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Background The majority of patients with suspected acute coronary syndrome presenting to the emergency department will be discharged once myocardial infarction has been ruled out, although a proportion will have unrecognised coronary artery disease. In this setting, high-sensitivity cardiac troponin identifies those at increased risk of future cardiac events. In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been ruled out, this trial aims to investigate whether outpatient computed tomography coronary angiography (CTCA) reduces subsequent myocardial infarction or cardiac death. Methods TARGET-CTCA is a multicentre prospective randomised open label with blinded endpoint parallel group event driven trial. After myocardial infarction and clear alternative diagnoses have been ruled out, participants with intermediate cardiac troponin concentrations (5 ng/L to 99th centile upper reference limit) will be randomised 1:1 to outpatient CTCA plus standard of care or standard of care alone. The primary endpoint is myocardial infarction or cardiac death. Secondary endpoints include clinical, patient-centred, process and cost-effectiveness. Recruitment of 2270 patients will give 90% power with a two-sided P value of 0.05 to detect a 40% relative risk reduction in the primary endpoint. Follow-up will continue until 97 primary outcome events have been accrued in the standard care arm with an estimated median follow-up of 36 months. Discussion This randomised controlled trial will determine whether high-sensitivity cardiac troponin-guided CTCA can improve outcomes and reduce subsequent major adverse cardiac events in patients presenting to the emergency department who do not have myocardial infarction. Trial registration ClinicalTrials.gov Identifier: NCT03952351. Registered on May 16, 2019.

Although guidelines recommend fixed cardiac troponin thresholds for the diagnosis of myocardial infarction, troponin concentrations are influenced by age, sex, comorbidities and time from symptom onset. To improve diagnosis, we developed machine learning models that integrate cardiac troponin concentrations at presentation or on serial testing with clinical features and compute the Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) score (0–100) that corresponds to an individual’s probability of myocardial infarction. The models were trained on data from 10,038 patients (48% women), and their performance was externally validated using data from 10,286 patients (35% women) from seven cohorts. CoDE-ACS had excellent discrimination for myocardial infarction (area under curve, 0.953; 95% confidence interval, 0.947–0.958), performed well across subgroups and identified more patients at presentation as low probability of having myocardial infarction than fixed cardiac troponin thresholds (61 versus 27%) with a similar negative predictive value and fewer as high probability of having myocardial infarction (10 versus 16%) with a greater positive predictive value. Patients identified as having a low probability of myocardial infarction had a lower rate of cardiac death than those with intermediate or high probability 30 days (0.1 versus 0.5 and 1.8%) and 1 year (0.3 versus 2.8 and 4.2%; P  < 0.001 for both) from patient presentation. CoDE-ACS used as a clinical decision support system has the potential to reduce hospital admissions and have major benefits for patients and health care providers. A clinical decision support system for diagnosis of myocardial infarction, based on machine learning models that use a single measurement of high-sensitivity troponin, outperforms clinical guidelines that use fixed cardiac troponin thresholds for diagnosis.

BackgroundType 2 myocardial infarction occurs due to a reduction in myocardial oxygen supply or an increase in demand without evidence of atherosclerotic plaque rupture. It is common representing around 20% of myocardial infarctions (1-4). Outcomes are poor with up to one third alive at five years, with cardiovascular outcomes comparable to type 1 myocardial infarction (1,5,6). Despite this, there are no evidence-based guidelines to guide assessment and management for clinicians.PurposeTo gain consensus on the assessment and management of type 2 myocardial infarction from an international group of experts.MethodsA systematic review of type 2 myocardial infarction was undertaken to identify the corresponding or senior author of all original research studies. We identified 73 experts from multiple clinical specialties. A three-round international eDelphi study was circulated, with round one consisting of open questioning to generate statements for deductive analysis. Consensus was defined a priori as >70% agreement on a 5-point Likert scale. Statements for which no consensus could be obtained were adapted and recirculated in round three (Figure 1).ResultsOf the 68 experts contacted there was a 56% (38/68), 54% (37/68) and 72% (49/68) response rate in round one, two and three, respectively. Consensus was achieved on 64% (43/67) of statements. Consensus varied across the following domains i) definition and diagnosis 42% (5/12), ii) risk stratification 75% (3/4), iii) assessment of coronary artery disease and cardiac function 50% (9/18), iv) specialty management 60% (6/10), v) treatment and secondary prevention 100% (9/9) and vi) communication and rehabilitation 79% (11/15). The panel agreed that all patients should undergo echocardiography (mean [SD] 2.08 [1.23]) and CT coronary imaging or a functional test should be performed on those with intermediate probability of future cardiovascular events (mean [SD] 1.81 [0.52]). Over 90% of the panel agreed that both patient and clinician understanding of type 2 myocardial infarction was poor and that further randomised controlled trials are need to direct care.ConclusionThere remains uncertainty regarding the current definition of type 2 myocardial infarction and overall patient and clinician understanding was thought to be poor. However, it is generally accepted that the mainstay of management should be on the identification of coronary artery disease and left ventricular impairment with optimisation of therapies with proven benefit. Management should involve an individualised assessment and the multidisciplinary team.Abstract 60 Figure 1Conflict of InterestNil

BackgroundAcute myocardial injury and type 2 myocardial infarction typically occur in the setting of a concurrent illness. Differentiating acute myocardial injury from type 2 myocardial infarction is challenging as it relies on the assessment of myocardial ischaemia. Indeed, some have questioned whether this distinction is important, as patients with both conditions are at increased risk of future cardiovascular events. Whether this risk is similar and the role of identifying those with coronary artery disease is uncertain.MethodsWe conducted a secondary analysis of a multi-centre randomised controlled trial of 48,282 consecutive patients with suspected acute coronary syndrome. Patients with an adjudicated diagnosis of acute myocardial injury and type 2 myocardial infarction were stratified according to whether they were known previously to have coronary artery disease defined as prior coronary revascularisation, myocardial infarction, or angina. Cardiovascular death or myocardial infarction adjusted for the competing risk of non-cardiovascular death and all-cause death at one year was compared.ResultsIn 9,115 patients with elevated cardiac troponin concentrations, 1,676 (18%) and 1,121 (12%) had acute myocardial injury and type 2 myocardial infarction, respectively. Patients with either condition known to have coronary artery disease were older (mean [standard deviation] age 78 [11] versus 73 [16] years) and more likely to be female (55% versus 45%) than those with no prior history. Coronary artery disease was previously identified in 40% (454/1,121) and 30% (509/1,167) of those with type 2 myocardial infarction and acute myocardial injury, respectively. Cardiovascular death or myocardial infarction at one year was more common in patients known to have coronary artery disease than those without for both acute myocardial injury (23% [115/509]) versus 14% [158/1,167]; P<0.001) and type 2 myocardial infarction (20% [91/454] versus 10% [69/667]; log-rank P<0.001) (Figure 1). Similarly all-cause death at one year was higher in patients with known coronary artery disease for both acute myocardial injury (31% [357/1,167] versus 18% [123/667]; P<0.001) and type 2 myocardial infarction (40% [115/509] versus 30% [135/454]; P<0.001) (Figure 2).Abstract 48 Figure 1Cumulative incidence plot of cardiovascular death or MI (myocardial infraction) at one year in patients with acute myocardial injury and type 2 MI stratified by the presence of coronary disease (CAD)Abstract 48 Figure 2Cumulative incidence plot of all-cause death at one year in patients with acute myocardial injury and type 2 MI (myocardial infraction) stratified by the presence of coronary disease (CAD)ConclusionCoronary artery disease is recognised in around one third of patients with acute myocardial injury and type 2 myocardial infarction and is associated with higher rates of cardiovascular events and all-cause death. Risk doubled in those with coronary artery disease and was similar whether the index diagnosis was myocardial injury or infarction, suggesting that coronary investigation and secondary prevention may have a role in both conditionsConflict of Interestnone

The application of high-sensitivity cardiac troponins in clinical practice has led to an increase in the recognition of elevated concentrations in patients without myocardial ischaemia. The Fourth Universal Definition of Myocardial Infarction encourages clinicians to classify such patients as having an acute or chronic myocardial injury based on the presence or absence of a rise or a fall in cardiac troponin concentrations. Both conditions may be caused by a variety of cardiac and non-cardiac conditions, and evidence suggests that clinical outcomes are worse than patients with myocardial infarction due to atherosclerotic plaque rupture, with as few as one-third of patients alive at 5 years. Major adverse cardiovascular events are comparable between populations, and up to three-fold higher than healthy individuals. Despite this, no evidence-based strategies exist to guide clinicians in the investigation of non-ischaemic myocardial injury. This review explores the aetiology of myocardial injury and proposes a simple framework to guide clinicians in early assessment to identify those who may benefit from further investigation and treatment for those with cardiovascular disease.

IntroductionObjective risk stratification based is recommended in all patients with a new diagnosis of stable ischaemic heart disease. However, more than half of patients with chronic coronary syndromes who have a future myocardial infarct do not have obstructive coronary disease on coronary imaging, or the ischaemic substrate to enable effective risk stratification with functional testing. There is need for an effective risk stratification tool that can be applied to all patients with chronic coronary syndrome to help guide management decisions.PurposeTo evaluate the role of cardiac troponin testing in the risk stratification of patients with chronic coronary syndrome.Method: Consecutive patients attending a tertiary cardiac centre for investigation of chronic coronary syndrome with coronary angiography were eligible for enrolment into this prospective observational study. High-sensitivity cardiac troponin I was measured in all patients immediately prior to angiography with clinicians blinded to the results. Troponin concentrations were log transformed and evaluated as a continuous variable in adjusted Cox regression models, and categorised as low (<5 ng/L), intermediate (5 ng/L - 99th centile), or high (>99th centile). The primary outcome was a composite of myocardial infarction or cardiovascular death over a median follow-up of 2.5 years.ResultsIn total, 4,344 consecutive patients were enrolled (median age 66 years (IQR 59 - 73), 32.4% female). The majority had obstructive coronary disease on angiography (62.4%, 2,712/4,344), with fewer having non-obstructive disease (27.4%, 1,193/4,344) or angiographically normal coronary arteries (10.2%, 442/4,344). Patients with obstructive disease had higher troponin levels (median 4.0 ng/L, IQR 2.1 - 8.6) than those with non-obstructive disease (2.7 ng/L, IQR 1.4 - 5.1; P<0.001). Patients with the highest troponin concentration were most likely to have a primary outcome (62.8 events per 1,000 patient-years) as compared to those with intermediate (45.5 per 1,000 patient-years) or low troponin levels (15.1 per 1,000 patient-years). In patients with obstructive disease, the incidence of the primary outcome was highest in those with the highest troponin (64.5 per 1,000 patient-years) as compared to those with obstructive disease and either intermediate or low troponin levels (53.2 and 21.2 per 1,000 patient-years, respectively). After adjusting for coronary disease severity, troponin remained an important independent predictor of the primary outcome (aHR 3.1 95%CI 2.4–3.9).Abstract 167 Figure 1Cumulative incidence of the primary outcome (myocardial infarction or cardiovascular death) in patients with obstructive coronary disease, stratified by cardiac troponin concentration [low (green, <5 ng/), intermediate (orange, 5 ng/L - 99th centile), or high (red, >99th centile)ConclusionIn patients with chronic coronary syndrome, cardiac troponin can reliably identify individuals at the highest risk of myocardial infarction or cardiovascular death. Combined with angiographic indices of disease severity, troponin testing in the chronic coronary syndrome could augment current risk stratification strategies and may inform optimised treatment decisions.Conflict of InterestNone

BackgroundEarly rule-out pathways for myocardial infarction using high-sensitivity cardiac troponin are widely recommended in the assessment of patients with suspected acute coronary syndrome. Although developed in selected patients participating in research studies, these pathways are applied more widely in clinical practice where the diagnostic performance and effectiveness of these pathways may differ.PurposeTo evaluate the performance of an early rule-out pathway for myocardial infarction using high-sensitivity cardiac troponin in selected and consecutive unselected patients with suspected acute coronary syndrome.MethodsPresentation and serial high-sensitivity cardiac troponin I concentrations were measured in two cohorts of patients with suspected acute coronary syndrome presenting to the Emergency Departments across three acute care hospitals in Scotland. In the unselected cohort, electronic health record data were collected on consecutive patients in whom the usual care clinician measured cardiac troponin for suspected acute coronary syndrome. In the selected cohort, patients with suspected acute coronary syndrome were approached between 8am and 8pm by research staff and written informed consent obtained. In both cohorts, the performance of the High-STEACS early rule-out pathway was evaluated for an adjudicated diagnosis of myocardial infarction (type 1, type 4b or type 4c) during the index hospital admission.ResultsThe unselected and selected patient cohorts comprised of 1,242 (median age 60 [interquartile range 47–75] years, 46% women) and 1,695 (median age 61 [52–73] years, 40% women) patients respectively. Myocardial infarction was diagnosed in 6% (74/1,242) and 14% (232/1,695) of patients in the unselected and selected patient cohorts respectively. More patients had myocardial infarction ruled-out in the unselected (74%[828/1,112] versus 66% [1,102/1,678]; P<0.001), with similar negative predictive value (99.9% [95% CI 99.7%-100%] versus 99.7% [95% CI 99.4%-99.0%) and sensitivity (99.3% [95% CI 97.4%-100%] versus 98.9% [95% CI 97.6%-99.9%]; Figure). In the selected cohort, more patients had intermediate troponin concentrations requiring serial testing (36% versus 29%) or had myocardial infarction diagnosed (34% versus 26%; P<0.001 for both). In contrast, the positive predictive value for myocardial infarction was lower in unselected patients (26.1% [95% CI 21.2%-31.4%] versus 39.9% [95% CI 35.9%-44.0%]).Abstract 61 Figure 1ConclusionThe prevalence of myocardial infarction is lower in patients with suspected acute coronary syndrome evaluated in routine practice compared to those selected to participate in a research study. Whilst more patients have myocardial infarction accurately ruled out, the positive-predictive value in those ruled in is lower resulting in more hospital admissions with elevated cardiac troponin due to other conditions.Conflict of InterestNothing to declare

In a randomised trial of more than 4,000 patients referred to hospital with a suspected diagnosis of angina, the addition of CTCA to standard care increased diagnostic accuracy and permitted targeting of treatments and interventions to those patients who gained most benefit.6 The use of CTCA reduced the need for further stress testing.6 Although a short-term increase in the use of invasive coronary angiography was observed with CTCA, after five years' follow-up rates were similar between both cohorts.7 Ultimately, this led to a 40% reduction in the risk of death from coronary heart disease or nonfatal myocardial infarction (MI) at 5 years; 2.3% vs. 3.9%, HR 0.59 (95% CI: 0.41-0.84; P = 0.004).7 DRUG THERAPY The objectives of pharmacological therapy in patients with stable angina are to prevent future vascular events and to alleviate symptoms of angina. NICE currently recommends initiating treatment with atorvastatin 80 mg once daily for the prevention of cardiovascular events in patients with stable angina.10 A lower initial dose should be considered if there are potential drug interactions, a high risk of adverse effects or in light of patient preference.10 The target for treatment is a 40% reduction in non HDL cholesterol.10 If this is not achieved with initial treatment, review adherence to medication and lifestyle measures, and consider increasing the dose or switching to a more potent statin. In a randomised trial enrolling more than 19,000 patients with stable CAD without heart failure, the addition of ivabradine to contemporary medical therapy had no effect on all cause mortality, cardiac death or non-fatal MI.13 A prespecified subgroup analysis of patients with limiting angina, reported a small but significant increase in the combined risk of cardiovascular death or non-fatal MI with ivabradine use.13 Ivabradine is currently recommended as second-line treatment for patients with stable angina who are either intolerant of beta-blockade or in whom a rate-limiting CCB fails to achieve adequate heart rate control, and in combination with a beta-blocker in patients whose heart rate is inadequately controlled with an optimal beta-blocker dose.34 Ivabradine should not be initiated in patients with stable angina if the resting heart rate is < 70 beats per minute and should be withdrawn or the dose reduced if the heart rate on treatment falls below 50 beats per minute. The recent ORBITA study confirmed existing evidence that in patients with a low burden of CAD, good exercise tolerance and minimal symptoms on optimal medical therapy, revascularisation with coronary stents confers no additional benefit.15 Factors influencing the choice of revascularisation technique include the burden and location of underlying CAD, the presence of left ventricular dysfunction or valvular heart disease, comorbidity including diabetes mellitus or renal dysfunction, and patient age.