hs-cTn Assays Research Articles

Imprecision and real-time clinical performance of a whole blood high sensitivity point of care troponin i: ready for prime time?

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

False-positive cardiac troponin I values in healthy athletes post COVID-19 Infection: concerning insights from a prospective cohort study

Abstract Background Cardiac troponin I and T (cTnI, cTnT) are cardiac-specific biomarkers that detect and quantify cardiomyocyte injury. In patients with symptoms possibly indicating acute myocardial infarction (AMI), detection of elevated cTnT or cTnI concentrations usually mandates invasive coronary angiography. Accordingly, false-positive cTnT or cTnI concentrations could have detrimental consequences. Unfortunately, little is known about the prevalence and triggers of false-positive cTnI concentrations. Based on two index cases seen by one of us, we hypothesized that false-positive cTnI values may be common after COVID-19 infection and that macrotroponin, a complex formed between endogenous cTn autoantibodies and circulating cTn, may be the underlying cause. Purpose We aimed to test these hypotheses in a prospective cohort study. Methods We prospectively investigated professional athletes coming to the mandatory return to sports investigation at least 10 days after COVID-19 infection between 2022 and 2023 in an observational study. The presence of false-positive cTnI was centrally adjudicated in individuals that had elevated cTnI concentrations with one (or two) high-sensitivity cTnI assays, but normal high-sensitivity cardiac troponin T concentrations and normal electrocardiography (ECG), normal echocardiography, and normal cardiac magnetic resonance imaging (CMR). Divergences in hs-cTn concentrations were investigated using sex-specific upper limits of normal (ULN) of 4 different assays (hs-cTnI: Alinity/Abbott Diagnostic, hs-cTnI: Atellica/Siemens Healthineers, hs-cTnI: Access Beckman Coulter; hs-cTnT: Cobas/Roche Diagnostics). Athletes were instructed to cease training 48 hours before blood testing. Athletes with divergent hs-cTn assay results underwent further analysis for macrotroponin using sucrose gradient ultracentrifugation. Results Among 35 enrolled athletes (median age 24 years, 19 women and 16 men), 18 athletes had normal hs-cTn concentrations with all four hs-cTnT/I assays. In 17 athletes (48.6%), hs-cTn concentration was increased in at least one assay above the ULN, mostly one hs-cTnI method (hs-cTnI, Alinity) with normal concentrations of the other assays and normal cardiac imaging results. In contrast, two athletes had elevations in all hs-cTnI/T assays. Sucrose gradient ultracentrifugation provided evidence of macrotroponin in 15 of the 17 athletes (88%). Conclusions False-positive cTnI values are common after COVID-19 infection and should be considered in the differential diagnosis. Assay interference by macrotroponin seems to be the underlying mechanisms in most individuals. Documentation of normal hs-cTnT concentrations helps in the early detection of false-positive cTnI values.

Emergency Department use of a high-sensitivity Point-of-Care troponin assay reduces length of stay: an implementation study preliminary report.

Point-of-care (POC) high-sensitivity troponin (hs-cTn) assays within a clinical pathway may safely reduce length of stay (LoS) for patients presenting to the emergency department (ED) with possible acute myocardial infarction (AMI). In this early-report we present the first evaluation of a POC hs-cTn in real-life care. In adult patients presenting to ED investigated for possible AMI we compared the LoS in patients assessed with a troponin in the 8-weeks before (usual-care phase) and the 8-weeks following introduction of the Siemens Atellica VTLi POC hs-cTnI for decision-making (intervention phase). The VTLi replaced the laboratory (Beckman Coulter) assay as the default hs-cTn test within the clinical pathway. This was the only change to the pathway process. The safety outcome was first event AMI or cardiac death within 30-days. There were 2376 presentations in the usual-care phase with 188 individuals with AMI and 2392 in the intervention phase with 198 AMI. In the intervention phase there was a mean (95% CI) reduction in LoS of 32 minutes (22 mins to 41 mins) compared with the usual-care phase. This represents 21.4 fewer patient-hours in the ED each day (1196 in the 8-week period). In both phases the pathway correctly identified all cases of AMI at index attendance. There were four follow-up events (2 usual-care, 2 intervention) within 30d. The deployment of a hs-cTn POC analyser into a large ED safely reduced length of stay. If translatable to other EDs this could represent an important advancement to patient care.

High-Sensitivity Troponin: Finding a Meaningful Delta.

High-sensitivity cardiac troponin (hs-cTn) assays have significantly refined the resolution of biomarker-level detection and have emerged as the gold standard cardiac biomarker in evaluating myocardial injury. Since its introduction, hs-cTn has been integrated into the Fourth Universal Definition of Myocardial Infarction and various European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the evaluation and diagnosis of chest pain syndromes. However, despite its integral role in caring for patients with chest pain, there are still substantive gaps in our knowledge of the clinical interpretation of dynamic changes in hs-cTn values. Whether a relative or absolute hs-cTn delta should be used to detect acute myocardial injury remains debatable. There are also emerging considerations of possible sex and racial/ethnic differences in clinically significant troponin deltas. In the emergency department, there is debate about the optimal time frame to recheck hs-cTn after symptom onset for myocardial infarction rule-out and whether hs-cTn deltas should be integrated into clinical risk scores. In this review, we will provide an overview of the history of clinical utilization of cardiac biomarkers, the development of hs-cTn assays, and the ongoing search for a meaningful delta that can be clinically applicable.

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

A-002 Analytical Validation of the Zybio High Sensitivity Cardiac Troponin I CLIA Assay

Abstract Background High-sensitivity cardiac troponin (hs-cTn) plays a pivotal role in the early diagnosis of Acute Coronary Syndrome (ACS). With technological advancements, the sensitivity of troponin assays has significantly improved. The International Federation of Clinical Chemistry (IFCC) criteria for hs-cTn assays include a total imprecision (Coefficient of Variation, CV) ≤10% at the gender-specific 99th percentile value and detectable levels in ≥50% of a healthy population. This study aims to evaluate the performance of Zybio's hs-cTnI assay against these high-sensitivity standards Methods This study involved 1661 individuals undergoing routine health checks at Chongqing Medical University Third Hospital. Exclusion criteria included recent medication use, abnormal NT-proBNP levels, significant cardiac silhouette changes in chest X-rays, age <20, incomplete data, pregnancy, or history of severe chronic diseases. Participants were classified into apparent healthy and healthy groups based on blood pressure, lipid profiles, and electrocardiogram results. Laboratory examinations included hs-cTn and NT-ProBNP concentrations using Zybio's chemiluminescence instrument EXI2400 and associated reagent kits, with other parameters measured using standard biochemical and high-performance liquid chromatography methods. Results Of the 1247 participants (556 males, 691 females) included in the final analysis, 1157 showed detectable hs-cTnI levels above the limit of detection (LOD), yielding an overall detection rate of 92.78%. Detection rates were 93.71% in males and 92.04% in females. The total imprecision (CV) of hs-cTnI at gender-specific 99th percentile values over 20 days was below 10%, meeting the high-sensitivity criteria. This finding was consistent across lower and higher concentration ranges. Conclusions The Zybio hs-cTnI assay demonstrated a high detection rate in a healthy population, with 92.78% detectability overall, 93.71% in males, and 92.04% in females. The assay met the high-sensitivity criteria of IFCC, with a total imprecision (CV) of less than 10% at the gender-specific 99th percentile levels. These results validate the utility of Zybio's hs-cTnI assay for clinical application in the early diagnosis of ACS.

Diagnostic accuracy of a machine learning algorithm using point-of-care high-sensitivity cardiac troponin I for rapid rule-out of myocardial infarction: a retrospective study

Point-of-care (POC) high-sensitivity cardiac troponin (hs-cTn) assays have been shown to provide similar analytical precision despite substantially shorter turnaround times compared with laboratory-based hs-cTn assays. We applied the previously developed machine learning based personalised Artificial Intelligence in Suspected Myocardial Infarction Study (ARTEMIS) algorithm, which can predict the individual probability of myocardial infarction, with a single POC hs-cTn measurement, and compared its diagnostic performance with standard-of-care pathways for rapid rule-out of myocardial infarction. We retrospectively analysed pooled data from consecutive patients of two prospective observational cohorts in geographically distinct regions (the Safe Emergency Department Discharge Rate cohort from the USA and the Suspected Acute Myocardial Infarction in Emergency cohort from Australia) who presented to the emergency department with suspected myocardial infarction. Patients with ST-segment elevation myocardial infarction were excluded. Safety and efficacy of direct rule-out of myocardial infarction by the ARTEMIS algorithm (at a pre-specified probability threshold of <0·5%) were compared with the European Society of Cardiology (ESC)-recommended and the American College of Cardiology (ACC)-recommended 0 h pathways using a single POC high-sensitivity cardiac troponin I (hs-cTnI) measurement (Siemens Atellica VTLi as investigational assay). The primary diagnostic outcome was an adjudicated index diagnosis of type 1 or type 2 myocardial infarction according to the Fourth Universal Definition of Myocardial Infarction. The safety outcome was a composite of incident myocardial infarction and cardiovascular death (follow-up events) at 30 days. Additional analyses were performed for type I myocardial infarction only (secondary diagnostic outcome), and for each cohort separately. Subgroup analyses were performed for age (<65 years vs ≥65 years), sex, symptom onset (≤3 h vs >3 h), estimated glomerular filtration rate (<60 mL/min per 1·73 m2vs ≥60 mL/min per 1·73 m2), and absence or presence of arterial hypertension, diabetes, a history of coronary artery disease, myocardial infarction, or heart failure, smoking, and ischaemic electrocardiogram signs. Among 2560 patients (1075 [42%] women, median age 58 years [IQR 48·0-69·0]), prevalence of myocardial infarction was 6·5% (166/2560). The ARTEMIS-POC algorithm classified 899 patients (35·1%) as suitable for rapid rule-out with a negative predictive value of 99·96% (95% CI 99·64-99·96) and a sensitivity of 99·68% (97·21-99·70). For type I myocardial infarction only, negative predictive value and sensitivity were both 100%. Proportions of missed index myocardial infarction (0·05% [0·04-0·42]) and follow-up events at 30 days (0·07% [95% CI 0·06-0·59]) were low. While maintaining high safety, the ARTEMIS-POC algorithm identified more than twice as many patients as eligible for direct rule-out compared with guideline-recommended ESC 0 h (15·2%) and ACC 0 h (13·8%) pathways. Superior efficacy persisted across all clinically relevant subgroups. The patient-tailored, medical decision support ARTEMIS-POC algorithm applied with a single POC hs-cTnI measurement allows for very rapid, safe, and more efficient direct rule-out of myocardial infarction than guideline-recommended pathways. It has the potential to expedite the safe discharge of low-risk patients from the emergency department including early presenters with symptom onset less than 3 h at the time of admission and might open new opportunities for the triage of patients with suspected myocardial infarction even in ambulatory, preclinical, or geographically isolated care settings. The German Center for Cardiovascular Research (DZHK).

THE ANALYSIS STUDY OF DIAGNOSTIC ACCURACY OF SINGLE SAMPLE RULE-OUT OF HIGH-SENSITIVITY CARDIAC TROPONIN IN DIAGNOSIS OF ACUTE MYOCARDIAL INFARCTION IN EMERGENCY DEPARTEMENT: A COMPREHENSIVE SYSTEMATIC REVIEW FROM LABORATORY DEPARTMENT

Background: High-sensitivity cardiac troponin (hs-cTn) assays has significantly enhanced the diagnostic of acute myocard infark (AMI). Recent studies have shown that hs-cTn assays can effectively rule out AMI with a single sample. This systematic review aim to evaluate the diagnostic accuracy of single sample rule-out of high-sensitivity cardiac troponin in diagnosis of acute myocardial infarction in emergency departement based on literatures of the last 10 years. Methods: The study adhered to PRISMA 2020 standards, examining English literature from 2014 to 2024. It excluded editorials, reviews from the same journal, and submissions without a DOI. PubMed, SagePub, SpringerLink, and Google Scholar were utilized as literature sources. Result: Initially retrieving 360 articles from online databases (PubMed, SagePub, SpringerLink and Google Scholar) eight relevant papers were selected after three rounds of screening for full-text analysis. Conclusion: High-sensitivity cardiac troponin I assays enable rapid AMI rule-out in emergency departments, offering high sensitivity and negative predictive value. However, caution is needed when ruling in AMI, and further research is required to optimize their use.

Prehospital tirofiban increases the rate of disrupted myocardial infarction in patients with ST-segment elevation myocardial infarction: insights from the On-TIME 2 trial.

In patients with ST-segment elevation myocardial infarction (STEMI), prehospital tirofiban significantly improved myocardial reperfusion. However, its impact on the rate of disrupted myocardial infarction (MI), particularly in the context of high-sensitivity cardiac troponin (hs-cTn) assays, is still unclear. The On-TIME 2 (Ongoing Tirofiban In Myocardial infarction Evaluation 2) trial randomly assigned STEMI patients to prehospital tirofiban or placebo before transportation to a percutaneous coronary intervention (PCI) centre. In this post hoc analysis, we evaluated STEMI patients that underwent primary PCI and had measured hs-cTn levels. Troponin T levels were collected at 18-24 and 72-96 h after PCI. Disrupted MI was defined as peak hs-cTn T levels ≤ 10 times the upper limit of normal (≤140 ng/L). Out of 786 STEMI patients, 47 (6%) had a disrupted MI. Disrupted MI occurred in 31 of 386 patients (8.0%) in the tirofiban arm and in 16 of 400 patients (4.0%) in the placebo arm (P = 0.026). After multivariate adjustment, prehospital tirofiban remained independently associated with disrupted MI (odds ratio 2.03; 95% confidence interval 1.10-3.87; P = 0.027). None of the patients with disrupted MI died during the 1-year follow-up, compared with a mortality rate of 2.6% among those without disrupted MI. Among STEMI patients undergoing primary PCI, the use of prehospital tirofiban was independently associated with a higher rate of disrupted MI. These results, highlighting a potential benefit, underscore the need for future research focusing on innovative pre-treatment approaches that may increase the rate of disrupted MI.

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

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. 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. 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. 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.

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

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. 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. 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. 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.

Effect of transitioning from conventional cardiac troponin to high-sensitivity cardiac troponin on resource utilization- a single center experience

BackgroundCompared to conventional cardiac troponin (cTn), the high-sensitivity cardiac troponin (hs-cTn) assay is associated with improved detection of myocardial infarction (MI). MethodsWe performed a descriptive retrospective analysis of resource utilization at Rush University Medical Center over the transition period (July 1, 2021) from a cTn to a hs-cTn assay. Inclusion criteria included emergency department (ED) encounters between January 1 to December 31, 2021, with chief complaints of “chest pain” or “dyspnea” with associated troponin orders. The primary endpoint was the percentage of ED discharges. Secondary endpoints included the number of cardiac studies ordered. Univariable comparisons of these endpoints were performed using Student's t-test for continuous variables and Chi-square tests for binary/categorical variables. ResultsA total of 5113 encounters were analyzed. Hs-cTn was associated with an overall increase in ED patient discharges with negative troponin tests (44.1% vs. 29.9%, P < 0.01). In terms of cardiac testing per encounter, hs-cTn was associated with significant increases in the number of troponin tests (1.9 vs. 1.6, P < 0.01), electrocardiograms (3.0 vs. 2.9, P = 0.01), and echocardiograms (0.5 vs. 0.4, P < 0.01). There was a significant decrease in the utilization of stress testing (0.21 vs. 0.26, P < 0.01). There was a significant increase in total coronary angiography use during the hs-cTn period compared to cTn (227/2471 (9.2%) vs. 195/2642 (7.4%), P = 0.02). ConclusionTransitioning from cTn to hs-cTn was associated with significantly increased ED discharges and an increase in troponin tests, ECG, echocardiograms, and coronary angiograms. There was a decrease in the number of stress tests.

Distribution and prognostic value of high-sensitivity cardiac troponin T and I across glycemic status: a population-based study

BackgroundWhether distributions and prognostic values of high-sensitivity cardiac troponin (hs-cTn) T and I are different across normoglycemic, prediabetic, and diabetic populations is unknown.Methods10127 adult participants from the National Health and Nutrition Examination Survey 1999–2004 with determined glycemic status and measurement of at least one of hs-cTn assays were included, from whom healthy participants and presumably healthy diabetic and prediabetic participants were selected to investigate pure impacts of glycemic status on distributions of hs-cTn. The nonparametric method and bootstrapping were used to derive the 99th upper reference limits of hs-cTn and 95% CI. Participants with available follow-up and hs-cTn concentrations of all 4 assays were included in prognostic analyses. Associations of hs-cTn with all-cause and cardiac-specific mortality were modeled by Cox proportional hazard regression under the complex survey design. The incremental value of hs-cTn to an established risk score in predicting cardiac-specific mortality was assessed by the 10-year area under time-dependent receiver operating characteristic curve (AUC) using the Fine-Grey competing risk model.ResultsAmong 9714 participants included in prognostic analyses, 5946 (61.2%) were normoglycemic, 2172 (22.4%) prediabetic, and 1596 (16.4%) diabetic. Hyperglycemic populations were older than the normoglycemic population but sex and race/ethnicity were similar. During the median follow-up of 16.8 years, hs-cTnT and hs-cTnI were independently associated with all-cause and cardiac-specific mortality across glycemic status. In the diabetic population, adjusted hazard ratios per 1-standard deviation increase of log-transformed hs-cTnT and hs-cTnI (Abbott) concentrations were 1.77 (95% CI 1.48–2.12; P < .001) and 1.83 (95% CI 1.33–2.53; P < .001), respectively, regarding cardiac-specific mortality. In the diabetic but not the normoglycemic population, adding either hs-cTnT (difference in AUC: 0.062; 95% CI 0.038–0.086; P < 0.001) or hs-cTnI (Abbott) (difference in AUC: 0.071; 95% CI 0.046–0.097; P < 0.001) would significantly increase the discriminative ability of the risk score; AUC of the score combined with hs-cTnT would be further improved by incorporating hs-cTnI (0.018; 95%CI 0.006–0.029; P = 0.002). The 99th percentile of hs-cTnT of the presumably healthy diabetic population was higher than the healthy population and had no overlap in 95% CIs, however, for hs-cTnI 99th percentiles of the two populations were very close and 95% CIs extensively overlapped.ConclusionsHs-cTnT and hs-cTnI demonstrated consistent prognostic associations across glycemic status but incremental predictive values in hyperglycemic populations only. The susceptibility of hs-cTnT 99th percentiles to diabetes plus the additive value of hs-cTnI to hs-cTnT in diabetic cardiovascular risk stratification suggested hs-cTnI and hs-cTnT may be differentially associated with glycemic status, but further research is needed to illustrate the interaction between hyperglycemia and hs-cTn.

Imprecision of high-sensitivity cardiac troponin assays at the female 99th-percentile

BackgroundAn analytical benchmark for high-sensitivity cardiac troponin (hs-cTn) assays is to achieve a coefficient of variation (CV) of ≤ 10.0 % at the 99th percentile upper reference limit (URL) used for the diagnosis of myocardial infarction. Few prospective multicenter studies have evaluated assay imprecision and none have determined precision at the female URL which is lower than the male URL for all cardiac troponin assays. MethodsHuman serum and plasma matrix samples were constructed to yield hs-cTn concentrations near the female URLs for the Abbott, Beckman, Roche, and Siemens hs-cTn assays. These materials were sent (on dry ice) to 35 Canadian hospital laboratories (n = 64 instruments evaluated) participating in a larger clinical trial, with instructions for storage, handling, and monthly testing over one year. The mean concentration, standard deviation, and CV for each instrument type and an overall pooled CV for each manufacturer were calculated. ResultsThe CVs for all individual instruments and overall were ≤ 10.0 % for two manufacturers (Abbott CVpooled = 6.3 % and Beckman CVpooled = 7.0 %). One of four Siemens Atellica instruments yielded a CV > 10.0 % (CVpooled = 7.7 %), whereas 15 of 41 Roche instruments yielded CVs > 10.0 % at the female URL of 9 ng/L used worldwide (6 cobas e411, 1 cobas e601, 4 cobas e602, and 4 cobas e801) (CVpooled = 11.7 %). Four Roche instruments also yielded CVs > 10.0 % near the female URL of 14 ng/L used in the United States (CVpooled = 8.5 %). ConclusionsThe number of instruments achieving a CV ≤ 10.0 % at the female 99th-percentile URL varies by manufacturer and by instrument. Monitoring assay precision at the female URL is necessary for some assays to ensure optimal use of this threshold in clinical practice.

Could Computed Tomography Coronary Angiography Replace Invasive Coronary Angiography as a First-Line Diagnostic Investigation in Suspected Acute Coronary Syndromes? A Decision-Analytic Model

The implementation of high-sensitivity cardiac troponin (hs-cTn) assays into clinical practice has resulted in the identification of a novel cohort of patients with modestly increased troponin concentrations. Subsequent increases in rates of coronary angiography have been observed, without significant increases in rates of coronary revascularisation. Computed tomography coronary angiography (CTCA) is a non-invasive investigation that offers the opportunity to decouple investigation from the impetus to revascularise, and may provide an alternative, more risk-appropriate initial investigative strategy for the cohort with low to moderate hs-cTn increases. This analysis seeks to define the threshold of pre-test probability of coronary revascularisation in patients with suspected acute coronary syndrome at which a strategy of initial CTCA is safe and a more cost-effective approach than standard invasive coronary angiography (ICA). A cost-benefit evaluation was conducted using a decision-analytic model. The primary outcome measure was the incremental cost-effectiveness ratio (ICER) of CTCA in comparison with ICA as an initial diagnostic investigation for patients with hs-cTnT levels between 5 and 100 ng/L. Secondary outcome measures of costs, patient outcomes, and quality-adjusted life years were analysed. Median base case ICER over 1,000 trials was $17,163 AUD but demonstrated large variability. Sensitivity analysis demonstrated that CTCA was cost-effective until the probability of requiring revascularisation was ∼60%, beyond which point CTCA was associated with higher costs and poorer outcomes than ICA. Computed tomography coronary angiography may be a cost-effective first-line investigation for patients with moderate hs-cTnT rises until/up to a 60% pre-test probability for receiving coronary revascularisation. To objectively assess the optimal circumstances of cost-effectiveness, prospective evaluation incorporating the estimated probability of revascularisation will be required.

To rule-in, or not to falsely rule-out, that is the question: evaluation of hs-cTnT EQA performance in light of the ESC-2020 guideline.

To accurately evaluate non-ST-elevated acute cardiac syndrome (NSTE-ACS), the quality of high-sensitive cardiac troponin (hs-cTn) assays is of vital importance. The 2020 revision of the NSTE-ACS guideline includes clinical decision-limits (CDL's) to both rule-in and rule-out NSTE-ACS for most commercially available platforms, providing both 0/1 h and 0/2 h delta limits. Our study evaluated whether laboratories are able to meet the analytical performance specifications for imprecision (APS) for hs-cTnT. Results from external quality assurance (EQA) in commutable samples were used to evaluate the current and historic performance of analyzers. The performance of analyzers that either passed or failed to comply with 0/1 h-APS were used on a real-world dataset of first hs-cTnT-values to simulate 10.000 samples of t=0, t=1 and t=2 h values with multiple delta's for all relevant CDL's. We compared the simulated values to the input values to obtain the percentage of aberrant results simulated. The majority of analyzers complies with APS for rule-in in 2022 (0/1 h: 90.4 % and 0/2 h: 100 %), compliance for the 0/1 h rule-out is still far from optimal (0/1 h: 30.7 %, 0/2 h: 75.4 %), with improving compliance over the past years (rule-in p=<0.0001, rule-out p=0.011, χ2). Whilst 0/1 h-APS-passing analyzers have a minute risk to falsely rule-out patients whom should be ruled-in (0.0001 %), failing performance increases this risk to 2.1 % upon using 0/1 h CDL's. Here, adopting 0/2 h CDL's is favorable (0.01 %). Laboratories that fail to meet hs-cTnT 0/1 h-APS should improve their performance to the required and achievable level. Until performance is reached clinics should adopt the 0/2 h CDL's.

Four high sensitivity troponin assays and mortality in US adults with cardiovascular disease: The national health and nutrition examination survey, 1999–2004

ObjectiveHigh sensitivity cardiac troponin (hs-cTn) may be useful to monitor residual risk in secondary prevention. Our objective was to study the correlations and comparative associations with mortality of four hs-cTn assays in US adults with known cardiovascular disease (CVD). MethodsWe studied 1,211 adults with a history of CVD who participated in the National Health and Nutrition Examination Survey (NHANES) 1999–2004. Using stored samples, we measured hs-cTnT (Roche) and three hs-cTnI assays (Abbott, Siemens, and Ortho). Outcomes were all-cause and CVD mortality, with follow-up through December 31, 2019. ResultsMean age was 64 years, 48 % were female, and 80 % identified as non-Hispanic White. Pearson's correlation coefficients between hs-cTn assays ranged from 0.67 to 0.85. There were 848 deaths (365 from CVD). Among adults with a history of prior non-fatal CVD, each hs-cTn assay (log-transformed, per 1-SD) was independently associated with CVD death (HRs ranging from 1.55 to 2.16 per 1-SD, all p-values <0.05) and with all-cause death (HRs ranging from 1.31 to 1.62 per 1-SD, all p-values <0.05). Associations of hs-cTnT and all-cause and CVD death remained significant after adjusting for hs-cTnI (and vice versa). Associations between hs-cTnI and CVD death remained significant after mutually adjusting for other individual hs-cTnI assays: e.g., HR 2.21 (95 % CI 1.60, 3.05) for Ortho (hs-cTnI) after adjustment for Siemens (hs-cTnI) and HR 1.81 (95 % CI 1.35, 2.43) for Ortho (hs-cTnI) after adjustment for Abbott (hs-cTnI). ConclusionIn US adults with a history of CVD, we found modest correlations between 4 hs-cTn assays. All assays were associated with all-cause and CVD mortality. The hs-cTnT assay was associated with mortality independent of the hs-cTnI assays. Hs-cTnI assays also appeared to be independent of each other. Thus, hs-cTn assays may provide distinct information for residual risk in secondary prevention adults.

Knowledge of the high-sensitivity cardiac troponin assay among medical officers in Gampaha District, Sri Lanka

Introduction: The high-sensitivity cardiac troponin (hs-cTn) assay is a crucial diagnostic test that is obligatory in the triage of patients presenting with chest pain. It is essential for medical officers to have adequate knowledge regarding the procedures for testing and the interpretation of test outcomes to deliver optimal healthcare for patients. It has been observed that medical officers are lacking in awareness regarding this testing method, resulting in a greater likelihood of errors in testing and interpretation. This study aims to evaluate the level of understanding among medical officers regarding the hs-cTn assay in relation to the most recent European Society of Cardiology guideline released in 2020.Methodology: We conducted a cross-sectional study at two government hospitals in Gampaha District in June 2022. A self-administered e-questionnaire was used to assess knowledge regarding hs-cTn. Knowledge was measured by calculating a cumulative score for the answers to a questionnaire and categorised into good or poor knowledge. A score less than 60% was categorized as poor and vice versa. Descriptive statistics were used to summarize the data.Results: Of the 227 medical officers, only 14.5% (n=33) had good knowledge of the analytical component while 41.9% (n=95) had good knowledge on the clinical component. A score ≥60% on the analytical component knowledge was significantly associated with designation being a senior registrar or consultant (p&lt;0.001), postgraduate enrolment (p&lt;0.001), participation in continuous professional development programmes (p&lt;0.001), and employment in a teaching hospital (p=0.025), but not with age (p=0.066) or private practice (p=0.118). Clinical component knowledge score ≥60% was significantly associated with age between 25 and 35 years (p=0.006), designation being a consultant (p&lt;0.001), postgraduate enrolment (p&lt;0.001), participation in continuous professional development programs (p&lt;0.001), and employment in a teaching hospital(p=0.001) but not with doing private practice (p=0.170).Conclusions: In Sri Lanka, medical officers’ general knowledge on the hs-cTn assay seems lacking. There is a need for continuous training to improve knowledge on hs-cTn testing among medical officers.

Optimizing the Clinical Use of High-Sensitivity Troponin Assays: A Review.

Ischemic heart diseases (IHDs) remain a global health concern. Many IHD cases go undiagnosed due to challenges in the initial diagnostic process, particularly in cases of acute myocardial infarction (AMI). High-sensitivity cardiac troponin (hs-cTn) assays have revolutionized myocardial injury assessment, but variations in diagnostic cut-off values and population differences have raised challenges. This review addresses essential laboratory and clinical considerations for hs-cTn assays. Laboratory guidelines discuss the importance of establishing standardized 99th-percentile upper reference limits (URLs) considering factors such as age, sex, health status, and analytical precision. The reference population should exclude individuals with comorbidities like diabetes and renal disease, and rigorous selection is crucial. Some clinical guidelines emphasize the significance of sex-specific URL limits while others do not. They highlight the use of serial troponin assays for AMI diagnosis. In addition, timely reporting of accurate hs-cTn results is essential for effective clinical use. This review aims to provide a clearer understanding among laboratory professionals and clinicians on how to optimize the use of hs-cTn assays in clinical settings in order to ensure accurate AMI diagnosis and thus improve patient care and outcomes.

Prognostic significance of chronic myocardial injury diagnosed by three different cardiac troponin assays in patients admitted with suspected acute coronary syndrome.

Chronic myocardial injury (CMI) is defined as stable concentrations of cardiac troponin T or I (cTnT or cTnI) above the assay-specific 99th percentile upper reference limit (URL) and signals poor outcome. The clinical implications of diagnosing CMI are unclear. We aimed to assess prevalence and association of CMI with long-term prognosis using three different high-sensitivity cTn (hs-cTn) assays. A total of 1,292 hospitalized patients without acute myocardial injury had cTn concentrations quantified by hs-cTn assays by Roche Diagnostics, Abbott Diagnostics and Siemens Healthineers. The median follow-up time was 4.1 years. The prevalence of CMI and hazard ratios for mortality and cardiovascular (CV) events were calculated based on the URL provided by the manufacturers and compared to the prognostic accuracy when lower percentiles of cTn (97.5, 95 or 90), limit of detection or the estimated bioequivalent concentrations between assays were used as cutoff values. There was no major difference in prognostic accuracy between cTnT and cTnI analyzed as continuous variables. The correlation between cTnT and cTnI was high (r=0.724-0.785), but the cTnT assay diagnosed 3.9-4.5 times more patients with having CMI based on the sex-specific URLs (TnT, n=207; TnI Abbott, n=46, TnI Siemens, n=53) and had higher clinical sensitivity and AUC at the URL. The prevalence of CMI is highly assay-dependent. cTnT and cTnI have similar prognostic accuracy for mortality or CV events when measured as continuous variables. However, a CMI diagnosis according to cTnT has higher prognostic accuracy compared to a CMI diagnosis according to cTnI.