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

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.)

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.)

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.

Background: The diagnosis and management of myocardial infarction are increasingly complex, and establishing the presence of intracoronary thrombosis has major implications for both the classification and treatment of myocardial infarction., Objectives: The aim of this study was to investigate whether positron emission tomographic (PET) and computed tomographic (CT) imaging could noninvasively detect in vivo thrombus formation in human coronary arteries using a novel glycoprotein IIb/IIIa receptor antagonist-based radiotracer, 18 F-GP1., Methods: In a single-center observational case-control study, patients with or without acute myocardial infarction underwent coronary 18 F-GP1 PET/CT angiography. Coronary artery 18 F-GP1 uptake was assessed visually and quantified using maximum target-to-background ratios., Results: 18 F-GP1 PET/CT angiography was performed in 49 patients with and 50 patients without acute myocardial infarction (mean age: 61 ± 9 years, 75% men). Coronary 18 F-GP1 uptake was apparent in 39 of the 49 culprit lesions (80%) in patients with acute myocardial infarction. False negative results appeared to relate to time delays to scan performance and low thrombus burden in small-caliber distal arteries. On multivariable regression analysis, culprit vessel status was the only independent variable associated with higher 18 F-GP1 uptake. Extracoronary cardiac 18 F-GP1 findings included a high frequency of infarct-related intramyocardial uptake (35%) as well as left ventricular (8%) or left atrial (2%) thrombus., Conclusions: Coronary 18 F-GP1 PET/CT angiography is the first noninvasive selective technique to identify in vivo coronary thrombosis in patients with acute myocardial infarction. This novel approach can further define the role and location of thrombosis within the heart and has the potential to inform the diagnosis, management, and treatment of patients with acute myocardial infarction. (In-Vivo Thrombus Imaging With 18 F-GP1, a Novel Platelet PET Radiotracer [iThrombus]; NCT03943966)., Competing Interests: Funding Support and Author Disclosures The Edinburgh Clinical Research Facilities and Edinburgh Imaging facility is supported by the National Health Service Research Scotland through the National Health Service Lothian Health Board. This work was supported by several grant funding organizations. Drs Tzolos (FS/CRTF/20/24086), Williams (FS/ICRF/20/26002, FS/11/014, and CH/09/002), Newby (CH/09/002, RG/16/10/32375, and RE/18/5/34216), and Dweck (FS/14/78/31020) are supported by the British Heart Foundation. 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. Dr Mills is supported by the British Heart Foundation through the award of Personal Chair and a Programme Grant (CH/F/21/90010 and RG/20/10/34966). Dr Dweck is supported by the Sir Jules Thorn Biomedical Research Award 2015 (15/JTA). Dr Slomka and FusionQuant analysis tools are supported by National Heart, Lung, and Blood Institute grant 5R01HL135557. Dr Dey and Autoplaque analysis tools are supported by National Heart, Lung, and Blood Institute grant 1R01HL148787-01A1. Drs Koglin and Stephens are employees of Life Molecular Imaging, which provided reagents for radiotracer production. Dr Williams is a member of the Speakers Bureau for Canon Medical Systems. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The identification of intracoronary thrombus and atherothrombosis is central to the diagnosis of acute myocardial infarction, with the differentiation between type 1 and type 2 myocardial infarction being crucial for immediate patient management. Invasive coronary angiography has remained the principal imaging modality used in the investigation of patients with myocardial infarction. More recently developed invasive intravascular imaging approaches, such as angioscopy, intravascular ultrasound and optical coherence tomography, can be used as adjunctive imaging modalities to provide more direct visualisation of coronary atheroma and the causes of myocardial infarction as well as to improve the sensitivity of thrombus detection. However, these invasive approaches have practical and logistic constraints that limit their widespread and routine application. Non-invasive angiographic techniques, such as CT and MRI, have become more widely available and have improved the non-invasive visualisation of coronary artery disease. Although they also have a limited ability to reliably identify intracoronary thrombus, this can be overcome by combining their anatomical and structural characterisation of coronary anatomy with positron emission tomography. Specific radiotracers which bind with high specificity and sensitivity to components of thrombus, such as activated platelets, fibrin and factor XIIIa, hold promise for the non-invasive detection of intracoronary thrombus. The development of these novel non-invasive approaches has the potential to inform clinical decision making and patient management as well as to provide a non-invasive technique to assess the efficacy of novel antithrombotic therapies or interventional strategies. However, these have yet to be realised in routine clinical practice., Competing Interests: Competing interests: MCW has given talks for Canon Medical Systems and Siemens Healthineers. MRD and DEN are on the Editorial Board for BMJ Heart., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

Background: Assessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures., Objectives: We aimed to investigate somatostatin receptor 2 (SST 2 ) as a novel inflammation-specific molecular imaging target in LVV., Methods: In a prospective, observational cohort study, in vivo arterial SST 2 expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using 68 Ga-DOTATATE and 18 F-FET-βAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing., Results: Sixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST 2 maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST 2 signal was not elevated in any of the control subjects. SST 2 PET/MRI was generally consistent with 18 F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST 2 maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST 2 expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macrophages coexpressed proinflammatory markers., Conclusions: SST 2 PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810)., Competing Interests: Funding Support and Author Disclosures This work was funded by grants to Dr Tarkin from the Wellcome Trust (Clinical Research Career Development Fellowship 211100/Z/18/Z), the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (BRC); and the British Heart Foundation (BHF) (Clinical Research Training Fellowship for Dr Ćorović [FS/CRTF/20/24035]). This work was additionally supported by the Cambridge BHF Centre of Research Excellence (18/1/34212) and the Cancer Research UK Cambridge Centre (A25177). For the purpose of open access, the lead author has applied a CC BY public copyright license to any Author Accepted Manuscript. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care. Dr Nus; authors Imaz and Lambert; Dr Frontini (FS/18/53/33863); Dr Davenport (TG/18/4/33770); and Drs Huang, Mallat, Dweck, Newby, and Bennett are supported by the BHF. Author Zulcinski is supported by the European Union’s Horizon 2020 Research and Innovation Programme (Marie Skłodowska-Curie grant agreement no. 813545). Drs Jayne, Rassl, and Graves are supported by the NIHR Cambridge BRC. Dr Fayad is supported by the National Institutes of Health/National Heart, Lung, and Blood Institute (R01HL135878). Dr Reynolds is supported by the Wellcome Trust. Dr Morgan is supported by the Medical Research Council (MRC) (MR/N011775/1), the NIHR Leeds BRC, the NIHR Leeds Medtech, and In Vitro Diagnostics Co-operative as well as an NIHR Senior Investigator award. Dr Aboagye acknowledges support from Imperial Experimental Cancer Research Centre and MRC (MR/J007986/1, MR/N020782/1); and is an inventor on the patent that developed the (18)F-FET-βAG-TOCA radiotracer. Dr Peters is supported by a UK Research and Innovation Fellowship at Health Data Research UK (MR/S004068/2). Dr Rudd is partly supported by the NIHR Cambridge BRC, the BHF, the Higher Education Funding Council for England, the Engineering and Physical Sciences Research Council, and the Wellcome Trust. Drs Gopalan, Maughan, Pericleous, Barwick, Aboagye, Peters, and Mason acknowledge support from the NIHR Imperial BRC. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Computational tomography coronary angiography (CTCA) is increasingly the diagnostic test of choice for investigating patients with stable anginal symptoms., Objectives: We sought to conduct a systematic review and meta-analysis comparing CTCA with invasive coronary angiography (ICA) with regards to major adverse cardiovascular events (MACE), procedural complications and rates of revascularisation., Methods: We conducted a systematic review and meta-analysis in line with the PRISMA statement. A literature search was conducted using PubMed, MEDLINE Ovid and Embase, with three studies included in meta-analysis. Statistical analysis was undertaken using Review Manager 5.3 for MacOS software and outcomes expressed as odds ratio, with 95% confidence intervals and sensitivity analysis was conducted., Results: A total of 5662 patients were included in this study level meta-analysis. There was no difference in MACE between CT and angiography [2.97% v 3.45%, fixed-effect model, OR: 0.84 (0.62-1.14), p = 0.26, I 2 0%] and no difference found in rates of myocardial infarction, death or stroke. CTCA was associated with a reduced rate of revascularisation [12.6% v 18.3%, fixed-effects model, OR: 0.64 (0.55-0.75), p<0.00001, I 2 =0%]. However, CTCA was not associated with a significantly lower complication rate [0.5% v 1.72%, random effects model, OR: 0.52 (0.06-4.38), p = 0.55, I 2 52%]., Conclusion: CTCA is a safe strategy for investigating patients with stable angina with no associated increase in MACE but a reduction in revascularisation rates., Competing Interests: Conflict of interest statement Dr Natasha Corballis and Dr Vasiliki Tsampasian are NIHR Academic Clinical Fellows. Dr Simon Eccleshall received funding for lectures and proctorship from B Braun, Medtronic and MedAlliance and funding for investigator-initiated research unrelated to this work from B Braun. Professor Dweck MRD is supported by the British Heart Foundation (FS/14/78/31020) and is the recipient of a Sir Jules Thorn Award for Biomedical Research 2015 (15/JTA). Professor Vassiliou receives funding for investigator initiated research unrelated to this work from B Braun and Medtronic. This work was partially supported by the Norfolk Heart Trust., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

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.)

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.)

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: 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.)

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.

The incidence of left ventricular (LV) thrombus following acute myocardial infarction has markedly declined in recent decades caused by advancements in reperfusion and antithrombotic therapies. Despite this, embolic events remain the most feared complication of LV thrombus necessitating systemic anticoagulation. Mechanistically, LV thrombus development depends on Virchow's triad (ie, endothelial injury from myocardial infarction, blood stasis from LV dysfunction, and hypercoagulability triggered by inflammation, with each of these elements representing potential therapeutic targets). Diagnostic modalities include transthoracic echocardiography with or without ultrasound-enhancing agents and cardiac magnetic resonance. Most LV thrombi develop within the first 2 weeks post-acute myocardial infarction, and the role of surveillance imaging appears limited. Vitamin K antagonists remain the mainstay of therapy because the efficacy of direct oral anticoagulants is less well established. Only meager data support the routine use of prophylactic anticoagulation, even in high-risk patients., Competing Interests: Funding Support and Author Disclosures Dr Giustino has received honoraria from Bristol Myers Squibb. Dr Halperin has performed consulting activities with Bayer HealthCare, Boehringer Ingelheim, and Ortho-McNeil-Janssen; and has served on the Steering Committee of the CATALYST trial, sponsored by Abbott. Dr Sharma has received consulting fees or honoraria from Abbott, Boston Scientific, Abiomed, and Cardiovascular Systems, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022. Published by Elsevier Inc.)

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.)

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.)

Myocardial infarction (MI) is one of the leading causes of death worldwide, and inflammation is central to tissue response and patient outcomes. The 18-kDa translocator protein (TSPO) has been used in PET as an inflammatory biomarker. The aims of this study were to screen novel, fluorinated, TSPO radiotracers for susceptibility to the rs6971 genetic polymorphism using in vitro competition binding assays in human brain and heart; assess whether the in vivo characteristics of our lead radiotracer, 18 F-LW223, are suitable for clinical translation; and validate whether 18 F-LW223 can detect macrophage-driven inflammation in a rat MI model. Methods: Fifty-one human brain and 29 human heart tissue samples were screened for the rs6971 polymorphism. Competition binding assays were conducted with 3 H-PK11195 and the following ligands: PK11195, PBR28, and our novel compounds (AB5186 and LW223). Naïve rats and mice were used for in vivo PET kinetic studies, radiometabolite studies, and dosimetry experiments. Rats underwent permanent coronary artery ligation and were scanned using PET/CT with an invasive input function at 7 d after MI. For quantification of PET signal in the hypoperfused myocardium, K 1 (rate constant for transfer from arterial plasma to tissues) was used as a surrogate marker of perfusion to correct the binding potential for impaired radiotracer transfer from plasma to tissue (BP TC ). Results: LW223 binding to TSPO was not susceptible to the rs6971 genetic polymorphism in human brain and heart samples. In rodents, 18 F-LW223 displayed a specific uptake consistent with TSPO expression, a slow metabolism in blood (69% of parent at 120 min), a high plasma free fraction of 38.5%, and a suitable dosimetry profile (effective dose of 20.5-24.5 μSv/MBq). 18 F-LW223 BP TC was significantly higher in the MI cohort within the infarct territory of the anterior wall relative to the anterior wall of naïve animals (32.7 ± 5.0 vs. 10.0 ± 2.4 cm 3 /mL/min, P ≤ 0.001). Ex vivo immunofluorescent staining for TSPO and CD68 (macrophage marker) resulted in the same pattern seen with in vivo BP TC analysis. Conclusion: 18 F-LW223 is not susceptible to the rs6971 genetic polymorphism in in vitro assays, has favorable in vivo characteristics, and is able to accurately map macrophage-driven inflammation after MI., (© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)

Recent EACVI recommendations described the importance of limiting cardiovascular imaging during the COVID-19 pandemic in order to reduce virus transmission, protect healthcare professionals from contamination, and reduce consumption of personal protective equipment. However, an elevated troponin remains a frequent request for cardiac imaging in COVID-19 patients, partly because it signifies cardiac injury due to a variety of causes and partly because it is known to convey a worse prognosis. The present paper aims to provide guidance to clinicians regarding the appropriateness of cardiac imaging in the context of troponin elevation and myocardial injury, how best to decipher the mechanism of myocardial injury, and how to guide patient management., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

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.

Gadolinium chelates are widely used in cardiovascular magnetic resonance imaging (MRI) as passive intravascular and extracellular space markers. Manganese, a biologically active paramagnetic calcium analogue, provides novel intracellular myocardial tissue characterisation. We previously showed manganese-enhanced MRI (MEMRI) more accurately quantifies myocardial infarction than gadolinium delayed-enhancement MRI (DEMRI). Here, we evaluated the potential of MEMRI to assess myocardial viability compared to gold-standard 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) viability. Coronary artery ligation surgery was performed in male Sprague-Dawley rats (n = 13) followed by dual MEMRI and 18 F-FDG PET imaging at 10-12 weeks. MEMRI was achieved with unchelated (EVP1001-1) or chelated (mangafodipir) manganese. T 1 mapping MRI was followed by 18 F-FDG micro-PET, with tissue taken for histological correlation. MEMRI and PET demonstrated good agreement with histology but native T 1 underestimated infarct size. Quantification of viability by MEMRI, PET and MTC were similar, irrespective of manganese agent. MEMRI showed superior agreement with PET than native T 1 . MEMRI showed excellent agreement with PET and MTC viability. Myocardial MEMRI T 1 correlated with 18 F-FDG standard uptake values and influx constant but not native T 1 . Our findings indicate that MEMRI identifies and quantifies myocardial viability and has major potential for clinical application in myocardial disease and regenerative therapies.

Background: Within the SCOT-HEART (Scottish COmputed Tomography of the HEART Trial) trial of patients with stable chest pain, the use of coronary computed tomography angiography (CTA) reduced the rate of death from coronary heart disease or nonfatal myocardial infarction (primary endpoint)., Objectives: This study sought to assess the consistency and mechanisms of the 5-year reduction in this endpoint., Methods: In this open-label trial, 4,146 participants were randomized to standard care alone or standard care plus coronary CTA. This study explored the primary endpoint by symptoms, diagnosis, coronary revascularizations, and preventative therapies., Results: Event reductions were consistent across symptom and risk categories (p = NS for interactions). In patients who were not diagnosed with angina due to coronary heart disease, coronary CTA was associated with a lower primary endpoint incidence rate (0.23; 95% confidence interval [CI]: 0.13 to 0.35 vs. 0.59; 95% CI: 0.42 to 0.80 per 100 patient-years; p < 0.001). In those who had undergone coronary CTA, rates of coronary revascularization were higher in the first year (hazard ratio [HR]: 1.21; 95% CI: 1.01 to 1.46; p = 0.042) but lower beyond 1 year (HR: 0.59; 95% CI: 0.38 to 0.90; p = 0.015). Patients assigned to coronary CTA had higher rates of preventative therapies throughout follow-up (p < 0.001 for all), with rates highest in those with CT-defined coronary artery disease. Modeling studies demonstrated the plausibility of the observed effect size., Conclusions: The beneficial effect of coronary CTA on outcomes is consistent across subgroups with plausible underlying mechanisms. Coronary CTA improves coronary heart disease outcomes by enabling better targeting of preventative treatments to those with coronary artery disease. (Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590)., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Although coronary computed tomographic angiography (CTA) improves diagnostic certainty in the assessment of patients with stable chest pain, its effect on 5-year clinical outcomes is unknown., Methods: In an open-label, multicenter, parallel-group trial, we randomly assigned 4146 patients with stable chest pain who had been referred to a cardiology clinic for evaluation to standard care plus CTA (2073 patients) or to standard care alone (2073 patients). Investigations, treatments, and clinical outcomes were assessed over 3 to 7 years of follow-up. The primary end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years., Results: The median duration of follow-up was 4.8 years, which yielded 20,254 patient-years of follow-up. The 5-year rate of the primary end point was lower in the CTA group than in the standard-care group (2.3% [48 patients] vs. 3.9% [81 patients]; hazard ratio, 0.59; 95% confidence interval [CI], 0.41 to 0.84; P=0.004). Although the rates of invasive coronary angiography and coronary revascularization were higher in the CTA group than in the standard-care group in the first few months of follow-up, overall rates were similar at 5 years: invasive coronary angiography was performed in 491 patients in the CTA group and in 502 patients in the standard-care group (hazard ratio, 1.00; 95% CI, 0.88 to 1.13), and coronary revascularization was performed in 279 patients in the CTA group and in 267 in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91 to 1.27). However, more preventive therapies were initiated in patients in the CTA group (odds ratio, 1.40; 95% CI, 1.19 to 1.65), as were more antianginal therapies (odds ratio, 1.27; 95% CI, 1.05 to 1.54). There were no significant between-group differences in the rates of cardiovascular or noncardiovascular deaths or deaths from any cause., Conclusions: In this trial, the use of CTA in addition to standard care in patients with stable chest pain resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years than standard care alone, without resulting in a significantly higher rate of coronary angiography or coronary revascularization. (Funded by the Scottish Government Chief Scientist Office and others; SCOT-HEART ClinicalTrials.gov number, NCT01149590 .).

Objectives: Macrophages play a central role in the cellular inflammatory response to myocardial infarction (MI) and predict subsequent clinical outcomes. We aimed to assess temporal changes in cellular inflammation and tissue oedema in patients with acute MI using ultrasmallsuperparamagnetic particles of iron oxide (USPIO)-enhanced MRI., Methods: Thirty-one patients were recruited following acute MI and followed up for 3 months with repeated T2 and USPIO-enhanced T2*-mapping MRI. Regions of interest were categorised into infarct, peri-infarct and remote myocardial zones, and compared with control tissues., Results: Following a single dose, USPIO enhancement was detected in the myocardium until 24 hours (p<0.0001). Histology confirmed colocalisation of iron and macrophages within the infarcted, but not the non-infarcted, myocardium. Following repeated doses, USPIO uptake in the infarct zone peaked at days 2-3, and greater USPIO uptake was detected in the infarct zone compared with remote myocardium until days 10-16 (p<0.05). In contrast, T2-defined myocardial oedema peaked at days 3-9 and remained increased in the infarct zone throughout the 3-month follow-up period (p<0.01)., Conclusion: Myocardial macrophage activity can be detected using USPIO-enhanced MRI in the first 2 weeks following acute MI. This observed pattern of cellular inflammation is distinct, and provides complementary information to the more prolonged myocardial oedema detectable using T2 mapping. This imaging technique holds promise as a non-invasive method of assessing and monitoring myocardial cellular inflammation with potential application to diagnosis, risk stratification and assessment of novel anti-inflammatory therapeutic interventions., Trial Registration Number: Trial registration number: 14663. Registered on UK Clinical Research Network (http://public.ukcrn.org.uk) and also ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT02319278?term=DECIFER&rank=2)., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Preclinical data suggest that an acute inflammatory response following myocardial infarction (MI) accelerates systemic atherosclerosis. Using combined positron emission and computed tomography, we investigated whether this phenomenon occurs in humans., Methods and Results: Overall, 40 patients with MI and 40 with stable angina underwent thoracic 18F-fluorodeoxyglucose combined positron emission and computed tomography scan. Radiotracer uptake was measured in aortic atheroma and nonvascular tissue (paraspinal muscle). In 1003 patients enrolled in the Global Registry of Acute Coronary Events, we assessed whether infarct size predicted early (≤30 days) and late (>30 days) recurrent coronary events. Compared with patients with stable angina, patients with MI had higher aortic 18F-fluorodeoxyglucose uptake (tissue-to-background ratio 2.15±0.30 versus 1.84±0.18, P<0.0001) and plasma C-reactive protein concentrations (6.50 [2.00 to 12.75] versus 2.00 [0.50 to 4.00] mg/dL, P=0.0005) despite having similar aortic (P=0.12) and less coronary (P=0.006) atherosclerotic burden and similar paraspinal muscular 18F-fluorodeoxyglucose uptake (P=0.52). Patients with ST-segment elevation MI had larger infarcts (peak plasma troponin 32 300 [10 200 to >50 000] versus 3800 [1000 to 9200] ng/L, P<0.0001) and greater aortic 18F-fluorodeoxyglucose uptake (2.24±0.32 versus 2.02±0.21, P=0.03) than those with non-ST-segment elevation MI. Peak plasma troponin concentrations correlated with aortic 18F-fluorodeoxyglucose uptake (r=0.43, P=0.01) and, on multivariate analysis, independently predicted early (tertile 3 versus tertile 1: relative risk 4.40 [95% CI 1.90 to 10.19], P=0.001), but not late, recurrent MI., Conclusions: The presence and extent of MI is associated with increased aortic atherosclerotic inflammation and early recurrent MI. This finding supports the hypothesis that acute MI exacerbates systemic atherosclerotic inflammation and remote plaque destabilization: MI begets MI., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01749254., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

The assessment of myocardial ischemia represents a cornerstone in our approach to coronary artery disease. Indeed many of the clinical decisions we make revolve around the results of stress testing, the assessment of coronary luminal stenoses and, more recently, fractional flow reserve measurements. Whilst the assessment of ischemia is often useful with respect to diagnosis and its treatment important in terms of symptom relief, whether ischemia directly leads to adverse cardiovascular outcomes, in particular myocardial infarction, is much more controversial. Indeed this is one of the key questions facing cardiology practice today and the focus of an ongoing multimillion-dollar study, the ISCHEMIA trial. In this editorial the authors examine some of the underlying evidence and ask the question: is ischemia itself really bad for you?

OBJECTIVES Risk assessment of patients with aortic stenosis (AS) undergoing aortic valve replacement (AVR) is challenging. We set out to determine the impact of myocardial late gadolinium enhancement (LGE), as detected by cardiovascular magnetic resonance (CMR), on postoperative outcomes following AVR. METHODS A prospective observational study was conducted on patients undergoing CMR using the LGE technique within 1 year of subsequent AVR. Patients were categorized into absent, mid-wall or infarct patterns of LGE by independent observers blinded to all clinical data, and data were collected with regard to 30-day mortality, major adverse cardiac and cerebrovascular events (MACCE) and postoperative complications. RESULTS A total of 63 patients were studied. Twenty-five patients had no LGE; 20 had mid-wall LGE and 18 had an infarct pattern. The incidence of MACCE, cerebrovascular accident (CVA) and heart block were significantly higher in the mid-wall group compared with the other two groups (MACCE: 25 vs. 0 vs. 5%, P = 0.014; CVA: 20 vs. 0 vs. 0%, P = 0.013; heart block: 30 vs. 4 vs. 12%, P = 0.050). Patients with no LGE had no 30-day MACCE events and no deaths up to 2 years of follow-up. CONCLUSIONS The myocardial LGE holds promise as a means of predicting risk prior to AVR for AS.

Coronary 18F-sodium fluoride (18F-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 18F-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 18F-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 18F-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 18F-NaF PET), we achieved a substantial improvement (P = 0.008 versus 18F-NaF PET alone) in the model performance (c-statistic 0.85, 95% CI 0.79-0.91). Conclusion: Both 18F-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.

BackgroundReliable methods for predicting myocardial infarction in patients with established coronary artery disease are lacking. Coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) provides an assessment of atherosclerosis activity.ObjectivesThis study assessed whether 18F-NaF PET predicts myocardial infarction and provides additional prognostic information to current methods of risk stratification.MethodsPatients with known coronary artery disease underwent 18F-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 18F-NaF uptake was determined by the coronary microcalcification activity (CMA).ResultsIn 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 18F-NaF activity (CMA >0). Fatal or nonfatal myocardial infarction occurred only in patients with increased coronary 18F-NaF activity (20 of 203 with a CMA >0 vs. 0 of 90 with a CMA of 0; p 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.ConclusionsIn patients with established coronary artery disease, 18F-NaF PET provides powerful independent prediction of fatal or nonfatal myocardial infarction.

Background: 18F-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 18F-fluoride uptake in the aortic valve and coronary arteries.Methods and Results: 18 patients with aortic stenosis or recent myocardial infarction underwent 18F-fluoride PET/CT followed immediately by PET/MR. Valve and coronary 18F-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 18F-fluoride uptake was similar on PET/CT and PET/MR. TBRMAX 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, 18F-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 18F-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. [ABSTRACT FROM AUTHOR]

Myocardial infarction with non-obstructive coronary arteries (MINOCA) was first described over 80 years ago. The term has been widely and inconsistently used in clinical practice, influencing various aspects of disease classification, investigation and management. MINOCA encompasses a heterogenous group of conditions that include both atherosclerotic and non-atherosclerotic disease resulting in myocardial damage that is not due to obstructive coronary artery disease. In many ways, it is a term that describes a moment in the diagnostic pathway of the patient and is arguably not a diagnosis. Central to the definition is also the distinction between myocardial infarction and injury. The universal definition of myocardial infarction distinguishes acute myocardial infarction, including those with MINOCA, from other causes of myocardial injury by the presence of clinical evidence of ischaemia. However, these ischaemic features are often non-specific causing diagnostic confusion, and can create difficulties for patient management and follow-up. The purpose of this review is to summarise our current understanding of MINOCA and highlight important issues relating to the diagnosis, investigation and management of patients with MINOCA. [ABSTRACT FROM AUTHOR]