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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: 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.)

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: 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.)

Background: Lowering the diagnostic threshold for troponin is controversial because it may disproportionately increase the diagnosis of myocardial infarction in patients without acute coronary syndrome. We assessed the impact of lowering the diagnostic threshold of troponin on the incidence, management, and outcome of patients with type 2 myocardial infarction or myocardial injury., Methods: Consecutive patients with elevated plasma troponin I concentrations (≥50 ng/L; n = 2929) were classified with type 1 (50%) myocardial infarction, type 2 myocardial infarction or myocardial injury (48%), and type 3 to 5 myocardial infarction (2%) before and after lowering the diagnostic threshold from 200 to 50 ng/L with a sensitive assay. Event-free survival from death and recurrent myocardial infarction was recorded at 1 year., Results: Lowering the threshold increased the diagnosis of type 2 myocardial infarction or myocardial injury more than type 1 myocardial infarction (672 vs 257 additional patients, P < .001). Patients with myocardial injury or type 2 myocardial infarction were at higher risk of death compared with those with type 1 myocardial infarction (37% vs 16%; relative risk [RR], 2.31; 95% confidence interval [CI], 1.98-2.69) but had fewer recurrent myocardial infarctions (4% vs 12%; RR, 0.35; 95% CI, 0.26-0.49). In patients with troponin concentrations 50 to 199 ng/L, lowering the diagnostic threshold was associated with increased healthcare resource use (P < .05) that reduced recurrent myocardial infarction and death for patients with type 1 myocardial infarction (31% vs 20%; RR, 0.64; 95% CI, 0.41-0.99), but not type 2 myocardial infarction or myocardial injury (36% vs 33%; RR, 0.93; 95% CI, 0.75-1.15)., Conclusions: After implementation of a sensitive troponin assay, the incidence of type 2 myocardial infarction or myocardial injury disproportionately increased and is now as frequent as type 1 myocardial infarction. Outcomes of patients with type 2 myocardial infarction or myocardial injury are poor and do not seem to be modifiable after reclassification despite substantial increases in healthcare resource use., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)