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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 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.

Ticagrelor is a potent and orally active P2Y12 inhibitor. Ticagrelor has been extensively tested in Phase II and Phase III trials in patients with coronary artery disease. The pharmacokinetics and pharmacodynamics of ticagrelor result in more rapid and effective inhibition of platelet activation compared with other P2Y12 inhibitors. This has resulted in a reduction in recurrent major cardiovascular events in initial randomized controls trials comparing ticagrelor with clopidogrel. More recently, clinical trials have investigated the use of ticagrelor in patients with stable coronary artery disease and a high residual risk of coronary thrombotic events. In patients with stable coronary artery disease, the potent antiplatelet effect of ticagrelor is counterbalanced by an increased risk of major bleeding. Further research is ongoing to determine the optimal duration of ticagrelor therapy.

Supplemental Digital Content is available in the text., 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

Background Arterial 18F-sodium fluoride (18F-NaF) activity on positron emission tomography (PET) is a marker of active microcalcification and atherosclerosis. Coronary 18F-NaF activity (CMA) predicts coronary artery disease progression and subsequent myocardial infarction. Objective To investigate whether aortic 18F-NaF activity (AMA) predicts thoracic aortic atherosclerotic disease progression and subsequent ischaemic stroke or myocardial infarction in patients with established cardiovascular disease. Methods In a post-hoc observational cohort study, we evaluated AMA and CMA in patients with stable coronary artery disease (n=239) or aortic stenosis (n=158) who had underwent thoracic 18F-NaF PET and computed tomography (CT). We assessed the associations between AMA or CMA and progression of calcified atherosclerotic plaque in both thoracic aortic and coronary territories on follow up CT, as well as subsequent ischaemic stroke or myocardial infarction. Results In 141 and 231 patients with repeat aortic and coronary CT imaging respectively at 12.7±2.7 months, AMA correlated with log progression of thoracic aortic calcium scores (r=0.21, p=0.011), volume (r=0.29, p0.80) calcium score progression. In 397 patients, 16 had an ischaemic stroke and 25 had a myocardial infarction after 4.7±1.6 years. After adjusting for clinical risk factors, CMA and calcium scoring, AMA was associated with stroke (hazard ratio, 1.71 [95% confidence interval 1.00–2.90], p=0.048]). AMA was superior to clinical risk and calcium scores in identifying patients with stroke (c-statistic 0.76 versus 0.58 versus 0.63 respectively, p Conclusions In patients with established cardiovascular disease, AMA is associated with progression of aortic atherosclerosis and future ischaemic stroke. Arterial 18F-NaF identifies localised areas of atherosclerotic disease activity that relate to regional atherothrombotic events. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): British Heart Foundation AMA, disease progression and outcomesVariables associated with stroke

Being born preterm (PT, &lt, 37 weeks gestation) or at very low birth weight (VLBW, &lt, 1500 g) is associated with increased rates of cardiopulmonary disorders in childhood. As survivors age, late cardiac effects, including right ventricular (RV) remodelling and occult pulmonary hypertension are emerging. In this population-based study, we aimed to investigate right heart structure and function in young adults born PT at VLBW compared to normal-weight term-born controls. The New Zealand VLBW Study has followed all infants born in 1986 with birth weight &lt, 1500 g. All were born preterm from 24 to 37 weeks. A total of 229 (71% of survivors) had echocardiograms aged 26–30 years which were compared to age-matched, term-born, normal-weight controls (n = 100). Young adults born preterm at very low birth weight exhibited smaller RV dimensions compared to term-born peers. Standard echocardiographic measures of RV function did not differ, but mildly reduced function was detected by RV longitudinal strain. This difference was related to birth weight and gestational age but not lung function or left ventricular function. Echocardiographic strain imaging may be an important tool to detect differences in RV function preterm and VLBW.

The European Society of Cardiology (ESC) clinical practice guideline for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation was updated in 2020.1 Here, we highlight and discuss some of the notable changes (table 1) focusing on the diagnostic pathway, decision-making regarding coronary imaging and optimal antithrombotic strategy. View this table: Table 1 Summary of key changes to the guidance. The previous ESC clinical practice guideline recommended the use of high-sensitivity cardiac troponin testing and accelerated sampling intervals to rule in or rule out myocardial infarction earlier. The central recommendation was a 0/3-hour pathway using the 99th centile upper reference limit to rule out myocardial infarction.2 Studies have since shown that the ESC 0/3-hour pathway missed up to 1 in 10 patients, with myocardial infarction detected at later time points and this pathway is no longer recommended.3 Multiple studies now support the superior safety and efficacy of using thresholds well below the 99th centile to rule out myocardial infarction and in recognition of this, the new guideline advocates a single troponin measurement in patients presenting at least 3 hours from symptoms onset.4 Myocardial infarction can be safely ruled out if concentrations are ‘very low’ and ruled in if values are ‘high’ using multiple assay-specific thresholds. Repeat testing at 1 or 2 hours is recommended for those presenting early or with ‘low’ but detectable concentrations on arrival.5 However, for patients with intermediate troponin concentrations, which may be up to a third of those assessed, the guideline recommends further observation and investigation, creating potential uncertainty for clinicians. The sole randomised trial assessing the safety and effectiveness of implementing the ESC 0/1-hour pathway was stopped prematurely with only a small number of safety outcomes accrued following discharge from hospital.6 It provided little insight into the role of further investigation in …

BACKGROUND Treatment advances have improved cancer-related outcomes and shifted interest towards minimising long-term iatrogenic complications, particularly chemotherapy-related cardiotoxicity. High-sensitivity cardiac troponin I (hs-cTnI) assays accurately quantify very low concentrations of plasma troponin and enable early detection of cardiomyocyte injury prior to development of myocardial dysfunction. The profile of hs-cTnI in response to anthracycline-based treatment has not previously been described. PATIENTS AND METHODS This was a multi-centre prospective observational cohort study. Female patients with newly-diagnosed invasive breast cancer scheduled to receive adjuvant or neo-adjuvant anthracycline-based (epirubicin) chemotherapy were recruited. Blood sampling was performed before, during and 24 hours after each treatment cycle. Plasma hs-cTnI concentrations were measured using the Abbott ARCHITECTSTAT assay (limit of detection 1.2 ng/L, coefficient of variation ≤10% at 4.7 ng/L, 99th centile upper reference limit in women 16 ng/L). RESULTS We recruited 78 women with a mean (standard deviation) age of 53.6 (9.6). The median (IQR) baseline troponin concentration was 1 (1 to 4) ng/L and median (IQR) cumulative epirubicin dose was 394 (300 to 405) mg/m2. Following an initial 33% fall 24 hours following anthracycline dosing (p Citation Format: Olga Oikonomidou, Evangelos Tzolos, Philip D Adamson, Peter S Hall, Iain R MacPherson, Morag MacLean, Steff Lewis, Heather McVicars, David E Newby, Nicholas L Mills, Ninian Lang, Peter A Henriksen. Dynamic changes in high-sensitivity cardiac troponin I in response to anthracycline-based chemotherapy-The Cardiac Care Trial pilot data [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-13-02.

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.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.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.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).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.

Left ventricular thrombus formation is a complication of acute myocardial infarction. However, the incidence and risk of systemic thromboembolism in the era of primary angioplasty for ST elevation myocardial infarction (STEMI) is unclear. This study aims to determine clinical outcomes in patients with STEMI treated with primary angioplasty and left ventricular thrombus at 1 year.Patients who underwent primary angioplasty for STEMI and had a transthoracic echocardiogram were recruited. The primary endpoint was a composite of all-cause mortality, stroke, and systemic thromboembolism at 1 year. For the primary endpoint, the difference between the presence and absence of left ventricular thrombus was compared using a logistic regression, adjusting for minimization variables including age, diabetes mellitus, hypertension, and previous stroke.Of 2608 patients who underwent primary angioplasty for STEMI, 1645 (63%) patients had a transthoracic echocardiogram performed during the index hospital admission. Forty patients (2.4%) had evidence of left ventricular thrombus on transthoracic echocardiography. Patients with left ventricular thrombus were more likely to develop atrial fibrillation in the immediate postinfarction period (6 [15%] vs 87 [5.4%], P = 0.025). At 1 year, the primary endpoint occurred in 4 (10%) patients with left ventricular thrombus and 146 (9.1%) who did not (logistic regression hazard ratio 0.79, 95% confidence interval 0.23-2.70).In the contemporary era of mechanical reperfusion for STEMI, echocardiographic detection of left ventricular thrombus was observed in3% patients. The presence of left ventricular thrombus was not associated with an increased risk of systemic thromboembolism.

Objectives This study sought to compare the performance of history-based risk scores in predicting obstructive coronary artery disease (CAD) among patients with stable chest pain from the SCOT-HEART study. Background Risk scores for estimating pre-test probability of CAD are derived from referral-based populations with a high prevalence of disease. The generalizability of these scores to lower prevalence populations in the initial patient encounter for chest pain is uncertain. Methods We compared 3 scores among patients with suspected CAD in the coronary computed tomographic angiography (CTA) randomized arm of the SCOT-HEART study for the outcome of obstructive CAD by coronary CTA: the updated Diamond-Forrester score (UDF), CAD Consortium clinical score (CAD2), and CONFIRM risk score (CRS). We tested calibration with goodness-of-fit, discrimination with area under the receiver-operating curve (AUC), and reclassification with net reclassification improvement (NRI) to identify low-risk patients. Results In 1,738 patients (age 58 ± 10 years and 44.0% women), overall calibration was best for UDF, with underestimation by CRS and CAD2. Discrimination by AUC was highest for CAD2 at 0.79 (95% confidence interval [CI]: 0.77 to 0.81) than for UDF (0.77 [95% CI: 0.74 to 0.79]) or CRS (0.75 [95% CI: 0.73 to 0.77]) (p Conclusions In this multicenter clinic-based cohort of patients with suspected CAD and uniform CAD evaluation by coronary CTA, CAD2 provided the best discrimination and classification, despite overestimation of obstructive CAD as evaluated by coronary CTA. CRS exhibited intermediate performance followed by UDF for discrimination and reclassification.

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 registrationNCT01149590; Post-results.

ObjectiveAssess the relative incidence and compare characteristics and outcome of unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI).DesignTwo independent prospective multicentre diagnostic studies (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] and High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome [High-STEACS]) enrolling patients with acute chest discomfort presenting to the emergency department. Central adjudication of the final diagnosis was done by two independent cardiologists using all clinical information including serial measurements of high-sensitivity cardiac troponin (hs-cTn). All-cause death and future non-fatal MI were assessed at 30 days and 1 year.Results8992 patients were enrolled at 11 centres. UA was adjudicated in 8.9%(95% CI 8.0 to 9.7) and 2.8% (95% CI 2.3 to 3.3) patients in APACE and High-STEACS, respectively, and NSTEMI in 15.1% (95% CI 14.0 to 16.2) and 13.4% (95% CI 12.4 to 14.3). Coronary artery disease was pre-existing in 73% and 76% of patients with UA. At 30 days, all-cause mortality in UA was substantially lower as compared with NSTEMI (0.5% vs 3.7%, p=0.002 in APACE, 0.7% vs 7.4%, p=0.004 in High-STEACS). Similarly, at 1 year in UA all-cause mortality was 3.3% (95% CI 1.2 to 5.3) vs 10.4% (95% CI 7.9 to 12.9) in APACE, and 5.1% (95% CI 0.7 to 9.5) vs 22.9% (95% CI 19.3 to 26.4) in High-STEACS, and similar to non-cardiac chest pain (NCCP). In contrast, future non-fatal MI in APACE was comparable in UA and NSTEMI (11.2%, 95% CI 7.8 to 14.6 and 7.9%, 95% CI 5.7 to 10.2), and higher than in NCCP (0.6%, 95% CI 0.2 to 1.0).ConclusionsThe relative incidence and mortality of UA is substantially lower than that of NSTEMI, while the rate of future non-fatal MI is similar.

Introduction Pericoronary adipose tissue (PCAT) attenuation has emerged as a surrogate marker of pericoronary inflammation. To date, no studies have compared the impact of pericoronary adipose tissue(PCAT) attenuation and quantitative plaque burden on cardiac outcomes. We aimed to establish the relative merits of these approaches to risk prediction and hypothesised that the combination of PCAT attenuation and quantitative plaque burden measures could provide additive and improved prediction of myocardial infarction in patients with stable chest pain. Methods In a post-hoc analysis of a randomized controlled trial, we investigated the association between the future risk of fatal or non-fatal myocardial infarction and PCAT attenuation measured from CT coronary angiography using multivariable Cox regression models including plaque burden, obstructive coronary disease and cardiac risk score (incorporating age, sex, diabetes, smoking, hypertension, hyperlipidaemia and family history of cardiovascular disease). Results In 1697 evaluable participants (mean age 58±10 years), there were 37 myocardial infarctions after a median follow-up of 4.7 [interquartile interval, 4.0-5.7] years. Median low-attenuation plaque burden was 4.20[0-6.86] % and mean PCAT -76±8 Hounsfield units (HU). PCAT-RCA attenuation was higher in patients who suffered a myocardial infarction (-72.5±8.3 HU versus -76.5± 7.8 HU, p=0.0063), but there was no difference in PCAT-LAD (-76.3±8.6 HU vs -77.0±7.8 HU, p=0.54) or PCAT-LCx(-71.6±7.3 HU vs -73.3±7.7 HU, p=0.33). Patients sustaining a myocardial infarction also had higher total, non-calcified, low-attenuation and calcified plaque burden, higher Agatston calcium score, higher cardiovascular risk score and increased presence of obstructive disease on CCTA (table 1). On univariable analysis, PCAT-RCA attenuation was a predictor of myocardial infarction (HR 1.55, 95% CI 1.08 to 2.22, p=0.017), but PCAT-LAD or PCAT-LCx were not. Univariable analysis also identified the burden of non-calcified, low-attenuation and calcified plaque as well as Agatston coronary calcium score, presence of obstructive coronary artery disease and cardiovascular risk score were predictors of myocardial infarction (table 2). Male sex, age and body-mass index were not predictors of future myocardial infarction (p=0.06, p=0.86 and 0.26 respectively). In multivariable analysis, only the low-attenuation plaque burden (HR 1.80, 95% CI 1.16 to 2.81, p=0.011, per doubling) and PCAT-RCA (HR 1.47 95%1.02 to 2.13, p=0.040, per standard deviation increment) remained predictors of myocardial infarction (table 2). Based on the Youden’s index of the ROC curves, the optimal cut-off of the right coronary artery PCAT attenuation was –70.5 HU for the primary endpoint of fatal or non-fatal myocardial infarction. Patients with PCAT-RCA above ≥–70.5 HU were nearly 2.5 times more likely to suffer a myocardial infarction (HR 2.45, 95% CI 1.23 to 4.80; p=0.001). Patients with low-attenuation plaque burden (greater than 4%) were nearly 5 times more likely to suffer a myocardial infarction (HR 4.87, 95% CI 2.03 to 11.78, p 4% and PCAT-RCA ≥-70.5 HU were at the greatest risk of myocardial infarction (HR 11.7, 95% CI 3.3 to 40.9, p 4% and PCAT-RCA Conclusion CT coronary angiography defined PCAT attenuation and low-attenuation plaque have marked and additive predictive value for the risk of fatal or non-fatal myocardial infarction. Conflict of Interest Nil

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).

Despite significant advances in the treatment of ST elevation myocardial infarction (STEMI), there remains a significant short-term and long-term increased mortality risk. Risk stratification to target those who may benefit from more intensive therapy postrevascularisation therefore remains an important goal. Risk stratification models in acute coronary syndrome (ACS) have been researched for many years, but few risk scores have been developed and validated specifically for the STEMI population. Only 27% of the cohort for the Global Registry of Acute Coronary Events (GRACE) score was derived from those undergoing percutaneous intervention (PCI), and the GRACE score performs less accurately in those undergoing PCI compared with medical therapy. Nevertheless European1 (but not American2) guidelines recommend its use for clinical risk stratification in the STEMI cohort. Risk scores derived specifically for STEMI include the Global Utilization of Streptokinase and Tissue plasminogen activator to treat Occluded arteries (GUSTO) risk score, which was developed in the era of thrombolysis, while risk scores assessing mortality in primary PCI patients include the Primary Angioplasty in Myocardial Infarction (PAMI) risk score, Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) risk score, Assessment of Pexelizumab in Acute Myocardial Infarction (APEX-AMI) score, Soroka Acute Myocardial Infarction (SAMI) score, and the Zwolle risk score. Coelho-Lima and colleagues3 examine the prognostic value of troponin specifically in the STEMI population, a group where troponin is not used to guide initial treatment. Their major findings are that admission troponin, but not troponin measured 12 hours post-reperfusion, was a significant independent predictor of both inpatient or overall mortality, with a median follow-up time of over 4 years. The authors are to be commended for this large retrospective study—in particular, the clinical …

Preterm birth affects 1 in 10 pregnancies worldwide, with increasing survival rates over the last 30 years. However, as this new generation of long-term survivors approaches middle age, recent studies have revealed increased cardiovascular risk factors and higher rates of ischaemic heart disease and heart failure. Cardiovascular imaging has identified smaller cardiac chamber size, changes in myocardial mass and impaired ventricular function, particularly under physiological stress. Accordingly, this population should be recognised as having a higher risk of heart failure as they age. In this review, we present current evidence for increased rates of heart failure and evidence of alterations in cardiac structure and function in those born preterm. We discuss potential mechanisms to explain this risk including greater frequency of co-morbidities known to be associated with heart failure. We also explore potential mechanistic links specific to the preterm-born population, including the impact of premature birth on myocardial and vascular development and the effects of perinatal haemodynamic changes and chronic lung disease on the developing heart. We highlight gaps in our knowledge and consider implications for patient management relevant to the adult physician.

Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): British Heart Foundation Clinical Research Training Fellowship Background Calcification of the thoracic aorta is associated with poor vessel wall health. Early detection of this disease process may highlight those at risk of future cardiovascular events. Purpose To investigate the potential of hybrid 18F-sodium fluoride (18F-NaF, a marker of vascular disease and microcalcification activity) positron emission tomography/computed tomography (PET/CT) to predict aortic disease progression and adverse cardiovascular events in patients with established risk factors. Methods Between 2015 and 2017, 197 patients underwent 18F-NaF PET/CT of the thoracic aorta as part of a randomised controlled trial. Baseline 18F-NaF aortic microcalcification activity (AMA) was calculated as the cumulative uptake in a standardised volume of interest of the arch and ascending aorta. Thirty-seven patients underwent follow up CT enabling aortic calcium score progression calculation. Fatal/non-fatal stroke (primary endpoint) and fatal/non-fatal myocardial infarction (MI, secondary endpoint) were recorded up to May 2020. The association between baseline AMA and both the progression of aortic calcium score and defined endpoints was analysed. AMA was stratified into tertiles (low, moderate or high). Data is presented as mean(SD) or median [IQR]. Results 18F-NaF AMA correlated with the progression of aortic calcium score (R = 0.42, P = 0.01). During 3.8 (0.9) years of follow up, 14 patients experienced the primary (stroke, n = 5) or secondary (MI, n = 9) endpoint. Patients who experienced stroke had higher AMA (171 [162-176] vs 150 [141 - 157], P = 0.0015). Increased cumulative incidence of stroke was seen in the highest AMA tertile (Figure, P = 0.019). There was no association between AMA and MI (P > 0.05). Conclusion Aortic microcalcification activity, as measured using 18F-NaF PET/CT, predicts the progression of aortic wall calcification and is associated with an increased risk of stroke but not MI. Consolidating these findings in further studies will improve stroke risk prediction using 18F-NaF PET/CT. Table Baseline characteristics Overall n = 197 Low AMA (155) n = 65 p-value (ANOVA / X2) Age (±sd) 65.17 (8.30) 64.02 (9.43) 65.47 (7.40) 66.03 (7.95) 0.364 Male Sex (%) 157 (80.5) 54 (83.1) 52 (78.8) 51 (79.7) 0.808 Ever Smoked (%) 101 (60.5) 37 (71.2) 32 (56.1) 32 (55.2) 0.164 Hypertension (%) 110 (56.4) 31 (47.7) 35 (53.0) 44 (68.8) 0.043 High Cholesterol (%) 188 (96.4) 60 (92.3) 65 (98.5) 63 (98.4) 0.093 Type II Diabetes (%) 37 (19.0) 16 (24.6) 9 (13.6) 12 (18.8) 0.277 AMA = aortic microcalcification activity, MI = myocardial infarction, sd = standard deviation, TIA = transient ischaemic attack, X2 = Chi squared Abstract Figure: AMA and Stroke

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 18 F-fluoride uptake (from 95 [30–209] to 148 [61–289] AU; P 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 18 F-fluoride activity was an independent predictor of calcium score at 12 months ( P 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.

Introduction: Pulmonary artery pressure (PAP)-guided treatment reduces heart failure hospitalizations (HFH) in randomized and “real world” studies. Underlying CKD in HF patients portends poorer outcomes. This analysis was performed to determine if benefit of PAP-guided HF therapy persists with increasing CKD severity. Methods: This retrospective cohort study was conducted in NYHA Class III HF recipients of the PAP sensor enrolled in the CardioMEMS Post Approval Study. Patients were subdivided into quartiles of glomerular filtration rates estimated by MDRD equation (eGFR). Rates of HFH 1 year before versus 1 year after PAP sensor implantation were compared across quartiles of eGFR using the Andersen-Gill Cox proportional hazards model, while accounting for competing risk of death, advanced HF therapies, and progression to end-stage kidney disease. Multivariate analysis was performed to identify independent predictors of CKD (baseline eGFR < 90 mL/min/1,73m 2 ) progression. Results: Among 1200 PAP sensor recipients, 1119 had concomitant CKD with CKD stages 3 and 4 occurring in 754 patients (67.4%). In CKD patients, 40.6%, 42.1%, and 17.3%, respectively, demonstrated worse, unchanged, or improved CKD stage. Compared to 12 pre-implant months, HFH rates dropped in 12 months after implant across all eGFR quartiles (Table). PA systolic, diastolic, and mean pressures decreased from baseline to 24 months in all GFR quartiles. The baseline mean PAP as a continuous variable independently predicted CKD progression (OR: 1.027, p= 0.0006). Conclusion: Reduction of HFH by PAP-guided therapy occurred across CKD stages in a large HF population receiving the CardioMEMS sensor after Food and Drug Administration approval. Thus, PAP monitoring enables safe HF therapy optimization even in patients with advanced CKD. Since higher baseline mean PAP independently forecasts CKD worsening, HF patients with this unfavorable hemodynamic value require intensified monitoring.

Introduction Being born at very low birth weight (VLBW, Purpose To assess differences in right heart function using strain in young adults born at VLBW, compared to normal weight term born controls. Methods The New Zealand Very Low Birth Weight Study has followed all infants born in 1986 with birth weight Results VLBW subjects were smaller than their peers as young adults (Table 1). Strain measurement showed reduced myocardial deformation among VLBW subjects (RV myocardial GLS: −22.4% vs −23.5%, p=0.008; RV endocardial GLS: −23.6% vs −24.9%, p=0.005; free wall myocardial GLS −25.2% vs −26.1%, p=0.039; free wall endocardial GLS −26.7% vs −27.9%, p=0.009). TR velocity was higher in VLBW: 224 cm/s v 210 cm/s (p=0.002). RV S', and FAC were not different. Conclusion Young adults born at VLBW have impaired myocardial strain despite preserved RV function as assessed by standard techniques. Echocardiographic strain imaging may be an important tool to detect subclinical RV dysfunction. Graph 1 Funding Acknowledgement Type of funding source: None

BackgroundBalloon aortic valvuloplasty (BAV) remains a treatment option for the selected patients with severe aortic stenosis. We examined clinical outcomes and predictors of prognosis in patients undergoing BAV for severe aortic stenosis.MethodsWe identified all patients undergoing BAV from January 2010 to March 2018 (n=167) at a single transcatheter aortic valve implantation (TAVI) centre. Patient demographics, investigations, subsequent interventions and clinical outcomes were obtained from electronic health records.ResultsPatients undergoing BAV were elderly (median age 80, IQR 73–86 years) and half (n=87, 52%) were male. All-cause mortality at 30 days and 12 months was 11% and 43%, respectively. Reduce ejection fraction (EF 30%–50%: HR 1.76, 95% CI 1.05 to 2.94; EF ConclusionBAV as a bridge to definitive aortic valve intervention in carefully selected patients offers acceptable outcomes. These contemporary observational findings demonstrate the ongoing potential utility of BAV in the TAVI era.

Background: Countries with a high incidence of coronavirus 2019 (COVID-19) reported reduced hospitalisations for acute coronary syndromes (ACS) during the pandemic. This study describes the impact of a nationwide lockdown on ACS hospitalisations in New Zealand (NZ), a country with a low incidence of COVID-19. Methods: All patients admitted to a NZ Hospital with ACS who underwent coronary angiography in the All NZ ACS Quality Improvement registry during the lockdown (23 March – 26 April 2020) were compared with equivalent weeks in 2015–2019. Ambulance attendances and regional community troponin-I testing were compared for lockdown and non-lockdown (1 July 2019 to 16 February 2020) periods. Findings: Hospitalisation for ACS was lower during the 5-week lockdown (105 vs. 146 per-week, rate ratio 0•72 [95% CI 0•61–0•83], p = 0.003). This was explained by fewer admissions for non-ST-segment elevation ACS (NSTE-ACS; p = 0•002) but not ST-segment elevation myocardial infarction (STEMI; p = 0•31). Patient characteristics and in-hospital mortality were similar. For STEMI, door-to-balloon times were similar (70 vs. 72 min, p = 0•52). For NSTE-ACS, there was an increase in percutaneous revascularisation (59% vs. 49%, p

Aims Valvular heart disease can be identified by calcification on coronary computed tomography angiography (CCTA) and has been associated with adverse clinical outcomes. We assessed aortic and mitral valve calcification in patients presenting with stable chest pain and their association with cardiovascular risk factors, coronary artery disease, and cardiovascular outcomes. Methods and results In 1769 patients (58 ± 9 years, 56% male) undergoing CCTA for stable chest pain, aortic and mitral valve calcification were quantified using Agatston score. Aortic valve calcification was present in 241 (14%) and mitral calcification in 64 (4%). Independent predictors of aortic valve calcification were age, male sex, hypertension, diabetes mellitus, and cerebrovascular disease, whereas the only predictor of mitral valve calcification was age. Patients with aortic and mitral valve calcification had higher coronary artery calcium scores and more obstructive coronary artery disease. The composite endpoint of cardiovascular mortality, non-fatal myocardial infarction, or non-fatal stroke was higher in those with aortic [hazard ratio (HR) 2.87; 95% confidence interval (CI) 1.60–5.17; P Conclusion Aortic and mitral valve calcification occurs in one in six patients with stable chest pain undergoing CCTA and is associated with concomitant coronary atherosclerosis. Whilst valvular calcification is associated with a higher risk of cardiovascular events, this was not independent of the burden of coronary artery disease.

Aims Treatment advances have improved cancer-related outcomes and shifted interest towards minimising long-term iatrogenic complications, particularly chemotherapy-related cardiotoxicity. High-sensitivity cardiac troponin I (hs-cTnI) assays accurately quantify very low concentrations of plasma troponin and enable early detection of cardiomyocyte injury prior to the development of myocardial dysfunction. The profile of hs-cTnI in response to anthracycline-based treatment has not previously been described. Materials and methods This was a multicentre prospective observational cohort study. Female patients with newly diagnosed invasive breast cancer scheduled to receive anthracycline-based (epirubicin) chemotherapy were recruited. Blood sampling was carried out before and 24 h after each cycle. Hs-cTnI concentrations were measured using the Abbott ARCHITECTSTAT assay. Results We recruited 78 women with a median (interquartile range) age of 52 (49–61) years. The median baseline troponin concentration was 1 (1–4) ng/l and the median cumulative epirubicin dose was 394 (300–405) mg/m2. Following an initial 33% fall 24 h after anthracycline dosing (P, Highlights • Plasma hs-cTnI concentrations showed an anthracycline dose-dependent increase. • Hs-cTnI could act as an early and sensitive anthracycline cardiotoxicity prediction tool. • Hs-cTnI measurement should happen before rather than after each cycle.

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, Central Illustration

The Authors’ reply: We thank the author for their interest in our report documenting the long-term prognostic importance of convalescent cardiac troponin concentrations.1 First, we agree that when used for risk stratification low cardiac troponin concentrations miss fewer events than applying the sex-specific 99th centile upper reference limit as a single threshold, and indeed we identified the lower troponin threshold of 5 ng/L to be associated with a 5-year negative predictive value for cardiovascular death of 97.1% (95% CI 95.5 to …

Background: Patients with chronic obstructive pulmonary disease (COPD) have increased risk of cardiovascular events.Objectives: This study evaluated the association between high-sensitivity cardiac troponin I concentration and cardiovascular events in patients with COPD and heightened cardiovascular risk.Methods: In a double-blind randomized controlled trial, 16,485 patients with COPD and cardiovascular disease or risk factors were randomized to once daily inhaled placebo, fluticasone furoate (100 μg), vilanterol (25 μg), or their combination. Plasma high-sensitivity cardiac troponin I concentrations were measured in a subgroup of 1,599 patients. Outcomes were on-treatment cardiovascular events and COPD exacerbations over a median of 18 months, and cardiovascular death over a median of 27 months.Results: Baseline plasma cardiac troponin I concentrations were above the limit of detection (1.2 ng/l) in 1,542 (96%) patients. Concentrations were unaffected by inhaled therapies at 3 months (p > 0.05). Compared with the lowest quintile (cardiac troponin Conclusions: In patients with COPD and heightened cardiovascular risk, plasma cardiac troponin I concentrations are a specific and major indicator of future cardiovascular events and cardiovascular death. Inhaled therapies did not affect cardiac troponin I concentrations consistent with their neutral effect on mortality and cardiovascular outcomes. (Study to Evaluate the Effect of Fluticasone Furoate/Vilanterol on Survival in Subjects With Chronic Obstructive Pulmonary Disease [SUMMIT]; NCT01313676)

Primary percutaneous coronary intervention (PPCI) is a cornerstone of treatment for acute myocardial infarction (AMI). Despite major achievements in the procedure itself and in the infrastructure allowing timely delivery of PPCI, a substantial proportion of patients will suffer significant myocardial injury despite successful treatment of the epicardial coronary artery. Microvascular obstruction (MVO), due to a combination of distal thrombotic embolisation, ischaemia reperfusion injury and related endothelial dysfunction, myocardial oedema and intramyocardial haemorrhage (IMH), is postulated as a mechanism for this residual myocardial injury. When measured by cardiac magnetic resonance (CMR) early after AMI, MVO is predictive of subsequent longer-term outcomes. At the time of PPCI, potential predictors of MVO include AMI characteristics, such as anterior territory AMI, and procedurally assessed characteristics, the most common being reduced or slow intracoronary flow. Many approaches have been proposed to minimise the extent of MVO—thrombus aspiration prior to PCI, glycoprotein IIb/IIIa inhibitors and conventional dose fibrinolysis, with no therapy showing significant clinical efficacy once assessed in randomised trials. On the basis that MVO might be reduced by reducing the overall thrombus burden, low-dose fibrinolytic therapy has been proposed as a potential treatment in this setting. The T-TIME trial examined whether low-dose (one-fifth or one-tenth full dose) intracoronary alteplase would reduce MVO and IMH when administered during PPCI, after reperfusion of the infarct related artery, but before …

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 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.

Supplemental Digital Content is available in the text., Background: The introduction of more sensitive cardiac troponin assays has led to increased recognition of myocardial injury in acute illnesses other than acute coronary syndrome. The Universal Definition of Myocardial Infarction recommends high-sensitivity cardiac troponin testing and classification of patients with myocardial injury based on pathogenesis, but the clinical implications of implementing this guideline are not well understood. Methods: In a stepped-wedge cluster randomized, controlled trial, we implemented a high-sensitivity cardiac troponin assay and the recommendations of the Universal Definition in 48 282 consecutive patients with suspected acute coronary syndrome. In a prespecified secondary analysis, we compared the primary outcome of myocardial infarction or cardiovascular death and secondary outcome of noncardiovascular death at 1 year across diagnostic categories. Results: Implementation increased the diagnosis of type 1 myocardial infarction by 11% (510/4471), type 2 myocardial infarction by 22% (205/916), and acute and chronic myocardial injury by 36% (443/1233) and 43% (389/898), respectively. Compared with those without myocardial injury, the rate of the primary outcome was highest in those with type 1 myocardial infarction (cause-specific hazard ratio [HR] 5.64 [95% CI, 5.12–6.22]), but was similar across diagnostic categories, whereas noncardiovascular deaths were highest in those with acute myocardial injury (cause specific HR 2.65 [95% CI, 2.33–3.01]). Despite modest increases in antiplatelet therapy and coronary revascularization after implementation in patients with type 1 myocardial infarction, the primary outcome was unchanged (cause specific HR 1.00 [95% CI, 0.82–1.21]). Increased recognition of type 2 myocardial infarction and myocardial injury did not lead to changes in investigation, treatment or outcomes. Conclusions: Implementation of high-sensitivity cardiac troponin assays and the recommendations of the Universal Definition of Myocardial Infarction identified patients at high-risk of cardiovascular and noncardiovascular events but was not associated with consistent increases in treatment or improved outcomes. Trials of secondary prevention are urgently required to determine whether this risk is modifiable in patients without type 1 myocardial infarction. Clinical Trial Registration: https://www.clinicaltrials.gov. Unique identifier: NCT01852123.

Background Major disparities between women and men in the diagnosis, management, and outcomes of acute coronary syndrome are well recognized. Objectives The aim of this study was to evaluate the impact of implementing a high-sensitivity cardiac troponin I assay with sex-specific diagnostic thresholds for myocardial infarction in women and men with suspected acute coronary syndrome. Methods Consecutive patients with suspected acute coronary syndrome were enrolled in a stepped-wedge, cluster-randomized controlled trial across 10 hospitals. Myocardial injury was defined as high-sensitivity cardiac troponin I concentration >99th centile of 16 ng/l in women and 34 ng/l in men. The primary outcome was recurrent myocardial infarction or cardiovascular death at 1 year. Results A total of 48,282 patients (47% women) were included. Use of the high-sensitivity cardiac troponin I assay with sex-specific thresholds increased myocardial injury in women by 42% and in men by 6%. Following implementation, women with myocardial injury remained less likely than men to undergo coronary revascularization (15% vs. 34%) and to receive dual antiplatelet (26% vs. 43%), statin (16% vs. 26%), or other preventive therapies (p, Central Illustration

Background Combined positron emission tomography and computed tomography (PET-CT) using 18F-sodium fluoride (18F-NaF) to detect microcalcification provides the opportunity to gain important insights into disease activity in coronary atherosclerosis. However, the relationship between 18F-NaF uptake and progression of coronary calcification has not been determined. Purpose To determine the relationship between 18F-NaF uptake and progression of coronary calcification in patients with clinically stable coronary artery disease (CAD). Methods Patients with established, multivessel CAD underwent 18F-NaF PET-CT and CT coronary calcium scoring at baseline, with repeat CT calcium scoring at one year. Coronary arterial PET uptake was analysed qualitatively and semi-quantitatively in diseased vessels by measuring maximum tissue-to-background ratio (TBRmax) – defined as the maximum standardised uptake value in a plaque divided by mean blood pool activity measured in the right atrium. Coronary calcification was quantified by measuring calcium mass, volume, average calcium density and total Agatston score (AU). Results In total, 185 patients underwent baseline and repeat imaging (median age 66 years, 80% men), and 118 (64%) had increased 18F-NaF uptake in at least one vessel. Median total calcium score, volume, mass and average density were higher in patients with compared to those without increased 18F-NaF uptake (Table 1). At one year, patients with evidence of increased 18F-NaF uptake demonstrated more rapid progression of coronary calcification (97 [39–166] AU) versus those without uptake (35 [7–93] AU; p Coronary calcification at baseline in PET-negative and PET-positive patients All patients (n=185) 18F-NaF Positive (n=118) 18F-NaF Negative (n=67) P value Agatston Score (AU) 381 [107–892] 541 [245–1130] 136 [55–361] p Conclusions Coronary 18F-NaF uptake identifies both patients and individual coronary segments with greater disease and more rapid progression of coronary calcification over one year. Acknowledgement/Funding AstraZeneca (unrestricted educational grant). British Heart Foundation (CH/09/002, RE/13/3/30183, FS/17/79/33226) Wellcome Trust (WT103782AIA).

Background The Universal Definition of Myocardial Infarction recommends the 99th centile diagnostic threshold using a high-sensitivity cardiac troponin (hs-cTn) assay and classification of patients by the etiology of myocardial injury. Whether implementation of this definition improves risk stratification, treatment or outcomes is unknown. Methods In a stepped-wedge cluster randomized controlled trial, we implemented the recommendations of the Universal Definition of Myocardial Infarction in consecutive patients attending the Emergency Department with suspected acute coronary syndrome across ten hospitals in Scotland. All patients with hs-cTnI concentrations above the sex-specific 99th centile were classified according to the Fourth Universal Definition. The primary outcome was myocardial infarction (type 1 or type 4b) or cardiovascular death at 1 year. In this pre-specified secondary analysis, we compared the primary outcome with the secondary outcome of non-cardiovascular death. Based on prior observations of an excess in non-cardiovascular death in patients with type 2 myocardial infarction and myocardial injury, we applied competing risks methodology in all analyses. Results We enrolled 48,282 consecutive patients with suspected acute coronary syndrome. Implementation of the recommendations of the Universal Definition increased the diagnosis of type 1 myocardial infarction by 11% (510/4,471), type 2 myocardial infarction by 22% (205/916), acute myocardial injury by 36% (443/1,233) and chronic myocardial injury by 43% (389/898). The proportion of deaths from a cardiovascular and non-cardiovascular cause differed significantly across diagnostic categories (figure 1). Compared to those without myocardial injury, the rate of the primary outcome was highest in those with type 1 myocardial infarction (cause-specific hazard ratio [csHR] 5.64, 95% confidence interval [CI] 5.12 to 6.22), whereas non-cardiovascular death was highest in those with acute myocardial injury (csHR 2.65, 95%CI 2.33 to 3.01, figure 2). Despite increases in anti-platelet therapy and coronary revascularization after implementation, the primary outcome was unchanged in patients with type 1 myocardial infarction (csHR 1.00, 95%CI 0.82 to 1.21), or in any other category. Conclusion Diagnostic classification by the Universal Definition of Myocardial Infarction identifies patients with different risks of future cardiovascular and non-cardiovascular events. Increases in the diagnosis and treatment of myocardial infarction and injury are not associated with improved clinical outcomes. Conflict of Interest NA

Introduction High-risk coronary atherosclerotic plaque is associated with higher plasma troponin concentrations suggesting ongoing myocardial injury that may be a target for dual antiplatelet therapy. The aim of this study is to determine whether ticagrelor reduces high-sensitivity troponin I concentrations in patients with established coronary artery disease and high-risk coronary plaque using coronary 18F-fluoride positron emission tomography-computed tomography. Methods In a randomised double-blind placebo-controlled trial, patients with multivessel coronary artery disease underwent coronary 18F-fluoride positron emission tomography-computed tomography and measurement of high-sensitivity cardiac troponin I and were randomised (1:1) to ticagrelor 90 mg twice daily or matched placebo. The primary endpoint was troponin I concentration at 30 days in patients with increased coronary 18F-fluoride uptake. Results In total, 202 patients were randomized and 191 met the pre-specified criteria for inclusion in the primary analysis. In patients with increased coronary 18F-fluoride uptake (n=120/191) there was no evidence that ticagrelor had an effect on plasma troponin concentrations at 30 days (ratio of geometric means for ticagrelor versus placebo, 1.11, [95% confidence interval 0.90 to 1.36], p=0.32). Over 1 year, ticagrelor had no effect on troponin concentrations in patients with increased coronary 18F-fluoride uptake (ratio of geometric means, 0.86, 95% confidence interval 0.63 to 1.17, p=0.33). Conclusion Dual antiplatelet therapy with ticagrelor does not reduce plasma troponin concentrations in patients with coronary 18F-fluoride uptake. This suggests that subclinical plaque thrombosis does not contribute to ongoing myocardial injury in this setting.

Introduction Combined positron emission tomography and computed tomography (PET-CT) using the radiotracer 18F-sodium fluoride (18F-NaF) to detect microcalcification provides imaging of both coronary artery anatomy and disease activity simultaneously. While recent studies have suggested that 18F-NaF activity may help identify high-risk coronary atherosclerosis, the role of 18F-NaF uptake in predicting progression of coronary atherosclerosis is unknown. In this study, we aimed to investigate the relationship between baseline coronary arterial 18F-NaF activity and the subsequent progression of coronary arterial calcification in patients with clinically stable coronary artery disease. Methods Patients with clinically stable, multivessel coronary artery disease underwent combined 18F-NaF PET-CT and CT coronary calcium scoring at baseline with repeat CT coronary calcium scoring at one year. Coronary arterial PET uptake was analysed qualitatively and semi-quantitatively in diseased vessels by measuring maximum tissue-to-background ratio (TBRmax) – defined as the maximum standardised uptake value in a plaque divided by the mean blood pool activity measured in the right atrium. Coronary calcification was quantified by measuring calcium mass (mg), volume (mm3), average calcium density (mg/mm3) and total Agatston score (AU). Results One hundred and eighty-three patients who underwent baseline and repeat imaging at one year were included in the study (81% male, median age 66). Of these participants, 116 (63%) had evidence of increased 18F-NaF activity in at least one vessel. Patients with increased 18F-NaF uptake had a higher total calcium score (524[242–1091] AU), volume (491[247–984], mm3) mass (99[46–212] mg) and average calcium density (0.20[0.18–0.23] mg/mm3) at baseline compared to patients without increased uptake (136[55–361] AU, 131[54–343] mm3, 24[11–69] mg, 0.18[0.16–0.20] mg/mm3; P Conclusion Coronary PET-CT using 18F-NaF identifies patients with a higher calcification burden and predicts progression of coronary arterial calcification at one year. Conflict of Interest none

Objectives The goal of this study was to determine whether ticagrelor reduces high-sensitivity troponin I concentrations in patients with established coronary artery disease and high-risk coronary plaque. Background High-risk coronary atherosclerotic plaque is associated with higher plasma troponin concentrations suggesting ongoing myocardial injury that may be a target for dual antiplatelet therapy. Methods In a randomized, double-blind, placebo-controlled trial, patients with multivessel coronary artery disease underwent coronary 18F-fluoride positron emission tomography/coronary computed tomography scanning and measurement of high-sensitivity cardiac troponin I. Patients were randomized (1:1) to receive ticagrelor 90 mg twice daily or matched placebo. The primary endpoint was troponin I concentration at 30 days in patients with increased coronary 18F-fluoride uptake. Results In total, 202 patients were randomized to treatment, and 191 met the pre-specified criteria for inclusion in the primary analysis. In patients with increased coronary 18F-fluoride uptake (120 of 191), there was no evidence that ticagrelor had an effect on plasma troponin concentrations at 30 days (ratio of geometric means for ticagrelor vs. placebo: 1.11; 95% confidence interval: 0.90 to 1.36; p = 0.32). Over 1 year, ticagrelor had no effect on troponin concentrations in patients with increased coronary 18F-fluoride uptake (ratio of geometric means: 0.86; 95% confidence interval: 0.63 to 1.17; p = 0.33). Conclusions Dual antiplatelet therapy with ticagrelor did not reduce plasma troponin concentrations in patients with high-risk coronary plaque, suggesting that subclinical plaque thrombosis does not contribute to ongoing myocardial injury in this setting. (Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND]; NCT02110303), Central Illustration

Aims The relative benefits of computed tomography coronary angiography (CTCA)-guided management in women and men with suspected angina due to coronary heart disease (CHD) are uncertain. Methods and results In this post hoc analysis of an open-label parallel-group multicentre trial, we recruited 4146 patients referred for assessment of suspected angina from 12 cardiology clinics across the UK. We randomly assigned (1:1) participants to standard care alone or standard care plus CTCA. Fewer women had typical chest pain symptoms (n = 582, 32.0%) when compared with men (n = 880, 37.9%; P Conclusion Following the addition of CTCA, women were more likely to be found to have normal coronary arteries than men. This led to more women being reclassified as not having CHD, resulting in more downstream tests and treatments being cancelled. There were similar prognostic benefits of CTCA for women and men.

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 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

We assessed whether non-calcific low-density plaque on coronary CT angiography (CCTA) might improve risk stratification independent of classic risk markers. In the multicenter SCOT-HEART randomized controlled trial, we investigated associations between the risk of fatal or non-fatal myocardial

There are no reliable methods for predicting myocardial infarction (MI) in patients with known coronary artery disease (CAD). 18F-Sodium fluoride (18F-NaF) positron emission tomography (PET) provides an assessment of coronary atherosclerosis activity. We assessed whether it might fulfill this unmet

Suspected stable angina is a common presenting complaint, and the process of establishing the etiology of these symptoms consumes substantial diagnostic resources. Perhaps the greatest challenge relates to individuals with low to intermediate pretest probability for obstructive coronary artery disease. In these patients, additional noninvasive testing—either functional or anatomic—is frequently required to provide patients and clinicians alike with sufficient reassurance that invasive coronary angiography can be deferred. Demand for further investigation continues to grow despite falling baseline risk, and as a consequence, there has been a marked reduction in the prevalence of functionally significant coronary artery disease in patients undergoing stress imaging in recent years (1). Clearly then, there is a need to improve the selection of patients for whom further testing is necessary, and cardiac troponin appears a suitable candidate for such an indication. High-sensitivity assays allow accurate quantification of plasma or serum troponin concentrations in the majority of adults, and numerous studies have demonstrated the prognostic importance of troponin in primary prevention populations (2, 3) and among patients with a variety of stable (4, 5) and acute (6) cardiac disorders. Furthermore, when compared to the reference standard of obstructive disease identified on coronary computed tomography angiography, high-sensitivity troponin I assays have been shown to improve the accuracy of existing risk models for the estimation of pretest probability (7, 8). Within this context, Mueller et al. report in this issue of Clinical Chemistry on a large, well-conducted investigation that reinforces the potential diagnostic value of troponin in the setting of suspected inducible myocardial ischemia (9). An important strength is the use of the most widely available high-sensitivity troponin (hs-cTn) I and T assays with blinded classification of functionally relevant coronary artery disease (fCAD)4, determined from myocardial perfusion imaging with single-photon emission computed …

Introduction Abdominal aortic aneurysm (AAA) growth is non-linear, yet surveillance relies on ultrasound-derived measures of diameter to predict future growth. Biology plays a key part in aneurysm evolution but is not routinely assessed. 18F-Sodium Fluoride (18F-NaF) PET-CT identifies active vascular calcification associated with high-risk atherosclerotic plaque. In patients with AAA, we evaluated the use of 18F-NaF PET-CT to predict aneurysm growth and outcomes. Methods In prospective case-control (n=20 per group) and longitudinal cohort studies (patients with AAA ≥4 cm, n=72), subjects underwent ultrasound, 18F-NaF PET-CT, CT angiography and calcium scoring. Endpoints were aneurysm expansion and AAA repair or rupture. Results Higher uptake of 18F-NaF was observed in AAA vs nonaneurysmal aorta within the same subjects (p=0.004) and aortas of control subjects (p=0.023). 18F-NaF uptake localised to areas of aneurysm disease and active calcification on histology and micro-PET-CT. In the cohort study of predominantly elderly (mean age 73) men (85%), there were 19 AAA repairs (26.4%) and 3 ruptures (4.2%) after 510±196 days. Aneurysms in the highest tertile of 18F-NaF uptake expanded 2.5 times more rapidly than those in the lowest tertile (3.10 [IQR 2.34–5.92 mm/yr] vs 1.24 [IQR 0.52 to 2.92 mm/yr]; p=0.008) and were almost 3 times more likely to rupture or be repaired (15.3% vs 5.6%; log-rank p=0.043), even when adjusted for aneurysm diameter. Agatston score was not associated with future growth or clinical events. Conclusion 18F-NaF uptake is an independent predictor of AAA growth. This is a novel and promising approach to the identification of disease activity in patients with AAA.

Introduction Recently, PET-MR has emerged as a novel imaging technique capable of assessing myocardial disease, inflammation and microcalcification. We aimed to investigate aortic valve and coronary 18F-NaF activity in subjects with aortic stenosis (AS) and coronary disease. Methods 25 patients underwent 18F-NaF PET-MR scanning. PET data was acquired in list mode with a standard Dixon attenuation correction technique. MR angiography was performed following infusion of Gadolinium. PET activity was quantified by calculating standardised uptake values (SUV) and tissue to background ratios (TBR) on fused PET-MR images. Culprit arteries were identified during preceding invasive coronary angiography. Results 22 of 25 patients completed the protocol. Patients with aortic stenosis had higher aortic valve SUVmax and TBRmax (Valve SUV max/left atrial SUV mean) than those without (SUVmax 1.89±0.60 vs 1.15±0.38, p=0.001 and TBRmax 2.87±0.98 vs 1.77±0.43, p=0.001). 13/13 patients with MI had focal 18F-NaF uptake in the culprit vessel with an SUV max and TBR max greater than the proximal referent vessel (SUV max 1.05±0.26 vs 0.74±0.13, p=0.002 and TBRmax 1.64±0.47 vs 1.16±0.26, p=0.004). Conclusion Similar to previous 18F-NaF PET CT studies, 18F-NaF PET-MR uptake is significantly greater in those with confirmed AS than those without. 18F-NaF uptake also accurately identifies culprit arteries in those with recent MI. The results share similarities with recently published valvular and coronary 18F-NaF PET-CT studies and thus promote further research into the utility of cardiovascular PET-MR as a complementary hybrid imaging technique.

Introduction 18F-Fluoride is a highly sensitive positron emission tomography tracer that binds to microcalcification. When combined with computed tomography angiography (PET-CT), it enables simultaneous anatomical and metabolic imaging that non-invasively identifies high-risk plaques in coronary arteries. Uncertainty persists regarding the optimal parameter to quantify metabolic activity in coronary arteries and reliably discriminate 18F-fluoride from the surrounding myocardium. This prospective clinical study evaluates the precision of 18F-fluoride quantification. Methods Thirty patients with multi-vessel coronary artery disease underwent serial 18F-fluoride coronary PET-CT within 2 weeks. Coronary 18F-fluoride maximum activity (SUVMAX) was referenced to left atrial activity (TBRMAX) to evaluate the accuracy of repeated measures. Coefficient of variance of 18F-fluoride was calculated to establish a threshold of precision measurement. Results Twenty patients with stable coronary artery disease and ten patients with recent acute coronary syndrome. All coronary artery segments (n=171) were measured in sextuplicate with diagnostic precision of 18F-fluoride activity (coefficient of variation 0.9. A single plaque TBRMAX >0.9 was present in 90% (n=9/10) of acute coronary syndrome patients and 60% (n=12/20) of stable coronary artery disease patients. On a per-patient level, the overall agreement for visual assessment of 18F-fluoride uptake was good (κ=0.64) and was significantly improved with the application of a quantitative threshold (κ=0.84). Conclusion 18F-fluoride PET-CT provides a precise measurement of calcification activity in the coronary vasculature. These assessment techniques will support prospective trials of this radiotracer as a non-invasive imaging biomarker of plaque vulnerability.

Introduction Sudden unexpected death is a leading cause of cardiovascular mortality worldwide. Coronary plaque rupture is the most frequent cause of all cardiac deaths, however the assessment of coronary artery disease at autopsy is remains a technical challenge. The use of post-mortem computed tomography coronary angiography (CTCA) has been shown to increase the diagnostic accuracy of post-mortem autopsy findings. This study aims to assess the validity of vulnerable plaque imaging using post-mortem CTCA. Methods A cohort of sudden death victims underwent double contrast-enhanced CT coronary angiography. Cannulation of the right common carotid artery with Foley catheter balloon occlusion of the ascending aorta facilitated air injection and contrast enhancement (10% Iohexol, Omnipaque 300, GE Healthcare) of the aortic root and coronary arteries. Contrast enhanced CT images were assessed for features of coronary plaque vulnerability including positive remodelling, spotty calcification, low CT attenuation, napkin ring sign and intra-coronary thrombus in proximal coronary artery segments. Results Eight sudden death victims had a mean age of 63.6 (±8.8) years and 37.5% (n=3) were male. Features of vulnerable plaque (Positive remodelling and low attenuation) were present in 50% of sudden death victims. Obstructive coronary artery disease with vulnerable plaque features were the most frequent observation in sudden death victims. Conclusion Vulnerable plaque can be detected in victims of sudden death. Post-mortem CTCA can be used to identify the coronary pathophysiological mechanisms that result in sudden cardiac death.