Explore the vast range of titles available.

In a randomized trial, patients with chest pain underwent a standard diagnostic evaluation with or without coronary CT angiography (CTA). The group assigned to CTA had a lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years.

ObjectivesTo 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.MethodsPost 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).ResultsIn 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).ConclusionsNICE-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 numberClinicalTrials.gov: NCT01149590;post results.

IntroductionObjective risk stratification based is recommended in all patients with a new diagnosis of stable ischaemic heart disease. However, more than half of patients with chronic coronary syndromes who have a future myocardial infarct do not have obstructive coronary disease on coronary imaging, or the ischaemic substrate to enable effective risk stratification with functional testing. There is need for an effective risk stratification tool that can be applied to all patients with chronic coronary syndrome to help guide management decisions.PurposeTo evaluate the role of cardiac troponin testing in the risk stratification of patients with chronic coronary syndrome.Method: Consecutive patients attending a tertiary cardiac centre for investigation of chronic coronary syndrome with coronary angiography were eligible for enrolment into this prospective observational study. High-sensitivity cardiac troponin I was measured in all patients immediately prior to angiography with clinicians blinded to the results. Troponin concentrations were log transformed and evaluated as a continuous variable in adjusted Cox regression models, and categorised as low (<5 ng/L), intermediate (5 ng/L - 99th centile), or high (>99th centile). The primary outcome was a composite of myocardial infarction or cardiovascular death over a median follow-up of 2.5 years.ResultsIn total, 4,344 consecutive patients were enrolled (median age 66 years (IQR 59 - 73), 32.4% female). The majority had obstructive coronary disease on angiography (62.4%, 2,712/4,344), with fewer having non-obstructive disease (27.4%, 1,193/4,344) or angiographically normal coronary arteries (10.2%, 442/4,344). Patients with obstructive disease had higher troponin levels (median 4.0 ng/L, IQR 2.1 - 8.6) than those with non-obstructive disease (2.7 ng/L, IQR 1.4 - 5.1; P<0.001). Patients with the highest troponin concentration were most likely to have a primary outcome (62.8 events per 1,000 patient-years) as compared to those with intermediate (45.5 per 1,000 patient-years) or low troponin levels (15.1 per 1,000 patient-years). In patients with obstructive disease, the incidence of the primary outcome was highest in those with the highest troponin (64.5 per 1,000 patient-years) as compared to those with obstructive disease and either intermediate or low troponin levels (53.2 and 21.2 per 1,000 patient-years, respectively). After adjusting for coronary disease severity, troponin remained an important independent predictor of the primary outcome (aHR 3.1 95%CI 2.4–3.9).Abstract 167 Figure 1Cumulative incidence of the primary outcome (myocardial infarction or cardiovascular death) in patients with obstructive coronary disease, stratified by cardiac troponin concentration [low (green, <5 ng/), intermediate (orange, 5 ng/L - 99th centile), or high (red, >99th centile)ConclusionIn patients with chronic coronary syndrome, cardiac troponin can reliably identify individuals at the highest risk of myocardial infarction or cardiovascular death. Combined with angiographic indices of disease severity, troponin testing in the chronic coronary syndrome could augment current risk stratification strategies and may inform optimised treatment decisions.Conflict of InterestNone

Abstract Aims  To assess contemporary pre-test probability estimates for obstructive coronary artery disease in patients with stable chest pain. Methods and results  In this substudy of a multicentre randomized controlled trial, we compared 2019 European Society of Cardiology (ESC)-endorsed pre-test probabilities with observed prevalence of obstructive coronary artery disease on computed tomography coronary angiography (CTCA). We assessed associations between pre-test probability, 5-year coronary heart disease death or non-fatal myocardial infarction and study intervention (standard care vs. CTCA). The study population consisted of 3755 patients (30–75 years, 46% women) with a median pre-test probability of 11% of whom 1622 (43%) had a pre-test probability of >15%. In those who underwent CTCA (n = 1613), the prevalence of obstructive disease was 22%. When divided into deciles of pre-test probability, the observed disease prevalence was similar but higher than the corresponding median pre-test probability [median difference 2.3 (1.3–5.6)%]. There were more clinical events in patients with a pre-test probability >15% compared to those at 5–15% and <5% (4.1%, 1.5%, and 1.4%, respectively, P < 0.001). Across the total cohort, fewer clinical events occurred in patients who underwent CTCA, with the greatest difference in those with a pre-test probability >15% (2.8% vs. 5.3%, log rank P = 0.01), although this interaction was not statistically significant on multivariable modelling. Conclusion  The updated 2019 ESC guideline pre-test probability recommendations tended to slightly underestimate disease prevalence in our cohort. Pre-test probability is a powerful predictor of future coronary events and helps select those who may derive the greatest absolute benefit from CTCA.

ObjectiveTroponin and B-type natriuretic peptide (BNP) concentrations are associated with cardiovascular risk in stable patients. Understanding their determinants and identifying modifiable clinical targets may improve outcomes. We aimed to establish clinical and cardiac determinants of these biomarkers.MethodsThis was a prespecified substudy from the randomised Scottish Computed Tomography of the Heart trial, which enrolled patients 18–75 years with suspected stable angina between 2010 and 2014 (NCT01149590). We included patients from six centres in whom high-sensitivity troponin I and BNP were measured (Singulex Erenna). Patients with troponin >99th centile upper reference limit (10.2 ng/L) or BNP ≥400 ng/L were excluded to avoid inclusion of patients with myocardial injury or heart failure. Multivariable linear regression models were constructed with troponin and BNP as dependent variables.ResultsIn total, 885 patients were included; 881 (99%) and 847 (96%) had troponin and BNP concentrations above the limit of detection, respectively. Participants had a slight male preponderance (n=513; 56.1%), and the median age was 59.0 (IQR 51.0–65.0) years. The median troponin and BNP concentrations were 1.4 (IQR 0.90–2.1) ng/L and 29.1 (IQR 14.0–54.0) ng/L, respectively. Age and atherosclerotic burden were independent predictors of both biomarkers. Male sex, left ventricular mass and systolic blood pressure were independent predictors of increased troponin. In contrast, female sex and left ventricular volume were independent predictors of increased BNP.ConclusionsTroponin and BNP are associated with coronary atherosclerosis but have important sex differences and distinct and contrasting associations with CT-determined left ventricular mass and volume.Clinical Trial registration NCT01149590; Post-results.

BackgroundMachine learning based on clinical characteristics has the potential to predict coronary CT angiography (CCTA) findings and help guide resource utilisation.MethodsFrom the SCOT-HEART (Scottish Computed Tomography of the HEART) trial, data from 1769 patients was used to train and to test machine learning models (XGBoost, 10-fold cross validation, grid search hyperparameter selection). Two models were separately generated to predict the presence of coronary artery disease (CAD) and an increased burden of low-attenuation coronary artery plaque (LAP) using symptoms, demographic and clinical characteristics, electrocardiography and exercise tolerance testing (ETT).ResultsMachine learning predicted the presence of CAD on CCTA (area under the curve (AUC) 0.80, 95% CI 0.74 to 0.85) better than the 10-year cardiovascular risk score alone (AUC 0.75, 95% CI 0.70, 0.81, p=0.004). The most important features in this model were the 10-year cardiovascular risk score, age, sex, total cholesterol and an abnormal ETT. In contrast, the second model used to predict an increased LAP burden performed similarly to the 10-year cardiovascular risk score (AUC 0.75, 95% CI 0.70 to 0.80 vs AUC 0.72, 95% CI 0.66 to 0.77, p=0.08) with the most important features being the 10-year cardiovascular risk score, age, body mass index and total and high-density lipoprotein cholesterol concentrations.ConclusionMachine learning models can improve prediction of the presence of CAD on CCTA, over the standard cardiovascular risk score. However, it was not possible to improve the prediction of an increased LAP burden based on clinical factors alone.

Microcalcification is a key pathological feature of vulnerable atherosclerotic plaques. 18F-Sodium fluoride (18F-NaF) is a highly sensitive radiotracer that preferentially binds to microcalcification in the carotid vasculature. In the coronary arteries, 18F-NaF identifies high-risk and culprit plaques following myocardial infarction and improves cardiovascular risk stratification. However there is a need to better understand its mechanism of binding in coronary atheroma, ideally using histology as a gold standard comparator. In this study, we sought to develop a model that might provide this validation, establishing a method for scanning cadaveric hearts ex-vivo using 18F-NaF microPET-CTCA.Selective catheterisation of the coronary ostia was established in ten cadaveric porcine hearts. 18F-NaF and CT contrast were then administered down the coronary arteries and the optimal dosing and time course of injection for both agents investigated. Contrast opacification of vessel lumens using varying dilutions of a contrast-starch mixture were investigated for CT imaging. Different concentrations (MBq/mL) of 18F-NaF were administered and the PET signal assessed over varying bed-times using micro-PET/CT. Phantom and ex-vivo studies on intact porcine hearts demonstrated that the optimal contrast-starch mixture was 2% Omnipaque and 3% methyl cellulose. 18F-NaF infusion with 100kBq/mL, over 20 minutes at an infusion rate of 1.0 mL/min provided excellent signal-to-noise images of coronary artery microcalcification. Longer incubation times did not increase measured 18F-NaF activity. Using this protocol, we obtained high-resolution PET/CT images of the coronary arteries, indicating that it holds major potential in the validation of this imaging technique and the study of sudden cardiac death.

ObjectivesThe circadian clocks are internal timing mechanisms that drive ∼24-hour rhythms in a tissue-specific manner. Many aspects of the physiology of the intervertebral disc (IVD) show clear diurnal rhythms. However, it is unknown whether IVD tissue contains functional circadian clocks and if so, how their dysregulation is implicated in IVD degeneration.MethodsClock gene dynamics in ex vivo IVD explants (from PER2:: luciferase (LUC) reporter mice) and human disc cells (transduced with lentivirus containing Per2::luc reporters) were monitored in real time by bioluminescence photon counting and imaging. Temporal gene expression changes were studied by RNAseq and quantitative reverse transcription (qRT)-PCR. IVD pathology was evaluated by histology in a mouse model with tissue-specific deletion of the core clock gene Bmal1.ResultsHere we show the existence of the circadian rhythm in mouse IVD tissue and human disc cells. This rhythm is dampened with ageing in mice and can be abolished by treatment with interleukin-1β but not tumour necrosis factor α. Time-series RNAseq revealed 607 genes with 24-hour patterns of expression representing several essential pathways in IVD physiology. Mice with conditional knockout of Bmal1 in their disc cells demonstrated age-related degeneration of IVDs.ConclusionsWe have established autonomous circadian clocks in mouse and human IVD cells which respond to age and cytokines, and control key pathways involved in the homeostasis of IVDs. Genetic disruption to the mouse IVD molecular clock predisposes to IVD degeneration. These results support the concept that disruptions to circadian rhythms may be a risk factor for degenerative IVD disease and low back pain.