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The 4th Universal Definition of Myocardial Infarction has stimulated considerable debate since its publication in 2018. The intention was to define the types of myocardial injury through the lens of their underpinning pathophysiology. In this review, we discuss how the 4th Universal Definition of Myocardial Infarction defines infarction and injury and the necessary pragmatic adjustments that appear in clinical guidelines to maximize triage of real-world patients.

Background High-sensitivity cardiac troponin may be a promising biomarker that could be used for personalised cardiovascular risk prediction and monitoring in the general population. Temporal changes in high-sensitivity cardiac troponin before cardiovascular death are largely unexplored. Purpose Using the longitudinal Whitehall II cohort, we evaluated whether three serial high-sensitivity cardiac troponin I measurements over 15 years improved prediction of cardiovascular death when compared to a single time point at baseline. Methods Whitehall II is an ongoing longitudinal observation cohort study of 10,308 civil servants, and we included participants who had at least one cardiac troponin measurement and outcome data available. We constructed time trajectories to evaluate the temporal pattern of cardiac troponin I in those who died from cardiovascular disease as compared to those who did not. Cox regression and joint models were used to investigate the association of cardiac troponin I in relation to cardiovascular death using single time point (at baseline) and repeated measurements (at baseline, 10 and 15 years), respectively. The discriminative ability was assessed by the concordance index. Results In total, we included 7,293 individuals (mean age of 58 years [SD 7] at baseline, 29.4% women). Of these, 5,818 (79.8%) and 4,045 (55.5%) individuals had a second and third cardiac troponin I concentration measured, respectively. Cardiovascular death occurred in 281 (3.9%) individuals during a median follow-up of 21.4 [IQR, 15.8 to 21.8] years. In the 21-year trajectories of cardiac troponin I, we observed higher baseline concentrations in those who died due to cardiovascular disease as compared to those who did not (median 5 [IQR, 2 to 9] ng/L versus 3 [IQR, 2 to 5] ng/L respectively, Figure). Cardiac troponin I was an independent predictor of cardiovascular death, and the hazard ratio (HR) derived from the joint model that included serial cardiac troponin measurements was higher than the HR derived from the single time point model (single time point model: adjusted HR 1.53, 95% Confidence Interval [CI] 1.37 to 1.70 per naturally log transformed unit of cardiac troponin I, versus repeated measurements model: adjusted HR 1.79, 95% CI 1.58 to 2.02). The discriminative ability of the cardiac troponin model improved when using repeated measurements (concordance index of unadjusted cardiac troponin models, single time point: 0.668 versus repeated measurements: 0.724). Conclusions Our study shows that cardiac troponin I trajectories were persistently higher among individuals who died from cardiovascular disease. Cardiac troponin I is a strong independent predictor of cardiovascular death, and incorporating repeated measurements of cardiac troponin improves cardiovascular risk prediction in the general population. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Cardiac troponin I measurements and analysis were supported by were supported by Siemens Healthineers. The study was supported by Health Data Research UK which receives its funding from HDR UK Ltd (HDR-5012) funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and the Wellcome Trust. NLM is supported by the British Heart Foundation through a Senior Clinical Research Fellowship (FS/16/14/32023), Programme Grant (RG/20/10/34966) and a Research Excellence Award (RE/18/5/34216). The funders had no role in the study and the decision to submit this work to be considered for publication.

Background The long-term frequencies of cardiac arrhythmias in hospitalized coronavirus disease 2019 (COVID-19) patients have not been thoroughly investigated. Purpose To describe the prevalence of cardiac arrhythmias, 3–4 months after hospitalization for COVID-19. Methods and results Participants with COVID-19 discharged from five large Norwegian hospitals were invited to participate in a prospective cohort study. We examined 201 participants (44% females, mean age 58.5 years) with 24-hour electrocardiogram 3–4 months after discharge. Body mass index (BMI) was 28.3±4.5 kg/m2 (mean ± SD), and obesity (BMI >30) was found in 70 participants (34%). Clinically significant arrhythmias were defined as; ventricular tachycardia (non-sustained or sustained), premature ventricular contractions (PVC) exceeding 200/24 h, or coupled PVC, atrial fibrillation/flutter, second-degree atrioventricular block (AV-block) type 2, complete AV-block, sinoatrial (SA) block exceeding 3 s, premature AV-nodal beats in bigeminy, supraventricular tachycardia (SVT) exceeding 30 s, and sinus bradycardia with less than 30 beats/min. High-sensitive cardiac troponin T (hs-cTnT) was measured at the 3-month follow-up. Results Cardiac arrhythmias were found in 27% (n=54) of the participants. Ventricular premature contractions and non-sustained ventricular tachycardia were the most common arrhythmias, found in 22% (n=44) of the participants. Premature ventricular contractions were the most frequent cardiac arrhythmia. More than 200 PVCs per day were observed in 37 participants (18%) with a mean of 1300 PVC/day, and in 35 (95%) of these participants, the PVCs were polymorphic. Among 10 patients experiencing NSVT, 5 participants had previous CVD, including coronary heart disease (n=1), 1 atrial fibrillation, 2 venous thromboembolism, 4 heart failure. Atrial fibrillation was found in seven patients (3%), none of them of new-onset. SA block >3 seconds was only observed in one patient, and no incidence of high degree AV block was discovered. Pre-existing cardiovascular disease or hypertension (CVDH) were reported in 40% (n=81) of the participants. The CVDH group had an increased amount of arrhythmia compared to the group free of CVDH (p=0.04). High PVCs showed a fair correlation with hs-cTnT levels at 3 months (ρ=0.21 p=0.048). Conclusions Three months following hospital discharge with COVID-19, cardiac arrhythmia was found in every fourth participant and was associated with a higher concentration of hs-cTnT at 3 months. The clinical implications of persistent ventricular arrhythmia following COVID-19 is not clear, but ventricular ectopy has been linked to increased risk of cardiac disease, including cardiomyopathy and sudden cardiac death. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The National Association for Heart, Lung diseases and the Norwegian Health Association and Akershus University Hospital.

Background Measures taken to mitigate the spread of coronavirus disease 2019 (COVID-19) have been correlated to a decline in the number of patients seeking medical care for emergency cardiovascular illness. Here we evaluate the impact of a state-wide lockdown on ST-elevation myocardial infarction (STEMI) care. Purpose The purpose of this study is to help understand the impact of COVID-related lockdowns on STEMI interventions. Methods All consecutive adult patients admitted with an acute STEMI diagnosis and percutaneous intervention (PCI) performed between January 17, 2020, and July 14, 2020, at five sites across our health care network, were included in this study. Patient demographics, medical history and procedure details were collected retrospectively from electronic medical records. Data were segregated according to date into pre-lockdown, lockdown (March 17 to May 13, 2020) and post-lockdown groups. Results A total of 225 patients formed the study cohort. Median age was 62 (IQR: 53–71) years. Patients were predominantly male (n=154, 68%), white (n=208, 92%), hypertensive (n=139, 61%) and dyslipidemic (n=135, 60%). The average weekly rate of STEMI PCIs performed pre-lockdown decreased by 40% during the lockdown from 10.9 to 6.5 PCIs per week (p Conclusion Adverse effects of COVID-19-related lockdowns on acute STEMI care include a decrease in PCI volumes and prolonged D2B times. Our results provide valuable data-driven criteria to help inform patient decisions to seek care and to find ways to protect healthcare workers without compromising timely critical intervention. Funding Acknowledgement Type of funding sources: None.

Background Myocardial injury is associated with adverse outcomes in patients with COVID-19. However, the prognostic role of myocardial injury in COVID-19 compared to other acute illnesses and the underlying mechanisms of injury are poorly understood. Methods In a prospective, multi-centre, cohort study conducted in secondary and tertiary care hospitals in Scotland, all consecutive patients with suspected COVID-19 underwent cardiac troponin (ARCHITECTSTAT high-sensitive troponin I (hs-cTnI) assay; Abbott Laboratories) testing in plasma that was surplus to clinical requirements. The results were not reported unless required by the attending clinician. We evaluated the prevalence of myocardial injury, mechanisms and outcomes in all patients. In those with any hs-cTnI concentration above the sex-specific 99th centile the diagnosis was adjudicated according to the 4th Universal Definition of Myocardial Infarction. The primary outcome of all-cause mortality was compared in those with and without myocardial injury and COVID-19 by cox regression adjusted for age, sex, renal function and co-morbidities. Results A total of 2,916 (median age 69 [interquartile range, IQR 54–79] years, 53% women) consecutive patients with suspected COVID-19 were followed up for 228 [IQR 203–249] days. Myocardial injury occurred in 26% (750/2,916) with a median troponin concentration of 66 [35–178] ng/L; the prevalence was 41% (46/112) and 25% (704/2,804) in those with and without COVID-19, respectively. The most common mechanism was acute non-ischaemic myocardial injury occurring in 80% (37/46) and 71% (502/704) of patients with and without COVID-19, respectively. Type 1 myocardial infarction (2% and 4%), type 2 myocardial infarction (7% and 14%) and chronic myocardial injury (11% and 11%) were less common and only one patient had confirmed myocarditis. In patients with myocardial injury mortality was increased compared to those without (P Conclusion Myocardial injury is common in hospitalised patients with suspected COVID-19 whether or not COVID-19 was the cause of their presentation. The majority of patients had acute non-ischaemic myocardial injury rather than a defined cardiac condition. Despite this the presence of myocardial injury was an independent predictor of death in all hospitalised patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation Kaplan-Meier curve for all-cause death

Background Myocardial injury that occurs after non-cardiac surgery (MINS) increases mortality in 30 days. However, few studies have assessed the impact of MINS occurrence on long-term mortality. Methods Retrospective study including all non-cardiac surgery patients admitted to an postoperative care unit who stayed at least one night in this unit, and had at least one measurement of high-sensitive cardiac troponin. Patients undergoing coronary angiography and patients with an underlying disease with a poor prognosis were excluded. The study period was from January/2011 to December/2019, ensuring a minimum follow-up of 2 years. Clinical characteristics and the occurrence of MINS were assessed between deaths and survivors using the chi-square test and Student's t-test. Variables with p Results 2532 patients were included, with a mean follow-up of 8.62±2.72 years, mean age = 63.23±16.5 years and 53.6% women. The prevalence of MINS was 12.5% (317 patients). There were 620 deaths (24.5%). In the univariate analysis, the following variables were associated with death: MINS (OR 2.65; p Conclusion In patients undergoing non-cardiac surgery, the increase in high-sensitive troponin increased the risk of death from all causes in the long term. Funding Acknowledgement Type of funding sources: None. Survival curve

Background Coronavirus disease 2019 (COVID-19) pandemic continues to overwhelm healthcare systems worldwide, due to high numbers of critical cases over a short period of time (1,2). Elevated cardiac troponin (cTn), suggestive for myocardial damage, was associated with increased mortality of COVID-19 patients (3,4). However, data addressing the role of cTn in major adverse cardiovascular events (MACE) in COVID-19 patients is scarce. Objectives We aimed to assess the role of baseline cTnT and cTnT kinetics in the prediction of MACE and in - hospital mortality in COVID-19 patients. Furthermore, we assessed the association between cTnT kinetics and the need of cardiac imaging evaluation. Methods 310 patients were included prospectively (age 64.6±16.7 years, 180 (58.1%) males), between March 2020 and April 2020. Clinical data including demographics,medical history,comorbidities,clinical evaluation,laboratory exams,in-hospital treatment,complications and outcomes were collected at admission and during hospitalization by physicians in charge. Two hundred and two patients (65.1%) with at least two cTnT values assessed during hospitalization, at 24–48 hours interval were included in the final analysis. cTnT-values >0.011 micrograms/L were considered elevated, according to hospital laboratory cut-offs. Patients were divided into 3 groups according to cTnT kinetics profile: 1 – variable, 2 – descending and 3 – constant. cTnT slope was defined as the ratio of the cTnT change and the change in time. MACE were considered as the primary endpoint and were composed by all-cause mortality, acute heart failure, acute coronary syndrome, pericarditis, myocarditis, atrial fibrillation or flutter and pulmonary embolism. In-hospital mortality was considered as the secondary endpoint. Results Mean hospitalization was 13.9±0.9 days. MACE occurred in 60 patients (29.7%) and in-hospital mortality in 40 (19.8%) patients. Baseline cTnT independently predicted MACE, (p=0.047, HR 1.805, 95% CI 1.009–3.231) and in-hospital mortality (p=0.009, HR 2.322, 95% CI 1.234–4.369) (Figure 1A, 1B). An increased cTnT slope independently predicted in-hospital mortality (p=0.041, HR 1.006, 95% CI 1.000–1.011). Constant cTnT was associated with lower MACE and mortality rates (p=0,000, HR 3.080, 95% CI, 1.914–4.954, p=0.000, HR 2.851. 95% CI 1.828–4.447, respectively) (Figure 1C, 1D, 2). Cardiac imaging evaluation was performed in 8 (16%) patients with constant cTnT, 30 (60%) with variable cTnT, and 12 (24%) with descending cTnT.(p Conclusions Increased baseline cTnT independently predicted MACE and in-hospital mortality in COVID-19 patients. The magnitude of cTnT increase over time was associated with in-hospital mortality. On the contrary, patients with constant cTnT had lower MACE and in-hospital mortality rates. These finding emphasize the additional role of cTnT testing in COVID-19 patients for risk stratification and improved diagnostic pathway and management Funding Acknowledgement Type of funding sources: None. Figure 1. Kaplan Meier for MACE and mortalityFigure 2. Troponin kinetics as MACE predictors

Background Recent evidence confirms the elevation of CA 125 in non-tumor processes such as acute heart failure (AHF). However, the utility of this novel biomarker for diagnosis, prognosis, and therapy guidance in AHF remains unclear. Purpose To investigate the potential of CA 125 for diagnosis, prognosis and therapy guidance in unselected AHF patients presenting with acute dyspnea to the emergency department (ED). Methods We quantified CA 125 in a blinded fashion among patients presenting with acute dyspnea to the ED in a multicenter diagnostic study. Final diagnosis of AHF including AHF-phenotype was centrally adjudicated by two independent cardiologists. To further characterize CA 125's potential in AHF correlations with established biochemical and imaging markers were assessed. Diagnostic accuracy for AHF was quantified by the area under the receiver operating characteristic curve (AUC). All-cause mortality within 360 days was the prognostic endpoint. Results Among 470 patients eligible for this analysis, 268 (57.0%) had adjudicated AHF. CA 125 concentrations at presentation were significantly higher among AHF patients vs. patients with other final diagnoses (45.8 U/ml [interquartile range (IQR), 18.5–110.3] vs. 16.2 U/ml [IQR, 9.6–31.6], p Conclusion CA 125 may aid physicians in the risk stratification and rapid triage of patients with suspected AHF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swiss National Science FoundationSwiss Heart Foundation Figure 1. ROC curve comparisonFigure 2. Kaplan-Meier curve 360 days mortality

Research Letter - No abstract available.

This randomized clinical trial examines the use of high-sensitivity cardiac troponin testing for patients with kidney impairment.

Background Recurrence of acute chest pain after percutaneous coronary intervention (PCI) is common. The early detection of acute myocardial infarction (AMI) as a possible cause of acute chest pain can be challenging in patients with a history of PCI due to e.g. pre-existing electrocardiographic abnormalities. It is unknown, whether high-sensitivity cardiac troponin T (hs-cTnT) concentrations and hs-cTnT-based rapid algorithms perform equally well in patients with a history of PCI. Purpose To investigate the impact of prior PCI on the diagnostic performance of hs-cTnT concentrations for early rule-out and rule-in of AMI. Methods In an ongoing multicentre international study, we prospectively enrolled unselected patients presenting to the emergency department (ED) with symptoms suggestive of AMI. Final diagnoses were centrally adjudicated by two independent cardiologists using all available medical records obtained during clinical care including 90 day follow-up information and cardiac imaging. High-sensitivity cTnT concentrations at presentation and after 1h were compared against the adjudicated final diagnosis. Patients were stratified according to the presence or absence of previous PCI. Results Among 5536 patients (1313 with and 4223 without previous PCI), incidence of AMI was significantly higher in patients with previous PCI (26.3% versus 21.4%; p Conclusions History of PCI impacts on the diagnostic performance of hs-cTnT. Although the ESC 0/1h-algorithm still performs very safe when applied to patients with a history of PCI, its efficacy is significantly reduced. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation, the Swiss Heart Foundation, the KTI, the Stiftung für kardiovaskuläre Forschung Basel the University of Basel and the University Hospital Basel

Background Obesity strongly associates with subclinical myocardial injury as quantified by concentrations of cardiac troponin. Body mass index (BMI) is the most commonly used index of obesity, but BMI does not take into account the different phenotypes that arise on the basis of age, sex and body composition. We aimed to investigate the influence of these factors on the association of obesity with subclinical myocardial injury. Methods We analyzed total body fat and fat-free mass by bioelectrical impedance analysis and cardiac troponin I (cTnI) with a high-sensitivity assay in 30,778 participants of the prospective observational The Nord-Trøndelag Health Study at study visit 4 (2017–2019). All subjects were free from known cardiovascular disease at baseline, and we excluded subjects with BMI Results Median age was 52.1 (range 16.5 to 98.9) years and 56% were women. Concentrations of cTnI were detectable in 60.6% of study participants, and were median 1.5 (0.6 to 2.9) ng/L. Median BMI was 26.7 (24.0 to 29.9) kg/m2. There was a strong and linear association between BMI and cTnI in adjusted models, with a 37.3 (95% CI, 27.6 to 46.9) % increase in concentrations of cTnI per 10 units of BMI (Figure 1). When adjusting for body composition, strong associations were observed for both sexes. The association between BMI and cTnI was stronger with increasing age (Table 1). Conclusion Obesity is strongly associated with subclinical myocardial injury. The associations are stronger with increasing age and persisted after adjustment for body composition, suggesting a harmful effect of obesity on the myocardium independently of different obesity phenotypes. Figure 1. Association between BMI and cTnI Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): South-Eastern Norway Regional Health Authority

Introduction Acute coronary syndrome (ACS) is a leading cause of mortality and morbidity worldwide. Despite being the gold standard biomarkers, cTn and CK-MB have a major drawback as they are less sensitive in the first 3 hours of the onset of symptom. So, there is still a need for novel biomarkers, which can reliably rule in or rule out this disease immediately on admission. Aim of the work To evaluate the role of copeptin, miRNA-499 and miRNA-208 as novel biomarkers for early detection of unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) Patients and Methods: A total of 65 patients presenting within 4 h of onset of chest pain suggestive of ACS were enrolled in the study. They included 23 UA, 42 NSTEMI. Also 25 apparently healthy controls were included. Blood samples (first set within the first 3 hours and second set at 6 hours) were taken for estimation of copeptin by ELISA and miRNA-499 and miRNA-208 expression levels by real time PCR. Results Copeptin, miRNA-499 and miRNA-208 expression levels were significantly increased in UA and NSTEMI patients compared to controls (P Conclusions Copeptin, miRNA-499 and miRNA-208 expression might be novel biomarkers as they are associated with UA and NSTEMI presented in the first 3 hours of onset of pain. The combination of copeptin and miRNA with cTn accelerate the diagnosis of ACS and avoiding the gray zone of cTn. Copeptin and miRNAs representing a potential aid in early diagnosis as they have different pathogenesis and site of liberation. Funding Acknowledgement Type of funding source: None

Background The European Society of Cardiology (ESC) high sensitivity cardiac troponin T 0/1h-algorithm has substantially improved the management of patients with suspected acute myocardial infarction (AMI) by triaging about 75% of patients to rapid rule-out and/or rapid rule-in. However, about 25% of patients remain in the “observe-zone”, and the optimal management of these patients is unknown. Recently, a pilot single center study with a low prevalence of AMI suggested that an absolute change of less than 7ng/L between the 0h and 3h hs-cTnT concentration would allow to help in the evaluation of patients in the observe-zone and allow triage towards rule-out with very high negative predictive value [NPV]. Purpose To externally validate this suggested modification of the ESC 0/1h-algorithm for early rule out of AMI. Methods In an ongoing multicentre international study, we prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of MI. Final diagnoses were centrally adjudicated by two independent cardiologists using all available medical records obtained during clinical care including 90 day follow-up information and cardiac imaging. High sensitivity-cTnT (Elecsys) concentrations were measured at presentation and after 1 and 3 hours. The primary outcome was safety, quantified by the sensitivity and NPV for early rule out of NSTEMI. Results Among 1633 enrolled patients with available 0, 1 and 3h hs-cTnT concentrations, NSTEMI was the adjudicated final diagnosis in 337 (20.6%) patients. The ESC 0/1h-algorithm ruled out 918 (56.2%) patients, with a sensitivity of 98.8% (95% confidence interval [CI], 97.0–99.5) and a NPV of 99.6% (95% CI, 98.9–99.8). A total of 428 patients (26.2%) remained in the observe zone. After applying the suggested 0–3 hour absolute change cut-off criteria of 7ng/L, 393 (92.0%) additional patients from the observe zone were triaged towards ruled out. However, the safety of this triage step was poor with 62 patients with NSTEMI missed, resulting in a sensitivity of 33.3% and a NPV of 84.2% for rule-out. Conclusions The suggested 0/3h absolute change cut-off of 7ng/L for patients remaining in the observe zone of the ESC 0/1h-algorithm does NOT allow safe rule-out of AMI and should therefore NOT be implemented into routine clinical care. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation, the Swiss Heart Foundation, the Stiftung für kardiovaskuläre Forschung Basel, the University of Basel and the University Hospital Basel

Background Cardiac magnetic resonance (CMR) is the reference standard for left ventricular (LV) thrombus detection in patients with acute ST-elevation myocardial infarction (STEMI). However, routine CMR imaging is currently not recommended post-STEMI. Objective This observational study sought to develop a practical risk score for the prediction of early LV thrombus formation after STEMI to identify patients in whom routine CMR might be appropriate. Methods and results Five hundred and fifty-six consecutive patients underwent transthoracic echocardiography (TTE) and CMR at 3 [IQR: 2–4] days after primary percutaneous coronary intervention (PCI) for acute STEMI. A LV thrombus was visualized in 12 patients (2.2%) using TTE and in 22 patients (4%) using CMR. A weighted risk score including multivariable associates of LV thrombus formation (LV ejection fraction by TTE, peak high-sensitivity cardiac troponin T and peak high-sensitivity C-reactive protein) and left anterior descending coronary artery as culprit vessel, with a range of 0 to 7 points (median risk score: 2 points) showed a strong and significantly higher area under the curve (0.93 (95% CI 0.88–0.97; p Conclusions The proposed risk score provides incremental value for the prediction of early LV thrombus and could be useful to identify STEMI patients in whom routine CMR for LV thrombus evaluation could be most meaningful. Additional investigation is warranted to validate the clinical application of the score. Funding Acknowledgement Type of funding source: None

Introduction High-sensitivity cardiac troponin (hs-cTn) assays have enhanced sensitivity for myocardial injury and may lead to an increase in the diagnosis of myocardial infarction. Few real-world studies have investigated the transition from conventional cardiac troponin (cTn) to hs-cTn. We evaluated the impact of implementing hs-cTn assays and sex-specific thresholds in the Netherlands on the diagnosis of myocardial infarction in women and men. Methods Twelve Dutch hospitals were included (hs-cTnI assay [sex-specific thresholds], n=4; hs-cTnT assay [uniform threshold], n=8). Data from the health insurance claims of consecutive patients with anginal symptoms were collected before (cTn period) and after (hs-cTn period) implementation from January 2008 to December 2017. The proportion of patients with a diagnosis of myocardial infarction overall, and in men and women separately, and one-year mortality was compared before and after implementation of the hs-cTn assay. Results Across twelve hospitals, a total number of 77,464 patients presenting with anginal symptoms were included (cTn period: 35,409 [36.6% women]; hs-cTn period: 42,055 [34.6% women]). Following implementation of hs-cTn testing the proportion of patients with anginal symptoms diagnosed with myocardial infarction doubled from 24% (3,111/12,970) to 48% (7,014/14,560) in women, and from 25% (5,712/22,439) to 51% (13,912/27,495) in men, with similar increases in sites implementing hs-cTnI and hs-cTnT. The proportion of patients diagnosed with myocardial infarction who were women increased in sites implementing sex-specific thresholds (from 36.4% [1,435/3,941] to 37.5% [1,700/4,532], absolute change 1.1%), but did not increase in sites using a uniform threshold (from 34.3% [1,676/4,882] to 32.4% [5,314/16,394], absolute change −1.9%). In patients with a diagnosis of myocardial infarction, one-year mortality was 15.6% (485/3,111) and 11.6% (814/7,014) in women, and was 11.8% (673/5,712) and 9.4% (1,303/13,912) in men, before and after implementation of hs-cTn. Conclusions In patients presenting with anginal symptoms, the diagnosis of acute myocardial infarction doubled after implementation of hs-cTn testing in both women and men. Use of sex-specific thresholds increased the proportion of patients with myocardial infarction who were women compared to use of a uniform threshold. Implementation was associated with a reduction in one-year mortality, but further research is needed to understand whether this is due to differences in the risk profile of patients with myocardial infarction or improvements in treatment. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This study was supported by a grant from Abbott Laboratories to S.J.R.M.

Aims: The purpose of this study was to determine (a) the ability of serial high-sensitivity cardiac troponin T measurements to rule out acute myocardial infarction and (b) the ability of a single high baseline high-sensitivity cardiac troponin T measurement to rule in acute myocardial infarction in patients presenting to the emergency department with acute chest pain. Methods and results: Embase, Medline, Cochrane, Web of Science and Google scholar were searched for prospective cohort studies that evaluated parameters of diagnostic accuracy of serial high-sensitivity cardiac troponin T to rule out acute myocardial infarction and a single baseline high-sensitivity cardiac troponin T value>50 ng/l to rule in acute myocardial infarction. The search yielded 21 studies for the systematic review, of which 14 were included in the meta-analysis, with a total of 11,929 patients and an overall prevalence of acute myocardial infarction of 13.0%. For rule-out, six studies presented the sensitivity of serial measurements 50 ng/l. The summary specificity was 94.6% (91.5–97.1). Conclusion: Serial high-sensitivity cardiac troponin T measurement strategies to rule out acute myocardial infarction perform well, and a single baseline high-sensitivity cardiac troponin T value>50 ng/l to rule in acute myocardial infarction has a high specificity.

Objective This study was carried out to examine the usefulness of point-of-care (POC) cardiac troponin in diagnosing acute coronary syndrome (ACS) and to understand the limitations of a POC cardiac troponin I/T-based diagnoses. Methods Patients whose cardiac troponin levels were measured in the emergency department using a POC system (AQT System; Radiometer, Tokyo, Japan) between January and December 2016 were retrospectively examined (N=1,449). Patients who were < 20 years of age or who were admitted with cardiopulmonary arrest were excluded. The sensitivity and specificity of the POC cardiac troponin levels for the diagnosis of ACS were determined. Result One hundred and twenty of 1,449 total patients had ACS (acute myocardial infarction, n=88; unstable angina n=32). On comparing the receiver operating characteristic (ROC) curves, the area under the curve (AUC) values for POC cardiac troponin I and cardiac troponin T were 0.833 and 0.786, respectively. The sensitivity and specificity of POC cardiac troponin I when using the 99th percentile (0.023 ng/mL) as the diagnostic cut-off value were 69.0% and 88.1%, respectively. The sensitivity of POC cardiac troponin I (99th percentile) was higher in the patients sampled > 3 hours after symptom onset (83.3%) than in those sampled ≤ 3 hours after symptom onset (58.8%, p < 0.01). Conclusion When sampled > 3 hours after the onset of symptoms, the POC cardiac troponin I level is considered to be suitable for use in diagnosing ACS. However, when sampled ≤ 3 hours after the onset of symptoms, careful interpretation of POC cardiac troponins is therefore required to rule out ACS.

High-sensitivity cardiac troponin assays enable cardiac troponin measurement with a high degree of analytical sensitivity and a low level of analytical imprecision at the low measuring range. One of the most important advantages of these new assays is that they allow novel, more rapid approaches for ruling in or ruling out acute myocardial infarctions. The increase in the early diagnostic sensitivity of high-sensitivity cardiac troponin assays comes at the cost of a reduced acute myocardial infarction specificity of the biomarker, because more patients with other causes of acute or chronic myocardial injury without overt myocardial ischaemia are detected than with previous cardiac troponin assays. Increased troponin concentrations that do not fit with the clinical presentation are seen in the daily routine, mainly as a result of a variety of pathologies, and if tested in the same sample, even discrepancies between high-sensitivity cardiac troponin I and troponin T test results may sometimes be found as well. In addition, analytically false-positive test results occasionally may occur since no assay is perfect. In this review, we summarise the biochemical, pathophysiological and analytical background of the work-up for such a clinical setting.

Source Citation Nestelberger T, Boeddinghaus J, Wussler D, et al. Predicting major adverse events in patients with acute myocardial infarction. J Am Coll Cardiol. 2019;74:842-54. 31416527

The F88L mutation in cardiac troponin T (TnTF88L) is associated with hypertrophic cardiomyopathy. Reda and Chandra reveal that it abolishes length-mediated increase in myofilament Ca2+ sensitivity and attenuates cooperative mechanisms governing length-dependent activation., Recent clinical studies have revealed a new hypertrophic cardiomyopathy–associated mutation (F87L) in the central region of human cardiac troponin T (TnT). However, despite its implication in several incidences of sudden cardiac death in young and old adults, whether F87L is associated with cardiac contractile dysfunction is unknown. Because the central region of TnT is important for modulating the muscle length–mediated recruitment of new force-bearing cross-bridges (XBs), we hypothesize that the F87L mutation causes molecular changes that are linked to the length-dependent activation of cardiac myofilaments. Length-dependent activation is important because it contributes significantly to the Frank–Starling mechanism, which enables the heart to vary stroke volume as a function of changes in venous return. We measured steady-state and dynamic contractile parameters in detergent-skinned guinea pig cardiac muscle fibers reconstituted with recombinant guinea pig wild-type TnT (TnTWT) or the guinea pig analogue (TnTF88L) of the human mutation at two different sarcomere lengths (SLs): short (1.9 µm) and long (2.3 µm). TnTF88L increases pCa50 (−log [Ca2+]free required for half-maximal activation) to a greater extent at short SL than at long SL; for example, pCa50 increases by 0.25 pCa units at short SL and 0.17 pCa units at long SL. The greater increase in pCa50 at short SL leads to the abolishment of the SL-dependent increase in myofilament Ca2+ sensitivity (ΔpCa50) in TnTF88L fibers, ΔpCa50 being 0.10 units in TnTWT fibers but only 0.02 units in TnTF88L fibers. Furthermore, at short SL, TnTF88L attenuates the negative impact of strained XBs on force-bearing XBs and augments the magnitude of muscle length–mediated recruitment of new force-bearing XBs. Our findings suggest that the TnTF88L-mediated effects on cardiac thin filaments may lead to a negative impact on the Frank–Starling mechanism.

Background Few studies address long-term outcomes among patients with type 2 myocardial infarction (T2MI). It has been suggested that patients with T2MI with concomitant stable ischemic heart disease are at higher-risk. Purpose Our goals were two-fold. First, to examine 5-year mortality rates and mode of death among patients with type 1 (T1MI) and T2MI. Second, to evaluate the prognostic impact of coronary artery disease (CAD) on long-term outcomes among patients with T2MI. Methods Post-hoc analysis of UTROPIA (NCT02060760), a prospective, observational cohort study involving 1,640 consecutive emergency department patients with serial cardiac troponin (cTn) I measurements obtained on clinical indication. 5-year death rates, including mode of death, were examined among patients with T1MI and T2MI. CAD was defined as the presence of any of the following: history of CAD, prior MI, prior coronary artery bypass graft surgery, prior percutaneous coronary intervention, prior coronary stenting, or documented CAD (≥50%) on index admission angiography. Results Among 1640 patients, acute MI was diagnosed in 217 patients, including 77 (4.7%) classified as T1MI and 140 (8.5%) as T2MI. At 5-years, 23% (n=18) of patients with T1MI had died, with 61% (n=11) categorized as cardiac deaths. For T2MI, 37% (n=52) had died at 5-years, with 36% (n=19) categorized as cardiac deaths. Patients with T2MI had a higher 5-year mortality than T1MI (37% vs 23%, p=0.038) (Figure, Panel A), with T2MI more likely than T1MI to die from non-cardiac causes (64% vs. 39%, p=0.04). CAD was present in 22% (n=31) of patients with T2MI and associated with worse outcomes (p=0.0496) (Figure, Panel B). Conclusion T2MI has worse long term outcomes than T1MI. The predominant mode of death among patients with T2MI is non-cardiac. However, approximately 40% of deaths are cardiac. Further, we confirm the presence of CAD identifies a subset of patients with T2MI at high-risk. Acknowledgement/Funding Abbott Diagnostics and Hennepin Healthcare Research Institute (formerly MMRF)

Background The European Society of Cardiology (ESC) recommends the use of a 0/1h-algorithm for rapid triage of patients with suspected non-ST-elevation myocardial infarction (NSTEMI). To date, its impact on patient management and ultimately also safety when routinely applied in emergency departments (ED) is unknown. We therefore aimed to determine these important real-world outcome data. Methods In a prospective international multicenter study enrolling unselected patients presenting with suspected NSTEMI to the ED, we assessed the real-world feasibility, adherence, efficacy, effectiveness, and safety of the ESC 0/1h-algorithm using high-sensitivity cardiac troponin T embedded in routine clinical care. Patients with ST-segment elevation myocardial infarctions were excluded. Safety was quantified by the 30-day incidence of major adverse cardiac events (MACE, defined as the composite of cardiovascular death and myocardial infarction including the index event) in the rule-out group and in outpatients. Results Among 2296 patients, NSTEMI prevalence was 9.8% (224/2296). Feasibility was very high with a median time to the “1h-draw” of 65 minutes [q1 61, q3 72]. Adherence was very high with 94% (95% confidence interval [CI], 93–95) of patients managed without protocol violations. Effectiveness was very high: 98% (95% CI, 97–98) of patients triaged towards rule-out by the ESC 0/1h-algorithm did not require additional cardiac investigations including hs-cTnT measurements at later time points (e.g. 3–12h) or coronary CT-angiography in the ED. Median time to discharge from the ED was 150 [q1134, q3235] minutes in the overall population. The ESC 0/1h-algorithm triaged 62% (95% CI, 60–64) of patients towards rule-out and 13% (95% CI, 12–14) towards rule-in of NSTEMI. Overall, 71% (95% CI, 69–72) of patients underwent outpatient management (Figure 1). Safety of rule-out and outpatient management were very high with a 30-day MACE incidence of 0.2% (95% CI, 0–0.5) and 0.1% (95% CI, 0–0.2), respectively. These findings were consistent in several predefined subgroups. Figure 1 Conclusions These real-world data document the excellent feasibility, adherence, effectiveness, efficacy and safety of the ESC 0/1h-algorithm for the rapid management of patients presenting with suspected NSTEMI to the ED when applied in routine clinical practice.

Background Guidelines acknowledge the emerging role of high-sensitivity cardiac troponin (hs-cTn) assays for the risk stratification and rapid rule-out of myocardial infarction, but multiple approaches have been described. We previously demonstrated the utility of a single hs-cTnI concentration Purpose To assess the safety and efficacy of a hs-cTnI concentration Methods The High-STEACS trial was a stepped wedge cluster randomised controlled trial in ten hospitals across Scotland that included 48,282 patients in whom high-sensitivity cardiac troponin was requested by the attending clinician for evaluation of suspected ACS. Patients with ST-segment elevation myocardial infarction (STEMI) were excluded. We evaluated the negative predictive value (NPV) and sensitivity of a presentation hs-cTnI Results We included 47,101 consecutive patients in the analysis (mean 61±17 years old, 47% female). Of these patients, 27,500 (58%) had a cardiac troponin Conclusion A hs-cTnI concentration Acknowledgement/Funding British Heart Foundation

Objective Patients with suspected acute myocardial infarction (AMI) in the setting of left bundle branch block (LBBB) present an important diagnostic and therapeutic challenge to the clinician. Methods We prospectively evaluated incidence of AMI, and diagnostic performance of specific electrocardiographic (ECG) and high-sensitivity cardiac troponin (hs-cTn) criteria in patients presenting with chest discomfort to 26 emergency departments in three international, prospective, diagnostic studies. Presence of LBBB, ECG criteria, and final diagnoses were centrally adjudicated by two independent cardiologists using the fourth universal definition of myocardial infarction. Results Among 8830 patients, LBBB was present in 247 patients (2.8%). AMI was the final diagnosis in 30% of patients with LBBB, with similar incidence in those with known LBBB versus those with presumably new LBBB (29% vs 35%, p=0.42). ECG criteria had low sensitivity (1–12%), but high specificity (95–100%). The diagnostic accuracy as quantified by the receiver-operating-characteristics curve of hs-cTnT and hs-cTnI concentrations at presentation (AUC 0.91; 95% CI 0.85–0.96 and 0.89; 95% CI 0.83–0.95) as well as that of their 0/1h and 0/2h changes was very high. A diagnostic algorithm (Figure 1) combining ECG criteria with hs-cTnT/I concentrations and their absolute changes at 1h or 2h derived in cohort 1 (45 of 45 (100%) of patients with AMI correctly identified), showed high efficacy and accuracy when externally validated in cohort 2 & 3 (28 of 29 patients, 97%). Figure 1 Conclusion Most patients presenting with suspected AMI and LBBB will be found to have diagnoses other than AMI. Combining ECG criteria with Hs-cTn testing at 0/1h or 0/2h allows early and accurate diagnosis of AMI in LBBB. Acknowledgement/Funding European Union, Swiss National Foundation, University Hospital Basel, University Basel

Background Patients with suspected ST-elevation myocardial infarction (STEMI) and no obstructive coronary artery disease (CAD) comprise a heterogeneous group with varying prognoses. Purpose To evaluate the prognostic value of cardiac troponin T (cTnT) in patients with suspected STEMI and no obstructive CAD. Methods Patients with suspected STEMI and no obstructive ( Results The study included 502 patients with suspected STEMI and no obstructive CAD: 165 (33%) had normal cTnT, 293 (58%) had dynamic cTnT elevation and 44 (9%) had stationary cTnT elevation. Within one year after admission, 40 (8%) had MACE, 81 (16%) had cardiovascular readmission, and 8 (2%) underwent repeat coronary procedures. The risk of MACE was elevated in patients with stationary cTnT elevation compared with normal cTnT (OR 13.6, 95% CI 2.3–80.2, p=0.004). There was no statistically significant difference between those with dynamic cTnT elevation and normal cTnT (OR 2.9, 95% CI 0.6–14.0, p=0.189). Adding cTnT pattern to a conventional risk model, area under the receiver operating curve for predicting the 1-year risk of MACE improved significantly (80% vs. 85%, p=0.004, Figure 1). Figure 1 Conclusion In patients with suspected STEMI and no obstructive CAD, cTnT pattern during acute hospitalization is associated with the 1-year risk of MACE and improves risk prediction for the individual patient. Acknowledgement/Funding The Danish Heart Foundation, the A.P. Møller Foundation, the Foundation of Reinholdt W. Jorck and Wife, Rigshospitalet's Research Foundation

Background Patients with diabetes mellitus (DM) may have elevated levels of high-sensitive cardiac troponin (hs-Tn) despite acute myocardial ischemia being present. However, it is unclear whether this constrains diagnostic strategies in patients with suspected acute myocardial infarction (MI). Purpose We aimed to assess the diagnostic performance of the European Society of Cardiology (ESC) 0/1 hour (h) and 0/3h-algorithms comparing patients with and without DM and to derive optimized cut-offs. Methods We prospectively enrolled patients with symptoms suggestive of MI in two large clinical cohorts and measured hs-TnI at admission (baseline) and 1 (cohort A) and 3h (cohort A+B) thereafter. Patients with ST-elevation MI were excluded. Patients were stratified based on a diagnosis of DM at baseline. Final diagnoses were adjudicated independently by two cardiologists using all clinically available information, including hs-TnT, but blinded to hs-TnI values. Our primary outcomes of interest were safety of rule-out (defined by sensitivity and negative predictive value [NPV]), accuracy of rule-in (defined by specificity and positive predictive value [PPV]) and the overall performance (% of patients adjudicated to either rule-out or -in). For optimized cut-offs, a NPV >99.0% and a PPV >75.0% were targeted. Results DM was prevalent in 563 (15.29%) of 3683 included patients. MI was more prevalent among patients with DM (137 [24.3%] vs. 498 [16.0%], p Conclusion Application of the ESC 0/1h- and 0/3h-algorithms in diabetic patients provided reduced safety and accuracy for rule-out and rule-in of MI, respectively. Use of alternative cut-offs resulted in improved diagnostic safety and accuracy. Acknowledgement/Funding Abbott Diagnostics, German Center of Cardiovascular Research, German Heart Foundation, Else-Kröhner-Stiftung angegeben

Background Cardiac troponin (cTn) has been broadly accepted as the biomarker of choice in the diagnosis of patients presenting with Acute Coronary Syndrome (ACS). Point-of-care (POC) cTn testing, defined as testing near the patient with rapid availability of results, has attracted a strong interest in the emergency department (ED) setting. It offers the potential to improve workflows, expedite clinical decisions and to reduce the length of stay. Workflows could be further optimized when a first measurement can already be performed by the emergency medical services prior to admission to the hospital. Advances in assay technology have led to high sensitive (HS) cTn assays that have a profound impact on clinical practice, providing early results at presentation and 1 hour after admission which speed up clinical decision-making. Here we evaluate the Minicare HS cTnI POC test under development, which has the potential to combine the benefits of HS-cTnI protocols with a POC workflow. Objective Evaluate the analytical and clinical capability of the Minicare HS-cTnI test under development to meet the criteria‡ for HS cTn of having a 10% CV LoD) of >50%. Methods The evaluation is based on the Clinical Laboratory Standards Institute (CLSI) guidelines. Li-heparin whole blood and Li-heparin plasma samples were used to establish LoB, LoD, and LoQ, sample matrix comparison and linearity in the low range. The clinical performance for Minicare HS-cTnI was assessed and compared to Abbott Architect high-sensitivity troponin using banked samples from patients with ACS and collected at t=2–4h after admission. The percentage measurable was assessed and compared to Abbott Architect high-sensitivity troponin in a healthy population of 165 individuals. Results With a time to result within 10 minutes, the LoB is determined at 1.0 ng/L and the LoD at 2.1 ng/L. Plasma and whole blood results correlated well and showed comparable results. The 10% and 20% CV LoQ are established at 7.9 ng/L and 3.1 ng/L, well below the anticipated 99th percentile of 26 ng/L. With a percentage measurable of 77%, the criteria for a HS-cTnI assay are met in a POC device. A sensitivity of 93% and an NPV of 99% are found for Minicare HS-cTnI for a t=2–4h protocol vs 90% and 98% for Abbott Architect high-sensitivity troponin. In this study the area under the curve is 0.98 for Minicare HS-cTnI and 0.97 for Architect HS-cTnI. ROC curve t=2-4 h Conclusions With HS-cTnI capability on the Minicare platform, we show the potential to support a 0/1 h sampling protocol, combined with the speed of a POC workflow. This may enable even more rapid and safe rule-out of patients with ACS.

Background The European Society of Cardiology (ESC) recommends the use of a 0/1h-algorithm for rapid triage of patients with suspected non-ST-elevation myocardial infarction (NSTEMI) using high-sensitivity cardiac troponin (hs-cTn). Concerns were articulated about its efficacy and particularly safety when applied in patients presenting early (≤3 hours) after chest pain onset, as hs-cTn concentrations might still be very low or even undetectable in these high-risk patients. Purpose We aimed to assess the real-world effectiveness, efficacy, and ultimately safety of the ESC 0/1h-algorithm when routinely applied in early presenters. Methods In a prospective international multicenter study enrolling unselected patients presenting with suspected NSTEMI to the ED, patients were assessed according to the ESC 0/1h-algorithm using high-sensitivity cardiac troponin T embedded in routine clinical care. Patients with ST-segment elevation myocardial infarctions were excluded. Safety was quantified by the 30-day incidence of major adverse cardiac events (MACE, defined as the composite of cardiovascular death and myocardial infarction including the index event) in the rule-out group and in outpatients. Results Among 2296 patients, 819 (36%) were early presenters. NSTEMI prevalence in early presenters was 11%. Effectiveness was very high as 97% of patients triaged towards rule-out by the ESC 0/1h-algorithm did not require additional cardiac investigations including hs-cTnT measurements at later time points (e.g. 3–12h) or coronary CT-angiography in the ED. Median time to discharge or transfer from the ED was 150 minutes [q1130, q3215]. Efficacy of the ESC 0/1h-algorithm was very high: 67% of patients were triaged towards rule-out and 14% towards rule-in of NSTEMI. Overall, 75% of early presenters underwent outpatient management. Safety of rule-out and outpatient management were excellent in early presenters with a 30-day MACE incidence of both 0% and comparable with 0.3% and 0.1% in late presenters, respectively (p=ns). Conclusions These real-world data document for the first time the excellent effectiveness, efficacy and particularly safety of the ESC 0/1h-algorithm when routinely applied in early presenters. No differences in safety could be observed when compared with late presenters.

Background Patients with unstable angina (UA) are regarded to be at low risk for future coronary events. Guidelines discourage routine coronary angiography and recommend early discharge after individualized risk stratification. The relative value of clinical risk indicators as compared to cardiac troponin (cTn) alone is unsettled in the era of high-sensitivity cardiac troponin (hsTn) assays. Purpose We aimed to investigate the clinical characteristics, therapies and outcomes of UA patients with different hsTnT concentrations. Methods During 12 months, 2,525 patients were enrolled. UA was defined as unstable symptoms and either undetectable ( Results A total of 280 patients (11.1%) received a diagnosis of UA. Mortality rates at 12 months were 0%, 1.9% and 6.9% in presence of undetectable, normal and stable elevated hsTnT. Elevated hsTnT >99th percentile but not unstable symptoms carried an independent 3.25-fold (1.78–5.93) higher risk for all-cause death after adjustment for other clinical risk indicators or the GRACE score. Utilization of guideline recommended therapies was high albeit lower than for non-ST-elevation myocardial infarction (NSTEMI). Significantly fewer patients with UA received dual antiplatelet therapy (DAPT, odds ratio (OR): 0.51 [95% CI: 0.44–0.59], p Conclusions The current dichotomization of patients into UA and NSTEMI is no longer appropriate. Additional risk stratification seems warranted including the presence and magnitude of hsTn concentration and additional risk indicators. Acknowledgement/Funding Research Grant by Roche Diagnostics

Background Wilson's disease (WD) is an inherited autosomal recessive disorder resulting from abnormal copper metabolism. Relatively little is known about the effects of copper accumulation on the heart. Objective We aimed to determine if patients with Wilson's disease show signs of cardiac involvement and structural heart disease. Methods In this prospective trial, we studied 61 patients with Wilson's disease and compared them to 61 age- and gender-matched healthy controls. Results While left ventricular function assessed by global longitudinal and global radial strain did not differ significantly between the groups, Wilson's disease patients had significantly reduced global radial strain (table 1). Wilson's disease patients demonstrated significantly more late gadolinium enhancement than the control patients (4.9±1.4 vs. 1.1±0.2% p The severity of Wilson's disease, based on the Unified Wilson's Disease Rating Scale, was significantly correlated with the extent of late gadolinium enhancement (r=0.53, P=0.001), cardiac troponin (r=0.56, P=0.001), the number of premature ventricular contraction (r=0.66, P=0.001). Table 1. Myocardial strain and CMR characteristics of patients and controls Parameter Patients (n=61) Controls (n=61) p value Left ventricular parameters GLS, % −22.8 (4.8) −21.8 (5.1) 0.124 GRS, % 43.2 (13.2) 51.6 (13.8) 0.002 GCS, % −29.2 (5.2) −28.6 (4.7) 0.534 Late gadolinium enhancement LGE, %* 4.9 (1.4) 1.1 (0.2) 0.003 LGE at RVIP, n (%) 58 (95) 3 (5) Conclusion Our data demonstrate that cardiac involvement in Wilson's disease is possible and those patients who are severely affected by the disease carry a higher risk of developing structural heart disease.

Background Cardiac troponin (cTn) is the preferred biomarker for the diagnosis of acute myocardial infarction (AMI). Octogenarians who presented cTn positive AMI are not usually recruited in clinical trials. Therefore, their clinical characteristics and prognosis are rarely investigated. Objective To study the characteristics and prognosis in octogenarians who presented cTn positive AMI. Methods and results The Japanese registry of acute Myocardial INfarction diagnosed by Universal dEfiniTion (J-MINUET) is a prospective and multicenter registry. A total of 3,283 consecutive AMI patients who were diagnosed by cTn-based criteria were included. The patients were divided into non-octogenarians (n=2,593) and octogenarians (n=690). Compared with non- octogenarians, octogenarians showed significantly lower incidence of diabetes mellitus (37.6% and 31.9%, p=0.006) and dyslipidemia (53.6% and 45.6%, p Conclusions J-MINUET showed the poor prognosis of octogenarians who were diagnosed as AMI based on cTn. Acknowledgement/Funding None

Objectives The laboratory sought to monitor and eliminate reported patient cardiac troponin outlier results using the Abbott ARCHITECT STAT Contemporary Troponin-I test. Methods The laboratory implemented an immediate repeat test for all patient samples yielding an Abbott ARCHITECT STAT contemporary Troponin I concentration greater than the combined male and female 99th percentile of 28 ng/L. The lower troponin concentration of the paired testing was reported. Samples with reference range troponin concentration were reported without repeat testing. Blood collected in Becton Dickinson Vacutainer PST Gel and Lithium Heparin tubes was centrifuged using a HemoCue StatSpin Express 4 centrifuge 4,000 g × 5 minutes and immediately tested on the primary tube. Troponin outliers were defined as paired samples showing a percentage change based on the low value of the pair exceeding the significant change threshold of 4.7x%CVanalytical for brackets of troponin concentrations (P0.0005), representing a significant change value for serial tests of 1.41xZxCVa%, where Z is 3.3. Critical troponin outliers were sample pairs with one result exceeding and one result within the 99th percentile reference range. Turnaround time was defined as time of receipt to time of verification. Results The outlier rate, based on 4,575 troponin tests performed on 3,797 patient samples, was 0.48% (N = 22) of troponin determinations, 0.58% of test samples, and critical outliers 0.13% (N = 6) of troponin determinations, 0.16% of test samples. The significant change threshold at 28 ng/L was 37%. The worst outlier pair was 5,978 ng/L, true value 3,184 ng/L; critical outlier pair 146 ng/L, true value of 14 ng/L. Twenty-one percent of test samples were tested in duplicate; 777 samples had troponin concentration >28 ng/L. Median and mean turnaround time were 32 minutes; 90% of orders completed in 54 minutes. Conclusion The laboratory detected and prevented reporting erroneously high outlier troponin results in 0.58% and critical outlier troponin results in 0.16% of test samples using an immediate repeat testing protocol.

Cardiac troponin T (cTnT) assays are used for the diagnosis of acute myocardial infarctions and require serial measurements. Hemolysis is a common analytical interference for cTnT immunoassays, causing a false decrease in analyte concentration. Recollection of specimens that do not meet the recommended hemolysis threshold (H-index = 100) causes reporting delays and mistiming of serial measurements. This has been particularly disruptive to our emergency department and creates significant risk for patients whose diagnosis could be delayed by recollection due to hemolysis. Here we aimed to reevaluate the limits for acceptable hemolysis by determining the magnitude of cTnT concentration depression from hemolysis to evaluate whether more detailed thresholds could be established. To quantify the effects of hemolysis on cTnT, patient pools were prepared from residual serum with cTnT concentrations ranging from 10 to 100 ng/L and spiked with hemolysate prepared from lysed red blood cells to create H-indices ranging from 120 to 200. Samples were run in triplicate by the Elecsys Troponin T Gen. 5 STAT assay. Results demonstrated consistent percent decreases in cTnT across all concentrations tested for each level of hemolysis. The mean percent changes in cTnT concentrations in the presence of hemolysis for H-indices of 120, 140, 160, 180, and 200 were –3.4 ± 1.3%, –4.1 ± 1.2%, –6.3 ± 1.2%, –8.0 ± 1.7%, and –10.7 ± 1.22%, respectively. The observed decrease in cTnT was linearly related to the H index; predicted differences at higher H-indices (>200) agreed well with prior publications evaluating greater degrees of hemolysis. In our practice, a 2-hour delta ≥10 ng/L is considered significant for acute cardiac injury