of nitrite ion was in the range 2.4-4.2 mg/day in 1985. The main source of nitrate in the diet is from the consumption of vegetables.

Concentrations of tin and lead in canned foods have been monitored since 1983 to determine the effects of recent changes in can-making technology. In the sample studied the proportion of foods contained in non-soldered as opposed to soldered cans has risen consistently during the survey and now accounts for 83% of all samples (excluding sardines). Foods contained in non-soldered cans have lower lead concentrations than those contained in soldered cans and this changeover is likely to result in a decrease in dietary lead intakes in the UK.