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

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

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

Background Within the SCOT-HEART (Scottish COmputed Tomography of the HEART Trial) trial of patients with stable chest pain, the use of coronary computed tomography angiography (CTA) reduced the rate of death from coronary heart disease or nonfatal myocardial infarction (primary endpoint). Objectives This study sought to assess the consistency and mechanisms of the 5-year reduction in this endpoint. Methods In this open-label trial, 4,146 participants were randomized to standard care alone or standard care plus coronary CTA. This study explored the primary endpoint by symptoms, diagnosis, coronary revascularizations, and preventative therapies. Results Event reductions were consistent across symptom and risk categories (p = NS for interactions). In patients who were not diagnosed with angina due to coronary heart disease, coronary CTA was associated with a lower primary endpoint incidence rate (0.23; 95% confidence interval [CI]: 0.13 to 0.35 vs. 0.59; 95% CI: 0.42 to 0.80 per 100 patient-years; p, Central Illustration

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

Objectives This study sought to compare the performance of major guidelines for the assessment of stable chest pain including risk-based (American College of Cardiology/American Heart Association and European Society of Cardiology) and symptom-focused (National Institute for Health and Care Excellence) strategies. Background Although noninvasive testing is not recommended in low-risk individuals with stable chest pain, guidelines recommend differing approaches to defining low-risk patients. Methods Patient-level data were obtained from the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) and SCOT-HEART (Scottish Computed Tomography of the Heart) trials. Pre-test probability was determined and patients dichotomized into low-risk and intermediate-high–risk groups according to each guideline’s definitions. The primary endpoint was obstructive coronary artery disease on coronary computed tomography angiography. Secondary endpoints were coronary revascularization at 90 days and cardiovascular death or nonfatal myocardial infarction up to 3 years. Results In total, 13,773 patients were included of whom 6,160 had coronary computed tomography angiography. The proportions of patients identified as low risk by the American College of Cardiology/American Heart Association, European Society of Cardiology, and National Institute for Health and Care Excellence guidelines, respectively, were 2.5%, 2.5%, and 10.0% within PROMISE, and 14.0%, 19.8%, and 38.4% within SCOT-HEART. All guidelines identified lower rates of obstructive coronary artery disease in low- versus intermediate-high–risk patients with a negative predictive value of ≥0.90. Compared with low-risk groups, all intermediate-high–risk groups had greater risks of coronary revascularization (odds ratio [OR]: 2.2 to 24.1) and clinical outcomes (OR: 1.84 to 5.8). Conclusions Compared with risk-based guidelines, symptom-focused assessment identifies a larger group of low-risk chest pain patients potentially deriving limited benefit from noninvasive testing. (Scottish Computed Tomography of the Heart Trial [SCOT-HEART]; NCT01149590; Prospective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550), Graphical abstract

Background Fluorine-18–sodium fluoride (18F-NaF) uptake is a marker of active vascular calcification associated with high-risk atherosclerotic plaque. Objectives In patients with abdominal aortic aneurysm (AAA), the authors assessed whether 18F-NaF positron emission tomography (PET) and computed tomography (CT) predicts AAA growth and clinical outcomes. Methods In prospective case-control (n = 20 per group) and longitudinal cohort (n = 72) studies, patients with AAA (aortic diameter >40 mm) and control subjects (aortic diameter Results Fluorine-18-NaF uptake was increased in AAA compared with nonaneurysmal regions within the same aorta (p = 0.004) and aortas of control subjects (p = 0.023). Histology and micro-PET-CT demonstrated that 18F-NaF uptake localized to areas of aneurysm disease and active calcification. In 72 patients within the longitudinal cohort study (mean age 73 ± 7 years, 85% men, baseline aneurysm diameter 48.8 ± 7.7 mm), there were 19 aneurysm repairs (26.4%) and 3 ruptures (4.2%) after 510 ± 196 days. Aneurysms in the highest tertile of 18F-NaF uptake expanded 2.5× more rapidly than those in the lowest tertile (3.10 [interquartile range (IQR): 2.34 to 5.92 mm/year] vs. 1.24 [IQR: 0.52 to 2.92 mm/year]; p = 0.008) and were nearly 3× as likely to experience AAA repair or rupture (15.3% vs. 5.6%; log-rank p = 0.043). Conclusions Fluorine-18-NaF PET-CT is a novel and promising approach to the identification of disease activity in patients with AAA and is an additive predictor of aneurysm growth and future clinical events. (Sodium Fluoride Imaging of Abdominal Aortic Aneurysms [SoFIA3]; NCT02229006; Magnetic Resonance Imaging [MRI] for Abdominal Aortic Aneurysms to Predict Rupture or Surgery: The MA3RS Trial; ISRCTN76413758)

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

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

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

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

Despite recent advances, cardiovascular disease remains the leading cause of death globally. As such, there is a need to optimise our current diagnostic and risk stratification pathways in order to better deliver individualised preventative therapies. Non-invasive imaging of coronary artery plaque can interrogate multiple aspects of coronary atherosclerotic disease, including plaque morphology, anatomy and flow. More recently, disease activity is being assessed to provide mechanistic insights into in vivo atherosclerosis biology. Molecular imaging using positron emission tomography is unique in this field, with the potential to identify specific biological processes using either bespoke or re-purposed radiotracers. This review provides an overview of non-invasive vulnerable plaque detection and molecular imaging of coronary atherosclerosis.

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

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

Background 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. Electronic supplementary material The online version of this article (10.1007/s12350-019-01962-y) contains supplementary material, which is available to authorized users.

CoronaryIn a prospective observational study, patients with multi-vessel coronary artery disease underwent serialThirty 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±1.8CoronaryURL: http://www.clinicaltrials.gov. Unique identifiers: NCT02110303 and NCT02278211.

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.

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

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

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

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

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

Importance Recent European guidance supports a diminished role for exercise electrocardiography (ECG) in the assessment of suspected stable angina. Objective To evaluate the utility of exercise ECG in contemporary practice and assess the value of combined functional and anatomical testing. Design, Setting, and Participants This is a post hoc analysis of the Scottish Computed Tomography of the Heart (SCOT-HEART) open-label randomized clinical trial, conducted in 12 cardiology chest pain clinics across Scotland for patients with suspected angina secondary to coronary heart disease. Between November 18, 2010, and September 24, 2014, 4146 patients aged 18 to 75 years with stable angina underwent clinical evaluation and 1417 of 1651 (86%) underwent exercise ECG prior to randomization. Statistical analysis was conducted from October 10 to November 5, 2019. Interventions Patients were randomized in a 1:1 ratio to receive standard care plus coronary computed tomography (CT) angiography or to receive standard care alone. The present analysis was limited to the 3283 patients who underwent exercise ECG alone or in combination with coronary CT angiography. Main Outcomes and Measures The primary clinical end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years. Results Among the 3283 patients (1889 men; median age, 57.0 years [interquartile range, 50.0-64.0 years]), exercise ECG had a sensitivity of 39% and a specificity of 91% for detecting any obstructive coronary artery disease in those who underwent subsequent invasive angiography. Abnormal results of exercise ECG were associated with a 14.47-fold (95% CI, 10.00-20.41;P Conclusions and Relevance This study suggests that abnormal results of exercise ECG are associated with coronary revascularization and the future risk of adverse coronary events. However, coronary CT angiography more accurately detects coronary artery disease and is more strongly associated with future risk compared with exercise ECG. Trial Registration ClinicalTrials.gov Identifier:NCT01149590

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

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

We assessed the feasibility of utilizing previously acquired computed tomography angiography (CTA) with subsequent positron-emission tomography (PET)-only scan for the quantitative evaluation ofForty-five patients (age 67.1±6.9 years; 76% males) underwent CTA (CTA1) and combinedCoronary CTA/PET protocol with CTA first followed by PET-only allows for reliable and reproducible quantification of

BACKGROUND: High-sensitivity cardiac troponin assays permit use of lower thresholds for the diagnosis of myocardial infarction, but whether this improves clinical outcomes is unknown. We aimed to determine whether the introduction of a high-sensitivity cardiac troponin I (hs-cTnI) assay with a sex-specific 99th centile diagnostic threshold would reduce subsequent myocardial infarction or cardiovascular death in patients with suspected acute coronary syndrome. METHODS: In this stepped-wedge, cluster-randomised controlled trial across ten secondary or tertiary care hospitals in Scotland, we evaluated the implementation of an hs-cTnI assay in consecutive patients who had been admitted to the hospitals' emergency departments with suspected acute coronary syndrome. Patients were eligible for inclusion if they presented with suspected acute coronary syndrome and had paired cardiac troponin measurements from the standard care and trial assays. During a validation phase of 6-12 months, results from the hs-cTnI assay were concealed from the attending clinician, and a contemporary cardiac troponin I (cTnI) assay was used to guide care. Hospitals were randomly allocated to early (n=5 hospitals) or late (n=5 hospitals) implementation, in which the high-sensitivity assay and sex-specific 99th centile diagnostic threshold was introduced immediately after the 6-month validation phase or was deferred for a further 6 months. Patients reclassified by the high-sensitivity assay were defined as those with an increased hs-cTnI concentration in whom cTnI concentrations were below the diagnostic threshold on the contemporary assay. The primary outcome was subsequent myocardial infarction or death from cardiovascular causes at 1 year after initial presentation. Outcomes were compared in patients reclassified by the high-sensitivity assay before and after its implementation by use of an adjusted generalised linear mixed model. This trial is registered with ClinicalTrials.gov, number NCT01852123. FINDINGS: Between June 10, 2013, and March 3, 2016, we enrolled 48 282 consecutive patients (61 [SD 17] years, 47% women) of whom 10 360 (21%) patients had cTnI concentrations greater than those of the 99th centile of the normal range of values, who were identified by the contemporary assay or the high-sensitivity assay. The high-sensitivity assay reclassified 1771 (17%) of 10 360 patients with myocardial injury or infarction who were not identified by the contemporary assay. In those reclassified, subsequent myocardial infarction or cardiovascular death within 1 year occurred in 105 (15%) of 720 patients in the validation phase and 131 (12%) of 1051 patients in the implementation phase (adjusted odds ratio for implementation vs validation phase 1·10, 95% CI 0·75 to 1·61; p=0·620). INTERPRETATION: Use of a high-sensitivity assay prompted reclassification of 1771 (17%) of 10 360 patients with myocardial injury or infarction, but was not associated with a lower subsequent incidence of myocardial infarction or cardiovascular death at 1 year. Our findings question whether the diagnostic threshold for myocardial infarction should be based on the 99th centile derived from a normal reference population. FUNDING: The British Heart Foundation.

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

Non-invasive imaging of the coronary arteries is an enterprise in rapid development. From the research perspective, there is great demand for in vivo techniques that can reliably identify features of high-risk plaque that may offer insight into pathophysiological processes and act as surrogate indicators of response to therapeutic intervention. Meanwhile, there is clear clinical need for greater accuracy in diagnosis and prognostic stratification. Fortunately, ongoing technological improvements and emerging data from randomized clinical trials are helping make these elusive goals a reality. This review provides an update on the current status of non-invasive coronary imaging with computed tomography, magnetic resonance, and positron emission tomography with a focus on current clinical applications and future research directions.

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

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

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

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

Learning objectives Worldwide more than 17 million people die every year from cardiovascular disease (CVD) with this number projected to increase to over 23 million by 2030.1 Within Europe, CVD results in four million deaths annually, accounting for 47% of all-cause mortality. Between them, heart attacks and strokes are responsible for around 80% of this mortality.2 The vast majority of acute ischaemic vascular events occur in relation to an underlying atherosclerotic plaque. Plaque rupture is the dominant initiating event, responsible for 60–70% of acute coronary syndromes (ACS), while plaque erosion is responsible for most of the remainder.3 ,4 Irrespective of the mechanism, the consequence is exposure of a thrombogenic substrate to circulating blood. This in turn triggers platelet aggregation and the coagulation cascade which compromises vascular blood flow resulting in downstream end-organ ischaemia and infarction. These events occur abruptly and often without warning. Despite intensive therapies, they recur in as many as 25% of patients. Until recently, the high-risk plaque has only been identified by retrospective analysis, predominantly from pathological examination of autopsy specimens. This has limited our ability to appreciate the dynamic nature of plaque vulnerability and rupture, and has placed a heavy reliance on invasive angiography to describe the anatomical luminal stenosis severity rather than plaque biology. Prospective identification of plaque rupture events has suggested that the majority of culprit lesions is non-flow limiting, and often overlooked by angiographic and traditional functional investigations. Novel imaging techniques now have the potential to identify the pathological structures and processes associated with plaque rupture. This in turn has raised hopes for strategies …

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.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.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.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 0.001 for both comparisons). Reclassification of low-risk patients at the 10% probability threshold was best for CAD2 (NRI 0.31, 95% CI: 0.27 to 0.35) followed by CRS (NRI 0.21, 95% CI: 0.17 to 0.25) compared with UDF (p 0.001 for all comparisons), with a consistent trend at the 15% threshold.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.

Background: Suspected acute coronary syndrome is the commonest reason for emergency admission to hospital and is a large burden on health-care resources. Strategies to identify low-risk patients suitable for immediate discharge would have major benefits.Methods: We did a prospective cohort study of 6304 consecutively enrolled patients with suspected acute coronary syndrome presenting to four secondary and tertiary care hospitals in Scotland. We measured plasma troponin concentrations at presentation using a high-sensitivity cardiac troponin I assay. In derivation and validation cohorts, we evaluated the negative predictive value of a range of troponin concentrations for the primary outcome of index myocardial infarction, or subsequent myocardial infarction or cardiac death at 30 days. This trial is registered with ClinicalTrials.gov (number NCT01852123).Findings: 782 (16%) of 4870 patients in the derivation cohort had index myocardial infarction, with a further 32 (1%) re-presenting with myocardial infarction and 75 (2%) cardiac deaths at 30 days. In patients without myocardial infarction at presentation, troponin concentrations were less than 5 ng/L in 2311 (61%) of 3799 patients, with a negative predictive value of 99·6% (95% CI 99·3-99·8) for the primary outcome. The negative predictive value was consistent across groups stratified by age, sex, risk factors, and previous cardiovascular disease. In two independent validation cohorts, troponin concentrations were less than 5 ng/L in 594 (56%) of 1061 patients, with an overall negative predictive value of 99·4% (98·8-99·9). At 1 year, these patients had a lower risk of myocardial infarction and cardiac death than did those with a troponin concentration of 5 ng/L or more (0·6% vs 3·3%; adjusted hazard ratio 0·41, 95% CI 0·21-0·80; pInterpretation: Low plasma troponin concentrations identify two-thirds of patients at very low risk of cardiac events who could be discharged from hospital. Implementation of this approach could substantially reduce hospital admissions and have major benefits for both patients and health-care providers.Funding: British Heart Foundation and Chief Scientist Office (Scotland).

Importance: High-sensitivity cardiac troponin I testing is widely used to evaluate patients with suspected acute coronary syndrome. A cardiac troponin concentration of less than 5 ng/L identifies patients at presentation as low risk, but the optimal threshold is uncertain.Objective: To evaluate the performance of a cardiac troponin I threshold of 5 ng/L at presentation as a risk stratification tool in patients with suspected acute coronary syndrome.Data Sources: Systematic search of MEDLINE, EMBASE, Cochrane, and Web of Science databases from January 1, 2006, to March 18, 2017.Study Selection: Prospective studies measuring high-sensitivity cardiac troponin I concentrations in patients with suspected acute coronary syndrome in which the diagnosis was adjudicated according to the universal definition of myocardial infarction.Data Extraction and Synthesis: The systematic review identified 19 cohorts. Individual patient-level data were obtained from the corresponding authors of 17 cohorts, with aggregate data from 2 cohorts. Meta-estimates for primary and secondary outcomes were derived using a binomial-normal random-effects model.Main Outcomes and Measures: The primary outcome was myocardial infarction or cardiac death at 30 days. Performance was evaluated in subgroups and across a range of troponin concentrations (2-16 ng/L) using individual patient data.Results: Of 11 845 articles identified, 104 underwent full-text review, and 19 cohorts from 9 countries were included. Among 22 457 patients included in the meta-analysis (mean age, 62 [SD, 15.5] years; n = 9329 women [41.5%]), the primary outcome occurred in 2786 (12.4%). Cardiac troponin I concentrations were less than 5 ng/L at presentation in 11 012 patients (49%), in whom there were 60 missed index or 30-day events (59 index myocardial infarctions, 1 myocardial infarction at 30 days, and no cardiac deaths at 30 days). This resulted in a negative predictive value of 99.5% (95% CI, 99.3%-99.6%) for the primary outcome. There were no cardiac deaths at 30 days and 7 (0.1%) at 1 year, with a negative predictive value of 99.9% (95% CI, 99.7%-99.9%) for cardiac death.Conclusions and Relevance: Among patients with suspected acute coronary syndrome, a high-sensitivity cardiac troponin I concentration of less than 5 ng/L identified those at low risk of myocardial infarction or cardiac death within 30 days. Further research is needed to understand the clinical utility and cost-effectiveness of this approach to risk stratification.

Objective To evaluate how selection of patients for high sensitivity cardiac troponin testing affects the diagnosis of myocardial infarction across different healthcare settings. Design Prospective study of three independent consecutive patient populations presenting to emergency departments. Setting Secondary and tertiary care hospitals in the United Kingdom and United States. Participants High sensitivity cardiac troponin I concentrations were measured in 8500 consecutive patients presenting to emergency departments: unselected patients in the UK (n=1054) and two selected populations of patients in whom troponin testing was requested by the attending clinician in the UK (n=5815) and the US (n=1631). The final diagnosis of type 1 or type 2 myocardial infarction or myocardial injury was independently adjudicated. Main outcome measures Positive predictive value of an elevated cardiac troponin concentration for a diagnosis of type 1 myocardial infarction. Results Cardiac troponin concentrations were elevated in 13.7% (144/1054) of unselected patients, with a prevalence of 1.6% (17/1054) for type 1 myocardial infarction and a positive predictive value of 11.8% (95% confidence interval 7.0% to 18.2%). In selected patients, in whom troponin testing was guided by the attending clinician, the prevalence and positive predictive value were 14.5% (843/5815) and 59.7% (57.0% to 62.2%) in the UK and 4.2% (68/1631) and 16.4% (13.0% to 20.3%) in the US. Across both selected patient populations, the positive predictive value was highest in patients with chest pain, with ischaemia on the electrocardiogram, and with a history of ischaemic heart disease. Conclusions When high sensitivity cardiac troponin testing is performed widely or without previous clinical assessment, elevated troponin concentrations are common and predominantly reflect myocardial injury rather than myocardial infarction. These observations highlight how selection of patients for cardiac troponin testing varies across healthcare settings and markedly influences the positive predictive value for a diagnosis of myocardial infarction.

ObjectivesTo evaluate the diagnostic and prognostic benefits of CT coronary angiography (CTCA) using the 2016 National Institute for Health and Care Excellence (NICE) guidelines for the assessment of suspected stable angina.MethodsPost hoc analysis of the Scottish COmputed Tomography of the HEART (SCOT-HEART) trial of 4146 participants with suspected angina randomised to CTCA. Patients were dichotomised into NICE guideline-defined possible angina and non-anginal presentations. Primary (diagnostic) endpoint was diagnostic certainty of angina at 6 weeks and prognostic endpoint comprised fatal and non-fatal myocardial infarction (MI).ResultsIn 3770 eligible participants, CTCA increased diagnostic certainty more in those with possible angina (relative risk (RR) 2.22 (95% CI 1.91 to 2.60), pinteraction ConclusionsNICE-guided patient selection maximises the benefits of CTCA on diagnostic certainty, use of invasive coronary angiography and reductions in fatal and non-fatal myocardial infarction. Patients with non-anginal chest pain derive minimal benefit from CTCA and increase the rates of invasive investigation.Trial registration numberClinicalTrials.gov: NCT01149590;post results.