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The aim of this review was to discuss the current literature regarding the utility of noninvasive imaging in diagnosis and management of stable coronary artery disease (CAD) including recent data from large randomized trials assessing diagnosis and prognosis. Current guidelines recommend revascularization in patients with refractory angina and in those with potential prognostic benefit. Appropriate risk stratification through noninvasive assessment is important in ensuring patients are not exposed to unnecessary invasive coronary angiograms. The past 20 years have seen an unprecedented expansion in noninvasive imaging modalities for the assessment of stable CAD, with cardiovascular magnetic resonance and computed tomography complementing established techniques such as myocardial perfusion imaging, echocardiography and exercise electrocardiogram. In this review, we examine the current state-of-the-art in noninvasive imaging to provide an up-to-date analysis of current investigation and management options.

Pulmonary endarterectomy (PEA) may not achieve full clearance of vascular obstructions in patients with more distal chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) may be indicated to treat these residual vascular lesions. We compared whether patients post‐PEA (PP) treated by BPA derived similar benefit to those who had inoperable CTEPH (IC), and assessed predictors of BPA response after surgery. We treated 109 patients with BPA—89 with IC and 20 PP. Serial right heart catheterization performed at baseline (immediately before BPA) and 3 months after completing BPA, compared pulmonary vascular resistance (PVR), mean pulmonary artery pressure (mPAP) as well as change in WHO functional class and 6‐minute walk distance. We also assessed the impact of total thrombus tail length (TTTL) from photographed PEA surgical specimens and PP computed tomography pulmonary angiography (CTPA)‐quantified residual disease burden on BPA response. PP and IC groups did not differ significantly in terms of demographics, baseline hemodynamics or procedural characteristics. However, IC derived greater hemodynamic benefit from BPA: ΔPVR (−27.9 ± 20.2% vs. −13.9 ± 23.9%, p  < 0.05) and ΔmPAP (−17.1 ± 14.4% vs. −8.5 ± 18.0%, p  < 0.05). There was a negative correlation between pre‐BPA PVR and TTTL ( r  = −0.47, p  < 0.05) which persisted post‐BPA. PVR, mPAP, WHO FC and 6MWD were not improved significantly post‐BPA in PP patients. BPA response was not related to TTTL terciles or CTPA‐quantified residual disease burden. Patients PP experienced inferior response to BPA, despite similar baseline and procedural characteristics to IC. BPA does not abolish the relationship between TTTL and postsurgical PVR in PP patients, suggesting that BPA is less effective in treating residual PH after surgery in an experienced surgical center.

ObjectivesNoncardiac findings are common on coronary computed tomography angiography (CCTA). We assessed the clinical impact of noncardiac findings, and potential changes to surveillance scans with the application of new lung nodule guidelines.MethodsThis substudy of the SCOT-HEART randomized controlled trial assessed noncardiac findings identified on CCTA. Clinically significant noncardiac findings were those causing symptoms or requiring further investigation, follow-up or treatment. Lung nodule follow-up was undertaken following the 2005 Fleischner guidelines. The potential impact of the 2015 British Thoracic Society (BTS) and the 2017 Fleischner guidelines was assessed.ResultsCCTA was performed in 1,778 patients and noncardiac findings were identified in 677 (38%). In 173 patients (10%) the abnormal findings were clinically significant and in 55 patients (3%) the findings were the cause of symptoms. Follow-up imaging was recommended in 136 patients (7.6%) and additional clinic consultations were organized in 46 patients (2.6%). Malignancy was diagnosed in 7 patients (0.4%). Application of the new lung nodule guidelines would have reduced the number of patients undergoing a follow-up CT scan: 68 fewer with the 2015 BTS guidelines and 78 fewer with the 2017 Fleischner guidelines; none of these patients subsequently developed malignancy.ConclusionsClinically significant noncardiac findings are identified in 10% of patients undergoing CCTA. Application of new lung nodule guidelines will reduce the cost of surveillance, without the risk of missing malignancy.Key Points• Clinically significant noncardiac findings occur in 10% of patients undergoing CCTA.• Noncardiac findings may be an important treatable cause of chest pain• Further imaging investigations for noncardiac findings were recommended in 8% of patients after CCTA.• New lung nodule follow-up guidelines will result in cost savings.

Background Epicardial adipose tissue (EAT) is an emerging cardio-metabolic risk factor and has been shown to correlate with adverse cardiovascular (CV) outcome; however the underlying pathophysiology of this link is not well understood. The aim of this study was to evaluate the relationship between EAT and a comprehensive panel of cardiovascular risk biomarkers and pulse wave velocity (PWV) and indexed left ventricular mass (LVMI) in a cohort of patients with cardiovascular disease (CVD) and diabetes compared to controls. Methods One hundred forty-five participants (mean age 63.9 ± 8.1 years; 61% male) were evaluated. All patients underwent cardiovascular magnetic resonance (CMR) examination and PWV. EAT measurements from CMR were performed on the 4-chamber view. Blood samples were taken and a range of CV biomarkers was evaluated. Results EAT measurements were significantly higher in the groups with CVD, with or without T2DM compared to patients without CVD or T2DM (group 1 EAT 15.9 ± 5.5 cm 2 vs. group 4 EAT 11.8 ± 4.1 cm 2 , p  = 0.001; group 3 EAT 15.1 ± 4.3 cm 2 vs. group 4 EAT 11.8 ± 4.1 cm 2 , p  = 0.024). EAT was independently associated with IL-6 (beta 0.2, p  = 0.019). When added to clinical variables, both EAT (beta 0.16, p  = 0.035) and IL-6 (beta 0.26, p  = 0.003) were independently associated with PWV. EAT was significantly associated with LVMI in a univariable analysis but not when added to significant clinical variables. Conclusions In patients with cardio-metabolic disease, EAT was independently associated with PWV. EAT may be associated with CVD risk due to an increase in systemic vascular inflammation. Whether targeting EAT may reduce inflammation and/or cardiovascular risk should be evaluated in prospective studies.

Background Coronary computed tomography angiography (CCTA) is widely used as a first-line tool for diagnosing and managing coronary artery disease (CAD), and machine learning (ML)-based analysis shows promise for quantitative CAD assessment. Methods In this post hoc analysis of 909 participants from the SCOT-HEART trial (median follow-up, 5.8 years), we first evaluated the distribution of CCTA-derived imaging features in a cohort ( n  = 221) with a zero calcium score, stenoses < 10%, and no evidence of CAD on CCTA, across 21 image processing settings. Interpretable ML models were then developed and validated to quantify coronary calcification and stenoses in major coronary segments (LMA, LCX, LAD, pRCA, mRCA). Calcified plaques, stenoses, and myocardial infarction outcomes were comprehensively assessed. Results A total of 549 stable imaging features was identified across processing settings. Six ML algorithms (SVM, KNN, MLP, Naïve Bayes, gradient boosting, LightGBM) were evaluated for predicting coronary calcification and stenoses. The best model achieved an accuracy of 84.2% and an AUC of 0.973. Stenosis stratification accuracy exceeded 84.8% across all segments, with minimal (< 0.05) differences between models using all versus stable features. SHAP analysis indicated heterogeneous contributions of imaging phenotypes and clinical risk factors. Conclusions Stable imaging features provide a reference for future ML-based coronary quantitatively assessments. Interpretable ML models demonstrated promising performance in quantifying coronary calcification and segment-level stenoses. Graphical Abstract Highlights 1. Investigated the distribution and stability of pericoronary imaging phenotypes in populations without CAD using a median of 5.8-year follow-up multicentre datasets. 2. Conducted a machine learning-based analysis of coronary CTA and clinical risk factors to quantitatively evaluate outcomes in patients with coronary artery disease. 3. Explored the contributions of vascular risk factors and CTA imaging phenotypes in six kinds of predictive models for coronary artery disease outcomes.

Background Carotid-femoral pulse wave velocity (cf-PWV) and aortic PWV measured using MRI (MRI-PWV) show good correlation, but with a significant and consistent bias across studies. The aim of the current study was to evaluate whether the differences between cf.-PWV and MRI-PWV can be accounted for by inaccuracies of currently used distance measurements. Methods One hundred fourteen study participants were recruited into one of 4 groups: Type 2 diabetes melltus (T2DM) with cardiovascular disease (CVD) ( n  = 23), T2DM without CVD ( n  = 41), CVD without T2DM ( n  = 25) and a control group ( n  = 25). All participants underwent cf.-PWV, cardiac MRI and whole body MR angiography(WB-MRA). 90 study participants also underwent aortic PWV using MRI. cf.-PWV EXT was performed using a SphygmoCor device (Atcor Medical, West Ryde, Australia). The true intra-arterial pathlength was measured using the WB-MRA and then used to recalculate the cf.-PWV EXT to give a cf.-PWV MRA . Results Distance measurements were significantly lower on WB-MRA than on external tape measure (mean diff = −85.4 ± 54.0 mm, p  < 0.001). MRI-PWV was significantly lower than cf.-PWV EXT (MRI-PWV = 8.1 ± 2.9 vs. cf.-PWV EXT  = 10.9 ± 2.7 ms −1 , p  < 0.001). When cf.-PWV was recalculated using the inter-arterial distance from WB-MRA, this difference was significantly reduced but not lost (MRI-PWV = 8.1 ± 2.9 ms −1 vs. cf.-PWV MRA 9.1 ± 2.1 ms −1 , mean diff = −0.96 ± 2.52 ms −1 , p  = 0.001). Recalculation of the PWV increased correlation with age and pulse pressure. Conclusion Differences in cf.-PWV and MRI PWV can be predominantly but not entirely explained by inaccuracies introduced by the use of simple surface measurements to represent the convoluted arterial path between the carotid and femoral arteries.

Background Arteriosclerosis (arterial stiffening) is associated with future cardiovascular events, with this effect postulated to be due to its effect on cardiac afterload, atherosclerosis (plaque formation) progression or both, but with limited evidence examining these early in disease formation. The aim of the current study is to examine the association between arteriosclerosis, atherosclerosis and ventricular remodelling in a population at low-intermediate cardiovascular risk. Methods One thousand six hundred fifty-one subjects free of clinical cardiovascular disease and with a < 20% 10 year cardiovascular risk score underwent a cardiovascular magnetic resonance (CMR) study and whole body CMR angiogram. Arteriosclerosis was measured using total arterial compliance (TAC) - calculated as the indexed stroke volume divided by the pulse pressure. Atherosclerosis was quantified using a standardised atheroma score (SAS) which was calculated by scoring 30 arterial segments within the body based on the degree of stenosis, summating these scores and normalising it to the number of assessable segments. Left ventricular remodelling was measured using left ventricular mass to volume ratio (LVMVR). Results One thousand five hundred fifteen (38% male, 53.8 ± 8.2 years old) completed the study. On univariate analysis TAC was associated with SAS but this was lost after accounting for cardiovascular risk factors in both males (B = − 0.001 (− 0.004–0.002), p  = 0.62) and females (B = 0.000(95%CI -0.002--0.002), p  = 0.78). In contrast compliance correlated with LVMVR after accounting for cardiovascular risk factors (B = − 0.12(95%CI -0.16--0.091), p  < 0.001 in males; B = − 0.12(95%CI -0.15--0.086), p  < 0.001 in females). Conclusion Systemic arteriosclerosis is associated with left ventricular remodelling but not atherosclerosis. Future efforts in cardiovascular risk prevention should thus seek to address both arteriosclerosis and atherosclerosis individually.

Common carotid intima media thickness (CIMT) and ankle brachial pressure index (ABPI) are used as surrogate marker of atherosclerosis, and have been shown to correlate with arterial stiffness, however their correlation with global atherosclerotic burden has not been previously assessed. We compare CIMT and ABPI with atheroma burden as measured by whole body magnetic resonance angiography (WB-MRA). 50 patients with symptomatic peripheral arterial disease were recruited. CIMT was measured using ultrasound while rest and exercise ABPI were performed. WB-MRA was performed in a 1.5T MRI scanner using 4 volume acquisitions with a divided dose of intravenous gadolinium gadoterate meglumine (Dotarem, Guerbet, FR). The WB-MRA data was divided into 31 anatomical arterial segments with each scored according to degree of luminal narrowing: 0 = normal, 1 = <50%, 2 = 50-70%, 3 = 70-99%, 4 = vessel occlusion. The segment scores were summed and from this a standardized atheroma score was calculated. The atherosclerotic burden was high with a standardised atheroma score of 39.5±11. Common CIMT showed a positive correlation with the whole body atheroma score (β 0.32, p = 0.045), however this was due to its strong correlation with the neck and thoracic segments (β 0.42 p = 0.01) with no correlation with the rest of the body. ABPI correlated with the whole body atheroma score (β -0.39, p = 0.012), which was due to a strong correlation with the ilio-femoral vessels with no correlation with the thoracic or neck vessels. On multiple linear regression, no correlation between CIMT and global atheroma burden was present (β 0.13 p = 0.45), while the correlation between ABPI and atheroma burden persisted (β -0.45 p = 0.005). ABPI but not CIMT correlates with global atheroma burden as measured by whole body contrast enhanced magnetic resonance angiography in a population with symptomatic peripheral arterial disease. However this is primarily due to a strong correlation with ilio-femoral atheroma burden.

Background: Oxidative stress (OS) has been implicated in the development of pulmonary hypertension (PH) and ventricular hypertrophy. Xanthine oxidase is a well-recognised source of reactive oxygen species, which lead to OS. The aim of this proof of concept study was to assess whether allopurinol (xanthine oxidase inhibitor) would reduce right ventricular mass (RVM) in patients with PH-associated chronic lung disease (PH-CLD). Methods: We conducted a randomised, double-blind, parallel-group, placebo-controlled trial in patients with PH-CLD (93% COPD, 7% IPF) who were randomly assigned to receive allopurinol or placebo for 12 months. The primary outcome was the mean change in RVM, as assessed by cardiac magnetic resonance imaging (CMRI). Secondary outcomes included quality of life (QOL), spirometry and six-minute walk test (6MWT). Results: Seventy-one patients were recruited: mean age 71 years, mean pulmonary arterial pressure 30 mm Hg, FE[V.sub.1] 60% and resting Sp[O.sub.2] 96%. After 12 months, there was no significant difference in the change in RVM from baseline (allopurinol 1.85g vs placebo 0.97g with mean difference 0.88g, CI -4.77 to 3.01, p =0.7). There were also no significant changes in other cardiac parameters measured on MRI, in QOL, spirometry and 6MWT. Subgroup analysis showed that allopurinol significantly reduced RVM compared to placebo with -6.16g vs 0.75g and mean difference 6.92g (CI 1.14 to 12.69, p = 0.02) in COPD patients with more severe airflow limitation. Conclusion: Allopurinol had no overall impact on patients with PH-CLD but had potential benefit in COPD patients with more severe airflow limitation. Keywords: pulmonary hypertension, right ventricle, allopurinol, chronic lung disease

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.