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Objectives: To evaluate the diagnostic and prognostic benefits of CT coronary angiography (CTCA) using the 2016 National Institute for Health and Care Excellence (NICE) guidelines for the assessment of suspected stable angina.Methods: Post hoc analysis of the Scottish COmputed Tomography of the HEART (SCOT-HEART) trial of 4146 participants with suspected angina randomised to CTCA. Patients were dichotomised into NICE guideline-defined possible angina and non-anginal presentations. Primary (diagnostic) endpoint was diagnostic certainty of angina at 6 weeks and prognostic endpoint comprised fatal and non-fatal myocardial infarction (MI).Results: In 3770 eligible participants, CTCA increased diagnostic certainty more in those with possible angina (relative risk (RR) 2.22 (95% CI 1.91 to 2.60), p<0.001) than those with non-anginal symptoms (RR 1.30 (1.11 to 1.53), p=0.002; pinteraction <0.001). In the possible angina cohort, CTCA did not change rates of invasive angiography (p=0.481) but markedly reduced rates of normal coronary angiography (HR 0.32 (0.19 to 0.52), p<0.001). In the non-anginal cohort, rates of invasive angiography increased (HR 1.82 (1.13 to 2.92), p=0.014) without reducing rates of normal coronary angiography (HR 0.78 (0.30 to 2.05), p=0.622). At 3.2 years of follow-up, fatal or non-fatal MI was reduced in patients with possible angina (3.2% to 1.9%%; HR 0.58 (0.34 to 0.99), p=0.045) but not in those with non-anginal symptoms (HR 0.65 (0.25 to 1.69), p=0.379).Conclusions: NICE-guided patient selection maximises the benefits of CTCA on diagnostic certainty, use of invasive coronary angiography and reductions in fatal and non-fatal myocardial infarction. Patients with non-anginal chest pain derive minimal benefit from CTCA and increase the rates of invasive investigation.Trial Registration Number: ClinicalTrials.gov: NCT01149590;post results. [ABSTRACT FROM AUTHOR]

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

Importance: Recent European guidance supports a diminished role for exercise electrocardiography (ECG) in the assessment of suspected stable angina., Objective: To evaluate the utility of exercise ECG in contemporary practice and assess the value of combined functional and anatomical testing., Design, Setting, and Participants: This is a post hoc analysis of the Scottish Computed Tomography of the Heart (SCOT-HEART) open-label randomized clinical trial, conducted in 12 cardiology chest pain clinics across Scotland for patients with suspected angina secondary to coronary heart disease. Between November 18, 2010, and September 24, 2014, 4146 patients aged 18 to 75 years with stable angina underwent clinical evaluation and 1417 of 1651 (86%) underwent exercise ECG prior to randomization. Statistical analysis was conducted from October 10 to November 5, 2019., Interventions: Patients were randomized in a 1:1 ratio to receive standard care plus coronary computed tomography (CT) angiography or to receive standard care alone. The present analysis was limited to the 3283 patients who underwent exercise ECG alone or in combination with coronary CT angiography., Main Outcomes and Measures: The primary clinical end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years., Results: Among the 3283 patients (1889 men; median age, 57.0 years [interquartile range, 50.0-64.0 years]), exercise ECG had a sensitivity of 39% and a specificity of 91% for detecting any obstructive coronary artery disease in those who underwent subsequent invasive angiography. Abnormal results of exercise ECG were associated with a 14.47-fold (95% CI, 10.00-20.41; P < .001) increase in coronary revascularization at 1 year and a 2.57-fold (95% CI, 1.38-4.63; P < .001) increase in mortality from coronary heart disease death at 5 years or in cases of nonfatal myocardial infarction at 5 years. Compared with exercise ECG alone, results of coronary CT angiography had a stronger association with 5-year coronary heart disease death or nonfatal myocardial infarction (hazard ratio, 10.63; 95% CI, 2.32-48.70; P = .002). The greatest numerical difference in outcome with CT angiography compared with exercise ECG alone was observed for those with inconclusive results of exercise ECG (5 of 285 [2%] vs 13 of 283 [5%]), although this was not statistically significant (log-rank P = .05)., Conclusions and Relevance: This study suggests that abnormal results of exercise ECG are associated with coronary revascularization and the future risk of adverse coronary events. However, coronary CT angiography more accurately detects coronary artery disease and is more strongly associated with future risk compared with exercise ECG., Trial Registration: ClinicalTrials.gov Identifier: NCT01149590.

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

Objective: Using combined positron emission tomography and CT (PET-CT), we measured aortic inflammation and calcification in patients with abdominal aortic aneurysms (AAA), and compared them with matched controls with atherosclerosis., Methods: We prospectively recruited 63 patients (mean age 76.1±6.8 years) with asymptomatic aneurysm disease (mean size 4.33±0.73 cm) and 19 age-and-sex-matched patients with confirmed atherosclerosis but no aneurysm. Inflammation and calcification were assessed using combined 18F-FDG PET-CT and quantified using tissue-to-background ratios (TBRs) and Agatston scores., Results: In patients with AAA, 18F-FDG uptake was higher within the aneurysm than in other regions of the aorta (mean TBR max 2.23±0.46 vs 2.12±0.46, p=0.02). Compared with atherosclerotic control subjects, both aneurysmal and non-aneurysmal aortae showed higher 18F-FDG accumulation (total aorta mean TBR max 2.16±0.51 vs 1.70±0.22, p=0.001; AAA mean TBR max 2.23±0.45 vs 1.68±0.21, p<0.0001). Aneurysms containing intraluminal thrombus demonstrated lower 18F-FDG uptake within their walls than those without (mean TBR max 2.14±0.43 vs 2.43±0.45, p=0.018), with thrombus itself showing low tracer uptake (mean TBR max thrombus 1.30±0.48 vs aneurysm wall 2.23±0.46, p<0.0001). Calcification in the aneurysmal segment was higher than both non-aneurysmal segments in patients with aneurysm (Agatston 4918 (2901-8008) vs 1017 (139-2226), p<0.0001) and equivalent regions in control patients (442 (304-920) vs 166 (80-374) Agatston units per cm, p=0.0042)., Conclusions: The entire aorta is more inflamed in patients with aneurysm than in those with atherosclerosis, perhaps suggesting a generalised inflammatory aortopathy in patients with aneurysm. Calcification was prominent within the aneurysmal sac, with the remainder of the aorta being relatively spared. The presence of intraluminal thrombus, itself metabolically relatively inert, was associated with lower levels of inflammation in the adjacent aneurysmal wall., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objectives: The aim of this study was to assess the effect of sex on myocardial fibrosis as assessed by using cardiac magnetic resonance (CMR) imaging in aortic stenosis (AS)., Background: Previous studies reported sex-related differences in the left ventricular (LV) remodeling response to pressure overload in AS. However, there are very few data regarding the effect of sex on myocardial fibrosis, a key marker of LV decompensation and adverse cardiac events in AS., Methods: A total of 249 patients (mean age 66 ± 13 years; 30% women) with at least mild AS were recruited from 2 prospective observational cohort studies and underwent comprehensive Doppler echocardiography and CMR examinations. On CMR, T1 mapping was used to quantify extracellular volume (ECV) fraction as a marker of diffuse fibrosis, and late gadolinium enhancement (LGE) was used to assess focal fibrosis., Results: There was no difference in age between women and men (age 66 ± 15 years vs 66 ± 12 years; p = 0.78). However, women presented with a better cardiovascular risk profile than men with less hypertension, dyslipidemia, diabetes, and coronary artery disease (all, p ≤ 0.10). As expected, LV mass index measured by CMR imaging was smaller in women than in men (p < 0.0001). Despite fewer comorbidities, women presented with larger ECV fraction (median: 29.0% [25th to 75th percentiles: 27.4% to 30.6%] vs. 26.8% [25th to 75th percentiles: 25.1% to 28.7%]; p < 0.0001) and similar LGE (median: 4.5% [25th-75th percentiles: 2.3% to 7.0%] vs. 2.8% [25th-75th percentiles: 0.6% to 6.8%]; p = 0.20) than men. In multivariable analysis, female sex remained an independent determinant of higher ECV fraction and LGE (all, p ≤ 0.05)., Conclusions: Women have greater diffuse and focal myocardial fibrosis independent of the degree of AS severity. These findings further emphasize the sex-related differences in LV remodeling response to pressure overload., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess the prognostic implications of standardized reporting systems for coronary computed tomography angiography (CCTA) and coronary artery calcium scores (CACS) in patients with stable chest pain., Background: The Coronary Artery Disease Reporting And Data System (CAD-RADS) and Coronary Artery Calcium - Data and Reporting System (CAC-DRS) aim to improve communication of CACS and CCTA results, but its influence on prognostication is unknown., Methods: Images from 1769 patients who underwent CCTA as part of the Scottish Computed Tomography of the HEART (SCOT-HEART) multi-center randomized controlled trial were assessed. CACS were classified as CAC-DRS 0 to 3 based on Agatston scores. CCTA were classified as CAD-RADS 0 to 5 based on the most clinically relevant finding per patient. The primary outcome was the five-year events of fatal and non-fatal myocardial infarction., Results: Patients had a mean age of 58 ± 10 years and 56% were male. CAC-DRS 0, 1, 2 and 3 occurred in 642 (36%), 510 (29%), 239 (14%) and 379 (21%) patients respectively. CAD-RADS 0, 1, 2, 3, 4A, 4B and 5 occurred in 622 (35%), 327 (18%), 211 (12%), 165 (9%), 221 (12%), 42 (2%) and 181 (10%) patients respectively. Patients classified as CAC-DRS 3 were at an increased risk of fatal or non-fatal myocardial infarction compared to CAC-DRS 0 patients (hazard ratio (HR) 9.41; 95% confidence interval (CI) 3.24, 27.31; p < 0.001). Patients with higher CAD-RADS categories were at an increased risk of fatal or non-fatal myocardial infarction, with patients classified as CAD-RADS 4B at the highest risk compared to CAD-RADS 0 patients (HR 19.14; 95% CI 4.28, 85.53; p < 0.001)., Conclusion: Patients with higher CAC-DRS and CAD-RADS scores were at increased risk of subsequent fatal and non-fatal myocardial infarction. This confirms that the classification provides additional prognostic discrimination for future coronary heart disease events., Competing Interests: Conflicts of interest MCW has performed consultancy for GE Healthcare. RC has a research grant from GE Healthcare., (Copyright © 2020 [The Author/The Authors]. Published by Elsevier Inc. All rights reserved.)

Background: Aortic stenosis is accompanied by progressive left ventricular hypertrophy and fibrosis. We investigated the natural history of these processes in asymptomatic patients and their potential reversal post-aortic valve replacement (AVR)., Methods: Asymptomatic and symptomatic patients with aortic stenosis underwent repeat echocardiography and magnetic resonance imaging. Changes in peak aortic-jet velocity, left ventricular mass index, diffuse fibrosis (indexed extracellular volume), and replacement fibrosis (late gadolinium enhancement [LGE]) were quantified., Results: In 61 asymptomatic patients (43% mild, 34% moderate, and 23% severe aortic stenosis), significant increases in peak aortic-jet velocity, left ventricular mass index, indexed extracellular volume, and LGE mass were observed after 2.1±0.7 years, with the most rapid progression observed in patients with most severe stenosis. Patients with baseline midwall LGE (n=16 [26%]; LGE mass, 2.5 g [0.8-4.8 g]) demonstrated particularly rapid increases in scar burden (78% [50%-158%] increase in LGE mass per year). In 38 symptomatic patients (age, 66±8 years; 76% men) who underwent AVR, there was a 19% (11%-25%) reduction in left ventricular mass index ( P <0.0001) and an 11% (4%-16%) reduction in indexed extracellular volume ( P =0.003) 0.9±0.3 years after surgery. By contrast midwall LGE (n=10 [26%]; mass, 3.3 g [2.6-8.0 g]) did not change post-AVR (n=10; 3.5 g [2.1-8.0 g]; P =0.23), with no evidence of regression even out to 2 years., Conclusions: In patients with aortic stenosis, cellular hypertrophy and diffuse fibrosis progress in a rapid and balanced manner but are reversible after AVR. Once established, midwall LGE also accumulates rapidly but is irreversible post valve replacement. Given its adverse long-term prognosis, prompt AVR when midwall LGE is first identified may improve clinical outcomes., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01755936 and NCT01679431., (© 2018 The Authors.)

Background: We determined whether high-sensitivity cardiac troponin I can improve the estimation of the pretest probability for obstructive coronary artery disease (CAD) in patients with suspected stable angina., Methods and Results: In a prespecified substudy of the SCOT-HEART trial (Scottish Computed Tomography of the Heart), plasma cardiac troponin was measured using a high-sensitivity single-molecule counting assay in 943 adults with suspected stable angina who had undergone coronary computed tomographic angiography. Rates of obstructive CAD were compared with the pretest probability determined by the CAD Consortium risk model with and without cardiac troponin concentrations. External validation was undertaken in an independent study population from Denmark comprising 487 patients with suspected stable angina. Higher cardiac troponin concentrations were associated with obstructive CAD with a 5-fold increase across quintiles (9%-48%; P <0.001) independent of known cardiovascular risk factors (odds ratio, 1.35; 95% confidence interval, 1.25-1.46 per doubling of troponin). Cardiac troponin concentrations improved the discrimination and calibration of the CAD Consortium model for identifying obstructive CAD (C statistic, 0.788-0.800; P =0.004; χ 2 =16.8 [ P =0.032] to 14.3 [ P =0.074]). The updated model also improved classification of the American College of Cardiology/American Heart Association pretest probability risk categories (net reclassification improvement, 0.062; 95% confidence interval, 0.035-0.089). The revised model achieved similar improvements in discrimination and calibration when applied in the external validation cohort., Conclusions: High-sensitivity cardiac troponin I concentration is an independent predictor of obstructive CAD in patients with suspected stable angina. Use of this test may improve the selection of patients for further investigation and treatment., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01149590., (© 2018 The Authors.)

Background: The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers (18)F-sodium fluoride ((18)F-NaF) and (18)F-fluorodeoxyglucose ((18)F-FDG)., Methods: In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent (18)F-NaF and (18)F-FDG PET-CT, and invasive coronary angiography. (18)F-NaF uptake was compared with histology in carotid endarterectomy specimens from patients with symptomatic carotid disease, and with intravascular ultrasound in patients with stable angina. The primary endpoint was the comparison of (18)F-fluoride tissue-to-background ratios of culprit and non-culprit coronary plaques of patients with acute myocardial infarction., Findings: In 37 (93%) patients with myocardial infarction, the highest coronary (18)F-NaF uptake was seen in the culprit plaque (median maximum tissue-to-background ratio: culprit 1·66 [IQR 1·40-2·25] vs highest non-culprit 1·24 [1·06-1·38], p<0·0001). By contrast, coronary (18)F-FDG uptake was commonly obscured by myocardial uptake and where discernible, there were no differences between culprit and non-culprit plaques (1·71 [1·40-2·13] vs 1·58 [1·28-2·01], p=0·34). Marked (18)F-NaF uptake occurred at the site of all carotid plaque ruptures and was associated with histological evidence of active calcification, macrophage infiltration, apoptosis, and necrosis. 18 (45%) patients with stable angina had plaques with focal (18)F-NaF uptake (maximum tissue-to-background ratio 1·90 [IQR 1·61-2·17]) that were associated with more high-risk features on intravascular ultrasound than those without uptake: positive remodelling (remodelling index 1·12 [1·09-1·19] vs 1·01 [0·94-1·06]; p=0·0004), microcalcification (73% vs 21%, p=0·002), and necrotic core (25% [21-29] vs 18% [14-22], p=0·001)., Interpretation: (18)F-NaF PET-CT is the first non-invasive imaging method to identify and localise ruptured and high-risk coronary plaque. Future studies are needed to establish whether this method can improve the management and treatment of patients with coronary artery disease., Funding: Chief Scientist Office Scotland and British Heart Foundation., (Copyright © 2014 Joshi et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.)