Search

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: Bioprosthetic valve thrombosis may have implications for valve function and durability.OBJECTIVES: Using a novel glycoprotein IIb/IIIa receptor radiotracer 18F-GP1, we investigated whether positron emission tomography (PET)-computed tomography (CT) could detect thrombus formation on bioprosthetic aortic valves.METHODS: Ex vivo experiments were performed on human platelets and explanted bioprosthetic aortic valves. In a prospective cross-sectional study, patients with either bioprosthetic or normal native aortic valves underwent echocardiography, CT angiography, and 18F-GP1 PET-CT.RESULTS: Flow cytometric analysis, histology, immunohistochemistry, and autoradiography demonstrated selective binding of 18F-GP1 to activated platelet glycoprotein IIb/IIIa receptors and thrombus adherent to prosthetic valves. In total, 75 participants were recruited: 53 with bioprosthetic valves (median time from implantation 37 months [IQR: 12-80 months]) and 22 with normal native aortic valves. Three participants had obstructive valve thrombosis, and a further 3 participants had asymptomatic hypoattenuated leaflet thickening on CT angiography. All bioprosthetic valves, but none of the native aortic valves, demonstrated focal 18F-GP1 uptake on the valve leaflets: median maximum target-to-background ratio 2.81 (IQR: 2.29-3.48) vs 1.43 (IQR: 1.28-1.53) (P < 0.001). Higher 18F-GP1 uptake was independently associated with duration of valve implantation and hypoattenuated leaflet thickening. All 3 participants with obstructive valve thrombosis were anticoagulated for 3 months, leading to resolution of their symptoms, improvement in mean valve gradients, and a reduction in 18F-GP1 uptake.CONCLUSIONS: Adherence of activated platelets is a common and sustained finding on bioprosthetic aortic valves. 18F-GP1 uptake is higher in the presence of thrombus, regresses with anticoagulation, and has potential use as an adjunctive clinical tool. (18F-GP1 PET-CT to Detect Bioprosthetic Aortic Valve Thrombosis; NCT04073875).

Background Important disparities in the treatment and outcomes of women and men with atrial fibrillation (AF) are well recognized. Whether introduction of direct oral anticoagulants has reduced disparities in treatment is uncertain. Methods and Results All patients who had an incident hospitalization from 2010 to 2019 with nonvalvular AF in Scotland were included in the present cohort study. Community drug dispensing data were used to determine prescribed oral anticoagulation therapy and comorbidity status. Logistic regression modeling was used to evaluate patient factors associated with treatment with vitamin K antagonists and direct oral anticoagulants. A total of 172 989 patients (48% women [82 833 of 172 989]) had an incident hospitalization with nonvalvular AF in Scotland between 2010 and 2019. By 2019, factor Xa inhibitors accounted for 83.6% of all oral anticoagulants prescribed, while treatment with vitamin K antagonists and direct thrombin inhibitors declined to 15.9% and 0.6%, respectively. Women were less likely to be prescribed any oral anticoagulation therapy compared with men (adjusted odds ratio [aOR], 0.68 [95% CI, 0.67–0.70]). This disparity was mainly attributed to vitamin K antagonists (aOR, 0.68 [95% CI, 0.66–0.70]), while there was less disparity in the use of factor Xa inhibitors between women and men (aOR, 0.92 [95% CI, 0.90–0.95]). Conclusions Women with nonvalvular AF were significantly less likely to be prescribed vitamin K antagonists compared with men. Most patients admitted to the hospital in Scotland with incident nonvalvular AF are now treated with factor Xa inhibitors and this is associated with fewer treatment disparities between women and men.

Myocardial fibrosis is the heart’s common healing response to injury. While initially seeking to optimize the strength of diseased tissue, fibrosis can become maladaptive, producing stiff poorly functioning and pro-arrhythmic myocardium. Different patterns of fibrosis are associated with different myocardial disease states, but the presence and quantity of fibrosis largely confer adverse prognosis. Current imaging techniques can assess the extent and pattern of myocardial scarring, but lack specificity and detect the presence of established fibrosis when the window to modify this process may have ended. For the first time, novel molecular imaging methods, including gallium-68 (68Ga)-fibroblast activation protein inhibitor positron emission tomography (68Ga-FAPI PET), may permit highly specific imaging of fibrosis activity. These approaches may facilitate earlier fibrosis detection, differentiation of active vs. end-stage disease, and assessment of both disease progression and treatment–response thereby improving patient care and clinical outcomes.

Highlights • Activated platelets are associated with AS. • Platelets are a player in bioprosthetic valve dysfunction. • Randomized trials have assessed clinical outcomes with various antiplatelet/anticoagulation strategies in patients undergoing TAVR., Summary Aortic stenosis (AS) is the most common heart valve disease requiring surgery in developed countries, with a rising global burden associated with aging populations. The predominant cause of AS is believed to be driven by calcific degeneration of the aortic valve and a growing body of evidence suggests that platelets play a major role in this disease pathophysiology. Furthermore, platelets are a player in bioprosthetic valve dysfunction caused by their role in leaflet thrombosis and thickening. This review presents the molecular function of platelets in the context of recent and rapidly evolving understanding the role of platelets in AS, both of the native aortic valve and bioprosthetic valves, where there remain concerns about the effects of subclinical leaflet thrombosis on long-term prosthesis durability. This review also presents the role of antiplatelet and anticoagulation therapies on modulating the impact of platelets on native and bioprosthetic aortic valves, highlighting the need for further studies to determine whether these therapies are protective and may increase the life span of surgical and transcatheter aortic valve implants. By linking molecular mechanisms through which platelets drive disease of native and bioprosthetic aortic valves with studies evaluating the clinical impact of antiplatelet and antithrombotic therapies, we aim to bridge the gaps between our basic science understanding of platelet biology and their role in patients with AS and ensuing preventive and therapeutic implications., Central Illustration

Background Discordant echocardiographic measurements are observed in up to one third of patients with aortic stenosis (AS), in whom computed tomography (CT) derived aortic valve calcium scoring is now recommended. Nonetheless, CT calcium scoring only evaluates calcific valve thickening and is unable to assess non-calcific fibrotic thickening, which could be a relevant contributor of AS. Aim of the present study was to generate a quick and robust contrast-CT method based on a gaussian mixture model (GMM) for the assessment of fibro-calcific aortic valve thickening in AS patients, and to investigate its reproducibility and associations with echocardiographic parameters of AS severity and disease progression. Methods A post-hoc analysis of 136 patients with calcific AS (24 with severe, 81 moderate and 31 mild AS) enrolled in the SALTIRE2 trial (Study Investigating the Effects of Drugs used to Treat Osteoporosis on the Progression of Aortic Stenosis) (NCT-02132026) was performed. Aortic valve fibrocalcific volume was calculated using a GMM applied on contrast-CT at baseline and at 1-year follow up. The software estimated the Hounsfield Units (HU) distribution of 3 compartments (blood pool, non-calcific and calcific tissue) within the aortic valve volume of interest, automatically generating thresholds for non-calcific and calcific volumes, respectively computed as the lower 99.7 and the upper 99.7 percentile of the blood pool HU distribution (Figure). Thus, Fibrocalcific volume was measured as the sum of non-calcific and calcific volumes, indexed for CT annulus area and compared to echo parameters of AS severity. Scan-rescan reproducibility and analysis of AS progression were also assessed. Results Image analysis took 5.8 ± 1.0 minutes per scan and showed excellent scan-rescan reproducibility (mean difference -1%, limits of agreement -9% to 7%). Indexed-fibrocalcific volume correlated well with echocardiographic aortic peak velocity (rho=0.70, p Conclusions This contrast CT-based approach based on a GMM is able to provide robust and relatively rapid assessment of fibrocalcific thickening in patients with AS. Fibrocalcific volume measured using this method, correlates well with other markers of AS severity, predicts disease progression and holds promise in tracking disease progression and response to novel therapies.

BackgroundThe diagnosis and management of myocardial infarction is increasingly complex andestablishing the presence of intracoronary thrombosis has major implications for both theclassification and treatment of myocardial infarction.ObjectivesTo investigate whether positron emission tomography (PET) and computed tomography (CT)could non-invasively detect in vivo thrombus formation in human coronary arteries using anovel glycoprotein IIb/IIIa receptor antagonist-based radiotracer, 18F-GP1.MethodsIn a single centre observational case-control study, patients with or without acute myocardialinfarction underwent coronary 18F-GP1 PET-CT angiography. Coronary artery 18F-GP1 uptakewas assessed visually and quantified using maximum target-to-background ratios.Results18F-GP1 PET-CT angiography was performed in 49 patients with, and 50 patients without,acute myocardial infarction (61±9 years, 75% male). Coronary 18F-GP1 uptake was apparentin 39 (80%) of the 49 culprit lesions in patients with acute myocardial infarction. False negativescans appeared to relate to time delays to scan conduct and low thrombus burden in smallcalibre distal arteries. On multivariable regression analysis, culprit vessel status was the onlyindependent variable associated with higher 18F-GP1 uptake. Extra-coronary cardiac 18F-GP1findings included a high frequency of infarct-related intramyocardial uptake (35%) as well asleft ventricular (8%) or left atrial (2%) thrombus.ConclusionsCoronary 18F-GP1 PET-CT angiography is the first non-invasive selective technique to identifyin vivo coronary thrombosis in patients with acute myocardial infarction. This novel approachcan further define the role and location of thrombosis within the heart and has the potential toinform the diagnosis, management, and treatment of patients with acute myocardial infarction.

Objectives The authors explored the development and validation of machine-learning models for augmenting the echocardiographic grading of aortic stenosis (AS) severity. Background In AS, symptoms and adverse events develop secondarily to valvular obstruction and left ventricular decompensation. The current echocardiographic grading of AS severity focuses on the valve and is limited by diagnostic uncertainty. Methods Using echocardiography (ECHO) measurements (ECHO cohort, n = 1,052), we performed patient similarity analysis to derive high-severity and low-severity phenogroups of AS. We subsequently developed a supervised machine-learning classifier and validated its performance with independent markers of disease severity obtained using computed tomography (CT) (CT cohort, n = 752) and cardiovascular magnetic resonance (CMR) imaging (CMR cohort, n = 160). The classifier’s prognostic value was further validated using clinical outcomes (aortic valve replacement [AVR] and death) observed in the ECHO and CMR cohorts. Results In 1,964 patients from the 3 multi-institutional cohorts, 1,346 (68%) subjects had either nonsevere or discordant AS severity. Machine learning identified 1,117 (57%) patients as having high-severity and 847 (43%) as having low-severity AS. High-severity patients in CT and CMR cohorts had higher valve calcium scores and left ventricular mass and fibrosis, respectively than the low-severity group. In the ECHO cohort, progression to AVR and progression to death in patients who did not receive AVR was faster in the high-severity group. Compared with the conventional classification of disease severity, machine-learning–based severity classification improved discrimination (integrated discrimination improvement: 0.07; 95% confidence interval: 0.02 to 0.12) and reclassification (net reclassification improvement: 0.17; 95% confidence interval: 0.11 to 0.23) for the outcome of AVR at 5 years. For both ECHO and CMR cohorts, we observed prognostic value of the machine-learning classifications for subgroups with asymptomatic, nonsevere or discordant AS. Conclusions Machine learning can integrate ECHO measurements to augment the classification of disease severity in most patients with AS, with major potential to optimize the timing of AVR.

Learning objectives Aortic stenosis is the archetypal heart valve disease with which many doctors, cardiologists or otherwise, retain the most familiarity. The global healthcare burden of aortic stenosis continues to rise, yet it remains one of the last major cardiovascular diseases for which we have no preventative or disease-modifying medical therapy. Aortic valve replacement is the only ‘curative’ intervention and carries attendant risks, both peri-procedural and remote. Thus, the decision to offer intervention must be carefully considered and taken with the final objective that governs most treatments in mind: to improve symptoms or prognosis. There is also substantial debate surrounding the optimal timing of intervention. Intervene too early and patients may be unnecessarily exposed to the risks of valve replacement. Intervene too late and some patients may sustain irreversible cardiac damage that is associated with an increased risk of heart failure and death. Valve replacement in symptomatic patients with severe aortic stenosis is usually uncontroversial, given their poor prognosis and the strong probability of improving their quality of life. Decisions regarding the management of patients with asymptomatic, isolated, severe aortic stenosis, however, are more complex. In this group, the predominant purpose of intervention would be to improve prognosis. In the absence of robust data, standard care in most cases has remained close observation, usually until symptoms develop.1–3 Implicit in this strategy is the concept that patients with asymptomatic severe aortic stenosis have a very good prognosis, and that there is consequently no net benefit to aortic valve replacement. However, this paradigm has latterly become the subject of scrutiny for several reasons. Symptom assessment is frequently challenging in elderly, …

Background: Despite improvements in management, infective endocarditis remains associated with high mortality and morbidity. We describe temporal changes in the incidence, microbiology, and outcomes of infective endocarditis and the effect of changes in national antibiotic prophylaxis guidelines on incident infective endocarditis. Methods: Using a Scotland-wide, individual-level linkage approach, all patients hospitalized with infective endocarditis from 1990 to 2014 were identified and linked to national microbiology, prescribing, and morbidity and mortality datasets. Linked data were used to evaluate trends in the crude and age- and sex-adjusted incidence and outcomes of infective endocarditis hospitalizations. From 2008, microbiology data and associated outcomes adjusted for patient demographics and comorbidity were also analyzed. An interrupted time series analysis was performed to evaluate incidence before and after changes to national antibiotic prophylaxis guidelines. Results: There were 7638 hospitalizations (65±17 years, 51% females) with infective endocarditis. The estimated crude hospitalization rate increased from 5.3/100 000 (95% CI, 4.8-5.9) to 8.6/100 000 (95% CI, 8.1–9.1) between 1990 and 1995 but remained stable thereafter. There was no change in crude incidence following the 2008 change in antibiotic prophylaxis guidelines (relative risk of change 1.06 [95% CI, 0.94–1.20]). The incidence rate in patients >80 years of age doubled from 1990 to 2014 (17.7/100 000 [95% CI, 13.4–23.3] to 37.9/100 000 [95% CI, 31.5–45.5]). The predicted 1-year age- and comorbidity-adjusted case fatality rate for a 65-year-old patient decreased in women (27.3% [95% CI, 24.6–30.2] to 23.7% [95% CI, 21.1–26.6]) and men (30.7% [95% CI, 27.7–33.8] to 26.8% [95% CI, 24.0–29.7]) from 1990 to 2014. Blood culture data were available from 2008 (n=2267/7638, 30%), with positive blood cultures recorded in 42% (950/2267). Staphylococcus (403/950, 42.4%) and streptococcus (337/950, 35.5%) species were most common. Staphylococcus aureus and enterococcus had the highest 1-year mortality (adjusted odds ratio 4.34 [95% CI, 3.12–6.05] and 3.41 [95% CI, 2.04–5.70], respectively). Conclusions: Despite changes in antibiotic prophylaxis guidelines, the crude incidence of infective endocarditis has remained stable. However, the incidence rate has doubled in the elderly. Positive blood cultures were observed in less than half of patients, with Staphylococcus aureus and enterococcus bacteremia associated with worse outcomes.

A 38-year-old man presented with 4 weeks of exertional dyspnoea and abdominal bloating, culminating in an acute episode of paroxysmal nocturnal dyspnoea. He was known to have a cardiomyopathy based on history and echocardiography but had been lost to follow-up before further investigations were completed. There was no chest pain, infective prodrome or recent travel. He smoked tobacco occasionally and drank approximately 50 units of alcohol per week. On examination, blood pressure was 110/80 and heart rate was 90. The jugular venous pressure was elevated. An S3 was heard but lungs were clear to auscultation. The abdomen was soft and mildly tender. Inflammatory markers and renal function were normal and high-sensitivity troponin I was 14 ng/L. Soon after …

A 38-year-old Caucasian man presented with central chest heaviness at rest. There was a history of mild abdominal discomfort but no infective prodrome. There was no antecedent exertional or nocturnal chest pain. The patient had a 26-pack-year history of tobacco smoking and no known comorbidities. Recent social history was unremarkable. Examination and vital signs were normal. An ECG taken with mild residual chest discomfort is shown in figure 1A. High-sensitivity troponin I was 74 ng/L, peaking at 1405 ng/L. Echocardiography demonstrated a structurally normal heart with normal biventricular function. Medical therapy for an acute coronary syndrome was commenced and invasive coronary angiography was performed (figure 1B,C). Figure 1 Index presentation. (A) ECG and (B) coronary angiography: right anterior oblique–caudal view. (C) Coronary angiography: anterior–posterior cranial view. Insets show the proximal …

Acquired ventricular wall ruptures can be life-threatening. Depending on the pathological features and anatomy, surgical repair can be technically challenging and may be associated with high morbidity and mortality. We present 3 successful percutaneous repairs of different ruptures that used a variety of techniques. (Level of Difficulty: Advanced.), Central Illustration, Acquired ventricular wall ruptures can be life-threatening. Depending on the pathological features and anatomy, surgical repair can be technically…

Supplemental Digital Content is available in the text., Background: Major uncertainties remain regarding disease activity within the retained native aortic valve, and regarding bioprosthetic valve durability, after transcatheter aortic valve implantation (TAVI). We aimed to assess native aortic valve disease activity and bioprosthetic valve durability in patients with TAVI in comparison with subjects with bioprosthetic surgical aortic valve replacement (SAVR). Methods: In a multicenter cross-sectional observational cohort study, patients with TAVI or bioprosthetic SAVR underwent baseline echocardiography, computed tomography angiography, and 18F-sodium fluoride (18F-NaF) positron emission tomography. Participants (n=47) were imaged once with 18F-NaF positron emission tomography/computed tomography either at 1 month (n=9, 19%), 2 years (n=22, 47%), or 5 years (16, 34%) after valve implantation. Patients subsequently underwent serial echocardiography to assess for changes in valve hemodynamic performance (change in peak aortic velocity) and evidence of structural valve dysfunction. Comparisons were made with matched patients with bioprosthetic SAVR (n=51) who had undergone the same imaging protocol. Results: In patients with TAVI, native aortic valves demonstrated 18F-NaF uptake around the outside of the bioprostheses that showed a modest correlation with the time from TAVI (r=0.36, P=0.023). 18F-NaF uptake in the bioprosthetic leaflets was comparable between the SAVR and TAVI groups (target-to-background ratio, 1.3 [1.2–1.7] versus 1.3 [1.2–1.5], respectively; P=0.27). The frequencies of imaging evidence of bioprosthetic valve degeneration at baseline were similar on echocardiography (6% versus 8%, respectively; P=0.78), computed tomography (15% versus 14%, respectively; P=0.87), and positron emission tomography (15% versus 29%, respectively; P=0.09). Baseline 18F-NaF uptake was associated with a subsequent change in peak aortic velocity for both TAVI (r=0.7, 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

Background Coronary artery thrombus is typically present in type 1 myocardial infarction, but small volumes in the setting of an uncertain culprit lesion may be beyond the detection limit of current imaging modalities. Purpose Using a novel glycoprotein IIb/IIIa-receptor radiotracer, 18F-GP1, we investigated whether positron emission tomography-computed tomography (PET-CT) could detect thrombus formation in coronary arteries. Methods In a single centre cross-sectional study, patients over 40 years of age with myocardial infarction were recruited after myocardial infarction and underwent underwent CT angiography and 18F-GP1 PET-CT. Stable patients with and without coronary artery disease formed a control cohort. Coronary artery 18F-GP1 uptake was visually assessed and quantified using maximum target-to-background ratios (TBRmax). Results Ninety-four (44 post-myocardial infarction and 50 control patients) were included in the cross-sectional analysis. The mean age of the post-myocardial infarction group was 61±9 years, three-quarters were male and two thirds had presented with ST elevation on electrocardiography. 34 (80%) patients post-myocardial infarction, but none of the control patients, demonstrated focal 18F-GP1 uptake in the coronary arteries. Of 42 vessels with an angiographic culprit lesion, 35 (83%) had 18F-GP1 uptake which was significantly higher than non-culprit vessels (p A patient with ectatic vessel and visual thrombus demonstrated the most intense 18F-GP1 uptake (TBRmax 2.0, highest in the cohort) in the region of heaviest thrombus burden (Figure 2). Extra-coronary uptake was seen in regions of left ventricular thrombus, left atrial appendage thrombus, pulmonary thromboembolism and intramyocardial microvascular obstruction. Conclusions 18F-GP1 PET-CT is able to detect coronary artery thrombus in culprit lesions following myocardial infarction, as well as extra-coronary thrombotic pathologies that may be important in guiding patient management. 18F-GP1 is highly specific in recognising a culprit lesion from a non-culprit lesion both visually as well as quantitatively. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Figure 1Figure 2

Background First-phase ejection fraction (EF1; the ejection fraction measured during active systole up to the time of maximal aortic flow) measured by transthoracic echocardiography (TTE) is a powerful predictor of outcomes in patients with aortic stenosis. We aimed to assess whether cardiovascular magnetic resonance (CMR) might provide more precise measurements of EF1 than TTE and to examine the correlation of CMR EF1 with measures of fibrosis. Methods In 141 patients with at least mild aortic stenosis, we measured CMR EF1 from a short-axis 3D stack and compared its variability with TTE EF1, and its associations with myocardial fibrosis and clinical outcome (aortic valve replacement (AVR) or death). Results Intra- and inter-observer variation of CMR EF1 (standard deviations of differences within and between observers of 2.3% and 2.5% units respectively) was approximately 50% that of TTE EF1. CMR EF1 was strongly predictive of AVR or death. On multivariable Cox proportional hazards analysis, the hazard ratio for CMR EF1 was 0.93 (95% confidence interval 0.89–0.97, p = 0.001) per % change in EF1 and, apart from aortic valve gradient, CMR EF1 was the only imaging or biochemical measure independently predictive of outcome. Indexed extracellular volume was associated with AVR or death, but not after adjusting for EF1. Conclusions EF1 is a simple robust marker of early left ventricular impairment that can be precisely measured by CMR and predicts outcome in aortic stenosis. Its measurement by CMR is more reproducible than that by TTE and may facilitate left ventricular structure–function analysis.

In an era of incremental gains in preventative cardiology, the ongoing pursuit of reduction in ischaemic events has led to advances in the antiplatelet armamentarium that is available for use after percutaneous coronary intervention (PCI). The protection offered by antithrombotic may be enhanced by extending their duration of use, or through the application of more potent drugs—longer, stronger or both. The corollary, of course, is the potential for increased bleeding, which may carry significant associated morbidity and mortality. What combination and duration of aspirin, clopidogrel, ticagrelor or prasugrel is optimal in a given patient? This is a nuanced question that is pertinent in both acute and chronic coronary syndromes. Current guidelines broadly recommend the use of dual antiplatelet therapy (DAPT) for at least 12 months in patients undergoing PCI for an acute coronary syndrome (ACS) and at least 6 months in chronic coronary syndrome, with the proviso that shorter duration DAPT may be considered in patients at high risk of bleeding.1 2 Within these boundaries, clinicians must gauge the ischaemic and bleeding risk of an individual patient in order to optimise their DAPT regime. The advent of potent P2Y12 inhibitors and iterative improvements in drug-eluting stents (DES), the latest of which have thinner struts, improved drug delivery and are associated with lower rates of stent thrombosis and restenosis, have raised the possibility of a shorter duration of DAPT after PCI, with the goal of minimising bleeding while offering non-inferior protection from ischaemic events. Multiple randomised trials have studied various combinations of drugs and DAPT duration, including short-term DAPT followed by aspirin monotherapy and short-term DAPT followed by P2Y12 inhibitor monotherapy.3–5 Although somewhat heterogenous, collectively, these data suggest that short-term DAPT may be considered as a safe option in selected individuals. The authors of the current paper conducted one …

Determining the underlying etiology of chest pain remains a mainstay of modern cardiological practice and is focused on identifying coronary artery disease to improve both symptoms and prognosis. In the current age of multi-modality imaging, the expanding repertoire of tests has subjected clinicians to a tyranny of choices. In whom should we perform further investigations? What non-invasive modality should be used? Which test is the best gatekeeper for invasive coronary angiography? In this week's American Heart Journal, Houssany-Pissot and colleagues present real-world data from a large French cohort of patients who present with suspected stable coronary artery disease undergoing invasive coronary angiography. Their findings demonstrate that compared to functional testing, coronary computed tomography angiography is associated with fewer normal invasive coronary angiograms and more patients with actionable disease. Moreover, this was apparent irrespective of the pre-test probability of obstructive coronary artery disease. The consistency of this study with data from randomised trials and observational registries leads us to agree that computed tomography has primacy as gatekeeper for the cardiac catheter laboratory irrespective of the level of pre-test probability. This latest addition to the growing and large body of evidence does beg the question of why guidelines do not now recommend CCTA as the first line test of choice for the non-invasive investigation of all patients with stable coronary artery disease?

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.

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

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.

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.

Background Cardiovascular magnetic resonance (CMR) is increasingly used for risk stratification in aortic stenosis (AS). However, the relative prognostic power of CMR markers and their respective thresholds remains undefined. Objectives Using machine learning, the study aimed to identify prognostically important CMR markers in AS and their thresholds of mortality. Methods Patients with severe AS undergoing AVR (n = 440, derivation; n = 359, validation cohort) were prospectively enrolled across 13 international sites (median 3.8 years’ follow-up). CMR was performed shortly before surgical or transcatheter AVR. A random survival forest model was built using 29 variables (13 CMR) with post-AVR death as the outcome. Results There were 52 deaths in the derivation cohort and 51 deaths in the validation cohort. The 4 most predictive CMR markers were extracellular volume fraction, late gadolinium enhancement, indexed left ventricular end-diastolic volume (LVEDVi), and right ventricular ejection fraction. Across the whole cohort and in asymptomatic patients, risk-adjusted predicted mortality increased strongly once extracellular volume fraction exceeded 27%, while late gadolinium enhancement >2% showed persistent high risk. Increased mortality was also observed with both large (LVEDVi >80 mL/m2) and small (LVEDVi ≤55 mL/m2) ventricles, and with high (>80%) and low (≤50%) right ventricular ejection fraction. The predictability was improved when these 4 markers were added to clinical factors (3-year C-index: 0.778 vs 0.739). The prognostic thresholds and risk stratification by CMR variables were reproduced in the validation cohort. Conclusions Machine learning identified myocardial fibrosis and biventricular remodeling markers as the top predictors of survival in AS and highlighted their nonlinear association with mortality. These markers may have potential in optimizing the decision of AVR.

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 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.

Background 18F-GP1 is a novel radiotracer with a high affinity for the platelet glycoprotein IIb/IIIa receptor. Subclinical bioprosthetic valve thrombus has been postulated as a trigger for accelerated valve degeneration. Purpose To determine the feasibility of 18F-GP1 positron-emission tomography-computed tomography (PET-CT) for the detection of subclinical bioprosthetic aortic valve thrombus. Methods (i) Explanted degenerated aortic valve prostheses underwent histology and imaging. (ii) In a prospective observational study, patients with bioprosthetic aortic valve replacement (AVR) underwent echocardiography and 18F-GP1 PET-CT. Valves were assessed for hypoattenuating leaflet thickening (HALT), hypo-attenuation affection leaflet motion (HAM) and GP1 uptake. Results (i) GP1 correlated with thrombus on explanted valves (Figure). (ii) The first 6 patients (Table) were asymptomatic and had normally functioning surgical bioprostheses on echocardiography. At a median of 166 (range 122–189) days post-AVR, no patients had HALT or HAM on CT. There was avid focal GP1 uptake on the leaflets of all 6 patients which appeared most prominent along the leaflet edges (Figure). Only one patient had focal uptake in the valve frame, remote from the leaflets. In a separate cohort undergoing 18F-GP1 PET-CT for other conditions, there was no uptake on normal, native aortic valves (n=8). Conclusion For the first time, we demonstrate that 18F-GP1 PET-CT is a highly sensitive method of assessing platelet activation on bioprosthetic aortic valves. Despite the absence of CT evidence, early thrombus appeared to be a universal finding on recently implanted valve prostheses. The biological and clinical implications of subclinical bioprosthetic aortic valve thrombus have yet to be established. GP1 uptake in AVR Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

The readership of Heart will require no introduction to the epidemiology, assessment and treatment of calcific aortic stenosis in 2020. Although transcatheter aortic valve implantation has revolutionised the interventional paradigm and is an unequivocal success, we recognise that a prosthesis is not a cure for aortic valve disease, and that complications—both short- and long-term—cannot be completely abolished. Consequently, although recent clinical research has largely focused on iterative improvements in devices, procedural techniques and risk assessment with a view to optimising the delivery and timing of valve replacement, the search for an effective medical therapy to retard the inexorable progression of aortic stenosis continues. The only drugs to be tested prospectively in randomised controlled trials as disease modifiers are statins, with conclusively negative results.1 Observational data have hinted at possible roles for other therapies such as renin–angiotensin–aldosterone system blockade and antiosteoporosis medications (figure 1), but it is not possible to confirm causal relationships and draw actionable conclusions from these non-randomised data. Meanwhile, a deeper understanding of the complex processes governing aortic stenosis has shifted the field away from a purely degenerative disease model, with more emphasis on valve mineralisation, lipoprotein infiltration, active inflammation and tissue remodelling. This has led to the identification of multiple possible therapeutic targets, beyond simple correlations between clinical parameters and disease progression.2 Dipeptidyl peptidase-4 (DPP-4) has recently been proposed as one such target. DPP-4 inhibitors are most commonly used as oral hypoglycaemics for the treatment of diabetes mellitus. However, DPP-4 cleaves a variety of substrates beyond incretin hormones. The authors of the current study previously demonstrated that valve endothelial cell …

The Authors’ reply We thank Professor Otto and Dr Bermejo for their interest and astute comments regarding our study.1 The echo frame for determining left ventricular volume at peak aortic velocity is estimated by the measuring the total number of frames from the R wave to the end systole and multiplying this by the fraction of time from the R wave to the peak aortic velocity and from the R wave to the end systole. In the initial report of EF1 in aortic stenosis (AS),2 the intraobserver and interobserver coefficients of variation were 6.7% and 9.8%. We acknowledge that EF1 …

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.

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.

ObjectiveFirst-phase ejection fraction (EF1) is a novel measure of early left ventricular systolic dysfunction. We investigated determinants of EF1 and its prognostic value in aortic stenosis.MethodsEF1 was measured retrospectively in participants of an echocardiography/cardiovascular magnetic resonance cohort study which recruited patients with aortic stenosis (peak aortic velocity of ≥2 m/s) between 2012 and 2014. Linear regression models were constructed to examine variables associated with EF1. Cox proportional hazards were used to determine the prognostic power of EF1 for aortic valve replacement (AVR, performed as part of clinical care in accordance with international guidelines) or death.ResultsTotal follow-up of the 149 participants (69.8% male, 70 (65–76) years, mean gradient 33 (21–42) mm Hg) was 238 029 person-days. Sixty-seven participants (45%) had a low baseline EF1 (2 vs 20.6 (16.8–24.3) mL/m2, p=0.002; late gadolinium enhancement (LGE) prevalence 52% vs 20%, pConclusionEF1 quantifies early, potentially reversible systolic dysfunction in aortic stenosis, is associated with global afterload and myocardial fibrosis, and is an independent predictor of AVR.

ObjectiveCT quantification of aortic valve calcification (CT-AVC) is useful in the assessment of aortic stenosis severity. Our objective was to assess its ability to track aortic stenosis progression compared with echocardiography.MethodsSubjects were recruited in two cohorts: (1) a reproducibility cohort where patients underwent repeat CT-AVC or echocardiography within 4 weeks and (2) a disease progression cohort where patients underwent annual CT-AVC and/or echocardiography. Cohen’s d-statistic (d) was computed from the ratio of annualised progression and measurement repeatability and used to estimate group sizes required to detect annualised changes in CT-AVC and echocardiography.ResultsA total of 33 (age 71±8) and 81 participants (age 72±8) were recruited to the reproducibility and progression cohorts, respectively. Ten CT scans (16%) were excluded from the progression cohort due to non-diagnostic image quality. Scan-rescan reproducibility was excellent for CT-AVC (limits of agreement −12% to 10 %, intraclass correlation (ICC) 0.99), peak velocity (−7% to +17%; ICC 0.92) mean gradient (−25% to 27%, ICC 0.96) and dimensionless index (−11% to +15%; ICC 0.98). Repeat measurements of aortic valve area (AVA) were less reliable (−44% to +28%, ICC 0.85).CT-AVC progressed by 152 (65–375) AU/year. For echocardiography, the median annual change in peak velocity was 0.1 (0.0–0.3) m/s/year, mean gradient 2 (0–4) mm Hg/year and AVA −0.1 (−0.2–0.0) cm2/year. Cohen’s d-statistic was more than double for CT-AVC (d=3.12) than each echocardiographic measure (peak velocity d=0.71 ; mean gradient d=0.66; AVA d=0.59, dimensionless index d=1.41).ConclusionCT-AVC is reproducible and demonstrates larger increases over time normalised to measurement repeatability compared with echocardiographic measures.

This review focuses on the available data regarding the utility of advanced left ventricular (LV) imaging in aortic stenosis (AS) and its potential impact for optimising the timing of aortic valve replacement. Ejection fraction is currently the only LV parameter recommended to guide intervention in AS. The cut-off value of 50%, recommended for decision-making in asymptomatic patients with AS, is currently under debate. Several imaging parameters have emerged as predictors of disease progression and clinical outcomes in this setting. Global longitudinal LV strain by speckle tracking echocardiography is useful for risk stratification of asymptomatic patients with severe AS and preserved LV ejection fraction. Its prognostic value was demonstrated in these patients, but further work is required to define the best thresholds to aid the decision-making process. The assessment of myocardial fibrosis is the most studied application of cardiac magnetic resonance in AS. The detection of replacement fibrosis by late gadolinium enhancement offers incremental prognostic information in these patients. Clinical implementation of this technique to optimise the timing of aortic valve intervention in asymptomatic patients is currently tested in a randomised trial. The use of T1 mapping techniques can provide an assessment of interstitial myocardial fibrosis and represents an expanding field of interest. However, convincing data in patients with AS is still lacking. All these imaging parameters have substantial potential to influence the management decision in patients with AS in the future, but data from randomised clinical trials are awaited to define their utility in daily practice.

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.

Aims To describe the cardiac abnormalities in patients with COVID-19 and identify the characteristics of patients who would benefit most from echocardiography. Methods and results In a prospective international survey, we captured echocardiography findings in patients with presumed or confirmed COVID-19 between 3 and 20 April 2020. Patient characteristics, indications, findings, and impact of echocardiography on management were recorded. Multivariable logistic regression identified predictors of echocardiographic abnormalities. A total of 1216 patients [62 (52–71) years, 70% male] from 69 countries across six continents were included. Overall, 667 (55%) patients had an abnormal echocardiogram. Left and right ventricular abnormalities were reported in 479 (39%) and 397 (33%) patients, respectively, with evidence of new myocardial infarction in 36 (3%), myocarditis in 35 (3%), and takotsubo cardiomyopathy in 19 (2%). Severe cardiac disease (severe ventricular dysfunction or tamponade) was observed in 182 (15%) patients. In those without pre-existing cardiac disease (n = 901), the echocardiogram was abnormal in 46%, and 13% had severe disease. Independent predictors of left and right ventricular abnormalities were distinct, including elevated natriuretic peptides [adjusted odds ratio (OR) 2.96, 95% confidence interval (CI) 1.75–5.05) and cardiac troponin (OR 1.69, 95% CI 1.13–2.53) for the former, and severity of COVID-19 symptoms (OR 3.19, 95% CI 1.73–6.10) for the latter. Echocardiography changed management in 33% of patients. Conclusion In this global survey, cardiac abnormalities were observed in half of all COVID-19 patients undergoing echocardiography. Abnormalities were often unheralded or severe, and imaging changed management in one-third of patients.

Introduction Despite recent improvements in management, infective endocarditis remains associated with high morbidity and mortality. Over the last few decades, several factors have impacted on both the incidence and outcomes following infective endocarditis. Purpose Using a national linkage approach, we describe the changing age- and sex-stratified incidence and outcomes of infective endocarditis in Scotland over the last 25 years. Methods We conducted a consecutive retrospective individual patient linkage study across multiple national databases. Using data extracted from the Scottish hospital discharge dataset held by the Information Services Division of NHS National Services Scotland, we extracted episodes for all patients aged 20 years or older who were admitted with infective endocarditis between January 1, 1990, and December 31, 2014 in Scotland, UK. Patient episodes with infective endocarditis were linked to national prescribing and microbiology databases. The primary outcome was 1-year mortality following the index presentation. Generalised additive models were constructed to estimate the crude and age- and sex-stratified incidence rates (using a poison distribution) as well as trends in mortality (using a binomial distribution) adjusted for age, sex and comorbidity. Results Across 12,446 individual patients, there were a total of 12,667 hospitalisations (mean age 68±17 years, 55% females) with infective endocarditis using a 5-year look back period. The estimated crude rate of hospitalisation increased from 7.38 per 100,000 (95% CI 6.58 to 8.28) in 1990 to 15.09 per 100,000 (95% CI 13.90 to 16.39) in 2014 (p Conclusions Despite the crude incidence of infective endocarditis doubling over the last 25 years and case fatality remaining high, the risk of death has markedly fallen over the last two decades. Staphylococcus cultures remain an independent marker of poor prognosis in this cohort. Acknowledgement/Funding British Heart Foundation

Introduction Cardiac arrest is a major healthcare burden; survival has historically been poor. Contemporary therapies have been associated with improvements in out-of-hospital cardiac arrest survival in other healthcare systems. Purpose To determine temporal trends and predictors of 30-day and overall survival in patients with cardiac arrest who survive to hospital admission in Scotland. Methods We conducted a consecutive individual patient linkage study using data from the Scottish Morbidity Records held by the Information Services Division, National Health Service Scotland. We identified all patients who had an index cardiac arrest hospitalisation from 1st January 1990 to 31st December 2014. The primary outcome was 30-day mortality. Generalised additive models were used to estimate temporal trends. Year of admission was the primary explanatory variable, adjusted for age, sex, comorbidities (stroke, myocardial infarction, heart failure), Scottish Index of Multiple Deprivation (SIMD, a national deprivation score), and angiography within 30 days of admission. Cox regression models were constructed for overall mortality, adjusting for the above variables. Results In total, 47,692 patients had an index hospitalisation with cardiac arrest in Scotland between 1990 and 2014. The mean age was 69±16 years; 45% (n=21,257) were female. Most patients (n=24,867, 52.4%) were in top two SIMD quintiles (greater deprivation). Incidence was lowest in 1990 (27 per 100,000 population), rising until 1998 (47 per 100,000) before declining (mean 30 per 100,000 for 2010–2014) (Figure 1A). Overall rates of angiography and PCI at 30 days were low (5.4% and 3.1% respectively), albeit higher in more recent years (14.1% and 9.6% respectively for 2010–2014). Thirty-day mortality was high but decreased over time (73.7% from 1990–1994 to 63.1% from 2010–2014, p Temporal trends in cardiac arrest Conclusions Hospital episodes with cardiac arrest in Scotland peaked in the late 1990s and have since fallen. Thirty-day mortality remains high, with an improvement over time that is independent of baseline patient characteristics.

Cardiovascular disease is one of the leading causes of mortality and morbidity worldwide. Atherosclerosis imaging has traditionally focused on detection of obstructive luminal stenoses or ...

Background: Coronary 18 F-fluoride positron emission tomography identifies ruptured and high-risk atherosclerotic plaque. The optimal method to identify, to quantify, and to categorize increased coronary 18 F-fluoride uptake and determine its reproducibility has yet to be established. This study aimed to optimize the identification, quantification, categorization, and scan-rescan reproducibility of increased 18 F-fluoride activity in coronary atherosclerotic plaque. Methods: In a prospective observational study, patients with multi-vessel coronary artery disease underwent serial 18 F-fluoride positron emission tomography. Coronary 18 F-fluoride activity was visually assessed, quantified, and categorized with reference to maximal tissue to background ratios. Levels of agreement for both visual and quantitative methods were determined between scans and observers. Results: Thirty patients (90% male, 20 patients with stable coronary artery disease, and 10 with recent type 1 myocardial infarction) underwent paired serial positron emission tomography-coronary computed tomography angiography imaging within an interval of 12±5 days. A mean of 3.7±1.8 18 F-fluoride positive plaques per patient was identified after recent acute coronary syndrome, compared with 2.4±2.3 positive plaques per patient in stable coronary artery disease. The bias in agreement in maximum tissue to background ratio measurements in visually positive plaques was low between observers (mean difference, −0.01; 95% limits of agreement, −0.32 to 0.30) or between scans (mean difference, 0.06; 95% limits of agreement, −0.49 to 0.61). Good agreement in the categorization of focal 18 F-fluoride uptake was achieved using visual assessment alone (κ=0.66) and further improved at higher maximum tissue to background ratio values. Conclusions: Coronary 18 F-fluoride activity is a precise and reproducible metric in the coronary vasculature. The analytical performance of 18 F-fluoride is sufficient to assess the prognostic utility of this radiotracer as a noninvasive imaging biomarker of plaque vulnerability. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifiers: NCT02110303 and NCT02278211.

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

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