Safety and feasibility of triage and rapid discharge of patients with chest pain from emergency room: a pragmatic, randomised non-inferiority control trial of the European Society of Cardiology (ESC) 0-1 hour pathway vs. conventional 0-3 hour accelerated diagnostic protocol.

Patients presenting with chest pain represent a significant proportion of Emergency Department (ED) attendances but only a minority, typically 10%, have a final diagnosis of myocardial infarction (MI). Prompt discharge of patients without MI will alleviate ED overcrowding as well as improve patient satisfaction and reduce exposure to risk of hospital acquired infections such as Covid 19. The measurement of cardiac troponin (cTn) by a high sensitivity method is recommended by the National Institute for health and Care Excellence (NICE) for rapid categorisation of patients presenting with chest pain. Strategies proposed include measurement on admission and one hour from admission (ESC 0-1-hour pathway, the recent guideline approved pathway which has not been implemented widely), and measurement on admission and three hours from admission (0-3-hour pathway, which is conventional and widely adopted). The primary objective of this study is twofold: firstly, to assess the safety, feasibility, and impact of implementing the ESC (European Society of Cardiology) 0-1-hour pathway in clinical practice by reference to the more established ESC 0-3-hour protocol. The principal outcome measure will be the safety of the ESC 0-1-hour protocol. However, there are concerns that the time from sample draw to result availability (typically around 60 minutes) will impact on the feasibility of the ESC 0-1-hour pathway. Secondly, therefore, our goal is to evaluate whether measurement of high sensitivity troponin by a bedside analyser (point of care testing, POCT), which will produce results in 15 minutes is a feasible alternative to laboratory testing. We will compare the results produced by POCT with the laboratory results in the context of the ESC 0-1 hour and 0-3-hour pathway, as a nested controlled study in the context of a randomised controlled trial. (clinicaltrials.gov: NCT05322395).

Evaluation of the analytical and clinical performance of a high-sensitivity troponin I point-of-care assay in the Mersey Acute Coronary Syndrome Rule Out Study (MACROS-2).

OBJECTIVES: The objective of this study is to evaluate the analytical and diagnostic performance of a high-sensitivity point-of-care (POC) cardiac troponin I assay, the Quidel TriageTrue™ (QuidelOrtho Inc, San Diego, USA), compared to central laboratory testing (CLT) in accelerated diagnostic protocols (ADP) in real time in a clinical environment. METHODS: In a nested sub-study of a pragmatic randomised control trial, consecutive patients with suspected acute coronary syndrome (ACS) and chest pain <12 h duration were randomised to the ESC 0/1 and 0/3-h ADP. Subjects underwent sampling for Quidel TriageTrue POC hs-TnI whole blood and plasma, CLT hs-TnT Roche Elecsys and a validated, NICE approved CLT High sensitivity cardiac troponin I (hs-TnI) (Siemens Attellica) at each time point. Assay imprecision was assessed by repeat analysis of whole blood samples at three levels (low, near 10 % CV 5-10 ng/L, medium, approximating 99th percentile 15-25 ng/L and high, 3-5 times the 99th percentile, 60-100 ng/L). Final diagnosis was adjudicated at 6 weeks by Roche hs-TnT using the 4th universal definition of myocardial infarction (MI). RESULTS: A total of 1,157 patients consented and had both investigational POC whole blood and plasma and central lab hs-cTn available. The median age was 59, 47.2 % were female and 15 % had suffered a previous MI. Assay imprecision of whole blood POC TriageTrue revealed 10 % CV at 8.6 ng/L (>50 % lower than 99th percentile [20.5 ng/L]) and a 20 % CV at 1.2 ng/L. Receiver operator characteristics (ROC) curves were computed for each assay against adjudicated index type 1 MI to study clinical performance. At all-time points there were excellent performance for whole blood POC TriageTrue: area under the curve (AUC) 0.97 [95 % CI 0.94-098], 0.98 [95 % CI 0.97-1.00] and 0.95 [95 % CI 0.92-0.98] at time 0, 1 and 3 h respectively. There was statistical equivalence for performance of whole blood and plasma POC TriageTrue hs-TnI and laboratory Siemens Atellica hs-TnI. CONCLUSIONS: The whole blood POC TriageTrue hs-TnI assay demonstrates imprecision levels consistent with high sensitivity characteristics and has a clinical performance equivalent to an established, validated and NICE approved laboratory Siemens Atellica hs-TnI.

HEART Score Recalibration Using Higher Sensitivity Troponin T.

STUDY OBJECTIVE: We examined the diagnostic performance of a recalibrated History, Electrocardiogram, Age, Risk factors, Troponin (HEART), and Thrombolysis in Myocardial Infarction (TIMI) score in patients with suspected acute cardiac syndrome (ACS). Recalibration of troponin thresholds was performed, including shifting from the 99th percentile to the limit of detection (LOD) or to the limit of quantification (LOQ) We compared the discharge potential and safety of the recalibrated composite scores using a single presentation high-sensitivity cardiac troponin (hs-cTn) T to the conventional scores and with a LOD/LOQ troponin strategy alone. METHODS: We undertook a 2-center prospective cohort study in the United Kingdom (UK) (2018) (Clinicaltrials.gov NCT03619733) to specifically assess recalibrated risk scores (shifting the troponin subset scoring from 99th percentile to LOD [UK]) and combined the results of this with secondary analyses of 2 prospective cohort studies in the UK (2011) and the United States (2018, using LOQ rather than LOD). The primary outcome was major adverse cardiovascular events (MACE), defined as adjudicated type 1 myocardial infarction (MI), urgent coronary revascularization, and all-cause death, at 30 days. We evaluated the original scores using hs-cTn below the 99th percentile and recalibrated scores using hs-cTn

Hyperenhancement of the Pericardium on Cardiac Magnetic Resonance Imaging: A Marker of Acute Inflammation and Neovascularization or a Chronic Fibrotic State.

In cardiac magnetic resonance imaging, hyperenhancement of the pericardium post gadolinium administration in acute chest pain often signifies pericarditis with an acute inflammatory response and neovascularization. In the context of constrictive pericarditis, case series have indicated that the intensity of hyperenhancement and the thickness of the pericardium imply reversibility of the physiology of the constrictive pericarditis. We present a case of intense hyperenhancement and marked thickening of the pericardium in a patient with constrictive pericarditis with antecedent chest pain. Surgical resection of the pericardium and microscopy revealed a chronic fibrotic state with no evidence of inflammation or neovascularization, thus clarifying the failure of initial medical/anti-inflammatory treatment. Our case highlights the fact that hyperenhancement of the pericardium post gadolinium is non-specific for histology and does not necessarily imply the reversibility of pericardial constriction.

Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial.

BACKGROUND: Bivalirudin, with selective use of glycoprotein (GP) IIb/IIIa inhibitor agents, is an accepted standard of care in primary percutaneous coronary intervention (PPCI). We aimed to compare antithrombotic therapy with bivalirudin or unfractionated heparin during this procedure. METHODS: In our open-label, randomised controlled trial, we enrolled consecutive adults scheduled for angiography in the context of a PPCI presentation at Liverpool Heart and Chest Hospital (Liverpool, UK) with a strategy of delayed consent. Before angiography, we randomly allocated patients (1:1; stratified by age [<75 years vs ≥75 years] and presence of cardiogenic shock [yes vs no]) to heparin (70 U/kg) or bivalirudin (bolus 0·75 mg/kg; infusion 1·75 mg/kg per h). Patients were followed up for 28 days. The primary efficacy outcome was a composite of all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target lesion revascularisation. The primary safety outcome was incidence of major bleeding (type 3-5 as per Bleeding Academic Research Consortium definitions). This study is registered with ClinicalTrials.gov, number NCT01519518. FINDINGS: Between Feb 7, 2012, and Nov 20, 2013, 1829 of 1917 patients undergoing emergency angiography at our centre (representing 97% of trial-naive presentations) were randomly allocated treatment, with 1812 included in the final analyses. 751 (83%) of 905 patients in the bivalirudin group and 740 (82%) of 907 patients in the heparin group had a percutaneous coronary intervention. The rate of GP IIb/IIIa inhibitor use was much the same between groups (122 patients [13%] in the bivalirudin group and 140 patients [15%] in the heparin group). The primary efficacy outcome occurred in 79 (8·7%) of 905 patients in the bivalirudin group and 52 (5·7%) of 907 patients in the heparin group (absolute risk difference 3·0%; relative risk [RR] 1·52, 95% CI 1·09-2·13, p=0·01). The primary safety outcome occurred in 32 (3·5%) of 905 patients in the bivalirudin group and 28 (3·1%) of 907 patients in the heparin group (0·4%; 1·15, 0·70-1·89, p=0·59). INTERPRETATION: Compared with bivalirudin, heparin reduces the incidence of major adverse ischaemic events in the setting of PPCI, with no increase in bleeding complications. Systematic use of heparin rather than bivalirudin would reduce drug costs substantially. FUNDING: Liverpool Heart and Chest Hospital, UK National Institute of Health Research, The Medicines Company, AstraZeneca, The Bentley Drivers Club (UK).

The effect of carvedilol on B-type natriuretic peptide and cardiac function in patients with heart failure and persistent atrial fibrillation.

OBJECTIVES: We sought to determine the relationship between changes in natriuretic peptides and symptoms as a consequence of introducing beta-blocker therapy, in patients with chronic heart failure (CHF) and persistent atrial fibrillation (AF). METHODS: In a randomised, double-blind, placebo-controlled study involving 47 patients with CHF and persistent AF (mean age 68 years and 62% men), we analysed the individual change (Δ) in B-type natriuretic peptide (BNP) level to the introduction of carvedilol (titrated to a target dose of 25 mg twice daily, group A) or placebo (group B) in addition to background treatment with digoxin. Symptoms score, 6-min walk distance, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), heart rate (24-hour ECG) and BNP were measured at baseline and at 4 months. RESULTS: LVEF (Δ median +5 vs. +0.4, p = 0.048), symptoms score (Δ median -4 vs. 0, p = 0.04), NYHA class (Δ median -33% vs. +3% in NYHA class 3-4, p = 0.046) and heart rate [Δ median 24-hour ventricular rate (VR) -19 vs. -2, p < 0.0001] improved with combination therapy of digoxin and carvedilol compared to digoxin alone, but BNP (Δ median +28 vs. -6 , p = 0.11) trended in the opposite direction. There was no relationship between the degree of symptomatic improvement or VR control and BNP response. CONCLUSION: After the introduction of carvedilol, clinical outcome appears unrelated to BNP changes in patients with CHF and AF. Changes in BNP cannot be used as a marker of clinical response in terms of symptoms or cardiac function in this setting.

Case report: intravascular ultrasound-guided entry to an anomalous highly angulated circumflex coronary artery originating from the right sinus of Valsalva.

Background: Anomalous coronary arteries originating from the contralateral sinus of Valsalva constitute a rare congenital anomaly. Most of such anomalous coronary arteries exhibit slit-like orifice that are often compounded by external compressive factors. Consequently, percutaneous coronary intervention (PCI) of these vessels poses considerable challenges, both in terms of cannulation but also intervention in often acutely angulated vessels. Case summary: A 61-year-old man, with a history of previous coronary artery bypass graft surgery and PCI presented with a history consistent with unstable angina. Notably, the left circumflex artery (LCX) in this individual exhibited an anomalous origin. Due to unfavourable anatomy and ambiguous LCX ostium take-off, previous operators had elected PCI of the saphenous vein graft (SVG) anastomosed to the obtuse marginal branch. A computed tomography scan on this occasion confirmed occlusion of the SVG and defined precise origin of anomalous coronary artery. Real-time live intravascular ultrasound (IVUS) positioned in the ascending aorta, in the right sinus of Valsalva, allowed visualization of the origin and wiring of the anomalous circumflex coronary artery and also facilitated successful PCI. Discussion: As far as we are aware, this is the first description of IVUS assisted wiring of an anomalous coronary artery. Intravascular ultrasound also facilitated decision making in this complex angioplasty of an angulated and heavily diseased circumflex coronary artery.

The collateral circulation of the heart in coronary total arterial occlusions in man: systematic review of assessment and pathophysiology.

BACKGROUND: Anatomical and functional assessment of the collateral circulation of the heart in total arterial occlusions is challenging, and this is particularly true of the microcirculation. The pathophysiology of the collateral circulation has historically been and remains of considerable research focus but with diverging and sometimes conflicting results. Our purpose was to conduct a systematic review on the assessment and pathophysiology of the collateral circulation of the heart in total coronary arterial occlusions. METHODS: We extracted data from Pubmed, Ovid, EMBASE, and Cochrane database from 1966 to December 2012. Two investigators independently reviewed the identified articles for eligibility and extracted the data. RESULTS: Seventy-seven studies met inclusion criterion. An invasive assessment of the collateral circulation with pressure and/or Doppler wires is the gold standard in the assessment of collateral physiology and anatomy, although this can only be undertaken after successful passage of the sensor in the true lumen of the occluded vessel. A collateral circulation can provide resting metabolic requirements for the heart but invariably cannot meet demands on stress irrespective of the degree of collateralization as assessed by coronary angiography. In the case of myocardium subtending a totally occluded epicardial artery coronary collateral grading systems or physiological assessment of collateral flow is only moderately sensitive and poorly specific at predicting viability. Regression of collaterals seems more profound in totally occluded arteries versus nonoccluded lesions postrevascularization. CONCLUSIONS: Key controversies in the assessment and pathophysiology of the collateral circulation of the heart in total coronary arterial occlusions are systematically evaluated.

The intersection of atrial fibrillation and heart failure in a hospitalised population.

OBJECTIVES: This work set out to comprehensively characterize patients admitted to hospital with both atrial fibrillation (AF) and heart failure (HF) and to compare this cohort of patients to the global hospital population of patients with only one of these diagnoses. METHODS AND RESULTS: This was a retrospective analysis of all in-patients with HF and AF admitted to a large urban hospital over a 3-month period. Patients with AF were identified by both discharge codes and electrocardiograms. HF patients were identified by means of discharge codes for HF and by screening all patients with AF, a common comorbidity of HF. Evidence for left ventricular (LV) dysfunction was sought. Of patients with AF (n = 453), 43% had symptoms of HF and LV dysfunction. Of patients with a discharge code and confirmed HF (n = 286), 34% had AF, 60% of whom were in chronic AF. Compared to HF patients in sinus rhythm those in AF were older (70 +/- 10 y vs 67 +/- 12 y, P < 0.02), had a higher prevalence of valvular heart disease (25% vs 7%, P < 0.0001) and a lower prevalence of ischaemic heart disease (17% vs 40%, P < 0.0001). HF patients identified by discharge codes in AF were more likely to have QRS > or = 120 msec (18% vs 12% in sinus rhythm; P= ns). Patients with AF and deemed to suffer concomitant HF, as opposed to AF alone, were significantly more likely to have QRS prolongation (QRS > or = 120 msec 27% vs 8%, P < 0.05). 8% of patients with AF and HF had a QRS > 150 msec. CONCLUSIONS: AF and HF are frequent, concomitant pathologies in a hospitalised population. AF complicates HF assessment and treatment. Greater dyssynchrony, as denoted by ECG, in the AF and HF population suggests opportunities for treatment of HF by cardiac resynchronization therapy and ablative therapies.

Rapid diagnostic strategies using high sensitivity troponin assays: what is the evidence and how should they be implemented?

The introduction of high sensitivity measurement of cardiac troponin T (hs cTnT) and cardiac troponin I (hs cTnI) has given the laboratory the ability to measure very low levels of cardiac troponin. The limit of detection of these assays is well below the 99th percentile. These low levels can also be measured with small values of imprecision. A range of algorithms combining presentation measurement with repeat sample intervals of as little as one to 2 hours have been developed. These are able to predict with acceptable accuracy the diagnosis that would be achieved with continued repeat sampling out to six to 12 hours from presentation. In this article, we review the evidence for the diagnostic accuracy of these approaches and the practical aspects of implementation into routine clinical practice.

Unstable angina in the context of high-sensitive troponins: Still a marker of high risk? A comparison of outcomes with adjudicated type 1 myocardial infarction.

BACKGROUND: Unstable angina (UA), considered historically a marker of high risk, has rarely been studied in the high sensitive troponin era. We sought to characterise this population and determine short- and medium-term outcomes for UA and compared this to both patients with musculoskeletal chest pain and adjudicated type 1 MI (NSTEMI). METHOD: We conducted a post-hoc analysis of 2 prospective cohort studies of suspected acute coronary syndrome in 2 hospitals in the northwest of England. (n = 3018) We used a dedicated symptom score to diagnose unstable angina. Type 1 MI (NSTEMI) was diagnosed by independent physician adjudication according to 3rd universal definition of MI. Follow-up was 100% complete for all patients to 1 year. RESULTS: 185 (6.1%) and 249 (8.3%) were adjudicated as suffering from UA and NSTEMI respectively. We restricted our analysis of UA to 158 (5.2%) patients with UA with high sensitive troponin T (Roche Elecsys) ≤14 ng/L (≤99th percentile). Compared to the NSTEMI population, the UA cohort were younger (59 vs 74, p < 0.002), had a lower incidence of hypertension (56.3% vs 69.1%, p = 0.009), had significantly lower composite risk scores and had fewer ECG abnormalities (ST depression >1 mm, 5.1% vs 15.6%, p = 0.001, T wave flattened, biphasic or inverted 24.1% vs 47.8%, p < 0.0001). Subsequent Type 1 MI to 30 days and 1 year in the UA cohort was 1.9% and 1.9% respectively compared to 0.8% and 2.4% in the index type 1 MI (NSTEMI cohort) respectively. However, compared to patients presenting with musculoskeletal chest pain (n = 468) there was a significantly greater incidence of subsequent MI and coronary revascularisation in patients with unstable angina. All cause death at 30 days and 1 year was 0.0% and 0.6% (n = 1) for UA patients and 2.8% (n = 7) and 16.1% (n = 40) for the NSTEMI cohort respectively. CONCLUSION: UA, defined objectively by a symptom score and absence of myocyte necrosis, is still prevalent as an entity, with a risk of subsequent MI and urgent or emergency coronary revascularisation. However, mortality is >10-fold lower when compared to NSTEMI, indicating a less severe pathology in terms of atherosclerosis or plaque burden, and implying the need for a different management strategy to that of NSTEMI.

Implementation of the European Society of Cardiology 0/3-hour accelerated diagnostic protocol, using high sensitive troponin T: a clinical practice evaluation of safety and effectiveness involving 3003 patients with suspected acute coronary syndrome.

BACKGROUND: There have been relatively few studies detailing the real-world effectiveness and safety of accelerated diagnostic protocols (ADP), using high sensitivity cardiac troponin (hs-cTn). OBJECTIVE: To analyse the safety and effectiveness of early emergency department (ED) discharge following implementation of the European Society of Cardiology (ESC) 0/3-hour ADP for suspected acute coronary syndromes (ACS). METHOD: We prospectively studied 2 cohorts of consecutive suspected ACS presentations to ED before (n=1642) and after (n=1376, 2 centres) implementation of the ESC 0/3-hour ADP incorporating limit of detection rule out. Safety was defined by MACE (major adverse cardiac events) inclusive of type 1 myocardial infarction (MI) in patients discharged from ED, and clinical effectiveness by percentage ED discharge. Continuous variables and categorical data were evaluated by independent t-test and χ2 test, respectively. Time-to-event data were analysed as survival data and converted to Kaplan-Meier curves for interpretation. RESULTS: In the preimplementation period, there was a higher prevalence of MI. Discharge from ED increased by >100% (from 27.1% to 56.5% of the cohort) with no safety signal (MACE rate 4/444 (0.9%) vs 4/769 (0.52%), p=0.430 for the 2011 and 2018 cohort, respectively). This correlated with a marked reduction in length of stay overall but a more modest reduction for those discharged from ED (6 hours 10 min vs 5 hours 25 min, p<0.001) for the 2011 and 2018 cohort, respectively. There were improvements in presentation to blood draw (163-90 min, p<0.001). Time from presentation to first ECG actually increased (16.2 vs 31.2 min, p<0.001). Analysis of hs-cTn values and ECGs revealed a maximum ED discharge rate of 69%, by applying the 0/3-hour protocol, implying potential for increasing safe ED discharge. CONCLUSIONS: Implementation of an ADP with hs-cTn is safe and effective for early rule-out and discharge of suspected ACS but require considerable resources and education to optimise maximal patient flow.

Independent Predictors of Repeat Emergency Room Presentations: Insights from a Cohort of 1066 Consecutive Patients with Non-Cardiac Chest Pain Generating 4770 Repeat Presentations.

BACKGROUND AND IMPORTANCE: Chest pain (CP) is one of the most frequent presentations to the emergency department (ED), a large proportion of which is non-cardiac chest pain (NCCP). Repeat attendances to ED are common and impose considerable burden to overstretched departments. OBJECTIVE: Our aim was to determine drivers for repeat ED presentations using NCCP as the primary cause of index presentation. DESIGN, SETTING AND PARTICIPANTS: This was a retrospective cohort study of 1066 consecutive presentations with NCCP to a major urban hospital ED in North England. Index of Multiple Deprivation (IMD), a postcode-derived validated index of deprivation, was computed. Charlson comorbidity index (CCI) was determined by reference to known comorbidity variables. Repeat presentation to ED to any national hospital was determined by a national linked database (population 53.5 million). Independent predictors of ED representation were computed using logistic regression analysis. RESULTS: Median age was 43 (IQR 28-59), and 50.8% were male. Furthermore, 27.8%, 8.1% and 3.8% suffered from chronic obstructive pulmonary disease (COPD), hypertension and diabetes mellitus, respectively. The most frequent diagnoses, using ICD-10 coding, were non-cardiac chest pain (55.1%), followed by respiratory conditions (14.7%). One-year incidence of adjudicated myocardial infarction, urgent or emergency coronary revascularisation and all-cause death was 0.6%, 2% and 5.3%, respectively. There was a total of 4770 ED repeat presentations 1 year prior to or following index presentation with NCCP in this cohort. Independent (multivariate) predictors for frequent re-presentation (defined as ≥2 representations) were a history of COPD (OR [odds ratio] 2.06, p = 0.001), previous MI (OR3.6, p = 0.020) and a Charlson comorbidity index ≥1 (OR 1.51, p = 0.030). The frequency of previous MI was low as only 3% had sustained a previous MI. CONCLUSIONS: This analysis indicates that COPD and complex health care needs (represented by high CCI), but not socio-economic deprivation, should be health policy targets for lessening repeat ED presentations. What is already known on this topic: Repeat presentations with non-ischaemic chest pain are common, placing a considerable burden on emergency departments. WHAT THIS STUDY ADDS: COPD and complex health care needs, denoted by Charlson comorbidity index, are implicated as drivers for repeat presentation to accident and emergency department. Socio-economic deprivation was not an independent predictor of re-presentation. How might this study affect research, practice, or policy: Community-based support for COPD and complex health care needs may reduce frequency of ED attendance.

Challenges in Primary PCI: How to Treat a Large Intracoronary Thrombus With TIMI 3 Flow?

This case highlights 2 important issues: the immediate management of large intracoronary thrombus in the ST-segment elevation myocardial infarction setting with TIMI 3 flow, and the risks/benefits associated with sealing a plaque in an unobstructed artery by stenting. Potent antithrombotic therapy with a view to subsequent intracoronary imaging to define etiology and plaque morphology appears to be a reasonable initial strategy in this specific population. Furthermore, for patients with acute coronary syndromes diagnosed with plaque erosion by optical coherence tomography and residual diameter stenosis <70%, deferred stenting appears a viable option.

Risk of Major Bleeding With Potent Antiplatelet Agents After an Acute Coronary Event: A Comparison of Ticagrelor and Clopidogrel in 5116 Consecutive Patients in Clinical Practice.

Background Major bleeding after acute coronary syndrome predicts a poor outcome but is challenging to define. The choice of antiplatelet influences bleeding risk. Methods and Results Major bleeding, subsequent myocardial infarction (MI), and all-cause mortality to 1 year were compared in consecutive patients with acute coronary syndrome treated with clopidogrel (n=2491 between 2011 and 2013) and ticagrelor (n=2625 between 2012 and 2015) in 5 English hospitals. Clinical outcomes were identified from national hospital episode statistics. Bleeding and MI events were independently adjudicated by 2 experienced clinicians, blinded to drug, sequence, and year. Bleeding events were categorized using Bleeding Academic Research Consortium 3 to 5 and PLATO (Platelet Inhibition and Patient Outcomes) criteria and MI by the Third Universal Definition. Multivariable regression analysis was used to adjust outcomes for case mix. The median age was 68 years and 34% were women. 39% underwent percutaneous coronary intervention and 13% coronary artery bypass graft surgery. Clinical outcome data were 100% complete for bleeding and 99.7% for MI. No statistically significant difference was seen in crude or adjusted major bleeding for ticagrelor compared with clopidogrel (Bleeding Academic Research Consortium 3-5, hazard ratio [HR], 1.23; 95% CI, 0.90-1.68; P=0.2, PLATO major adjusted HR, 1.30; 95% CI, 0.98-1.74; P=0.07) except in the non-coronary artery bypass graft cohort (n=4464), where bleeding was more frequent with ticagrelor (Bleeding Academic Research Consortium 3-5, adjusted HR, 1.58; 95% CI, 1.09-2.31; P=0.017; and PLATO major HR, 1.67; 95% CI, 1.18-2.37; P=0.004). There was no difference in crude or adjusted subsequent MI (adjusted HR, 1.20; 95% CI, 0.87-1.64; P=0.27). Crude mortality was higher in the clopidogrel group but not after adjustment, using either Cox proportional hazards or propensity matched population (HR, 0.90; 95% CI, 0.76-1.10; P=0.21) as was the case for stroke (HR, 0.82; 95% CI, 0.52-1.32; P=0.42). Conclusions This observational study indicates that the apparent benefit of ticagrelor demonstrated in a clinical trial population may not be observed in the broader population encountered in clinical practice. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02484924.

Identification of high-risk non-ST elevation myocardial infarction at presentation to emergency department. A prospective observational cohort study in North West England.

OBJECTIVES: Early access to invasive coronary angiography and revascularisation for high-risk non-ST elevation myocardial infarction (NSTEMI) improves outcomes and is supported by current guidelines. We sought to determine the most effective criteria at presentation to emergency department (ED) to identify high-risk NSTEMI. SETTING: Secondary care centre northwest England with national follow-up. PARTICIPANTS: 1642 consecutive patients (median age 59, 52% male) presenting to ED with a primary symptom of chest pain in whom there is suspicion of NSTEMI. PRIMARY AND SECONDARY MEASURES: Multivariate logistic regression analysis for the prediction of all-cause death (primary) and major adverse cardiac event (MACE defined as all-cause death, unplanned coronary revascularisation and adjudicated NSTEMI (third universal definition)) (secondary measure) at 1 year. RESULTS: The incidence of adjudicated NSTEMI was 10.7%, and 1-year mortality was 6.3%. Independent predictors for all-cause death at 1 year were Global Registry of Acute Coronary Events (GRACE) >140, age (per decade increase) and high-sensitive cardiac troponin T (hs-cTnT) >50 ng/L. hs-cTnT >50 ng/L was associated with adjudicated index presentation NSTEMI in the greatest proportion of patients (61.7%). When using MACE at 12 months, as opposed to all-cause death, as an end point History, ECG, Age, Risk factors and Troponin (HEART) score ≥7 was included in the multivariate model and had better prediction of index NSTEMI than GRACE>140. Combining hs-cTnT >50 ng/L and a second independent predictor identified both a high proportion of index NSTEMI and elevated risk of all-cause death at 1 year. CONCLUSIONS: hs-cTnT >50 ng/L or HEART score ≥7 appear effective strategies to identify high-risk NSTEMI at presentation to emergency room with chest pain. Multicentre prospective studies enriched with early presenters, and with competitor high-sensitive and point-of-care troponins, are required to validate and extend these findings. TRIAL REGISTRATION NUMBER: NCT02581540.