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Objectives: The purpose of this study was to investigate whether thoracic 18F-sodium fluoride positron emission tomography (PET) could improve the identification of patients at the highest risk of ischemic stroke. Background: Aortic atherosclerosis represents an important contributor to ischemic stroke risk. Identifying patients with high-risk aortic atheroma could improve preventative treatment strategies for future ischemic stroke. Methods: In a post hoc observational cohort study, we quantified thoracic aortic and coronary 18F-sodium fluoride activity in 461 patients with stable cardiovascular disease undergoing PET combined with computed tomography (CT). Progression of atherosclerosis was assessed by change in aortic and coronary CT calcium volume. Clinical outcomes were determined by the occurrence of ischemic stroke and myocardial infarction. We compared the prognostic utility of 18F-sodium fluoride activity for predicting stroke to clinical risk scores and CT calcium quantification using survival analysis and multivariable Cox regression. Results: After 12.7 ± 2.7 months, progression of thoracic aortic calcium volume correlated with baseline thoracic aortic 18F-sodium fluoride activity (n = 140; r = 0.31; P = 0.00016). In 461 patients, 23 (5%) patients experienced an ischemic stroke and 32 (7%) a myocardial infarction after 6.1 ± 2.3 years of follow-up. High thoracic aortic 18F-sodium fluoride activity was strongly associated with ischemic stroke (HR: 10.3 [3.1 to 34.8]; P = 0.00017), but not myocardial infarction (P = 0.40). Conversely, high coronary 18F-sodium fluoride activity was associated with myocardial infarction (HR: 4.8 [1.9 to 12.2]; P = 0.00095) but not ischemic stroke (P = 0.39). In a multivariable Cox regression model including imaging and clinical risk factors, thoracic aortic 18F-sodium fluoride activity was the only variable associated with ischemic stroke (HR: 8.19 (2.33 to 28.7), P = 0.0010). Conclusions: In patients with established cardiovascular disease, thoracic aortic 18F-sodium fluoride activity is associated with the progression of atherosclerosis and future ischemic stroke. Arterial 18F-sodium fluoride activity identifies localized areas of atherosclerotic disease activity that are directly linked to disease progression and downstream regional clinical atherothrombotic events. (DIAMOND - Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND], NCT02110303; Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis [SALTIRE II], NCT02132026; Novel Imaging Approaches To Identify Unstable Coronary Plaques, NCT01749254; and Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis, NCT01358513).

Background: Assessments of coronary disease activity with 18 F-sodium fluoride positron emission tomography and radiomics-based precision coronary plaque phenotyping derived from coronary computed tomography angiography may enhance risk stratification in patients with coronary artery disease. We sought to investigate whether the prognostic information provided by these 2 approaches is complementary in the prediction of myocardial infarction. Methods: Patients with known coronary artery disease underwent coronary 18 F-sodium fluoride positron emission tomography and coronary computed tomography angiography on a hybrid positron emission tomography/computed tomography scanner. Coronary 18 F-NaF uptake was determined by the coronary microcalcification activity. We performed quantitative plaque analysis of coronary computed tomography angiography datasets and extracted 1103 radiomic features for each plaque. Using weighted correlation network analysis, we derived latent morphological features of coronary lesions which were aggregated to patient-level radiomics nomograms to predict myocardial infarction. Results: Among 260 patients with established coronary artery disease (age, 65±9 years; 83% men), 179 (69%) participants showed increased coronary 18 F-NaF activity (coronary microcalcification activity>0). Over 53 (40–59) months of follow-up, 18 patients had a myocardial infarction. Using weighted correlation network analysis, we derived 15 distinct eigen radiomic features representing latent morphological coronary plaque patterns in an unsupervised fashion. Following adjustments for calcified, noncalcified, and low-density noncalcified plaque volumes and 18 F-NaF coronary microcalcification activity, 4 radiomic features remained independent predictors of myocardial infarction (hazard ratio, 1.46 [95% CI, 1.03–2.08]; P =0.03; hazard ratio, 1.62 [95% CI, 1.04–2.54]; P =0.02; hazard ratio, 1.49 [95% CI, 1.07–2.06]; P =0.01; and hazard ratio, 1.50 (95% CI, 1.05–2.13); P =0.02). Conclusions: In patients with established coronary artery disease, latent coronary plaque morphological features, quantitative plaque volumes, and disease activity on 18 F-sodium fluoride positron emission tomography are additive predictors of myocardial infarction.

Use of CT coronary angiography (CTCA) to evaluate chest pain has rapidly increased over the recent years. While its utility in the diagnosis of coronary artery disease in stable chest pain syndromes is clear and is strongly endorsed by international guidelines, the role of CTCA in the acute setting is less certain. In the low-risk setting, CTCA has been shown to be accurate, safe and efficient but inherent low rates of adverse events in this population and the advent of high-sensitivity troponin testing have left little room for CTCA to show any short-term clinical benefit.In higher-risk populations, CTCA has potential to fulfil a gatekeeper role to invasive angiography. The high negative predictive value of CTCA is maintained while also identifying non-obstructive coronary disease and alternative diagnoses in the substantial group of patients presenting with chest pain who do not have type 1 myocardial infarction. For those with obstructive coronary disease, CTCA provides accurate assessment of stenosis severity, characterisation of high-risk plaque and findings associated with perivascular inflammation. This may allow more appropriate selection of patients to proceed to invasive management with no disadvantage in outcomes and can provide a more comprehensive risk stratification to guide both acute and long-term management than routine invasive angiography.

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.

Coronary artery disease (CAD) remains the leading cause of adult mortality globally. Targeting known modifiable risk factors has had substantial benefit, but there remains a need for new approaches. Improvements in invasive and noninvasive imaging techniques have enabled an increasing recognition of distinct quantitative phenotypes of coronary atherosclerosis that are prognostically relevant. There are marked differences in plaque phenotype, from the high-risk, lipid-rich, thin-capped atheroma to the low-risk, quiescent, eccentric, nonobstructive calcified plaque. Such distinct phenotypes reflect different pathophysiologic pathways and are associated with different risks for acute ischemic events. Noninvasive coronary imaging techniques, such as computed tomography, positron emission tomography, and coronary magnetic resonance imaging, have major potential to accelerate cardiovascular drug development, which has been affected by the high costs and protracted timelines of cardiovascular outcome trials. This may be achieved through enrichment of high-risk phenotypes with higher event rates or as primary end points of drug efficacy, at least in phase 2 trials, in a manner historically performed through intravascular coronary imaging studies. Herein, we provide a comprehensive review of the current technology available and its application in clinical trials, including implications for sample size requirements, as well as potential limitations. In its effort to accelerate drug development, the US Food and Drug Administration has approved surrogate end points for 120 conditions, but not for CAD. There are robust data showing the beneficial effects of drugs, including statins, on CAD progression and plaque stabilization in a manner that correlates with established clinical end points of mortality and major adverse cardiovascular events. This, together with a clear mechanistic rationale for using imaging as a surrogate CAD end point, makes it timely for CAD imaging end points to be considered. We discuss the importance of global consensus on these imaging end points and protocols and partnership with regulatory bodies to build a more informed, sustainable staged pathway for novel therapies.

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.

BACKGROUND: We aimed to establish the observer repeatability and interscan reproducibility of coronary (18)F-sodium-fluoride positron emission tomography (PET) uptake using, a novel semi-automated approach, coronary microcalcification activity (CMA). METHODS: Patients with multivessel coronary artery disease underwent repeated hybrid PET and computed tomography angiography (CTA) imaging (PET/CTA). CMA was defined as the integrated standardized uptake values (SUV) in the entire coronary tree exceeding 2 standard deviations above the background SUV. Coefficients of repeatability between the same observer (intraobserver repeatability), between 2 observers (interobserver repeatability) and coefficient of reproducibility between 2 scans (interscan reproducibility), were determined at vessel and patient level. RESULTS: In 19 patients, CMA was assessed twice in 43 coronary vessels on two PET/CT scans performed 12±5 days apart. There was excellent intraclass correlation for intraobserver and interobserver repeatability as well as interscan reproducibility (all ≥0.991). There was 100% intraobserver, interobserver and interscan agreement for the presence (CMA>0) or absence (CMA=0) of coronary(18)F-NaF uptake. Mean CMA was 3.12±0.62 with coefficients of repeatability of ≤10% for all measures: intraobserver 0.24 and 0.22, interobserver 0.30 and 0.29 and interscan 0.33 and 0.32 at a per-vessel and per-patient level respectively. CONCLUSIONS: CMA is a repeatable and reproducible global measure of coronary atherosclerotic activity.

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

OBJECTIVES: The aim of this study was to describe the potential of 18F-sodium fluoride ( 18F-NaF) positron emission tomography (PET) to identify graft vasculopathy and to investigate the influence of coronary artery bypass graft (CABG) surgery on native coronary artery disease activity and progression. BACKGROUND: As well as developing graft vasculopathy, CABGs have been proposed to accelerate native coronary atherosclerosis.METHODS: Patients with established coronary artery disease underwent baseline 18F-NaF PET, coronary artery calcium scoring, coronary computed tomographic angiography, and 1-year repeat coronary artery calcium scoring. Whole-vessel coronary microcalcification activity (CMA) on 18F-NaF PET and change in calcium scores were quantified in patients with and without CABG surgery. RESULTS: Among 293 participants (mean age 65 ± 9 years, 84% men), 48 (16%) underwent CABG surgery 2.7 years [IQR: 1.4-10.4 years] previously. Although all arterial and the majority (120 of 128 [94%]) of vein grafts showed no 18F-NaF uptake, 8 saphenous vein grafts in 7 subjects had detectable CMA. Bypassed native coronary arteries had 3 times higher CMA values (2.1 [IQR: 0.4-7.5] vs 0.6 [IQR: 0-2.7]; P < 0.001) and greater progression of 1-year calcium scores (118 Agatston unit [IQR: 48-194 Agatston unit] vs 69 [IQR: 21-142 Agatston unit]; P = 0.01) compared with patients who had not undergone CABG, an effect confined largely to native coronary plaques proximal to the graft anastomosis. In sensitivity analysis, bypassed native coronary arteries had higher CMA (2.0 [IQR: 0.4-7.5] vs 0.8 [IQR: 0.3-3.2]; P < 0.001) and faster disease progression (24% [IQR: 16%-43%] vs 8% [IQR: 0%-24%]; P = 0.002) than matched patients (n = 48) with comparable burdens of coronary artery disease and cardiovascular comorbidities in the absence of bypass grafting. CONCLUSIONS: Native coronary arteries that have been bypassed demonstrate increased disease activity and more rapid disease progression than nonbypassed arteries, an observation that appears independent of baseline atherosclerotic plaque burden. Microcalcification activity is not a dominant feature of graft vasculopathy.

Hepatosteatosis was associated with coronary artery disease at CT, including an increased burden of low-attenuation plaque, but this was not independent of other cardiovascular risk factors. PURPOSE: To assess the association between nonalcoholic fatty liver disease (NAFLD) and quantitative atherosclerotic plaque at CT. MATERIALS AND METHODS: In this post hoc analysis of the prospective Scottish Computed Tomography of the HEART trial (November 2010 to September 2014), hepatosteatosis and coronary artery calcium score were measured at noncontrast CT. Presence of stenoses, visually assessed high-risk plaque, and quantitative plaque burden were assessed at coronary CT angiography. Multivariable models were constructed to assess the impact of hepatosteatosis and cardiovascular risk factors on coronary artery disease. RESULTS: Images from 1726 participants (mean age, 58 years ± 9 [SD]; 974 men) were included. Participants with hepatosteatosis (155 of 1726, 9%) had a higher body mass index, more hypertension and diabetes mellitus, and higher cardiovascular risk scores (P < .001 for all) compared with those without hepatosteatosis. They had increased coronary artery calcium scores (median, 43 Agatston units [AU] [interquartile range, 0-273] vs 19 AU [0-225], P = .046), more nonobstructive disease (48% vs 37%, P = .02), and higher low-attenuation plaque burden (5.11% [0-7.16] vs 4.07% [0-6.84], P = .04). However, these associations were not independent of cardiovascular risk factors. Over a median of 4.7 years, there was no evidence of a difference in myocardial infarction between those with and without hepatosteatosis (1.9% vs 2.4%, P = .92). CONCLUSION: Hepatosteatosis at CT was associated with an increased prevalence of coronary artery disease at CT, but this was not independent of the presence of cardiovascular risk factors.Keywords: CT, Cardiac, Nonalcoholic Fatty Liver Disease, Coronary Artery Disease, Hepatosteatosis, Plaque QuantificationClinical trial registration no. NCT01149590 Supplemental material is available for this article. © RSNA, 2022See also commentary by Abohashem and Blankstein in this issue.

Background: We recently introduced the myocardial-ischemic-injury-index (MI3), a machine learning algorithm that predicts the likelihood of myocardial infarction in patients with suspected acute coronary syndrome. Whether this algorithm performs well in routine clinical practice or predicts subsequent events is unknown.Methods: MI3 was validated in a prespecified exploratory analysis from a multi-centre randomised trial that included consecutive patients with suspected acute coronary syndrome undergoing serial high-sensitivity cardiac troponin I measurement. Patients with ST-segment elevation myocardial infarction were excluded. MI3 incorporates age, sex, and two troponin measurements to compute a value (0-100) reflecting an individual’s likelihood of myocardial infarction during the index visit and estimates diagnostic performance metrics at the computed score. Model performance for an index diagnosis of myocardial infarction, and for subsequent myocardial infarction or cardiovascular death at one year was determined using previously defined low- and high-probability MI3 thresholds (1·6 and 49·7, respectively). Findings: In total, 20,761 patients (64±16 years, 46% women) were included of whom 3,272 (15·8%) had myocardial infarction. MI3 had an area under the receiver-operating-characteristic curve of 0·949 (95% confidence interval 0·946-0·952) identifying 12,983 (62·5%) patients as low-probability (sensitivity 99·3% [99·0-99·6%], negative predictive value 99·8% [99·8-99·9%]), and 2,961 (14·3%) as high-probability (specificity 95·0% [94·6-95·3%], positive predictive value 70·4% [68·7-72·0%]). At one year, subsequent myocardial infarction or cardiovascular death occurred more often in high-probability compared to low-probability patients (17·6% [520/2,961] versus 1·5% [197/12,983], PInterpretation: In consecutive patients undergoing serial cardiac troponin measurement for suspected acute coronary syndrome, the MI3 algorithm accurately estimates the likelihood of myocardial infarction and predicts subsequent adverse cardiovascular events.

Background Lipoprotein(a) [Lp(a)] is associated with increased risk of myocardial infarction, although the mechanism for this observation remains uncertain. Objectives This study aims to investigate whether Lp(a) is associated with adverse plaque progression. Methods Lp(a) was measured in patients with advanced stable coronary artery disease undergoing coronary computed tomography angiography at baseline and 12 months to assess progression of total, calcific, noncalcific, and low-attenuation plaque (necrotic core) in particular. High Lp(a) was defined as Lp(a) ≥ 70 mg/dL. The relationship of Lp(a) with plaque progression was assessed using linear regression analysis, adjusting for body mass index, segment involvement score, and ASSIGN score (a Scottish cardiovascular risk score comprised of age, sex, smoking, blood pressure, total and high-density lipoprotein [HDL]–cholesterol, diabetes, rheumatoid arthritis, and deprivation index). Results A total of 191 patients (65.9 ± 8.3 years of age; 152 [80%] male) were included in the analysis, with median Lp(a) values of 100 (range: 82 to 115) mg/dL and 10 (range: 5 to 24) mg/dL in the high and low Lp(a) groups, respectively. At baseline, there was no difference in coronary artery disease severity or plaque burden. Patients with high Lp(a) showed accelerated progression of low-attenuation plaque compared with low Lp(a) patients (26.2 ± 88.4 mm3 vs −0.7 ± 50.1 mm3; P = 0.020). Multivariable linear regression analysis confirmed the relation between Lp(a) and low-attenuation plaque volume progression (β = 10.5% increase for each 50 mg/dL Lp(a), 95% CI: 0.7%-20.3%). There was no difference in total, calcific, and noncalcific plaque volume progression. Conclusions Among patients with advanced stable coronary artery disease, Lp(a) is associated with accelerated progression of coronary low-attenuation plaque (necrotic core). This may explain the association between Lp(a) and the high residual risk of myocardial infarction, providing support for Lp(a) as a treatment target in atherosclerosis., Central Illustration

Coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) and computed tomography (CT) angiography-based quantitative plaque analysis have shown promise in refining risk stratification in patients with coronary artery disease. We combined both of these novel imaging approaches to develop an optimal machine-learning model for the future risk of myocardial infarction in patients with stable coronary disease. Methods: Patients with known coronary artery disease underwent coronary 18F-NaF PET and CT angiography on a hybrid PET/CT scanner. Machine-learning by extreme gradient boosting was trained using clinical data, CT quantitative plaque analysis measures and 18F-NaF PET, and it was tested using repeated 10-fold hold-out testing. Results: Among 293 study participants (65±9 years; 84% male), 22 subjects experienced a myocardial infarction over the 53 [40-59] months of follow-up. On univariable receiver-operator-curve analysis, only 18F-NaF coronary uptake emerged as a predictor of myocardial infarction (c-statistic 0.76, 95% confidence interval [CI] 0.68-0.83). When incorporated into machine-learning models, clinical characteristics showed limited predictive performance (c-statistic 0.64, 95% CI 0.53-0.76;) and were outperformed by a quantitative plaque analysis-based machine-learning model (c-statistic 0.72, 95% CI 0.60-0.84). After inclusion of all available data (clinical, quantitative plaque and 18F-NaF PET), we achieved a substantial improvement (P = 0.008 versus 18F-NaF PET alone) in the model performance (c-statistic 0.85, 95% CI 0.79-0.91). Conclusion: Both 18F-NaF uptake and quantitative plaque analysis measures are additive and strong predictors of outcome in patients with established coronary artery disease. Optimal risk stratification can be achieved by combining clinical data with these approaches in a machine-learning model.

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.

Aortic atherosclerosis represents an important contributor to ischemic stroke risk. Identifying patients with high-risk aortic atheroma could improve preventative treatment strategies for future ischemic stroke.The purpose of this study was to investigate whether thoracicIn a post hoc observational cohort study, we quantified thoracic aortic and coronaryAfter 12.7 ± 2.7 months, progression of thoracic aortic calcium volume correlated with baseline thoracic aorticIn patients with established cardiovascular disease, thoracic aortic

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.

Background 18F-Fluoride uptake denotes calcification activity in aortic stenosis and atherosclerosis. While PET/MR has several advantages over PET/CT, attenuation correction of PET/MR data is challenging, limiting cardiovascular application. We compared PET/MR and PET/CT assessments of 18F-fluoride uptake in the aortic valve and coronary arteries. Methods and results 18 patients with aortic stenosis or recent myocardial infarction underwent 18F-fluoride PET/CT followed immediately by PET/MR. Valve and coronary 18F-fluoride uptake were evaluated independently. Both standard (Dixon) and novel radial GRE) MR attenuation correction (AC) maps were validated against PET/CT with results expressed as tissue-to-background ratios (TBRs). Visually, aortic valve 18F-fluoride uptake was similar on PET/CT and PET/MR. TBRMAX values were comparable with radial GRE AC (PET/CT 1.55±0.33 vs. PET/MR 1.58 ± 0.34, P = 0.66; 95% limits of agreement − 27% to + 25%) but performed less well with Dixon AC (1.38 ± 0.44, P = 0.06; bias (−)14%; 95% limits of agreement − 25% to + 53%). In native coronaries, 18F-fluoride uptake was similar on PET/MR to PET/CT regardless of AC approach. PET/MR identified 28/29 plaques identified on PET/CT; however, stents caused artifact on PET/MR making assessment of 18F-fluoride uptake challenging. Conclusion Cardiovascular PET/MR demonstrates good visual and quantitative agreement with PET/CT. However, PET/MR is hampered by stent-related artifacts currently limiting clinical application.

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.

The last two decades in New Zealand have seen increased availability of primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) and early invasive coronary angiography (ICA) for other high-risk acute coronary syndrome (ACS) patients. One metric to assess the clinical appropriateness of these invasive strategies is to examine the false-positive rate for the investigation (ie, the rate of non-ACS diagnoses).All patients presenting to New Zealand public hospitals with suspected ACS who underwent ICA between 2015 and 2019 were recorded prospectively in the All New Zealand Acute Coronary Syndrome Quality Improvement registry. The cohort was divided according to clinical impression at presentation: (1) suspected STEMI24h and (2) other suspected ACS. The final discharge diagnosis for each patient were obtained from the registry.There were 6,059 (20%) patients with suspected STEMI24h and 24,258 (80%) with other suspected ACS. Of the suspected STEMIs24h, 90.6% had a final diagnosis of STEMI, 3.5% non-ST segment elevation ACS (NSTEACS) and only 5.9% had a non-ACS diagnosis. Of those with other suspected ACS, 80.7% had a final ACS diagnosis. Across all New Zealand district health boards (DHBs), the proportion of non-ACS diagnoses was similar for suspected STEMI presentations. However, for other suspected ACS, the proportions were higher in DHBs with rapid access to coronary interventional facilities than in those without (17.6% vs 7.0%, p0.001).False-positive catheter laboratory activations for suspected STEMI patients are low across New Zealand. The differences in the proportion of non-ACS diagnoses according to DHB interventional capability for other suspected ACS requires further investigation.

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

‘First, do no harm’ are oft misquoted words from Hippocrates’ 2500-year-old work Epidemics . A more complete and accurate translation of his exhortation reads: > The physician must be able to tell the antecedents, know the present, and foretell the future — must mediate these things, and have two special objects in view with regard to disease, namely, to do good or to do no harm.1 This is laudable sentiment but is it realistic for a diagnosis surrounding which much uncertainty remains? Looking back only 20 years, a case report in this publication described spontaneous coronary artery dissection (SCAD) as ‘an extremely rare cause of unstable angina and acute myocardial infarction’.2 That is no longer the case. There has been a surge in the recognition of the condition. One recent study found 33 (2.4%) cases of SCAD among 1375 patients who underwent invasive coronary angiography for acute coronary syndrome in 2019.3 This represents a 10-fold increase in relative diagnostic frequency since an earlier registry (1999–2007) identified only 22 (0.2%) cases from 11 175 patients.4 Presuming that the true incidence is unchanged, this growth reflects a remarkable ‘paradigm shift in clinical appreciation’.5 In contrast to many cardiovascular disorders, SCAD is predominantly a disease affecting middle-aged women with comparatively few traditional atherosclerotic risk factors. The epidemiology, pathophysiology and approach to diagnosis of SCAD have been informed by retrospective observational cohort studies but optimal management remains unclear. Invasive coronary angiography represents the primary imaging modality for identifying the condition, meaning definitive treatment decisions are commonly made in the catheter laboratory and herein lies the challenge. In contrast with atherosclerotic disease, percutaneous coronary intervention (PCI) is associated with less predictable outcomes in …

Background: Valvular calcification is central to the pathogenesis and progression of aortic stenosis, with preclinical and observational studies suggesting that bone turnover and osteoblastic differentiation of valvular interstitial cells are important contributory mechanisms. We aimed to establish whether inhibition of these pathways with denosumab or alendronic acid could reduce disease progression in aortic stenosis. Methods: In a single-center, parallel group, double-blind randomized controlled trial, patients >50 years of age with calcific aortic stenosis (peak aortic jet velocity >2.5 m/s) were randomized 2:1:2:1 to denosumab (60 mg every 6 months), placebo injection, alendronic acid (70 mg once weekly), or placebo capsule. Participants underwent serial assessments with Doppler echocardiography, computed tomography aortic valve calcium scoring, and 18 F-sodium fluoride positron emission tomography and computed tomography. The primary end point was the calculated 24-month change in aortic valve calcium score. Results: A total of 150 patients (mean age, 72±8 years; 21% women) with calcific aortic stenosis (peak aortic jet velocity, 3.36 m/s [2.93–3.82 m/s]; aortic valve calcium score, 1152 AU [655–2065 AU]) were randomized and received the allocated trial intervention: denosumab (n=49), alendronic acid (n=51), and placebo (injection n=25, capsule n=25; pooled for analysis). Serum C-terminal telopeptide, a measure of bone turnover, halved from baseline to 6 months with denosumab (0.23 [0.18–0.33 µg/L] to 0.11 µg/L [0.08–0.17 µg/L]) and alendronic acid (0.20 [0.14–0.28 µg/L] to 0.09 µg/L [0.08–0.13 µg/L]) but was unchanged with placebo (0.23 [0.17–0.30 µg/L] to 0.26 µg/L [0.16–0.31 µg/L]). There were no differences in 24-month change in aortic valve calcium score between denosumab and placebo (343 [198–804 AU] versus 354 AU [76–675 AU]; P=0.41) or alendronic acid and placebo (326 [138–813 AU] versus 354 AU [76–675 AU]; P =0.49). Similarly, there were no differences in change in peak aortic jet velocity or 18 F-sodium fluoride aortic valve uptake. Conclusions: Neither denosumab nor alendronic acid affected progression of aortic valve calcification in patients with calcific aortic stenosis. Alternative pathways and mechanisms need to be explored to identify disease-modifying therapies for the growing population of patients with this potentially fatal condition. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02132026.

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.

Background Standard methods for quantifying positron emission tomography (PET) uptake in the aorta are time consuming and may not reflect overall vessel activity. We describe aortic microcalcification activity (AMA), a novel method for quantifying 18F-sodium fluoride (18F-NaF) uptake in the thoracic aorta. Methods Twenty patients underwent two hybrid 18F-NaF PET and computed tomography (CT) scans of the thoracic aorta less than three weeks apart. AMA, as well as maximum (TBRmax) and mean (TBRmean) tissue to background ratios, were calculated by two trained operators. Intra-observer repeatability, inter-observer repeatability and scan-rescan reproducibility were assessed. Each 18F-NaF quantification method was compared to validated cardiovascular risk scores. Results Aortic microcalcification activity demonstrated excellent intra-observer (intraclass correlation coefficient 0.98) and inter-observer (intraclass correlation coefficient 0.97) repeatability with very good scan-rescan reproducibility (intraclass correlation coefficient 0.86) which were similar to previously described TBRmean and TBRmax methods. AMA analysis was much quicker to perform than standard TBR assessment (3.4min versus 15.1min, P Conclusions AMA is a simple, rapid and reproducible method of quantifying global 18F-NaF uptake across the ascending aorta and aortic arch that correlates with cardiovascular risk scores.

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

ObjectivesNon-contrast CT aortic valve calcium scoring ignores the contribution of valvular fibrosis in aortic stenosis. We assessed aortic valve calcific and non-calcific disease using contrast-enhanced CT.MethodsThis was a post hoc analysis of 164 patients (median age 71 (IQR 66–77) years, 78% male) with aortic stenosis (41 mild, 89 moderate, 34 severe; 7% bicuspid) who underwent echocardiography and contrast-enhanced CT as part of imaging studies. Calcific and non-calcific (fibrosis) valve tissue volumes were quantified and indexed to annulus area, using Hounsfield unit thresholds calibrated against blood pool radiodensity. The fibrocalcific ratio assessed the relative contributions of valve fibrosis and calcification. The fibrocalcific volume (sum of indexed non-calcific and calcific volumes) was compared with aortic valve peak velocity and, in a subgroup, histology and valve weight.ResultsContrast-enhanced CT calcium volumes correlated with CT calcium score (r=0.80, p3/cm2). Fibrocalcific volume correlated with ex vivo valve weight (r=0.72, pConclusionsContrast-enhanced CT assessment of aortic valve calcific and non-calcific volumes correlates with aortic stenosis severity and may be preferable to non-contrast CT when fibrosis is a significant contributor to valve obstruction.

Background The ability to characterize and to quantify the extent of coronary artery disease has the potential to improve the prognostic capability of coronary computed tomography angiography. Although reproducible techniques have been described in those with mild coronary disease, this has yet to be assessed in patients with advanced disease. Methods Twenty patients with known multivessel disease underwent repeated computed tomography coronary angiography, 2 weeks apart. Coronary artery segments were analysed using semi-automated software by two trained observers to determine intraobserver, interobserver and interscan reproducibility. Results Overall, 149 coronary arterial segments were analysed. There was excellent intraobserver and interobserver agreement for all plaque volume measurements (Lin’s coefficient 0.95 to 1.0). There were no substantial interscan differences (P ​> ​0.05 for all) for total (2063 ​± ​1246 ​mm3, mean of differences −35.6 ​mm3), non-calcified (1795 ​± ​910 ​mm3, mean of differences −4.3 ​mm3), calcified (298 ​± ​425 ​mm3, mean of differences −31.3 ​mm3) and low-attenuation (13 ​± ​13 ​mm3, mean of differences −2.6 ​mm3) plaque volumes. Interscan agreement was highest for total and noncalcified plaque volumes. Calcified and low-attenuation plaque (−236.6 to 174 ​mm3 and -15.8 to 10.5 ​mm3 respectively) had relatively wider 95% limits of agreement reflecting the lower absolute plaque volumes. Conclusion In the presence of advanced coronary disease, semi-automated plaque quantification provides excellent reproducibility, particularly for total and non-calcified plaque volumes. This approach has major potential to assess change in disease over time and optimize risk stratification in patients with established coronary artery disease.

Background Positron emission tomography (PET) using

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.

Early microcalcification is a feature of coronary plaques with an increased propensity to rupture and to cause acute coronary syndromes. In this ex vivo imaging study of coronary artery specimens, the non-invasive imaging radiotracer, 18F-fluoride, was highly selective for hydroxyapatite deposition in atherosclerotic coronary plaque. Specifically, coronary 18F-fluoride uptake had a high signal to noise ratio compared with surrounding myocardium that makes it feasible to identify coronary mineralisation activity. Areas of 18F-fluoride uptake are associated with osteopontin, an inflammation-associated glycophosphoprotein that mediates tissue mineralisation, and Runt-related transcription factor 2, a nuclear protein involved in osteoblastic differentiation. These results suggest that 18F-fluoride is a non-invasive imaging biomarker of active coronary atherosclerotic mineralisation.

Introduction: Effective management of ambulatory heart failure (HF) requires active patient (pt) participation. In telemonitoring of weights and symptoms, pt adherence to transmission is often halved within 6 months (M). Although ambulatory pulmonary pressure-guided management decreases hospitalizations and improves quality of life, the time course of pt perception of illness and sense of security in relation to monitoring frequency is not known. Hypothesis: Pts will perceive decreased impact of their HF during pulmonary pressure-guided management, which may contribute to their engagement in transmission of ambulatory PAP. Methods: The post-approval study for the implanted PA sensor was amended to include serial measurements of pt reported outcomes, (PRO, n=143), including the Brief Illness Perception Questionnaire (BIPQ). Treatment was adjusted to a target PA diastolic pressure 8 to 20 mmHg and adherence to transmitting pressure data from home was collected. Results: In the PRO cohort, mean age was 68 years, 58% were male, and 55% with HFpEF. Negative illness perception (BIPQ) decreased during each measurement interval. Pts reported improvement in symptoms, sense of security, sense of control and less impact of illness on their emotions at each time point, equally with HFpEF or HFrEF. In this cohort pt adherence to transmitting pressures was high throughout 24 M, Fig.1. Perception of illness was most favorable at 2 years, at which time there was a slight decline in transmission frequency. Conclusions: Pt perception of HF was positively impacted during ambulatory hemodynamic monitoring including improvement in symptoms, less emotional effect of illness, improved sense of security and control over their HF throughout follow-up. This was associated with high-level pt adherence to pressure data transmission. The optimal level of chronic monitoring for stable pts to maintain clinical benefit while minimizing disease awareness beyond 2 years is still unknown.

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.