Point-of-care high-sensitivity cardiac troponin in suspected acute myocardial infarction assessed at baseline and 2†h.

BACKGROUND AND AIMS: Strategies to assess patients with suspected acute myocardial infarction (AMI) using a point-of-care (POC) high-sensitivity cardiac troponin I (hs-cTnI) assay may expedite emergency care. A 2-h POC hs-cTnI strategy for emergency patients with suspected AMI was derived and validated. METHODS: In two international, multi-centre, prospective, observational studies of adult emergency patients (1486 derivation cohort and 1796 validation cohort) with suspected AMI, hs-cTnI (Siemens Atellica® VTLi) was measured at admission and 2 h later. Adjudicated final diagnoses utilized the hs-cTn assay in clinical use. A risk stratification algorithm was derived and validated. The primary diagnostic outcome was index AMI (Types 1 and 2). The primary safety outcome was 30-day major adverse cardiac events incorporating AMI and cardiac death. RESULTS: Overall, 81 (5.5%) and 88 (4.9%) patients in the derivation and validation cohorts, respectively, had AMI. The 2-h algorithm defined 66.1% as low risk with a sensitivity of 98.8% [95% confidence interval (CI) 89.3%-99.9%] and a negative predictive value of 99.9 (95% CI 99.2%-100%) for index AMI in the derivation cohort. In the validation cohort, 53.3% were low risk with a sensitivity of 98.9% (95% CI 92.4%-99.8%) and a negative predictive value of 99.9% (95% CI 99.3%-100%) for index AMI. The high-risk metrics identified 5.4% of patients with a specificity of 98.5% (95% CI 96.6%-99.4%) and a positive predictive value of 74.5% (95% CI 62.7%-83.6%) for index AMI. CONCLUSIONS: A 2-h algorithm using a POC hs-cTnI concentration enables safe and efficient risk assessment of patients with suspected AMI. The short turnaround time of POC testing may support significant efficiencies in the management of the large proportion of emergency patients with suspected AMI.

Lower Limits for Reporting High-Sensitivity Cardiac Troponin Assays and Impact of Analytical Performance on Patient Misclassification.

BACKGROUND: Cardiac troponin measurements are indispensable for the diagnosis of myocardial infarction and provide useful information for long-term risk prediction of cardiovascular disease. Accelerated diagnostic pathways prevent unnecessary hospital admission, but require reporting cardiac troponin concentrations at low concentrations that are sometimes below the limit of quantification. Whether analytical imprecision at these concentrations contributes to misclassification of patients is debated. CONTENT: The International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers (IFCC C-CB) provides evidence-based educational statements on analytical and clinical aspects of cardiac biomarkers. This mini-review discusses how the reporting of low concentrations of cardiac troponins impacts on whether or not assays are classified as high-sensitivity and how analytical performance at low concentrations influences the utility of troponins in accelerated diagnostic pathways. Practical suggestions are made for laboratories regarding analytical quality assessment of cardiac troponin results at low cutoffs, with a particular focus on accelerated diagnostic pathways. The review also discusses how future use of cardiac troponins for long-term prediction or management of cardiovascular disease may require improvements in analytical quality. SUMMARY: Clinical guidelines recommend using cardiac troponin concentrations as low as the limit of detection of the assay to guide patient care. Laboratories, manufacturers, researchers, and external quality assessment providers should extend analytical performance monitoring of cardiac troponin assays to include the concentration ranges applicable in these pathways.

Analytical validation of the Mindray CL1200i analyzer high sensitivity cardiac troponin I assay: MERITnI study.

OBJECTIVES: This study performed an analytical validation study of the Mindray high-sensitivity cardiac troponin I (hs-cTnI) assay addressing limit of blank (LoB), limit of detection (LoD), precision, linearity, analytical specificity and sex-specific 99th percentile upper reference limits. METHODS: LoB, LoD, precision, linearity and analytical specificity were studied according to Clinical and Laboratory Standards Institute. We used one reagent lot and one CL1200i analyzer. Skeletal troponin I and T, cardiac troponin T, troponin C, actin, tropomyosin, myosin light chain, myoglobin and creatine kinase (CK-MB) were studied for cross-reactivity. Interference with biotin was examined. Lithium heparin samples (one freeze thaw cycle) from healthy males and females were measured to determine the 99th percentiles by using the non-parametric method. Analyses were performed before and after excluding subjects with clinical conditions and/or increased surrogate biomarkers. RESULTS: The Mindray hs-cTnI assay met criteria to be considered as a hs-cTn assay. LoB and LoD was <0.1 ng/L and 0.1 ng/L, respectively. Repeatability had a coefficient of variation 1.2-3.8 %, and within-laboratory imprecision 1.7-5.0 %. The measuring interval ranged from 1.1 to 28,180 ng/L. The analytical specificity was clinically acceptable for the interferents studied. After exclusions, the 99th percentile URLs obtained were 10 ng/L overall, 5 ng/L for females and 12 ng/L for males. CONCLUSIONS: Analytical observations of the Mindray hs-cTnI assay demonstrated excellent LoB, LoD, precision, linearity and analytical specificity, that were in alignment with the manufacturer's claims and regulatory guidelines for hs-cTnI. The assay is suitable for clinical investigation for patient-oriented studies.

High-Sensitivity Cardiac Troponin and the 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR Guidelines for the Evaluation and Diagnosis of Acute Chest Pain.

The 2021 American Heart Association/American College of Cardiology/American Society of Echocardiography/American College of Chest Physicians/Society for Academic Emergency Medicine/Society of Cardiovascular Computed Tomography/Society for Cardiovascular Magnetic Resonance guidelines for the evaluation and diagnosis of acute chest pain make important recommendations that include the recognition of high-sensitivity cardiac troponin (hs-cTn) as the preferred biomarker, endorsement of 99th percentile upper reference limits to define myocardial injury, and the use of clinical decision pathways, as well as acknowledgment of the uniqueness of women and other patient subsets. Details on how to integrate hs-cTn into clinical practice are less extensively addressed. Clinicians should be aware of some of the analytical aspects related to hs-cTn assays regarding the limit of detection and the limit of quantitation and how they are used clinically, especially for the single sample strategy to rule out acute myocardial infarction. Likewise, it is important for clinicians to understand issues related to the derivation of the 99th percentile upper reference limit; the value of sex-specific 99th percentile upper reference limits; how to use changing concentrations (deltas) to facilitate diagnosis and risk stratification of patients with suspected acute coronary syndrome, including the differentiation of acute from chronic myocardial injury; and how to best integrate the use of hs-cTn with clinical decision pathways. With the use of hs-cTn, conditions such as type 2 myocardial infarction become more common, whereas others such as unstable angina become less frequent but still occur. Sections relating to these issues are included.

Single High-Sensitivity Point-of-Care Whole-Blood Cardiac Troponin I Measurement to Rule Out Acute Myocardial Infarction at Low Risk.

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) laboratory assays are used to rule out myocardial infarction (MI) on presentation, but prolonged result turnaround times can delay patient management. Our primary aim was to identify patients at low risk of index MI using a rapid point-of-care (POC) whole-blood hs-cTnI assay at presentation with potential early patient discharge. METHODS: Consecutive patients presenting to the emergency department from 2 prospective observational studies with suspected acute coronary syndrome were enrolled. A POC hs-cTnI assay (Atellica VTLi) threshold using whole blood at presentation, which resulted in a negative predictive value of ≥99.5% and sensitivity of >99% for index MI, was derived (SEIGE [Safe Emergency Department Discharge Rate]) and validated with plasma (SAMIE [Suspected Acute Myocardial Infarction in Emergency]). Event adjudications were established with hs-cTnI assay results from routine clinical care. The primary outcome was MI at 30 days. RESULTS: A total of 1086 patients (8.1% with MI) were enrolled in a US derivation cohort (SEIGE) and 1486 (5.5% MI) in an Australian validation cohort (SAMIE). A derivation whole-blood POC hs-cTnI concentration of <4 ng/L provided a sensitivity of 98.9% (95% CI, 93.8%-100%) and negative predictive value of 99.5% (95% CI, 97.2%-100%) for ruling out MI. In the validation cohort, the sensitivity was 98.8% (95% CI, 93.3%-100%), and negative predictive value was 99.8% (95% CI, 99.1%-100%); 17.8% and 41.8%, respectively, were defined as low risk for discharge. The 30-day adverse cardiac events were 0.1% (n=1) for SEIGE and 0.8% (n=5) for SAMIE. CONCLUSIONS: A POC whole-blood hs-cTnI assay permits accessible, rapid, and safe exclusion of MI and may expedite discharge from the emergency department. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04772157. URL: https://www.australianclinicaltrials.gov.au/anzctr_feed/form; Unique identifier: 12621000053820.

Defining myocardial infarction in trials of people receiving hemodialysis: consensus report from the SONG-HD MI Expert Working group.

Cardiovascular disease is the leading cause of death in patients receiving hemodialysis. Currently, there is no standardized definition of myocardial infarction (MI) for patients receiving hemodialysis. Through an international consensus process MI was established as the core CVD measure for this population in clinical trials. The Standardised Outcomes in Nephrology Group-Hemodialysis (SONG-HD) initiative convened a multidisciplinary, international working group to address the definition of MI in this population. On the basis of current evidence, the working group recommends using the Fourth Universal Definition of Myocardial Infarction with specific caveats with regard to the interpretation of "ischemic symptoms" and performing a baseline 12-lead electrocardiogram to facilitate interpretation of acute changes on subsequent tracings. The working group does not recommend obtaining baseline cardiac troponin values, though does recommend obtaining serial cardiac biomarkers in settings where ischemia is suspected. The application of an evidence-based uniform definition should increase the reliability and accuracy of trial results.

Rapid Rule-Out of Myocardial Infarction Using a Single High-Sensitivity Cardiac Troponin I Measurement Strategy at Presentation to the Emergency Department: The SAFETY Study.

BACKGROUND: Our study addressed the diagnostic performance of the Atellica® IM High-Sensitivity Troponin I (hs-cTnI) assay for the rapid rule-out of myocardial infarction (MI) using a single hs-cTnI measurement at presentation in patients presenting to a US emergency department (ED). METHODS: This was a prospective, observational, cohort study of consecutive ED patients with suspected acute coronary syndrome, using 12-lead electrocardiogram and serial hs-cTnI measurements ordered on clinical indication (SAFETY, NCT04280926). ST-segment elevation MI patients were excluded. The optimal threshold required a sensitivity ≥99% and a negative predictive value (NPV) ≥99.5% for MI during index hospitalization as primary outcome. Type 1 MI (T1MI), myocardial injury, and 30-day adverse events were considered secondary outcomes. Event adjudications were established using the hs-cTnI assay used in clinical care. RESULTS: In 1171 patients, MI occurred in 97 patients (8.3%), 78.3% of which were type 2 MI. The optimal rule out hs-cTnI threshold was <10 ng/L, which identified 519 (44.3%) patients as low risk at presentation, with sensitivity of 99.0% (95% CI, 94.4-100) and NPV of 99.8% (95% CI, 98.9-100). For T1MI, sensitivity was 100% (95% CI, 83.9-100) and NPV 100% (95% CI, 99.3-100). Regarding myocardial injury, the sensitivity and NPV were 99.5% (95% CI, 97.9-100) and 99.8% (95% CI, 98.9-100), respectively. For 30-day adverse events, sensitivity was 96.8% (95% CI, 94.3-98.4) and NPV 97.9% (95% CI, 96.2-98.9). CONCLUSIONS: A single hs-cTnI measurement strategy enabled the rapid identification of patients at low risk of MI and 30-day adverse events, allowing potential discharge early after ED presentation. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT04280926.

Cardiac troponin measurement at the point of care: educational recommendations on analytical and clinical aspects by the IFCC Committee on Clinical Applications of Cardiac Bio-Markers (IFCC C-CB).

The International Federation of Clinical Chemistry and Laboarator Medicine (IFCC) Committee on Clinical Applications of Cardiac Bio-Markers (C-CB) has provided evidence-based educational resources to aid and improve the understanding of important analytical and clinical aspects of cardiac biomarkers. The present IFCC C-CB educational report focuses on recommendations for appropriate use, analytical performance, and gaps in clinical studies related to the use of cardiac troponin (cTn) by point of care (POC) measurement, often referred to as a point of care testing (POCT). The use of high-sensitivity (hs)-cTn POC devices in accelerated diagnostic protocols used in emergency departments or outpatient clinics investigating acute coronary syndrome has the potential for improved efficacy, reduction of length of stay and reduced costs in the health care system. POCT workflow integration includes location of the instrument, assignment of collection and testing responsibility to (non-lab) staff, instrument maintenance, in-service and recurrent training, quality control, proficiency assessments, discrepant result trapping, and troubleshooting and inventory management.

Antibody-mediated interferences affecting cardiac troponin assays: recommendations from the IFCC Committee on Clinical Applications of Cardiac Biomarkers.

The International Federation of Clinical Chemistry Committee on Clinical Applications of Cardiac Biomarkers (IFCC C-CB) provides educational documents to facilitate the interpretation and use of cardiac biomarkers in clinical laboratories and practice. Our aim is to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay. Measurements of cardiac troponin (cTn) have a prominent place in the clinical work-up of patients with suspected acute coronary syndrome. It is therefore important that clinical laboratories know how to recognize and assess analytical issues. Two emerging analytical issues resulting in falsely high cTn concentrations, often several fold higher than the upper reference limit (URL), are antibody-mediated assay interference due to long-lived cTn-antibody complexes, called macrotroponin, and crosslinking antibodies that are frequently referred to as heterophilic antibodies. We provide an overview of antibody-mediated cTn assay interference and provide recommendations on how to confirm the interference and interpret the results.

Cardiac Troponin Thresholds and Kinetics to Differentiate Myocardial Injury and Myocardial Infarction.

BACKGROUND: Although the 99th percentile is the recommended diagnostic threshold for myocardial infarction, some guidelines also advocate the use of higher troponin thresholds to rule in myocardial infarction at presentation. It is unclear whether the magnitude or change in troponin concentration can differentiate causes of myocardial injury and infarction in practice. METHODS: In a secondary analysis of a multicenter randomized controlled trial, we identified 46 092 consecutive patients presenting with suspected acute coronary syndrome without ST-segment-elevation myocardial infarction. High-sensitivity cardiac troponin I concentrations at presentation and on serial testing were compared between patients with myocardial injury and infarction. The positive predictive value and specificity were determined at the sex-specific 99th percentile upper reference limit and rule-in thresholds of 64 ng/L and 5-fold of the upper reference limit for a diagnosis of type 1 myocardial infarction. RESULTS: Troponin was above the 99th percentile in 8188 patients (18%). The diagnosis was type 1 or type 2 myocardial infarction in 50% and 14% and acute or chronic myocardial injury in 20% and 16%, respectively. Troponin concentrations were similar at presentation in type 1 (median [25th-75th percentile] 91 [30-493] ng/L) and type 2 (50 [22-147] ng/L) myocardial infarction and in acute (50 [26-134] ng/L) and chronic (51 [31-130] ng/L) myocardial injury. The 99th percentile and rule-in thresholds of 64 ng/L and 5-fold upper reference limit gave a positive predictive value of 57% (95% CI, 56%-58%), 59% (58%-61%), and 62% (60%-64%) and a specificity of 96% (96%-96%), 96% (96%-96%), and 98% (97%-98%), respectively. The absolute, relative, and rate of change in troponin concentration were highest in patients with type 1 myocardial infarction (P<0.001 for all). Discrimination improved when troponin concentration and change in troponin were combined compared with troponin concentration at presentation alone (area under the curve, 0.661 [0.642-0.680] versus 0.613 [0.594-0.633]). CONCLUSIONS: Although we observed important differences in the kinetics, cardiac troponin concentrations at presentation are insufficient to distinguish type 1 myocardial infarction from other causes of myocardial injury or infarction in practice and should not guide management decisions in isolation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01852123.

High-Sensitivity Cardiac Troponin on Presentation to Rule Out Myocardial Infarction: A Stepped-Wedge Cluster Randomized Controlled Trial.

BACKGROUND: High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the safety and efficacy of this approach is uncertain. We investigated whether an early rule-out pathway is safe and effective for patients with suspected acute coronary syndrome. METHODS: We performed a stepped-wedge cluster randomized controlled trial in the emergency departments of 7 acute care hospitals in Scotland. Consecutive patients presenting with suspected acute coronary syndrome between December 2014 and December 2016 were included. Sites were randomized to implement an early rule-out pathway where myocardial infarction was excluded if high-sensitivity cardiac troponin I concentrations were <5 ng/L at presentation. During a previous validation phase, myocardial infarction was ruled out when troponin concentrations were <99th percentile at 6 to 12 hours after symptom onset. The coprimary outcome was length of stay (efficacy) and myocardial infarction or cardiac death after discharge at 30 days (safety). Patients were followed for 1 year to evaluate safety and other secondary outcomes. RESULTS: We enrolled 31 492 patients (59±17 years of age [mean±SD]; 45% women) with troponin concentrations <99th percentile at presentation. Length of stay was reduced from 10.1±4.1 to 6.8±3.9 hours (adjusted geometric mean ratio, 0.78 [95% CI, 0.73-0.83]; P<0.001) after implementation and the proportion of patients discharged increased from 50% to 71% (adjusted odds ratio, 1.59 [95% CI, 1.45-1.75]). Noninferiority was not demonstrated for the 30-day safety outcome (upper limit of 1-sided 95% CI for adjusted risk difference, 0.70% [noninferiority margin 0.50%]; P=0.068), but the observed differences favored the early rule-out pathway (0.4% [57/14 700] versus 0.3% [56/16 792]). At 1 year, the safety outcome occurred in 2.7% (396/14 700) and 1.8% (307/16 792) of patients before and after implementation (adjusted odds ratio, 1.02 [95% CI, 0.74-1.40]; P=0.894), and there were no differences in hospital reattendance or all-cause mortality. CONCLUSIONS: Implementation of an early rule-out pathway for myocardial infarction reduced length of stay and hospital admission. Although noninferiority for the safety outcome was not demonstrated at 30 days, there was no increase in cardiac events at 1 year. Adoption of this pathway would have major benefits for patients and health care providers. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03005158.

High-sensitivity cardiac troponin and the diagnosis of myocardial infarction in patients with kidney impairment.

The benefit and utility of high-sensitivity cardiac troponin (hs-cTn) in the diagnosis of myocardial infarction in patients with kidney impairment is unclear. Here, we describe implementation of hs-cTnI testing on the diagnosis, management, and outcomes of myocardial infarction in patients with and without kidney impairment. Consecutive patients with suspected acute coronary syndrome enrolled in a stepped-wedge, cluster-randomized controlled trial were included in this pre-specified secondary analysis. Kidney impairment was defined as an eGFR under 60mL/min/1.73m2. The index diagnosis and primary outcome of type 1 and type 4b myocardial infarction or cardiovascular death at one year were compared in patients with and without kidney impairment following implementation of hs-cTnI assay with 99th centile sex-specific diagnostic thresholds. Serum creatinine concentrations were available in 46,927 patients (mean age 61 years; 47% women), of whom 9,080 (19%) had kidney impairment. hs-cTnIs were over 99th centile in 46% and 16% of patients with and without kidney impairment. Implementation increased the diagnosis of type 1 infarction from 12.4% to 17.8%, and from 7.5% to 9.4% in patients with and without kidney impairment (both significant). Patients with kidney impairment and type 1 myocardial infarction were less likely to undergo coronary revascularization (26% versus 53%) or receive dual anti-platelets (40% versus 68%) than those without kidney impairment, and this did not change post-implementation. In patients with hs-cTnI above the 99th centile, the primary outcome occurred twice as often in those with kidney impairment compared to those without (24% versus 12%, hazard ratio 1.53, 95% confidence interval 1.31 to 1.78). Thus, hs-cTnI testing increased the identification of myocardial injury and infarction but failed to address disparities in management and outcomes between those with and without kidney impairment.

Analytical Considerations in Deriving 99th Percentile Upper Reference Limits for High-Sensitivity Cardiac Troponin Assays: Educational Recommendations from the IFCC Committee on Clinical Application of Cardiac Bio-Markers.

The International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers provides evidence-based educational documents to facilitate uniform interpretation and utilization of cardiac biomarkers in clinical laboratories and practice. The committee's goals are to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay in clinical practice. Measurement of high-sensitivity cardiac troponin (hs-cTn) assays is a cornerstone in the clinical evaluation of patients with symptoms and/or signs of acute cardiac ischemia. To define myocardial infarction, the Universal Definition of Myocardial Infarction requires patients who manifest with features suggestive of acute myocardial ischemia to have at least one cTn concentration above the sex-specific 99th percentile upper reference limit (URL) for hs-cTn assays and a dynamic pattern of cTn concentrations to fulfill the diagnostic criteria for MI. This special report provides an overview of how hs-cTn 99th percentile URLs should be established, including recommendations about prescreening and the number of individuals required in the reference cohort, how statistical analysis should be conducted, optimal preanalytical and analytical protocols, and analytical/biological interferences or confounds that can affect accurate determination of the 99th percentile URLs. This document also provides guidance and solutions to many of the issues posed.

A comparison of modelled serum cTnT and cTnI kinetics after 60 min swimming.

Post-exercise elevations of cardiac troponin T (cTnT) and I (cTnI) are often used in isolation but interpreted interchangeably. Research suggests, however, that post-exercise cTn kinetic might differ with each isoform. In this cross-sectional observational study, we collected blood samples before, immediately after (5 minutes), and at 1-, 3-, 6-, 12-, and 24-hour post-exercise in a mixed cohort of 56 participants after a distance-trial of 60 min continuous swimming (age range from 14 to 22, 57.1% female). Cardiac troponin kinetics were modelled using Bayesian mixed-effects models to estimate time to peak (TTP) and peak concentration (PC) for each isoform, while controlling for participants sex, tanner stage and average relative heart rate during the test. Exercise induced an elevation of cTnT and cTnI in 93% and 75% of the participants, respectively. Cardiac troponin T peaked earlier, at 2.9 h (CI: 2.6 - 3.2 h) post-exercise, whereas cTnI peaked later, at 4.5 h (CI: 4.2 - 4.9 h). Peak concentrations for cTnT and cTnI were 2.5 ng/L, CI: 0 - 11.2 ng/L and 2.16 ng/L, CI: 0 - 22.7 ng/L, respectively. Additionally, we did not observe a systematic effect of sex and maturational status mediating cTn responses.

Biomarkers Enhance Discrimination and Prognosis of Type 2 Myocardial Infarction.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Outpatient versus observation/inpatient management of emergency department patients rapidly ruled-out for acute myocardial infarction: Findings from the HIGH-US study.

BACKGROUND: The actual Emergency Department (ED) dispositions of patients enrolled in observational studies and meeting criteria for rapid acute myocardial infarction (AMI) rule-out are unknown. Additionally, their presenting clinical profiles, cardiac testing/treatments received, and outcomes have not been reported. METHODS: Patients in the HIGH-US study (29 sites) that ruled-out for AMI using a high-sensitivity cardiac troponin I 0/1-hour algorithm were evaluated. Clinical characteristics of patients having ED discharge were compared to patients placed in observation or hospital admitted (OBS/ADM). Reports of any OBS/ADM cardiac stress test (CST), cardiac catheterization (Cath) and coronary revascularization were reviewed. One year AMI/death and major adverse cardiovascular event rates were determined. RESULTS: Of the 1,020 ruled-out AMI patients 584 (57.3%) had ED discharge. The remaining 436 (42.7%) were placed in OBS/ADM. Patients with risk factors for AMI, including personal or family history of coronary artery disease, hypertension, previous stroke or abnormal ECG were more often placed in OBS/ADM. 175 (40.1%) had a CST. Of these 32 (18.3%) were abnormal and 143 (81.7%) normal. Cath was done in 11 (34.3%) of those with abnormal and 13 (9.1%) with normal CST. Of those without an initial CST 85 (32.6%) had Cath. Overall, revascularizations were performed in 26 (6.0%) patients. One-year AMI/death rates were low/similar (P = .553) for the groups studied. CONCLUSIONS: Rapidly ruled-out for AMI ED patients having a higher clinician perceived risk for new or worsening coronary artery disease and placed in OBS/ADM underwent many diagnostic tests, were infrequently revascularized and had excellent outcomes. Alternate efficient strategies for these patients are needed.

Implementation of High-Sensitivity and Point-of-Care Cardiac Troponin Assays into Practice: Some Different Thoughts.

BACKGROUND: The primary role of the International Federation of Clinical Chemistry (IFCC) Committee on Clinical Application of Cardiac Bio-Markers (C-CB) is to provide educational materials about cardiac biomarker use, emphasizing high-sensitivity cardiac troponin assays. CONTENT: This mini-review, regarding high-sensitivity cardiac and point-of-care troponin assays, addresses 1) new IFCC C-CB/AACC Academy laboratory practice recommendations; 2) new and updated concepts from the Fourth Universal Definition of Myocardial Infarction; 3) the role of point-of-care assays in practice and research; 4) regulatory challenges concerning point-of-care assays; e) testing in the COVID-19 world. SUMMARY: Implementation of high-sensitivity cardiac troponin assays makes a difference now and into the future in clinical practice and research. Providing point-of-care high-sensitivity cardiac troponin assays and optimizing studies to allow clearance of these assays by regulatory agencies, in a timely fashion, may provide improved patient management and outcomes.

Cardiac Troponin Testing in Patients with COVID-19: A Strategy for Testing and Reporting Results.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged late in 2019 causing COVID-19 (coronavirus disease-2019) may adversely affect the cardiovascular system. Publications from Asia, Europe, and North America have identified cardiac troponin as an important prognostic indicator for patients hospitalized with COVID-19. We recognized from publications within the first 6 months of the pandemic that there has been much uncertainty on the reporting, interpretation, and pathophysiology of an increased cardiac troponin concentration in this setting. CONTENT: The purpose of this mini-review is: a) to review the pathophysiology of SARS-CoV-2 and the cardiovascular system, b) to overview the strengths and weaknesses of selected studies evaluating cardiac troponin in patients with COVID-19, and c) to recommend testing strategies in the acute period, in the convalescence period and in long-term care for patients who have become ill with COVID-19. SUMMARY: This review provides important educational information and identifies gaps in understanding the role of cardiac troponin and COVID-19. Future, properly designed studies will hopefully provide the much-needed evidence on the path forward in testing cardiac troponin in patients with COVID-19.

How Well Do Laboratories Adhere to Recommended Guidelines for Cardiac Biomarkers Management in Europe? The CArdiac MARker Guideline Uptake in Europe (CAMARGUE) Study of the European Federation of Laboratory Medicine Task Group on Cardiac Markers.

BACKGROUND: The CARdiac MARker Guideline Uptake in Europe (CAMARGUE) program is a multi-country audit of the use of cardiac biomarkers in routine clinical practice. METHODS: An email link to a web-based questionnaire of 30 multiple-choice questions was distributed via the professional societies in Europe. RESULTS: 374 questionnaires were returned from 39 countries, the majority of which were in northern Europe with a response rate of 8.2%-42.0%. The majority of the respondents were from hospitals with proportionately more responses from central hospitals than district hospitals. Cardiac troponin was the preferred cardiac biomarker, evenly split between cardiac troponin T (cTnT) and cardiac troponin I (cTnI). Aspartate transaminase and lactate dehydrogenase are no longer offered as cardiac biomarkers. Creatine kinase, creatine kinase MB isoenzyme, and myoglobin continue to be offered as part of the cardiac biomarker profile in approximately on 50% of respondents. There is widespread utilization of high sensitivity (hs) troponin assays. The majority of cTnT users measure hs-cTnT. 29.5% of laboratories measure cTnI by a non-hs method but there has been substantial conversion to hs-cTnI. The majority of respondents used ng/L and use the 99th percentile as the upper reference limit (71.9% of respondents). A range of diagnostic protocols are in use. CONCLUSIONS: There is widespread utilization of hs troponin methods. A significant minority do not use the 99th percentile as recommended and there is, as yet, little uptake of very rapid diagnostic strategies. Education of laboratory professionals and clinicians remains a priority.

Determination of sex-specific 99th percentile upper reference limits for a point of care high sensitivity cardiac troponin I assay.

OBJECTIVES: High sensitivity (hs) cardiac troponin (cTn) assays are defined per the IFCC Committee on Clinical Application of Cardiac Biomarker (C-CB) by the ability to measure ≥ 50% of concentrations greater than the limit of detection (LoD) with an impression of ≤10% at sex-specific 99th percentiles. Our study determined the sex-specific 99th percentile upper reference limits for males and females utilizing heparinized plasma from AACC universal sample bank for the Siemens point of care (POC) Atellica® VTLi hs-cTnI immunoassay. METHODS: Apparently healthy subjects, included overall 693, males 363, and females 330, following exclusionary surrogate biomarker use of hemoglobin A1c, NT-proBNP, and eGFR, along with statin medication. hs-cTnI was measured in a central laboratory, on multiple POC Atellica® VTLi immunoassay analyzers. The LoD was 1.24 ng/L and the 10%CV concentration was 6.7 ng/L. 99th percentile URLs were determined by the nonparametric (NP) method. RESULTS: Histograms of the hs-cTnI concentrations (ng/L) for males and females were used to visualize the distributions and concentrations in men and women and differed significantly (pre- and post-exclusion, both p <0.001). 99th percentile URLs were: overall 23 ng/L (90% CI 20-32 ng/L); male 27 ng/L (CI 21-37 ng/L); female 18 ng/L (CI 9-78 ng/L). The percentages of subjects having a measurable concentration ≥ the LoD were: overall 83.7%, male 87.3%, female 79.7%. CONCLUSIONS: Our findings show the novel POC Atellica® VTLi hs-cTnI assay meets the designation of a 'high-sensitivity' assay using heparinized plasma.