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OBJECTIVES: To identify in a prospective observational study the cardiac structural and functional abnormalities and mortality in patients with end stage renal disease (ESRD) with a raised cardiac troponin T (cTnT) concentration. METHODS: 126 renal transplant candidates were studied over a two year period. Clinical, biochemical, echocardiographic, coronary angiographic, and dobutamine stress echocardiographic (DSE) data were examined in comparison with cTnT concentrations dichotomised at cut off concentrations of < 0.04 microg/l and < 0.10 microg/l. RESULTS: Left ventricular (LV) size and filling pressure were significantly raised and LV systolic and diastolic function parameters significantly impaired in patients with raised cTnT, irrespective of the cut off concentration. The proportions of patients with diabetes and on dialysis were higher in both groups with raised cTnT. With a cut off cTnT concentration of 0.04 microg/l but not 0.10 microg/l, significantly more patients had severe coronary artery disease and a positive DSE result. The total ischaemic burden during DSE was similar in cTnT positive and negative patients, irrespective of the cut off concentration used. LV end systolic diameter index and E:Ea ratio were independent predictors of cTnT rises > or = 0.04 microg/l and > or = 0.10 microg/l, respectively. Diabetes was independently associated with cTnT at both cut off concentrations. Mortality was higher in all patients with raised cTnT. CONCLUSIONS: Patients with ESRD with raised cTnT concentrations have increased mortality. Raised concentrations are strongly associated with diabetes, LV dilatation, and impaired LV systolic and diastolic function, but not with severe coronary artery disease. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess if the combination of cardiac troponin (cTn) and Ischemia Modified Albumin (IMA) can be used for early exclusion of acute myocardial infarction (AMI). METHODS: Prospective consecutive admissions to the emergency department (ED) with undifferentiated chest pain were assessed clinically and by electrocardiography. A total of 539 patients (335 men, 204 women; median age 51.9 years) considered at low risk of AMI had blood drawn on admission. If the first sample was less than 12 hours from onset of chest pain, a second sample was drawn two hours later, at least six hours from onset of chest pain. Creatine kinase MB isoenzyme (CKMB) mass was measured on the first sample and CKMB mass and cTnT on the second sample. An aliquot from the first available sample was frozen and subsequently analysed for IMA. If cTnT had not been measured on the original sample cTnI was measured (n = 189). RESULTS: Complete data were available for 538/539 patients. IMA or cTn was elevated in the admission sample of all patients with a final diagnosis of AMI (n = 37) with IMA alone elevated in 2/37, cTn alone in 19/37, and both in 16/37. In 173/501 patients in whom AMI was excluded both tests were negative. In the non-AMI group 22 patients had elevation of both IMA and cTn in the initial sample, suggesting ischaemic disease. CONCLUSION: Admission measurement of cardiac troponin plus IMA can be used for early classification of patients presenting to the ED to assist in patient triage. [ABSTRACT FROM AUTHOR]

Background: N-terminal pro-B type natriuretic peptide (NTpBNP) is a potential marker of cardiac failure. Methods: The Roche Elecsys™ 1010 and 2010 assays for NTpBNP were evaluated for precision, sample stability, and correlation between sample types and with other natriuretic peptides. Samples from 290 individuals aged 45–89 years with no cardiovascular risk factors, renal failure, electrocardiogram changes, evidence of structural abnormalities, or wall motion abnormalities on echocardiography and with an ejection fraction >50% were used to provide reference NTpBNP ranges. Results: The intra-assay imprecision was <10% across the analytical range and >3% at all concentrations analysed <30 ng/L. Inter-assay imprecision was 5.3–6.7% on the Elecsys 1010 and 4.4–5.0% on the Elecsys 2010, in the range 380–13000 ng/L. There was no statistically significant change in NTpBNP following storage in whole-blood samples at room temperature for 24 h before centrifugation; serum samples at room temperature for 7 days, at 4°C for up to 11 days on clot-activation gel or 22 days separated from the gel. NTpBNP concentrations were stable throughout five freeze–thaw cycles. There was a close correlation between NTpBNP concentrations in matched serum, EDTA plasma and lithium–heparin plasma samples. NTpBNP and BNP were more closely associated than were N-terminal proatrial natriuretic peptide and NTpBNP. This association was stronger at lower concentrations. NTpBNP concentrations increased with age, with values higher in women than men. Conclusions: NTpBNP is a stable molecule that can be measured easily and precisely using the Roche Elecsys 1010 or 2010 immunoassay analysers. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of cardiac ischaemia in patients attending emergency departments (ED) with symptoms of acute coronary syndromes is often difficult. Cardiac troponin (cTn) is sensitive and specific for the detection of myocardial damage but may not rise during reversible myocardial ischaemia. Ischemia Modified Albumin (IMA) has recently been shown to be a sensitive and early biochemical marker of ischaemia.Methods and Results: This study evaluated IMA in conjunction with ECG and cTn in 208 patients presenting to the ED within three hours of acute chest pain. At presentation, a 12-lead ECG was recorded and blood taken for IMA and cardiac troponin T (cTnT). Patients underwent standardised triage, diagnostic procedures, and treatment. Results of IMA, ECG, and cTnT, alone and in combination, were correlated with final diagnoses of non-ischaemic chest pain, unstable angina, ST segment elevation, and non-ST segment elevation myocardial infarction. In the whole patient group, sensitivity of IMA at presentation for an ischaemic origin of chest pain was 82%, compared with 45% of ECG and 20% of cTnT. IMA used together with cTnT or ECG, had a sensitivity of 90% and 92%, respectively. All three tests combined identified 95% of patients whose chest pain was attributable to ischaemic heart disease. In patients with unstable angina, sensitivity of IMA used alone was equivalent to that of IMA and ECG combined.Conclusions: IMA is highly sensitive for the diagnosis of myocardial ischaemia in patients presenting with symptoms of acute chest pain. [ABSTRACT FROM AUTHOR]

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., (© Association for Diagnostics & Laboratory Medicine 2023.)

Background: There have been relatively few studies detailing the real-world effectiveness and safety of accelerated diagnostic protocols (ADP), using high sensitivity cardiac troponin (hs-cTn)., Objective: To analyse the safety and effectiveness of early emergency department (ED) discharge following implementation of the European Society of Cardiology (ESC) 0/3-hour ADP for suspected acute coronary syndromes (ACS)., Method: We prospectively studied 2 cohorts of consecutive suspected ACS presentations to ED before (n=1642) and after (n=1376, 2 centres) implementation of the ESC 0/3-hour ADP incorporating limit of detection rule out. Safety was defined by MACE (major adverse cardiac events) inclusive of type 1 myocardial infarction (MI) in patients discharged from ED, and clinical effectiveness by percentage ED discharge. Continuous variables and categorical data were evaluated by independent t-test and χ 2 test, respectively. Time-to-event data were analysed as survival data and converted to Kaplan-Meier curves for interpretation., Results: In the preimplementation period, there was a higher prevalence of MI. Discharge from ED increased by >100% (from 27.1% to 56.5% of the cohort) with no safety signal (MACE rate 4/444 (0.9%) vs 4/769 (0.52%), p=0.430 for the 2011 and 2018 cohort, respectively). This correlated with a marked reduction in length of stay overall but a more modest reduction for those discharged from ED (6 hours 10 min vs 5 hours 25 min, p<0.001) for the 2011 and 2018 cohort, respectively. There were improvements in presentation to blood draw (163-90 min, p<0.001). Time from presentation to first ECG actually increased (16.2 vs 31.2 min, p<0.001). Analysis of hs-cTn values and ECGs revealed a maximum ED discharge rate of 69%, by applying the 0/3-hour protocol, implying potential for increasing safe ED discharge., Conclusions: Implementation of an ADP with hs-cTn is safe and effective for early rule-out and discharge of suspected ACS but require considerable resources and education to optimise maximal patient flow., Competing Interests: Competing interests: AK received a grant of £8000 for this work from Bayer medical. No conflict of interest from all other authors., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Aims: Whether a single cardiac troponin measurement can safely rule out myocardial infarction in patients presenting within a few hours of symptom onset is uncertain. The study aim was to assess the performance of troponin in early presenters., Methods and Results: In patients with possible myocardial infarction, the diagnostic performance of a single measurement of high-sensitivity cardiac troponin I at presentation was evaluated and externally validated in those tested ≤3, 4-12, and >12 h from symptom onset. The limit-of-detection (2 ng/L), rule-out (5 ng/L), and sex-specific 99th centile (16 ng/L in women; 34 ng/L in men) thresholds were compared. In 41 103 consecutive patients [60 (17) years, 46% women], 12 595 (31%) presented within 3 h, and 3728 (9%) had myocardial infarction. In those presenting ≤3 h, a threshold of 2 ng/L had greater sensitivity and negative predictive value [99.4% (95% confidence interval 99.2%-99.5%) and 99.7% (99.6%-99.8%)] compared with 5 ng/L [96.5% (96.2%-96.8%) and 99.3% (99.1%-99.4%)]. In those presenting ≥3 h, the sensitivity and negative predictive value were similar for both thresholds. The sensitivity of the 99th centile was low in early and late presenters at 71.4% (70.6%-72.2%) and 92.5% (92.0%-93.0%), respectively. Findings were consistent in an external validation cohort of 7088 patients., Conclusion: In early presenters, a single measurement of high-sensitivity cardiac troponin I below the limit of detection may facilitate the safe rule out of myocardial infarction. The 99th centile should not be used to rule out myocardial infarction at presentation even in those presenting later following symptom onset., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The term "single-sample rule-out" refers to the ability of very low concentrations of high-sensitivity cardiac troponin (hs-cTn) on presentation to exclude acute myocardial infarction with high clinical sensitivity and negative predictive value. Observational and randomized studies have confirmed this ability. Some guidelines endorse use of a concentration of hs-cTn at the assay's limit of detection, while other studies have validated the use of higher concentrations, allowing this approach to identify a greater proportion of patients at low risk. In most studies, at least 30% of patients can be triaged with this approach. The concentration of hs-cTn varies according to the assay used and sometimes how regulations permit reporting. It is clear that patients need to be at least 2 hours from the onset of symptoms being evaluated. Caution is warranted, particularly with older patients, women, and patients with underlying cardiac comorbidities., Competing Interests: Funding Support and Author Disclosures Dr Mills is supported by the British Heart Foundation through a Chair Award (CH/F/21/90010), a Programme Grant (RG/20/10/34966), and a Research Excellent Award (RE/18/5/34216). Dr Jaffe has consulted for Abbott, Beckman Coulter, Siemens, Roche, Ortho Diagnostics, ET Healthcare, SphingoTec, Radiometer, SpinChip, LumiraDX, Astellas, Amgen, Novartis, and RCE Technologies; and holds patent 20210401347 along with others. Dr Body has received consulting fees from Roche, Aptamer Group, Abbott, Psyros Diagnostics, Siemens Healthineers, Beckman Coulter, and Radiometer; and has participated on advisory boards for the FORCE Trial (funded by the National Institute for Health and Care Research), the REWIRE trial (Queen Mary University), the PRONTO trial (funded by the National Institute for Health and Care Research), and LumiraDx. Dr Mills has received research grants from Abbott Diagnostics and Siemens Healthineers; and has received personal fees for participation on advisory boards or speaking from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, LumiraDx, and Psyros Diagnostics. Dr Aakre is an associate editor of Clinical Biochemistry; is chair of the International Federation of Clinical Chemistry and Laboratory Medicine Committee on Clinical Applications of Cardiac Bio-Markers; has served on advisory boards for Roche Diagnostics and SpinChip; has received consulting honoraria from CardiNor; has received lecture honorarium from Siemens Healthineers and Snibe Diagnostics; and has received research grants from Siemens Healthineers and Roche Diagnostics. Dr Collinson is an associate editor of the Journal of Applied Laboratory Medicine; is an advisory board member for Psyros Diagnostics; and has previously advised LumiraDX, Radiometer, and Siemens. Dr Saenger has received consulting fees from Radiometer. Dr Hammarsten has stock options with Aligned Bio. Dr Omland has received consulting fees from Roche, Bayer, and CardiNor; has received honoraria from Roche; has a patent pending with Roche; has participated on advisory boards for Bayer and Roche; has a fiduciary role with CardiNor; holds stock in CardiNor; and has received equipment and material from Novartis and Abbott. Dr Sandoval has been on advisory boards and has served as a speaker for Abbott Diagnostics and Roche Diagnostics; and holds patent 20210401347 along with others. Dr Ordonez-Llanos has received consulting fees from AWE Medical and Hemcheck. Dr Apple has received consulting fees from HyTest and AWE Medical; has received advisory fees from Werfen, Siemens Healthineers, and Qorvo Biotechnology; has received nonsalaried grant support through the Hennepin Healthcare Research Institute from Abbott Diagnostics, Abbott POC, Roche Diagnostics, Siemens Healthineers, Quidel/Ortho, Becton Dickinson, and Beckman Coulter; and has received fees for serving as associate editor for Clinical Chemistry. Dr Wereski has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Methods to improve the safety, accuracy and efficiency of assessment of patients with suspected acute coronary symptoms have occupied decades of study and have supported significant changes in clinical practice. Much of the progress is reliant on results of laboratory-based high-sensitivity cardiac troponin assays that can detect low concentrations with high precision. Until recently, point-of-care (POC) platforms were unable to perform with similar analytical precision as laboratory-based assays, and recommendations for their use in accelerated assessment strategies for patients with suspected acute coronary syndrome has been limited. As POC assays can provide troponin results within 20 min, and can be used proximate to patient care, improvements in the efficiency of assessment of patients with suspected acute coronary syndrome is possible, particularly with new high-sensitivity assays., Competing Interests: Competing interests: LC reports research grants awarded to the Royal Brisbane and Women’s Hospital from Abbott Diagnostics, Siemens and Beckman Coulter, and consulting fees/honoraria from Abbott Diagnostics, Beckman Coulter, Glycardial and Siemens Healthineers. POC is the associate editor of The Journal of Applied Laboratory Medicine and consultant to the IFCC Cardiac Biomarkers group, both non-remunerated positions. EG reports no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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/1.73m 2 . 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., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

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.

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.

Background: We assessed the accuracy and clinical effectiveness of high-sensitivity cardiac troponin (hs-cTn) assays for early rule-out of non-ST-segment elevation myocardial infarction (NSTEMI) in adults presenting with acute chest pain., Methods: Sixteen databases were searched to September 2019. Review methods followed published guidelines. The bivariate model was used to estimate summary sensitivity and specificity with 95% confidence intervals for meta-analyses involving 4 or more studies, otherwise random-effects logistic regression was used., Results: Thirty-seven studies (124 publications) were included in the review. The hs-cTn test strategies evaluated in the included studies were defined by the combination of 4 factors (assay, number of tests, timing of tests, and threshold concentration or change in concentration between tests). Clinical opinion indicated a minimum acceptable sensitivity of 97%. A single test at presentation using a threshold at or near the assay limit of detection could reliably rule-out NSTEMI for a range of hs-cTn assays. Serial testing strategies, which include an immediate rule-out step, increased the proportion ruled out without loss of sensitivity. Finally, serial testing strategies without an immediate rule-out step had excellent sensitivity and specificity, but at the expense of the option for immediate patient discharge., Conclusion: Test strategies that comprise an initial rule-out step, based on low hs-cTn concentrations at presentation and a minimum symptom duration, and a second step for those not ruled-out that incorporates a small absolute change in hs-cTn at 1, 2, or 3 hours, produce the highest rule-out rates with a very low risk of missed NSTEMI., Prospero Registration: CRD42019154716., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Concerns exist regarding how the 99th percentile upper reference limit (URL) of cardiac troponin (cTn) is determined and whether it should be derived from normal healthy individuals., Content: The 99th percentile URL of cTn is an important criterion to standardize the diagnosis of myocardial infarction (MI) for clinical, research, and regulatory purposes. Statistical heterogeneity in its calculation exists but recommendations have been proposed. Some negativity has resulted from the fact that with some high-sensitivity (hs) cTn assays, a greater number of increases above the 99th percentile are observed when transitioning from a contemporary assay. Increases reflect acute or chronic myocardial injury and provide valuable diagnostic and prognostic information. The etiology of increases can sometimes be difficult to determine, making a specific treatment approach challenging. For those reasons, some advocate higher cutoff concentrations. This approach can contribute to missed diagnoses. Contrary to claims, neither clinical or laboratory guidelines have shifted away from the 99th percentile. To support the diagnosis of acute MI, the 99th percentile URL remains the best-established approach given the absence of cTn assay standardization. Importantly, risk stratification algorithms using hs-cTn assays predict the possibility of MI diagnoses established using the 99th percentile., Summary: The 99th percentile of cTn remains the best-established criterion for the diagnosis of acute MI. While not perfect, it is analytically and clinically evidence-based. Until there are robust data to suggest some other approach, staying with the 99th percentile, a threshold that has served the field well for the past 20 years, appears prudent., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: Competing interests: The authors are all members of the International Federation of Clinical Chemists Committee on Clinical Applications of Cardiac Bio-Markers (C-CB).

Background: The introduction of more sensitive cardiac troponin assays has led to increased recognition of myocardial injury in acute illnesses other than acute coronary syndrome. The Universal Definition of Myocardial Infarction recommends high-sensitivity cardiac troponin testing and classification of patients with myocardial injury based on pathogenesis, but the clinical implications of implementing this guideline are not well understood., Methods: In a stepped-wedge cluster randomized, controlled trial, we implemented a high-sensitivity cardiac troponin assay and the recommendations of the Universal Definition in 48 282 consecutive patients with suspected acute coronary syndrome. In a prespecified secondary analysis, we compared the primary outcome of myocardial infarction or cardiovascular death and secondary outcome of noncardiovascular death at 1 year across diagnostic categories., Results: Implementation increased the diagnosis of type 1 myocardial infarction by 11% (510/4471), type 2 myocardial infarction by 22% (205/916), and acute and chronic myocardial injury by 36% (443/1233) and 43% (389/898), respectively. Compared with those without myocardial injury, the rate of the primary outcome was highest in those with type 1 myocardial infarction (cause-specific hazard ratio [HR] 5.64 [95% CI, 5.12-6.22]), but was similar across diagnostic categories, whereas noncardiovascular deaths were highest in those with acute myocardial injury (cause specific HR 2.65 [95% CI, 2.33-3.01]). Despite modest increases in antiplatelet therapy and coronary revascularization after implementation in patients with type 1 myocardial infarction, the primary outcome was unchanged (cause specific HR 1.00 [95% CI, 0.82-1.21]). Increased recognition of type 2 myocardial infarction and myocardial injury did not lead to changes in investigation, treatment or outcomes., Conclusions: Implementation of high-sensitivity cardiac troponin assays and the recommendations of the Universal Definition of Myocardial Infarction identified patients at high-risk of cardiovascular and noncardiovascular events but was not associated with consistent increases in treatment or improved outcomes. Trials of secondary prevention are urgently required to determine whether this risk is modifiable in patients without type 1 myocardial infarction., Clinical Trial Registration: https://www.clinicaltrials.gov. Unique identifier: NCT01852123.

Objectives: To directly compare the diagnostic accuracy of four decision aids (Troponin-only Manchester Acute Coronary Syndromes (T-MACS), History, ECG, Age, Risk factors and Troponin (HEART), Thrombolysis in Myocardial Infarction (TIMI) and Emergency Department Assessment of Chest Pain (EDACS)) used to expedite the early diagnosis of acute coronary syndromes (ACS) in the ED., Methods: We prospectively included patients who presented to 14 EDs in England (February 2015 to June 2017) with suspected ACS within 12 hours of symptom onset. Data to enable evaluation of the T-MACS, HEART, TIMI and EDACS decision aids (without recalibration) were prospectively collected, blinded to patient outcome. We tested admission blood samples for high-sensitivity cardiac troponin I (hs-cTnI; Siemens ADVIA Centaur). Patients also underwent serial cardiac troponin testing over 3-12 hours. The target condition was an adjudicated diagnosis of acute myocardial infarction (AMI). We also evaluated the incidence of major adverse cardiac events (including death, AMI or coronary revascularisation) at 30 days. Diagnostic accuracy of each decision aid and hs-cTnI alone (using the limit of quantification cut-off, 3 ng/L) was evaluated by calculating sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV)., Results: Of 999 included patients, 132 (13.2%) had AMI. C-statistics were 0.96 for T-MACS, 0.78 for HEART and 0.69 for TIMI. The sensitivities of T-MACS, HEART, TIMI, EDACS and hs-cTnI <3 ng/L for AMI were 99.2% (95% CI 95.7% to 100.0%), 91.8% (85.0% to 96.2%), 97.5% (92.9% to 99.5%), 96.2% (92.2% to 99.4%) and 99.2% (95.9% to 100.0%), respectively. The respective strategies would have ruled out 46.5%, 34.9%, 19.4%, 48.3% and 28.8% patients. PPVs for the decision aids that identify 'high-risk' patients were 80.4% (T-MACS), 51.9% (TIMI) and 37.2% (HEART)., Conclusions: In this study, T-MACS could rule out AMI in 46.5% patients with 99.2% sensitivity. EDACS could rule out AMI in 48.3% patients with lower sensitivity, although the difference was not statistically significant. The HEART and TIMI scores had lower diagnostic accuracy., Competing Interests: Competing interests: RB: Speaker fees from Singulex, Roche, Abbott, Siemens, Beckman, Ortho, ET Healthcare, Alere; Research grants from Roche, Abbott Point of Care and Singulex; donation of reagents for research from Roche, Siemens, Singulex, Abbott, Alere, FABPulous BV, Beckman, Abbott Point of Care., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Major disparities between women and men in the diagnosis, management, and outcomes of acute coronary syndrome are well recognized., Objectives: The aim of this study was to evaluate the impact of implementing a high-sensitivity cardiac troponin I assay with sex-specific diagnostic thresholds for myocardial infarction in women and men with suspected acute coronary syndrome., Methods: Consecutive patients with suspected acute coronary syndrome were enrolled in a stepped-wedge, cluster-randomized controlled trial across 10 hospitals. Myocardial injury was defined as high-sensitivity cardiac troponin I concentration >99th centile of 16 ng/l in women and 34 ng/l in men. The primary outcome was recurrent myocardial infarction or cardiovascular death at 1 year., Results: A total of 48,282 patients (47% women) were included. Use of the high-sensitivity cardiac troponin I assay with sex-specific thresholds increased myocardial injury in women by 42% and in men by 6%. Following implementation, women with myocardial injury remained less likely than men to undergo coronary revascularization (15% vs. 34%) and to receive dual antiplatelet (26% vs. 43%), statin (16% vs. 26%), or other preventive therapies (p < 0.001 for all). The primary outcome occurred in 18% (369 of 2,072) and 17% (488 of 2,919) of women with myocardial injury before and after implementation, respectively (adjusted hazard ratio: 1.11; 95% confidence interval: 0.92 to 1.33), compared with 18% (370 of 2,044) and 15% (513 of 3,325) of men (adjusted hazard ratio: 0.85; 95% confidence interval: 0.71 to 1.01)., Conclusions: Use of sex-specific thresholds identified 5 times more additional women than men with myocardial injury. Despite this increase, women received approximately one-half the number of treatments for coronary artery disease as men, and outcomes were not improved. (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome [High-STEACS]; NCT01852123)., (Copyright © 2019. Published by Elsevier Inc.)

The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) formed a Task Force on the Application of Cardiac Bio-markers (TF-CB) in 2008, re-designated in 2018 as a committee (C-CB), to produce educational materials on cardiac biomarkers. Established in June 2017, definitive tables covering the majority of high-sensitivity, contemporary and point-of-care (POC) cTn assays have been developed by the C-CB and are available on the IFCC website. These tables provide extensive information about assays' analytical characteristics and encompass information on diagnostic discriminants, particularly the 99th percentiles, as provided by the manufacturers.