BACKGROUND:For suspected acute coronary syndrome (ACS), guidelines recommend using high-sensitivity troponins (hs-cTn) in accelerated diagnostic pathways (ADPs) with 0/1-hour recommended over 0/3-hour ADP. However, implementation of these ADPs, with universal use of hs-cTns, has not been directly compared in randomized trials OBJECTIVES: This study sought to compare the efficiency and safety of the European Society of Cardiology (ESC) 0/1-hour and a 0/3-hour ADP when implemented in real-world clinical practice. METHODS:This pragmatic, randomized, noninferiority implementation trial compared the safety and efficiency of clinician decision making using these 2 pathways. To prevent incorporation bias, an independent hs-cTnI was used for formal adjudication using the fourth universal definition of myocardial infarction (MI). Efficiency was judged by the proportion of patients discharged within 4 hours. The safety endpoint was major adverse cardiac events (MACE) within 30 days (adjudicated index or representation type 1 MI, cardiovascular death, and urgent coronary revascularization) for those who were considered not to have ACS and discharged. The noninferiority margin, for absolute difference in sensitivity, between the ESC 0/1-hour and the 0/3-hour ADP was set at 3%, assessed with a 1-sided 97.5% CI. RESULTS:From December 2021 to July 2024, of 13,983 screened 3,543 individual patients with suspected ACS were recruited and consented from 2 major emergency departments in North-West England, with 100% follow-up achieved for all representations to any national hospital. The median age was 60 years (IQR: 49.5-70.5 years), 53% were men, 6.7%, and 7.6% had adjudicated index type 1 MI and MACE within 30 days, respectively. The turnaround time from sample to result for central laboratory hs-cTnT was 81 minutes (IQR: 69-101 minutes). The proportion of patients discharged within 4 hours was relatively low and did not differ substantially (21.8% vs 19.2%, P = 0.07). In addition, the 0/1-hour pathway was noninferior for safety, in patients discharged, compared with the 0/3-hour pathway, absolute difference in sensitivity was +4.2% (1-sided 97.5% CI: -2.5) in favor of the 0/1-hour pathway. The calculated sensitivities were 93.7% (95% CI: 88.4%-97.1%) vs 89.5% (95% CI: 82.7%-94.3%), respectively. CONCLUSIONS:Implementation of the ESC 0/1-hour pathway failed to discharge significantly more patients within 4 hours of presentation compared with the 0/3-hour ADP. In addition, The ESC 0/1-hour was noninferior to the 0/3-hour hs-cTn pathway for safety of discharge, although safety for both pathways was less than that imputed by observational studies. This trial demonstrates that perceived benefits to emergency department efficiency of a reduced sampling interval are mitigated by central laboratory turnaround times as well as system constraints. (Pragmatic Randomised Trial of the ESC 0/​1 Versus 0/​3 Hour Troponin Pathway [MACROS2]; NCT05322395).

There have been considerable developments in the analytic precision of cardiac troponins in the last three decades. Whilst there has been near-universal uptake of this technology, there is considerable variability in how to assess acute chest pain patients using high-sensitivity cardiac troponins. This review describes the historical narrative for cardiac troponins and details the evidence base behind decision rules, such as single sample rule-out, single sample rule-in, and accelerated diagnostic protocols (ADPs). There is particular focus on the European Society of Cardiology (ESC) 0/1 and 0/3 h and the high-STEACS ADPs. The ESC 0/3 h ADP appears to have reduced rule-out safety compared to both the ESC 0/1 h and high-STEACS ADP. However, whilst high-STEACS performed well in its validation population, external validation in the US has been less impressive and warrants further investigation. The ESC 0/1 h pathway has demonstrated strong rule-out performance, helped by its observational zone. However, real world implementation studies comparing these ADPs are required to understand their impact on Emergency Department efficiency and the safety of clinician decision-making.

Myocardial infarction remains a significant cause of mortality globally. High-sensitivity cardiac troponin is an essential criterion in the fourth universal definition of myocardial infarction. Our understanding of the structure and release mechanisms of troponin has been updated over the last decade, facilitated by ever more sensitive assays. This review initially outlines the structure and function of the troponin complex, then details the currently proposed mechanisms of release and elimination of troponin. It concludes by using this updated understanding to critique the current universal definition of myocardial infarction and injury.

Measurement of high sensitivity cardiac troponin (hs-cTn) I using cartridge-based systems at the point of care (POC) requires an appropriate quality control system. The optimal strategy for this currently remains unclear. We report the results of our experience with such a system with measurement over 842 days. The Mersey Acute Coronary syndrome Rule Out Study (MACROS-2). MACROS-2 is a two-centre, pragmatic, randomised controlled trial (RCT) comparing the rule out of non ST-elevation myocardial infarction (NSTEMI), using the European Society of Cardiology (ESC) 0/1 or 0/3 hour diagnostic algorithms (ClinicalTrials.gov Identifier: NCT05322395). The inclusion period was 13/4/22-29/07/2024. Upon presentation with symptoms compatible with NSTEMI, the patient had blood drawn at presentation for central laboratory high sensitive cardiac troponin(hs-cTn) T (roche , elecsys [clinical biomarker in use]), but an additional research sample was drawn for immediate analysis in the ED (emergency department) of whole blood (EDTA tube) Quidel TriageTrueTM hs-cTn I test on the Quidel Triage Meterpro device. This process was repeated for any serial samples. The device includes two on-board quality control (QC) checks on the analytical process. Internal liquid QC was performed using manufacturer supplied EDTA plasma-based QC material. Both alow control (target 25 ng/L) and high control (target 500 ng/L) were use by expert laboratory operators with regular checks on a weekly basis. For plasma, the analytical range is 0.1-1000 ng/L, limit of detection (LoD) is 1.5 ng/L, limit of quantitation (LoQ) at 20% coefficient of variation (CV) 2.1 ng/L and at 10% CV 4.6ng/L. 99th percentile overall 20.5 ng/L. All IQC was downloaded to a central repository for analysis. Over 842 days 539triage true POC tests were run on patient samples and 382 QC samples. An invalid test result on first analysis occurred in 56/5391 (1%). On repeat analysis there were 24 analytical failures giving a total failure rate of 24/5291 (0.4%). 328 (165 low, 162 high) QC samples were run. There were 7 lots for the low QC and 9 lots for a high QC over 21 reagent lots. eight expert laboratory operators undertook IQC. For the low control, 4/165 (2.5%) samples exceeded the two standard deviation (SD) limit and none exceeded 3 SD. Mean value was 25.4 ng/L with a mean CV of 9.7%. There was only one analytical failure in the high control with only 2 (1.2% exceeded 2 SD and none 3 SD’s. The mean value was 519 ng/L with a mean CV of 9.5%. Time series regression analysis across reagent batches showed no evidence of significant lot to lot variation or evidence of QC drift across the entire period of the study. Analytical reliability of the system was robust. QC stability with time suggests that following lot verification, QC frequency can be such that only the midpoint and towards the end of a particular batch is measured.

BACKGROUND:There is increasing awareness of the differing characteristics of troponin subunits. CASE SUMMARY:We present a case where an elevation of high-sensitivity troponin T (hs-cTnT) (>6× 99th percentile) beyond the single-sample rule-in threshold led to an erroneous diagnosis of acute coronary syndrome (ACS). After exhaustive biochemical tests proving chronic myocardial injury, we also determined that 4 different high sensitivity assays for troponin I revealed values well below their respective 99th percentiles. This uniquely highlights the difference in troponin subunit characteristics in chronic myocyte injury and dispels any notion that the difference relates to assay characteristics. DISCUSSION:Chronic elevations of hs-cTnT can be sufficiently large to surpass single rule-in thresholds in some ACS pathways, but this case stresses the importance of the delta value regardless of the degree of elevation of the presentation sample. In cases of diagnostic doubt for ACS, clinicians should consider measuring hs-cTnI as an alternative troponin.

BACKGROUND:Multiple plaque ruptures and erosions, both culprit and remote, have been described and illustrated in the context of acute coronary syndrome. However, there is limited evidence for this phenomenon using optical coherence tomography, the highest resolution intracoronary imaging technology. CASE SUMMARY:In this report, the authors describe by optical coherence tomography, multiple spontaneous plaque erosions and a ruptured plaque, de novo and in-stent, resulting in 2-vessel occlusion in a patient with acute coronary syndrome. DISCUSSION:This case confirms, by means of optical coherence tomography, previous reports of multiple nonculprit plaque erosions and rupture in acute coronary syndrome.

BACKGROUND:Approximately 90% of patients presenting to the emergency department with suspected acute coronary syndrome have acute myocardial infarction excluded, but they remain at risk of major adverse cardiovascular events. This study assessed the long-term outcomes of such patients, focusing on the incremental value of multiple biomarkers combined with clinical risk scores for risk stratification. METHODS:In this prospective observational study, 487 patients with suspected acute coronary syndrome but excluded acute myocardial infarction were recruited from a large urban hospital, with a median follow-up of 5.8 years. The primary end point was major adverse cardiovascular events, including adjudicated type 1 myocardial infarction, unstable angina requiring urgent revascularization, and cardiovascular death. Biomarkers assessed were hs-cTnT (high-sensitivity cardiac troponin T), hs-cTnI (high-sensitivity cardiac troponin I), HFABP (heart-type fatty acid binding protein), GDF-15 (growth differentiation factor 15), NT-proBNP (N-terminal prohormone of brain naturetic peptide), galectin-3, and hs-CRP (high-sensitivity C-reactive protein (). Statistical methods included receiver operating characteristic analysis, Kaplan-Meier curves, net reclassification index, and Cox proportional hazards models to evaluate biomarker utility independently and combined with Thrombolysis in Myocardial Infarction and History, ECG, Age, Risk Factors, Troponin scores. RESULTS:Of the 487 patients (median age 56 years; 44% female), 9.9% experienced major adverse cardiovascular events. Annualized major adverse cardiovascular events rates for patients with troponin levels below the limit of detection were 0.5% (hs-cTnT) and 0.7% (hs-cTnI), with no cardiovascular deaths over 5 years. Both hs-cTnT and hs-cTnI levels modestly enhanced risk stratification when added to Thrombolysis in Myocardial Infarction or History, ECG, Age, Risk Factors, Troponinscores. Of the non-necrosis biomarkers, only GDF-15 demonstrated independent prognostic value in multivariable models. CONCLUSIONS:Hs-cTnT, hs-cTnI, and GDF-15 improve the long-term risk stratification of the History, ECG, Age, Risk Factors, Troponinand Thrombolysis in Myocardial Infarction scores in patients with suspected acute coronary syndrome and acute myocardial infarction excluded. Hs-cTn of either type at or below limit of detection was associated with excellent short- and long-term outcomes. REGISTRATION:URL: https://clinicaltrials.gov; Unique identifier: NCT03628586.

There is increasing awareness of the differing characteristics of troponin subunits. We present a case where an elevation of high-sensitivity troponin T (hs-cTnT) (>6× 99th percentile) beyond the single-sample rule-in threshold led to an erroneous diagnosis of acute coronary syndrome (ACS). After exhaustive biochemical tests proving chronic myocardial injury, we also determined that 4 different high sensitivity assays for troponin I revealed values well below their respective 99th percentiles. This uniquely highlights the difference in troponin subunit characteristics in chronic myocyte injury and dispels any notion that the difference relates to assay characteristics. Chronic elevations of hs-cTnT can be sufficiently large to surpass single rule-in thresholds in some ACS pathways, but this case stresses the importance of the delta value regardless of the degree of elevation of the presentation sample. In cases of diagnostic doubt for ACS, clinicians should consider measuring hs-cTnI as an alternative troponin.

OBJECTIVES:To assess the imprecision and stability of the point-of-care troponin I assay in the Emergency Department and its correlation and bias to two central laboratory troponin I assays (Siemens Atellica and Abbott Alinity). METHODS:Imprecision and stability testing was performed on opportunistically selected samples using whole blood in the emergency department by non-laboratory trained personnel. Assay comparisons were undertaken on samples taken from participants of the Mersey Acute Coronary syndrome Rule Out Study. RESULTS:The coefficient of variation (95 % confidence interval), at the 99th percentile for the point-of-care assay, was 8.1 % (6.1-12.1 %) but with a wide confidence interval reflective of considerable scatter at values just below the 99th percentile. The 10 % limit of quantification was 7.5 ng/L (1.7-61.8 ng/L). All samples met the ≤2 ng/L stability criteria for a duration of 4 h and under. The point-of-care assay very strongly correlated and had a negative bias with the Siemens Atellica and Abbott Alinity assays, Pearson's R=0.99 and 0.95, mean difference -29.7 ng/L and -13.3 ng/L respectively. CONCLUSIONS:The Siemens VTLi point-of-care assay fulfils high-sensitivity criteria when operated by non-laboratory trained staff using whole blood in its intended environment. Lithium heparin samples are likely stable up to 4 h. Significant bias between the point-of-care and two central laboratory assays negates the use of these assays interchangeably.

Abstract Introduction High sensitivity troponin (hs-cTn) measurement is central to rapid diagnostic algorithms in acute coronary syndrome (ACS). Point of care (POC) testing reduces turnaround time when compared to central lab (CL) testing. Currently there is very little data on the performance of POC hs-cTn assays in a clinical environment with non-expert operators. Method In a nested sub-study of a randomised controlled trial (RCT), patients with suspected ACS were randomised to either the ESC 0/1 or 0/3 hour algorithm. They underwent whole blood (WB) sampling for Siemens Atellica VTLi hs-cTnI POC (VTLi POC), CL hs-cTnI and CL hs-cTnT assays. This was for both initial and repeat samples. Assay imprecision of the VTLi POC assay was assessed by 2 runs of 10 tests with whole blood at 9 different troponin levels. 4 devices were used with samples stored at room temperature.Final diagnosis was adjudicated based on all relevant clinical and imaging data together with CL hs-cTnT as the diagnostic biomarker in clinical use (10% coefficient of variation (CV) 3-5 ng/L, 99th percentile 14 ng/L) and using the 4th universal definition of myocardial infarction (MI). Clinical performance was assessed using Receiver Operator Characteristics (ROC) curves. Results 2144 patients consented and had WB VTLi POC, CL hs-cTnI and CL hs-cTnT available. The index adjudicated type 1 MI rate was 6.1%. Assay imprecision of the VTLi POC assay demonstrated a 10% Coefficient of Variation (CV) at 9.8ng/l. This was >50% lower than the 99th centile of 23ng/l (average for males and females) (Figure 1). Clinical performance of the VTLi POC assay was acceptable and equivalent to CL hs-cTnT: Area Under Curve (AUC) 0.92 (0.89-0.96), 0.98 (0.96-0.99) and 0.93 (0.87-0.98) at presentation (Figure 2), 1 and 3 hours respectively. However, clinical performance was inferior to CL hs-cTnI: AUC 0.96 (0.95-0.98) and 0.96 (0.93-0.98) at presentation (p=0.0007) and 3 hours (p<0.0001) respectively. Conclusion The Siemens Altellica VTLi hs-cTnI POC assay has imprecision levels consistent with a high sensitivity troponin assay. It has acceptable clinical performance though inferior to the equivalent CL hs-cTnI. Further validation of this assay, particularly with optimised single sample rule-out, could facilitate its use in routine clinical practice.

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.

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 categorization of patients presenting with chest pain. Strategies proposed include measurement on admission and 1 hour from admission (ESC 0-1-hour pathway, the recent guideline approved pathway which has not been implemented widely), and measurement on admission and 3 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 to 1-hour pathway in clinical practice by reference to the more established ESC 0 to 3-hour protocol. The principal outcome measure will be the safety of the ESC 0 to 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 to 1-hour pathway. Secondly, therefore, our goal is to evaluate whether measurement of high sensitivity troponin by a bedside analyzer (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 to 1 hour and 0 to 3-hour pathway, as a nested controlled study in the context of a randomized controlled trial. (clinicaltrials.gov: NCT05322395).

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 <LOD/LOQ and compared these composite scores with a single hs-cTnT less than LOD/LOQ combined with a nonischemic ECG. For each discharge strategy, an assessment of clinical effectiveness was also made, defined as the proportion of patients eligible for discharge from the emergency department without the need for further inpatient testing. Results: We studied 3,752 patients (3,003 in the UK and 749 in the United States). Median age was 58 years, and 48% were female. At 30 days, 330/3,752 (8.8%) experienced MACE. The sensitivities of the original HEART less or equal to 3 and recalibrated HEART less or equal to 3 scores for rule-out were 96.1% (95% confidence interval [CI], 93.4 to 97.9) and 98.6% (95% CI, 96.5 to 99.5) respectively; the original TIMI less or equal to 1 and recalibrated TIMI less or equal to 1 scores' sensitivities were 79.7% (95% CI, 74.9 to 83.9) and 96.1% (95% CI, 93.4 to 97.9) respectively; and nonischemic ECG with hs-cTn T below the 99th percentile and hs-cTn T less than LOD/LOQ was 79.7% (95%CI, 0.749 to 0.839) and 99.1% (95% CI, 0.974 to 0.998), respectively. Recalibrated HEART less or equal to 3 was projected to discharge 14% more patients than hs-cTn T less than LOD/LOQ. The improved sensitivity of rule-out for recalibrated HEART less than or equal to 3 came at the cost of reduced specificity (50.8% versus 53.8% for recalibrated HEART and conventional HEART respectively). Conclusion: This study indicates that recalibrated HEART score of less or equal to 3 is a feasible and safe early discharge strategy using a single presentation hs-cTnT. This finding should be further tested using competitor hs-cTn assays in independent prospective cohorts before implementation. [Ann Emerg Med. 2023;82:449-462.]

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.

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, compared to NSTEMI suggesting less severe pathology in terms of atherosclerosis or plaque burden, and implying the need for a different management strategy to that of NSTEMI.

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.

Abstract Background Approximately 90% of patients presenting to ED (Emergency Department) with suspected Acute Coronary Syndrome (ACS) have Myocardial Infarction (MI) excluded. Long term outcome and risk stratification for this cohort has rarely been studied. Purpose To study long term cardiovascular outcomes in patients with acute Chest Pain (CP) in whom MI is excluded, and to investigate the incremental value of biomarkers of inflammation, myocardial ischaemia and stress, for risk stratification, to that of existing methods of stratifying risk including absolute values of two high sensitive troponins below the 99th percentile. Methods A prospective observational study in a large university teaching hospital with a median follow-up of 5.8-year. Cardiovascular outcomes studied included adjudicated type 1 MI (to 4th universal definition), unstable angina requiring urgent revascularisation and cardiovascular death. Inclusion criteria included CP with features of ischaemia but with MI excluded (High sensitive cardiac troponin [hs-cTn] T ≤99th percentile). Exclusion criteria included non-cardiac chest pain, chronic atrial fibrillation, heart failure and recent ACS. The biomarkers HFABP, GDF-15, NT-proBNP, Galectin-3, HS-CRP taken on first venepuncture for high sensitive cardiac troponins were investigated using univariable and multivariable backward stepwise elimination logistic modelling, receiver operator characteristic (ROC) analysis, and Net Reclassification Indices (NRI). They were compared to absolute values of both sub-99th percentile hs-cTnT (Roche Elecsys) and hs-cTnI (Abbot Architect) both as a single entity or when the troponin values were incorporated with HEART and TIMI scores. Results 487 consented patients were enrolled. The mean age of the population was 56 years (SD 11.8), 44% were female, 16.2% were diabetic, 20.9% had a previous MI, 13.8% previous PCI and 5.1% coronary artery bypass grafting. 100% follow-up was achieved. There were 48 events in follow-up. (event rate 9.9%). Multivariable Cox Proportional Hazards analysis including hs-cTnT or hs-cTnI (below 99th percentile) demonstrated incremental improvement in risk stratification with absolute values of either hs-cTn below the 99th percentile when added to either TIMI or HEART risk score. The results were consistent with NRI analysis. Only GDF-15 demonstrated significance in multivariable analysis when analysed with the HEART score regardless of troponin assay and the TIMI score with HS-cTnI but not with HS-cTnT. Conclusion Absolute values of hs-cTnT or I, below 99th percentiles, significantly improve risk modelling for cardiovascular outcomes in acute CP patients, presenting to ED, who have MI excluded. No other biomarker retains independent risk with the exception of GDF-15. Effective dichotomisation of sub99th percentile hstnT or I, used alone or incorporated into risk scores, could allow improved targeting of resources for investigation and management for this large pool of patients.

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.