Sensitive cTn Research Articles

Comparison of multiple high sensitivity cardiac troponin assays for early low risk rule out of myocardial infarction: SCORECARD

Abstract Background/Introduction The use of a single low high-sensitivity cardiac troponin measurement to rule out myocardial infarction (MI) at presentation is advocated by international guidelines. Studies have not systematically compared high-sensitivity cardiac troponin (hs-cTn) I and T assays to determine which values should be used to rule out MI in patients with suspected acute coronary syndrome. Methods In a pooled analysis from three prospective observational cohort studies the lowest cTn concentration was determined that gave a negative predictive value (NPV) of ≥99.5% for MI or death at 30 days on presentation to the emergency department. EDTA or lithium heparin plasma or serum samples collected at presentation were measured using five hs-cTnI assays (Abbott ARCHITECT i2000, Beckman Coulter Access 2, Siemens Atellica IM, Ortho-Clinical Diagnostics VITROS 5600, LSI Medience PATHFAST) and one hs-cTnT assay (Roche Cobas e411). The diagnostic outcome of MI or death at 30 days was adjudicated according to the Fourth Universal Definition of MI. Optimal thresholds were determined to identify the highest proportion of patients that could be considered for discharge for a NPV of ≥99.5% for each assay. Results Among 941 patients, MI or death at 30 days occurred in 113 (12%). Optimized thresholds varied between assays ranging from <2 to <7 ng/L (Table) that identified between 22% and 60% of patients as low risk (0-1%) for MI or death at 30 days. Conclusions Our data identify differences in the effectiveness of thresholds between hs-cTnI and hs-cTnT assays for the same safety performance to rule out MI on presentation using a single measurement. In some cases, these thresholds differ from those used in clinical practice. Due to lack of assay standardization, optimal decision thresholds should be defined and validated for each high sensitivity cTn assay.

A-019 Unexpectedly High Cardiac Troponin Values in Healthy Athletes after SARS-CoV-2 Infection

Abstract Background Elevated levels of cardiac troponin I or T (cTnI, cTnT) in general have immediate clinical consequences including invasive cardiac imaging and rhythm monitoring. Macro-troponin is a complex of antitroponin autoantibodies and cTnI or cTnT and may result in falsely elevated values. In athletes, a reliable exclusion of cardiac disease is crucial to allow for intensive exercise. The prevalence and causes of falsely elevated cTn in professional athletes after SARS-CoV-2 infection are unknown. Methods These are preliminary results of an observational study including 35 professional athletes (16 -75 years old, median 24 years; 19 females, 16 males) who had post-Covid-19 check-ups at their practicing sports physician mostly in the year 2022 (6 athletes in 2023). One female athlete did not have a proven SARS-CoV-2 infection but vaccination. Divergences in high sensitivity (hs) cTn concentrations were investigated according to the sex-specific cut-off values of 4 different assays (hs-cTnI: Alinity/Abbott Diagnostics, Atellica/Siemens Healthineers, Access/Beckman Coulter and hs-cTnT: Cobas/Roche Diagnostics). All athletes were advised to stop training 48h before routine blood drawing and if required underwent electrocardiography (ECG), echocardiography and magnetic resonance imaging to exclude myocardial involvement, particularly when suspicious symptoms were present. Athletes with divergent hs-cTn assay results were further analyzed for the presence of macro-troponin using the reference method sucrose gradient ultracentrifugation. Results The two main professional sports were cycling (mountain biking or road biking) and soccer, further sports comprised curling, swimming, running including marathon, floorball, cross-country skiing or rhythmic gymnastics. Athletes mostly suffered from postviral exhaustion, mild infectious symptoms like headache, sore throat, dry cough, subfebrile temperature, or sniffles or had atypical thoracic pain. There were two males with known secondary diagnoses, one 25 years old with diabetes mellitus type 1 and one 75 years old with atherosclerosis and hypercholesterolemia. Eighteen (18/35) athletes had hs-cTn concentrations within the sex-specific cut-off values in all assays and did not undergo further investigation for macro-troponin by sucrose gradient ultracentrifugation. However, in 17 athletes (17/35) hs-cTn was increased in at least one assay method which was mostly a hs-cTnI method (for 2/17 all assays elevated). The sucrose-gradient ultracentrifugation method proved macro-troponin in 15/17 with original hs-cTn values for Abbott Alinity: 5 - 170 ng/L; Siemens Atellica: 9.6 - 376 ng/L; Beckman Access: 0.5 - 55 ng/L and Roche Cobas 4 - 77 ng/L. However, 2/17 had the free troponin form, one with only a minor hs-cTnT increase above the sex-specific cut-off and the other with increased values in all hs-cTn assays but normal values in a 2- and 4-days control follow-up measurement. Notably, there were no ECG or cardiac imaging findings including echocardiography or cardiac magnetic resonance imaging suggestive of myocarditis in the investigated athletes. Conclusions After SARS-CoV-2 infection, cTn might be increased in athletes without a correlate in ECG or imaging reports. This should prompt physicians to consider an assay interference by macro-troponin, particularly if a second troponin method such as hs-cTnT remains normal. AHL & CK share first and OH & CM share last authorship

Implementation of high sensitivity troponin into routine clinical practice - results of the extended CARdiac MArkers guideline uptake in Europe group (CARMAGUE) survey

BackgroundMeasurement of cardiac troponin (cTn) by a high sensitivity method is now the recommended strategy for the detection of myocardial injury. An international survey was undertaken to assess how this has been implemented. MethodsA questionnaire based around 14 domains on cardiac biomarkers was distributed electronically with the aid of professional societies accessed by a web link within the invitation. Results were returned electronically then extracted into a relational database for analysis. ResultsResponses were obtained from 663 laboratories across 76 countries ranging from 1 to 69 largest country. The majority of responses (79.6%) came from the European area. Responses were grouped into broad geographic areas for analysis. Most responses came from hospitals providing a local and regional service of which the majority provided angioplasty. cTn measurement was the dominant biomarker. The majority of laboratories include creatine kinase (CK) in their cardiac profile and approximately 50% also offer the MB isoenzyme of CK. The majority of laboratories (91.9%) measure cTn by a high sensitivity method. Sex specific reference ranges were typically implemented for cardiac troponin I but not for cardiac troponin T. The preferred unit of measurement was nanograms/L. A structured decision-making pathway utilising high sensitivity cTn measurement was used by 83.3% of laboratories who responded. Single sample rule out is common but the majority used serial sampling strategy based on measurement on admission and three hours. ConclusionsMeasurement of cTn by a high sensitivity method is now well established internationally, the use of rapid diagnostic protocols lags behind.

Temporal trends in acute coronary syndrome hospitalisation rates: a comparison of administrative diagnosis coding and cardiac biomarker testing

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Victor Chang Cardiac Research Institute. Background/aims Accurate monitoring of trends in acute coronary syndromes (ACS) provides important information on the impacts of primary and secondary prevention. Use of cardiac troponin (cTn) assays with increasing sensitivity and specificity during the past 20 years have likely increased the rates of diagnosis of myocardial infarction (MI), particularly NSTEMI. We aimed to determine the correlation of ICD-coded ACS hospitalisation rates with biomarker-classified ACS rates to inform population-level monitoring of ACS trends in Australia. Methods We used linked hospitalisation, emergency department, mortality, and pathology data from all tertiary hospitals in Western Australia (WA). We identified all patients aged >20years with a principal diagnosis of STEMI or NSTEMI (ICD-10-AM I21.0-I21.4) or unstable angina (UA) (ICD-10-AM I20.0) from 2001-2017. Creatine kinase (CK) and cTn test results including high-sensitivity (hs-Tn) assays were classified as elevated based on the ESC/AHA Universal Definition using the upper reference limit value for each assay. We calculated age-standardised rates (ASRs) for ICD-10 coded STEMI, NSTEMI and UA hospitalisations, and those which were cTn positive (cTn+), or any biomarker positive including CK (Bm+). We assessed annual ASR ratios over time (reference: ICD-coded rates) and estimated annual % changes in admissions using Poisson regression models adjusting for 5-year age-group and sex. Results The cohort comprised 143,231 ICD-coded ACS hospitalisations for 91,701 patients. 60.5% of the patients were male and 95.2% of the ACS hospitalisations had linked cardiac biomarker records. Despite slightly lower ASRs, Bm+ based rates were consistent with patterns in ICD-coded admissions in both MI sub-types (Figure) with no significant differences stratified by sex. Average annual decline in STEMI admissions was -3.7% (95% CI -4.1%,-3.4%) and -3.2% (95% CI -3.6%, -2.9%) in ICD-coded and Bm+ hospitalisations respectively. The annual rise in ICD-coded NSTEMI ASRs was 4.1% (95% CI 3.9%, 4.4%) which correlated with the 4.4% (95% CI 4.1%, 4.7%) annual rise in Bm+ ACS hospitalisations. The age-standardised rate ratios of ICD-coded to Bm+ were 1.27 and 1.28 for STEMI and NSTEMI respectively in 2001 and remained consistent at 1.29 and 1.30 for STEMI and NSTEMI respectively in 2017, although this was not the case for cTn+:ICD-coded rate ratios. There was an inverse trend between ASRs of ICD-coded NSTEMI and UA over the study period which correlated with use of increasingly sensitive cTn assays. The proportion of UA admissions with Bm+ was consistently low (21%) over the study period. Conclusions Despite shifts from CK to cTn and hs-Tn assays during our study period, the present study highlights the validity of using linked hospitalisation data to monitor long term trends in ACS based on cardiac biomarker positivity. Figure legend. Age-standardised hospitalisation rates by classification status in ACS subtypes.

Abstract 12766: Tropsensor: A Rapid Non-Invasive Transdermal Solution For Troponin Measurement

Introduction: Early identification of Acute Myocardial Injury can prompt rapid triage and appropriate interventions to improve clinical outcomes. Over 10 million patients present at the ED with chest-pain, with the majority due to non-cardiac causes, resulting in unnecessary burdens for Emergency Departments (ED). An instant non-invasive method to measure cardiac troponin (cTn) would therefore be of great benefit. Identified need: All Guidelines recommend the use of high sensitivity (HS) cTn for the diagnosis of acute coronary syndromes (ACS). Current biochemical biomarker testing relies on labeling the cTn with turnaround times often an hour or more. Point-of-care solutions reduce the test time, but still depend on the proper handling of samples and blood processing techniques that could lead to difficulties. Tropsensor provides a non-invasive alternative to standard of care (SOC) hs-cTn measurements without the need for a blood draw. The molecular infrared spectroscopy-based transdermal device provides a cTn readout within 5 minutes and allows for serial measurements without any of the delays or complications of blood draws. Methods: A 26-patient (consented and IRB approved) study was conducted at Zuckerberg San Francisco General Hospital with recruitment based on ACS-related presenting symptoms at the ED. Wrist-worn Tropsensor was used on the patients while the corresponding troponin was determined using a high sensitivity (SOC) assay (Siemens ADVIA Centaur) via a blood draw. Results and conclusions: A Pearson’s correlation of 82% with the hs-cTnI was observed. AMI diagnosis sensitivity was 100%, Specificity=50%, PPV=81.8%, NPV=100% and accuracy=84.6%. The Tropsensor modality seems to provide data similar to that of a hs-cTn assay. If so, it would accelerate the assessment of patients presenting with chest pain. By not requiring a blood draw, the Tropsensor could provide a rapid, safe, standardized and reliable source for cTn while allowing bedside serial trending. It thus has the potential to streamline cardiac care workflow by ruling-out many non-cardiac patients and identifying those with high values who are at risk. Such an approach has the potential to facilitate appropriate patient triage towards early discharge of emergent treatment.

Predictors of elevated follow-up high sensitivity troponin after an initial normal value during acute exacerbations of chronic obstructive pulmonary disease

Abstract Funding Acknowledgements Type of funding sources: None. BACKGROUND Elevation of cardiac troponin (cTn) may be seen in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and is both diagnostic for myocardial injury and confers a poorer prognosis. Serial cTn testing after an initial normal value is often performed even though the yield is low. PURPOSE We aim to investigate factors predicting an abnormally elevated cTn after an initial normal cTn value. METHODS Retrospective data analysis of patients with AECOPD admitted between 1st January 2017 to 30th June 2017 with at least 2 serial high sensitivity cTn I (HScTnI) performed within 24 hours of presentation. Binary logistic regression was used to explore predictors of abnormally elevated (>40 ng/L) serial HScTnI after an initial normal value. RESULTS There were 240 cases with an initial normal HScTnI (mean age 74 years, 92.1% male). Amongst these, 97 cases had another follow-up HScTnI performed within 24 hours of presentation. Patients in the groups with or without follow-up HScTnI were similar in terms of demographics, COPD stage, cardiovascular risk factors, history of coronary disease and vital parameters. Significantly more patients in the group with follow-up HScTnI had ischaemic electrocardiographic changes (10.3 vs 2.1%, p = 0.006). There were 22/97 (22.7%) cases with abnormally elevated follow-up HScTnI. The mean time interval between the initial and follow-up HScTnI was not significantly different between the groups with or without elevated HScTnI (12.8 vs 10.4 hours, p = 0.858). Cases with elevated follow-up HScTnI had significantly higher heart rate (109 vs 97bpm, p = 0.007), initial HScTnI (24 vs 17ug/L, p = 0.009), C reactive protein (43.1 vs 7.6mg/L, p = 0.004) and procalcitonin (0.16 vs 0.07ug/L, p = 0.014) levels. They also had a greater proportion of chest radiographs showing consolidation (15 vs 9%, p = 0.046). On univariate analysis, heart rate (OR 1.037 [1.009 - 1.066], P = 0.009), temperature (OR 1.897 [1.119 - 3.217], p = 0.017), initial HScTnI value (OR 1.063 [1.014 - 1.115], p = 0.012) and neutrophil counts (OR 1.039 [1.000 - 1.078], p = 0.049) were significant predictors of an abnormally elevated follow-up HScTnI. Only heart rate remained as a significant predictor (Adj OR 1.050 [CI 1.015 - 1.086] p = 0.005) after multivariate analysis. CONCLUSIONS Less than a quarter of AECOPD patients with an initial HScTnI had an elevated level on serial testing. A higher heart rate is a significant predictor of a subsequent elevated HScTnI after an initial normal value and may identify patients for selective serial cTn testing. Larger studies are needed to identify predictors that can reliably risk stratify patients for serial cTn testing.

Troponin -T as a prognostic and diagnostic marker for myocardial infarction

Over the past decade, there has been a progressive evolution of cardiac marker testing in patients with acute coronary syndromes. Myocardial infarction (MI) is the leading cause of death in the developed world. Biomarkers have an vital role in analysis, risk stratification, administrative running and medical assessment making in the setting of patients presenting with signs and symptoms of MI. Cardiac troponin (cTn) rose to prominence during the 1990s and has evolved to be the cornerstone for diagnosis of MI. Cardiac troponins are released from myocytes following myocardial damage and loss of membrane integrity. Troponin T are member of a group of cardiac regulatory proteins which function to regulate the calcium mediated interaction of muscle filaments actin and myosin resulting in contraction and relaxation of striated muscle. New algorithms integrating Brain natriuretic peptide (BNP), NT-proBNP, and more sensitive cTn assays footing potential for more rapid diagnosis of MI, allowing for appropriate management steps to be initiated and more efficient and effective utilization of healthcare resources.

Interpretacja stężeń troponin sercowych w świetle czwartej uniwersalnej definicji zawału serca z 2018 roku

Cardiac troponin (cTn) is a laboratory test routinely used in patients with suspected acute coronary syndrome (ACS). Unfortunately, wide variety of laboratory assays and different cut-off values regarding gender may result in difficulties with diagnosis and delay the treatment. Troponin I and less specific troponin T are used to diagnose ACS. Dynamic changes in cTn concentration are required to confirm the diagnosis of myocardial infarction (MI). The fourth universal definition of myocardial infarction defines five major types of MI — atherosclerotic plaque disruption, imbalance between myocardial oxygen supply and demand unrelated to acute coronary atherothrombosis, cardiac death with symptoms suggestive of myocardial ischaemia and new ischaemic electrocardiographic changes, MI connected with percutaneous coronary intervention or coronary bypass grafting. Considering this definition, increased cTn concentrations are not always related to abnormal findings in coronary angiography and can be associated with many conditions. Increased high sensitivity cTn values in healthy individuals can be induced by intense physical activity, which is confirmed by studies performed in marathoners. While elevated cTn levels are observed in 20–60% of patients with acute ischemic stroke and are associated with an increased long-term mortality, acute MI is diagnosed only in 3,5% of patients. Elevated cTn levels often accompany chronic kidney disease, however changes in serial testing are obligatory for acute MI diagnosis. Deterioration of kidney function is more connected with elevated TnT rather than TnI levels. Regardless of the reason, increased cTn concentration is a negative predictive factor. Patients with elevated cTn levels need further diagnosis, risk stratification and a long-term follow-up.

Change in troponin concentrations in patients with macrotroponin: An in vitro mixing study

IntroductionMacrotroponin is a complex formed between endogenous cardiac troponin autoantibodies (cTnAABs) and circulating cardiac troponin (cTn). The potential effect of macrotroponin on current high sensitivity cTn assays has not been fully explored but has recently been identified as a major cause of discrepancy in cTn results between assays. In this study we investigated the effects of mixing troponin (cTn) standards to specimens with and without macrotroponin. MethodMacrotroponin was identified in specimens by a recovery of cTnI < 40% following protein A immunoglobulin depletion. Troponin standards containing cTn-IC and cTn-TIC complexes were mixed with serum samples, with (n = 20) and without (n = 10) the presence of macrotroponin. Specimens were tested for cTn before and after mixing by three commercially available high sensitivity cTn assays. Gel filtration chromatography was carried out on five specimens with macrotroponin and each fraction was analzyed by multiple cTn assays. FindingsFollowing mixing with cTn-TIC standard, all specimens with macrotroponin had a markedly reduced absolute increase in cTnI, indicating negative analytical interference due to macrotroponin. Following mixing with the cTn-IC standard, specimens with macrotroponin demonstrated highly variable changes in cTnI, suggesting significant heterogeneity in macrotroponin complex reactivity between individuals. When the ratio of change, calculated by dividing the absolute change between two cTn assays, was compared between specimens with and without macrotroponin, significant differences were observed (p < 0.001). These findings were supported by variable migration of peak cTn activity on gel filtration chromatography. ConclusionMacrotroponin leads to assay dependent analytical interference affecting current high sensitivity troponin I assays. Furthermore, endogenously occurring cTnAABs are conformationally specific and the analytical effects vary between assays and individuals.

Biomarkers Enhance Discrimination and Prognosis of Type 2 Myocardial Infarction.

The observed incidence of type 2 myocardial infarction (T2MI) is expected to increase with the implementation of increasingly sensitive cTn assays. However, it remains to be determined how to diagnose, risk-stratify, and treat patients with T2MI. We aimed to discriminate and risk-stratify T2MI using biomarkers. Patients presenting to the emergency department with chest pain, enrolled in the CHOPIN study (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction), were retrospectively analyzed. Two cardiologists adjudicated type 1 MI (T1MI) and T2MI. The prognostic ability of several biomarkers alone or in combination to discriminate T2MI from T1MI was investigated using receiver operating characteristic curve analysis. The biomarkers analyzed were cTnI, copeptin, MR-proANP (midregional proatrial natriuretic peptide), CT-proET1 (C-terminal proendothelin-1), MR-proADM (midregional proadrenomedullin), and procalcitonin. The prognostic utility of these biomarkers for all-cause mortality and major adverse cardiovascular event (a composite of acute myocardial infarction, unstable angina pectoris, reinfarction, heart failure, and stroke) at 180-day follow-up was also investigated. Among the 2071 patients, T1MI and T2MI were adjudicated in 94 and 176 patients, respectively. Patients with T1MI had higher levels of baseline cTnI, whereas those with T2MI had higher baseline levels of MR-proANP, CT-proET1, MR-proADM, and procalcitonin. The area under the receiver operating characteristic curve for the diagnosis of T2MI was higher for CT-proET1, MR-proADM, and MR-proANP (0.765, 0.750, and 0.733, respectively) than for cTnI (0.631). Combining all biomarkers resulted in a similar accuracy to a model using clinical variables and cTnI (0.854 versus 0.884, P=0.294). Addition of biomarkers to the clinical model yielded the highest area under the receiver operating characteristic curve (0.917). Other biomarkers, but not cTnI, were associated with mortality and major adverse cardiovascular event at 180 days among all patients, with no interaction between the diagnosis of T1MI or T2MI. Assessment of biomarkers reflecting pathophysiologic processes occurring with T2MI might help differentiate it from T1MI. All biomarkers measured, except cTnI, were significant predictors of prognosis, regardless of the type of myocardial infarction.

Laboratory-related issues in the measurement of cardiac troponins with highly sensitive assays.

A number of assay-related issues can affect the performance of cardiac troponin (cTn) measurement in everyday practice. In this respect, it is vital that all information on cTn assays is known and that the performance characteristics of assays are objectively assessed and adequately described. The advent of the latest generation of more sensitive cTn assays has heralded a new wave of information about low concentrations of cTn in blood. These recent generation assays have improved analytical sensitivity and corresponding performance at low cTn concentrations when compared to their predecessors, providing a convincing goal for laboratory medicine in helping clinicians in the diagnosis of acute myocardial infarction. Crucial to the clinical utility of highly sensitive cTn assays is the laboratorians' role in closely scrutinizing proposed assays and defining their value in relation to available evidence. Analytical, as well as pre-analytical and post-analytical, aspects must be documented. In this review, we describe what laboratory professionals should know about their cTn assay performance characteristics and the pre-analytical prerequisites for robustness to ensure optimal post-analytical reporting.

P3599Minicare high sensitivity troponin: a novel point-of-care tool to improve ACS workflows

Abstract 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 &lt;99th percentile and a percentage measurable (&gt;LoD) of &gt;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.

P3594Transition from 4th to 5th generation cardiac troponin T: testing patterns, myocardial infarction incident rates, and resource utilization across a multicenter United States regional healthcare system

Abstract Background Several high-sensitivity cardiac troponin (cTn) assays have been cleared by the United States (US) Food and Drug Administration (FDA) for clinical use. Although some of them have been used outside the US for some time, there is limited experience thus far across US sites. Following FDA clearance of the Roche 5th Gen cTnT assay in January 2017, a multicenter US regional healthcare system introduced this more sensitive cTnT assay into clinical practice in September 2018. Purpose To examine cTn testing patterns, incidence of acute myocardial infarction (MI), and resource utilization before and after implementation of the 5th Gen cTnT assay across a large US healthcare system. Methods Using electronic-health records reporting software (Cogito SlicerDicer, EPIC), administrative data was examined to evaluate the transition (4-months before and after implementation) from the 4th to 5th Gen cTnT assays across 16 hospitals but not the major hub hospital of the system that transitioned at a separate time. Adult patient visits (emergency and hospital encounters), cTnT testing, incidence of chest discomfort and acute MI, and resource utilization, including hospital admissions, were examined during the transition period. Results 98,558 adult ED patient visits occurred during an 8-month period across 16 hospitals, including 50,485 and 48,073 patient visits before (5/12/18 – 9/11/18) and after (9/12/18 – 1/11/19) implementation of the 5th Gen cTnT assay respectively. cTnT testing occurred in 20% (range 8.9–34.8%) of all ED visits, with testing performed in the absence of chest pain in 54% (range 37–67%) of cases. Acute MI was diagnosed in 5.6% (n=561) of cases using the 4th Gen cTnT assay as compared to 6.6% (n=608) of cases using the 5th Gen cTnT assay (absolute difference 1.0%, 95% CI: 0.32–1.68, p=0.004). Much of the increase in MI diagnoses were in women (2.2% vs. 2.8%, p=0.008). The proportion of ED patients requiring hospital admission did not differ between pre- and post-implementation periods (24.1% vs. 23.6%, p=0.4); however, among the subset of patients with chest pain, fewer admissions occurred post-implementation (17.9% vs. 15.8%, p=0.006). There was no increase in echocardiography (9.3% vs. 8.4%), coronary angiography (2.9% vs. 3.1%), or cardiac consultations (7.3% vs. 7.3%) utilization post-implementation. Conclusions Cardiac troponin testing occurs in nearly 20% of ED visits in a large multicenter regional healthcare system. About half of all tests are ordered in the absence of chest pain, with a low MI rate observed among the patients undergoing testing. Following implementation of the 5th Gen cTnT assay, testing rates/patterns remained unchanged, with a small but significant increase in MI diagnoses, primarily due to more women being diagnosed with MI. Fewer ED patients with chest pain required admission. Despite using a more sensitive cTn assay, hospital admissions and resource utilization did not increase post-implementation.

Studies MicroRNA 208 as a Novel Cardiac Marker in Acute Coronary Syndrome in Egyptian Patients

AbstractBackground: Acute coronary syndrome ACS patients presented to Emergency Department ED require rapid differ-ential diagnosis. Although troponin is the gold marker for ACS, there still undiagnosed patients. MicroRNAs circulate in human plasma and affected by varying cardiac pathologies. miRNA-208 was found to be elevated with ACS specially AMI.Aim of Study: The aim of this study was to investigate cTnI levels, correlated to miRNA-208 levels in ACS patients to evaluate rapid, accurate and final diagnosis in ED.Subjects and Methods: One hundred consecutive patients with ACS presenting to the Emergency Department of the National Heart Institute, Giza (Egypt) between March and June 2018, were recruited for the study, stratified into four groups according to the final diagnosis as AMI (including twenty five patients) and unstable angina UA (including twenty three patients), other cardiac patients (eighteen patients) and non cardiac (fourteen patients) twenty control subjects. Were included their cardiac markers and miRNA-208 levels were assayed and compared to the control healthy group on admis-sion.Results: Results revealed significant difference between cardiac levels on admission compared to that obtained for miRNA-208. Only miRNA-208 levels were diagnosed on admission compared to that of cTnI. MiRNA-208 was found to be increased up to 38.6 folds without differential cut off.Conclusion: Early measurement of both troponin I and miRNA-208 may revolutionize the diagnostic accuracy and therapeutic decision-making in patients with symptoms sug-gestive of ACS; differentiate between UA or AMI patients on admission. Cardiac troponin 1 cTnI alone require more time to be controlled as diagnostic while high sensitive cTn may lead to false positive results. MiRNA-208 can be used as a novel marker for early diagnosis of ACS although RT-PCR still time consuming, requires time improved techniques.

Cardiac troponins and beyond in acute coronary syndrome

Cardiac biomarkers are an integral component of the diagnostic work-up of patients with suspected acute coronary syndrome (ACS). Cardiac troponin (cTn) is the most sensitive diagnostic biomarker for patients with ACS and enables the differentiation of acute non-ST-elevation myocardial infarction (NSTEMI) from unstable angina. All cardiac and non-cardiac differential diagnoses must be taken into consideration. The use of cTn has a prognostic value in amultitude of acute and chronic diseases apart from ACS. Highly sensitive cTn (hsTn) assays should be preferentially used. Point-of-care (POC) troponin assays can be used for rule-in of acute MI but are generally not useful for rule-out of MI due to their lack of sensitivity compared to hsTn assays. This, however, may change with recent developments of newer and improved POC troponin assays. For exclusion of MI using hsTn assays, there are various protocols available, such as the instant rule-out with undetectable hsTn levels at admission or normal hsTn/cTn levels combined with normal copeptin levels or rule-out with serial controls of hsTn after 1, 2 or 3 h. This article provides an overview of guideline-recommended rule-out protocols for patients with suspected ACS and discusses recent advances in POC troponin assays.

Predicting Acute Myocardial Infarction with a Single Blood Draw.

We desired to determine cardiac troponin (cTn) concentrations necessary to achieve a positive predictive value (PPV) of ≥75% for acute myocardial infarction (AMI) to justify immediate admission of patients to a monitored unit and, in general, early coronary angiography. In a prospective multicenter diagnostic study enrolling patients presenting to the emergency department with symptoms suggestive of AMI, final diagnoses were adjudicated by 2 independent cardiologists based on clinical information including cardiac imaging. cTn concentrations were measured using 5 different sensitive and high-sensitivity cTn (hs-cTn) assays in a blinded fashion at presentation and serially thereafter. The diagnostic end point was PPV for rule-in of AMI of initial cTn concentrations alone and in combination with early changes. Among 3828 patients, 616 (16%) had an AMI. At presentation, 7% to 14% of patients had cTnT/I concentrations associated with a PPV of ≥75%. Adding absolute or relative changes did not significantly further increase the PPV. PPVs increased from 46.5% (95% CI, 43.6-49.4) for hs-cTnT at presentation >14 ng/L to 78.9% (95% CI, 74.7-82.5) for >52 ng/L (P < 0.001), whereas PPVs in higher hs-cTnT strata remained largely unchanged [e.g., 82.4% (95% CI, 77.5-86.7) for >80 ng/L vs 83.9% (95% CI, 76.0-90.1) for >200 ng/L (P = 0.72)]. The addition of early changes in hs-cTnT further increased the PPV up to 60 ng/L, but not for higher concentrations. Serial sampling does not seem necessary for predicting AMI and concurrent decision-making in about 10% of patients, as it only marginally increases the PPV for AMI and not in a statistically or clinically significant way. NCT00470587.

Myocardial injury in transient global amnesia: a case-control study.

Elevation of cardiac troponin (cTn), a sensitive biomarker of myocardial injury, is frequently observed in severe acute neurological disorders. Case reports suggest that cardiac dysfunction may also occur in patients with transient global amnesia (TGA). Until now, no study has systematically assessed this phenomenon. We performed a case-control study using data of consecutive patients presenting with TGA from 2010 to 2015. Multiple logistic regression analysis accounting for age, sex and cardiovascular risk factors was performed to compare the likelihood of myocardial injury [defined as elevation of cTn>99th percentile (≥14ng/L); highly sensitive cardiac troponin T assay] in TGA with three reference groups: migraine with aura, vestibular neuritis and transient ischaemic attack (TIA). Cardiac troponin elevation occurred in 28 (25%) of 113 patients with TGA. Patients with TGA with cTn elevation were significantly older, more likely to be female and had higher blood pressure on admission compared with those without. The likelihood of myocardial injury following TGA was at least more than twofold higher compared with all three reference groups [adjusted odds ratio, 5.5; 95% confidence interval (CI), 1.2-26.4, compared with migraine with aura; adjusted odds ratio, 2.2; 95% CI, 1.2-4.4, compared with vestibular neuritis; adjusted odds ratio, 2.3; 95% CI, 1.3-4.2, compared with TIA]. One out of four patients with TGA had evidence of myocardial injury as assessed by highly sensitive cTn assays. The likelihood of myocardial injury associated with TGA was even higher than in TIA patients with a more pronounced cardiovascular risk profile. Our findings suggest the presence of a TGA-related disturbance of brain-heart interaction that deserves further investigation.

Comparing analytical outliers and the percent of emergency department patients with results above the 99th percentile upper reference limit for 2 conventional and one high sensitivity troponin assay

ObjectivesWe compared rates of analytical outliers, and percent of emergency department (ED) patients with cardiac troponin (cTn) values above the 99th percentile upper reference limit (URL), for two conventional and one high sensitivity cTn assay. MethodsWe measured 3008 samples from 1931 ED patients by Roche e411 4th generation Troponin T (cTnT); and Abbott STAT Troponin I (cTnI) and high sensitivity troponin I (hscTnI) on an Architect i2000. Within 24h of initial measurement, samples were aliquoted, re-centrifuged, and repeated in duplicate by all methods. Outliers were defined as one or both replicates exceeding initial value by a critical difference (CD): where CD=z×2×SDanalytical (z=3.29 at a probability of 0.0005), and at least one replicate on a different side of 99th percentile URL compared to initial value. We also assessed percent of ED patients with values >99th percentile by all methods (excluding outliers), using both sex-neutral and sex-specific hscTnI URL. ResultsThe outlier rate for cTnI (3.66%) was significantly higher than the outlier rate for either cTnT (0.33%) or hscTnI (0.47%) (p<0.0001). More ED patients (33%) had elevated cTnT values compared to either cTnI (25%) or hscTnI (29%). Application of sex-specific URL did not change the percent of ED patients with >99th percentile hscTnI values. ConclusionAbbott STAT cTnI had more analytic outliers than Roche cTnT or Abbott hscTnI. Compared to cTnT, use of hscTnI will significantly decrease the percent of ED patients with elevated cTn values without increasing analytical outliers.

Unstable Angina in the Era of Cardiac Troponin Assays with Improved Sensitivity—A Clinical Dilemma

BackgroundThere is an expectation that with the adoption of more sensitive cardiac troponin (cTn) assays, unstable angina would become a rarity. However, recent data from the SWEDEHEART registry demonstrated that 15% of patients admitted with non-ST-elevation acute coronary syndrome still were regarded as having unstable angina. We aimed to further investigate the clinical characteristics and outcome of these patients. MethodsThis was a retrospective, registry-based analysis (SWEDEHEART) including 3204 unstable patients, 18,194 non-ST-elevation myocardial infarction (NSTEMI) patients, and 977 controls without acute cardiovascular disease. All patients had available data on peak cTnT levels (more sensitive assay) and 1-year outcome. ResultsThe annual proportions of patients with unstable angina (2009-2013) among those with non-ST-elevation acute coronary syndrome ranged from 9.4% to 15.3%. Only 1239 unstable angina patients (39.7%) had a peak cTnT level ≤14 ng/L. Patients with unstable angina tended to be younger than those with NSTEMI but had higher prevalence of most cardiovascular risk factors and more advanced coronary artery disease. Compared with controls, the adjusted hazard ratios (95% confidence interval) regarding major cardiovascular events were 2.97 (1.30-6.78) and 5.44 (2.54-11.65) in unstable angina patients with peak cTnT ≤14 ng/L and >14 ng/L, respectively. ConclusionThe diagnosis of unstable angina is still commonly used, even in the era of more sensitive cTn assays. Minor cTnT elevation is common, which makes unstable angina difficult to distinguish from NSTEMI. Patients with unstable angina have a nonneglectable cardiovascular risk. We suggest that the clinical management of patients presenting with unstable symptoms should depend on their estimated cardiovascular risk rather than on strictly applied diagnostic criteria.

Missed myocardial infarctions in ED patients prospectively categorized as low risk by established risk scores

Study objectivesFew studies have prospectively compared multiple cardiac risk prediction scores. We compared the rate of missed acute myocardial infarction (AMI) in chest pain patients prospectively categorized as low risk by unstructured clinical impression, and by HEART, TIMI, GRACE, and EDACS scores, in combination with two negative contemporary cardiac troponins (cTn) available in the U.S. MethodsWe enrolled 434 patients with chest pain presenting to one of seven emergency departments (ED). Risk scores were prospectively calculated and included the first two cTn. Low risk was defined for each score as HEART≤3, TIMI≤0, GRACE≤50, and EDACS≤15. AMI incidence was calculated for low risk patients and compared across scores using Χ2 tests and C statistics. ResultsThe patients' median age was 57, 58% were male, 60% white, and 80 (18%) had AMI. The missed AMI rate in low risk patients for each of the scores when combined with 2 cTn were HEART 3.6%, TIMI 0%, GRACE 6.3%, EDACS 0.9%, and unstructured clinical impression 0%. The C-statistic was greatest for the EDACS score, 0.94 (95% CI, 0.92–0.97). ConclusionsUsing their recommended cutpoints and non high sensitivity cTn, TIMI and unstructured clinical impression were the only scores with no missed cases of AMI. Using lower cutpoints (GRACE≤48, TIMI=0, EDACS≤11, HEART≤2) missed no case of AMI, but classified less patients as low-risk.