cTnT Assay Research Articles

Cardiac troponin fragmentation in marathon runners. The MaraCat2 study

Abstract Background Cardiac troponins(cTn) are in a key role in the diagnosis of acute myocardial infarction (MI). Minor cardiac troponin elevations are also common after strenuous exercise, while limited evidence suggests this elevation consists mostly of smaller cTn fragments. Purpose We aimed to determine if our novel cardiac troponin assay, measuring long molecular forms of cardiac troponin (long cTnT) can differentiate cardiac troponin elevation associated with strenuous exercise from that seen in MI. Methods In a Proof-of-Principle study, we developed a simple time-resolved immunofluorometric assay based on europium chelate labels for the measurement of long cardiac troponin T molecules, which showed high accuracy in discriminating between cTn elevations in MI and end-stage renal failure. In the present study, we compared the characteristics of cTn release after a marathon race and Type 1 MI using an improved version of the long troponin test and a commercially available cTnT test. Troponin composition was analyzed in heparin plasma samples taken from 45 runners <1h after marathon race and from 45 patients with Type 1 MI. The concentration of long cTnT was measured with a novel immunofluorometric assay, total cTnT was measured with a commercial high-sensitivity cTnT assay, and the ratio of long to total cTnT (troponin ratio) was determined. Results Conventional cTnT exceeded the upper reference limit in 37 (82%) runners with a median concentration of 25.0 (IQR 16-36)ng/l. Median long cTnT concentration was 4.1 (IQR 2.4-5.8)ng/l. The median total and long cTnT concentration and the troponin ratio were higher in patients with MI than in marathon runners (p<0.001). Troponin ratio decreased (r=-0.497, p<0.001) in marathon runners and increased (r=0.466, p=0.001) in patients with MI with increasing troponin release (Figure 1). In the receiver operating characteristics curve analyses of all patients with cTnT release >14ng/l, long cTnT showed good predictive power with area under curve 0.969 (CI95% 0.939-1.000) in discriminating marathon runners from MI patients. Conclusions Our novel highly sensitive long cTnT immunoassay shows that the troponin release after strenuous exercise is composed mainly of smaller troponin fragments. Our test could be useful in separating benign cTnT elevations caused by exercise from those of acute MI.

Novel troponin fragmentation assay to discriminate between Takotsubo syndrome and acute myocardial infarction.

Cardiac troponin levels are elevated in Takotsubo syndrome (TTS) with significant overlap to acute myocardial infarction (MI). Long and intact cardiac troponin T (cTnT) forms are typical for MI. This study sought to assess whether the fragmentation composition of cTnT release in TTS differs from MI. The concentration of long molecular forms of cTnT (long cTnT) was measured with a novel upconversion luminescence immunoassay and total cTnT with a commercial high-sensitivity cTnT assay in 24 TTS patients and in 84 Type 1 MI patients. The ratio of long to total cTnT (troponin ratio) was determined as a measure of cTnT fragmentation. Troponin ratio was lower in TTS patients 0.13 [0.10-0.20] vs. 0.62 [0.29-0.96], p<0.001). In the ROC curve analyses, troponin ratio showed a better predictive power than total cTnT in discriminating TTS and MI patients (AUC 0.869 [CI95% 0.789-0.948)] vs. 0.766 [CI95% 0.677-0.855], p=0.047). When restricting the analysis to patients with total cTnT below 1200 ng/L (maximal value in TTS patients), the respective AUC values for total cTnT and troponin ratio were 0.599 (CI 95% 0.465-0.732) and 0.816 (CI95% 0.712-0.921), p =0.003). At a cutoff point of 0.12, troponin ratio correctly identified 95% of MI patients and 50% of TTS patients. In contrast to Type 1 MI, only a small fraction of circulating cTnT in TTS exists in intact or long molecular forms. This clear difference in troponin composition could be of diagnostic value when evaluating patients with cTnT elevations and suspicion of TTS. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04465591.

A-023 Early Concentrations of Long Cardiac Troponin T Forms in Myocardial Infarction Patients

Abstract Background Long forms of cardiac troponin T (cTnT) represent a new promising biomarker for more specific diagnostics of myocardial infarction (MI). We studied for the first time the concentrations of long cTnT forms in a panel including very early samples of type 1 MI patients. Methods Heparin plasma samples were drawn from 94 type 1 MI patients 0.4-24 h after the symptom onset and analyzed with Roche hs-cTnT assay and with our novel highly sensitive upconversion luminescence-based long cTnT immunoassay. The long cTnT assay detects all cTnT forms not cleaved at the major C-terminal cleavage site at cTnT amino acid residues 189-220 while the Roche hs-cTnT assay detects all short and long cTnT forms containing the stable central part of cTnT. Troponin ratio, reflecting the fraction of the long cTnT forms, was calculated by dividing the long cTnT result by the Roche hs-cTnT result. Results The long cTnT and Roche hs-cTnT concentrations varied highly (median 107 [25th-75th percentile 20-1195] ng/L and 277 [62-1422] ng/L, respectively) and correlated significantly with each other (r=0.881, p&amp;lt;0.001). Neither had a significant correlation with time from symptom onset. Troponin ratio was highly variable especially at the first hours, but there was a clear decreasing trend in variability later (Figure). Troponin ratio showed significant negative correlation with time (r=-0.284, p=0.005) and the correlation became stronger with longer delays between symptom onset and sampling (6-24 h, r=-0.422, p&amp;lt;0.001). Conclusions A significant portion of circulating cTnT is in long forms in type 1 acute MI patients at early stage. The fraction of long cTnT forms is highly variable in the very early hours after MI, but shows a clear decreasing trend after 6 hours from the pain onset.

Half-Life and Clearance of Cardiac Troponin I and Troponin T in Humans.

Cardiac troponin (cTn) is key in diagnosing myocardial infarction (MI). After MI, the clinically observed half-life of cTn has been reported to be 7 to 20 hours, but this estimate reflects the combined elimination and simultaneous release of cTn from cardiomyocytes. More precise timing of myocardial injuries necessitates separation of these 2 components. We used a novel method for determination of isolated cTn elimination kinetics in humans. Patients with MI were included within 24 hours after revascularization and underwent plasmapheresis to obtain plasma with a high cTn concentration. After at least 3 weeks, patients returned for an autologous plasma retransfusion followed by blood sampling for 8 hours. cTn was measured with 5 different high-sensitivity cTn assays. Of 25 included patients, 20 participants (mean age, 64.5 years; SD, 8.2 years; 4 women [20%]) received a retransfusion after a median of 5.8 weeks (interquartile range, 5.0-6.9 weeks) after MI. After retransfusion of a median of 620 mL (range, 180-679 mL) autologous plasma, the concentration of cTn in participants' blood increased 4 to 445 times above the upper reference level of the 5 high-sensitivity cTn assays. The median elimination half-life ranged from 134.1 minutes (95% CI, 117.8-168.0) for the Elecsys high-sensitivity cTnT assay to 239.7 minutes (95% CI, 153.7-295.1) for the Vitros high-sensitivity cTnI assay. The median clearance of cTnI ranged from 40.3 mL/min (95% CI, 32.0-44.9) to 52.7 mL/min (95% CI, 42.2-57.8). The clearance of cTnT was 77.0 mL/min (95% CI, 45.2-95.0). This novel method showed that the elimination half-life of cTnI and cTnT was 5 to 16 hours shorter than previously reported. This indicates a considerably longer duration of cardiomyocyte cTn release after MI than previously thought. Improved knowledge of timing of myocardial injury may call for changes in the management of MI and other disorders with myocardial injury.

Highly Sensitive Immunoassay for Long Forms of Cardiac Troponin T Using Upconversion Luminescence.

Long cardiac troponin T (cTnT) has been proposed to be a promising and more specific biomarker of acute myocardial infarction (AMI). As it represents a subfraction of circulating cTnT, detection of very low concentrations is a requirement. The aim of this study was to develop a novel, highly sensitive immunoassay for long cTnT. A two-step sandwich-type immunoassay for long cTnT was developed, utilizing upconverting nanoparticles (UCNPs) as reporters. The limits of detection and quantitation were determined for the assay. Linearity and matrix effects were evaluated. Performance with clinical samples was assessed with samples from patients with non-ST elevation myocardial infarction (NSTEMI, n = 30) and end-stage renal disease (ESRD, n = 37) and compared to a previously developed time-resolved fluorescence (TRF)-based long cTnT assay and a commercial high-sensitivity cTnT assay. The novel assay reached a 28-fold lower limit of detection (0.40 ng/L) and 14-fold lower limit of quantitation (1.79 ng/L) than the previously developed TRF long cTnT assay. Li-heparin and EDTA plasma, but not serum, were found to be suitable sample matrixes for the assay. In a receiver operating characteristics curve analysis, the troponin ratio (long/total cTnT) determined with the novel assay showed excellent discrimination between NSTEMI and ESRD with an area under the curve of 0.986 (95% CI, 0.967-1.000). By utilizing upconversion luminescence technology, we developed a highly sensitive long cTnT assay. This novel assay can be a valuable tool for investigating the full potential of long cTnT as a biomarker for AMI. ClinicalTrials.gov Registration Number: NCT04465591.

AlphaLISA-Based Immunoassay for Detection of Troponin T in Serum of Patients with Acute Myocardial Infarction.

Survival and prognosis of patients with acute myocardial infarction (AMI) are highly dependent on rapid and accurate diagnosis of myocardial damage. Troponin T is the primary diagnostic biomarker and is widely used in clinical practice. Amplified luminescent proximity homogeneous assay (AlphaLISA) may provide a solution to rapidly detect a small amount of analyte through molecular interactions between special luminescent donor beads and acceptor bead. Here, a double-antibody sandwich assay was introduced into AlphaLISA for rapid detection for early diagnosis of AMI and disease staging evaluation. The performance of the assay was evaluated. The study found that the cTnT assay has a linear range of 48.66 to 20,000 ng/L with a limit of detection of 48.66 ng/L. In addition, the assay showed no cross-reactivity with other classic biomarkers of myocardial infarction and was highly reproducible with intra- and inter-batch coefficients of variation of less than 10%, notably, only 3min was taken, which is particularly suitable for clinical diagnosis. These results suggest that our method can be conveniently applied in the clinic to determine the severity of the patient's condition.

Characteristics and outcomes of patients with symptomatic chronic myocardial injury in a Tanzanian emergency department: A prospective observational study.

Chronic myocardial injury is a condition defined by stably elevated cardiac biomarkers without acute myocardial ischemia. Although studies from high-income countries have reported that chronic myocardial injury predicts adverse prognosis, there are no published data about the condition in sub-Saharan Africa. Between November 2020 and January 2023, adult patients with chest pain or shortness of breath were recruited from an emergency department in Moshi, Tanzania. Medical history and point-of-care troponin T (cTnT) assays were obtained from participants; those whose initial and three-hour repeat cTnT values were abnormally elevated but within 11% of each other were defined as having chronic myocardial injury. Mortality was assessed thirty days following enrollment. Of 568 enrolled participants, 81 (14.3%) had chronic myocardial injury, 73 (12.9%) had acute myocardial injury, and 412 (72.5%) had undetectable cTnT values. Of participants with chronic myocardial injury, the mean (± sd) age was 61.5 (± 17.2) years, and the most common comorbidities were CKD (n = 65, 80%) and hypertension (n = 60, 74%). After adjusting for CKD, thirty-day mortality rates (38% vs. 36%, aOR 1.03, 95% CI: 0.52-2.03, p = 0.931) were similar between participants with chronic myocardial injury and those with acute myocardial injury, but significantly greater (38% vs. 13.6%, aOR 3.63, 95% CI: 1.98-6.65, p<0.001) among participants with chronic myocardial injury than those with undetectable cTnT values. In Tanzania, chronic myocardial injury is a poor prognostic indicator associated with high risk of short-term mortality. Clinicians practicing in this region should triage patients with stably elevated cTn levels in light of their increased risk.

The specificity of cardiac troponin elevations for myocardial infarction declines with age

Abstract Background Cardiac troponin T (cTnT) and I (cTnI) are the gold standard biomarkers of myocardial infarction (MI). Studies have shown that the concentration of cTn increases with age among healthy individuals, but the clinical impact of this is unclear. Further, there seem to be a difference in the increases in cTnI and in cTnT - the latter being more sensitive to increasing age. Purpose To investigate the impact of age on the diagnostic ability of cTnT and cTnI for myocardial infarction. Methods This nationwide cohort study includes patients admitted with cTn measurements from 2009-2022 using one of five cTn assays: Roche high-sensitivity cTnT (hs-cTnT), Abbott Alinity high sensitivity cTnI (hs-cTnI), Siemens Vista Hs-cTnI, Siemens Atellica hs-cTnI and Beckman-Coulter hs-cTnI. We selected the peak concentration of cTn on admission and grouped patients into those who had cTnI and those who had cTnT measured which were divided into age groups of &amp;lt;40 years, 40-50 years, 50-60 years, 60-70 years, 70-80 years, 80-90 years and &amp;gt;90 years. The primary outcome was a diagnosis of MI during admission. Receiver operating characteristics (ROC) were used for the concentration of cTn normalized to the assays 99th percentile, and we explored the specificity of elevations of each assay above the 99th percentile. Results A total of 350,428 patients were included in this study with a median age of 67 years (IQR 52-77); 188,382 (54%) were males and 48,262 (14%) had a history of ischemic heart disease prior to the admission. When grouping for type of cTn used, more patients were treated when hs-cTnT (240,660, 69%) was used compared with hs-cTnI (109,768, 31%). The patient treated using hs-cTnT were slightly older than patients treated with hs-cTnI, 67 years (IQR 53-77) vs 65 years (53-77) p&amp;lt;0.001. During the admission 29,023 patients (8.3%) had a MI. Figure 1 panel A shows the ROC curve of hs-cTnT and hs-cTnI for each age group. Both biomarkers showed a decline in the area under the curve (AUC) with increasing age. Figure 1 panel B shows the AUC for each age group. Hs-cTnI had a higher AUC for all age groups and seemed to decrease less with age. Figure 2 shows the specificity for the 99th percentile of each assay for the age groups. There were substantial differences in the specificity at the 99th percentile between cTn assays, with the cTnT assay being the least specific for all age groups, while the two Siemens assays had the highest specificity. An elevation above the 99th percentile of the cTnT assay had a specificity of 3% in the group of patients &amp;gt;90 years old. Conclusion The specificity of elevation of cTn for MI declined with increasing age for all assays. This decline seemed to be largest for the cTnT assay were an elevation above the 99th percentile among patients &amp;gt;90 years old had a specificity of 3% for MI.Figure 1Figure 2

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.

Clinical performance of 0/1 h cardiac troponin algorithm for diagnosing non–STEMI in an emergency setting

BackgroundNon-ST-segment elevation myocardial infarction (NSTEMI) is a common form of acute myocardial infarction and rapid and accurate diagnosis is crucial for timely treatment. Current guidelines recommend using high-sensitivity cardiac troponin (hs-cTn) assays to determine circulating cTnI or cTnT levels. While the accuracy of the 0 h/1 h algorithm for diagnosing NSTEMI in different regions and patient populations remains controversial. Additionally, point-of-care testing (POCT) cTn assays have the potential to provide troponin readings to physicians within 15 min, but their accuracy in diagnosing NSTEMI in the emergency department (ED) requires further investigation. MethodsA single-center prospective observational cohort study was conducted at Shaanxi Provincial People's Hospital to assess the analytical and diagnostic performance of the laboratory-based Roche Modular E170 hs-cTnT using the 0 h/1 h algorithm with Radiometer AQT90-flex POCT cTnT assay in undifferentiated chest pain patients presenting to the ED. Whole-blood samples were collected and hs-cTnT and POCT cTnI were measured simultaneously at baseline and after 1 h. ResultsThe study results showed that the POCT cTnT assay using the 0 h/1 h algorithm had comparable diagnostic accuracy to the laboratory-based Roche Modular E170 hs-cTnT assay in diagnosing NSTEMI in patients with chest pain. ConclusionThe laboratory-based Roche Modular E170 hs-cTnT using the 0 h/1 h algorithm is reliable and accurate method for diagnosing NSTEMI in undifferentiated chest pain patients presenting to the ED. POCT cTnT assay has comparable diagnostic accuracy to the hs-cTnT assay and its rapid turnaround time makes it a valuable tool in expediting the diagnostic workup of chest pain patients.

Cardiomuscular Biomarkers in the Diagnosis and Prognostication of Immune Checkpoint Inhibitor Myocarditis.

Immune checkpoint inhibitors (ICIs) are approved for multiple cancers but can result in ICI-associated myocarditis, an infrequent but life-threatening condition. Elevations in cardiac biomarkers, specifically troponin-I (cTnI), troponin-T (cTnT), and creatine kinase (CK), are used for diagnosis. However, the association between temporal elevations of these biomarkers with disease trajectory and outcomes has not been established. We analyzed the diagnostic accuracy and prognostic performances of cTnI, cTnT, and CK in patients with ICI myocarditis (n=60) through 1-year follow-up in 2 cardio-oncology units (APHP Sorbonne, Paris, France and Heidelberg, Germany). A total of 1751 (1 cTnT assay type), 920 (4 cTnI assay types), and 1191 CK sampling time points were available. Major adverse cardiomyotoxic events (MACE) were defined as heart failure, ventricular arrhythmia, atrioventricular or sinus block requiring pacemaker, respiratory muscle failure requiring mechanical ventilation, and sudden cardiac death. Diagnostic performance of cTnI and cTnT was also assessed in an international ICI myocarditis registry. Within 72 hours of admission, cTnT, cTnI, and CK were increased compared with upper reference limits (URLs) in 56 of 57 (98%), 37 of 42 ([88%] P=0.03 versus cTnT), and 43 of 57 ([75%] P<0.001 versus cTnT), respectively. This increased rate of positivity for cTnT (93%) versus cTnI ([64%] P<0.001) on admission was confirmed in 87 independent cases from an international registry. In the Franco-German cohort, 24 of 60 (40%) patients developed ≥1 MACE (total, 52; median time to first MACE, 5 [interquartile range, 2-16] days). The highest value of cTnT:URL within the first 72 hours of admission performed best in terms of association with MACE within 90 days (area under the curve, 0.84) than CK:URL (area under the curve, 0.70). A cTnT:URL ≥32 within 72 hours of admission was the best cut-off associated with MACE within 90 days (hazard ratio, 11.1 [95% CI, 3.2-38.0]; P<0.001), after adjustment for age and sex. cTnT was increased in all patients within 72 hours of the first MACE (23 of 23 [100%]), whereas cTnI and CK values were less than the URL in 2 of 19 (11%) and 6 of 22 (27%) of patients (P<0.001), respectively. cTnT is associated with MACE and is sensitive for diagnosis and surveillance in patients with ICI myocarditis. A cTnT:URL ratio <32 within 72 hours of diagnosis is associated with a subgroup at low risk for MACE. Potential differences in diagnostic and prognostic performances between cTnT and cTnI as a function of the assays used deserve further evaluation in ICI myocarditis.

Correlation of serial high-sensitivity cardiac troponin t values to infarct mass determined by cardiac magnetic resonance imaging

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction The extent of myocardial injury is strongly associated with adverse outcome after acute myocardial infarction (AMI). Contrast-enhanced magnetic resonance imaging (CE-MRI) is the preferred technique for myocardial imaging. Its use in daily clinical practise, however, is restricted due to limited availability and high costs. High-sensitivity cardiac troponin T (hs-cTnT) correlates well with the extent of myocardial injury and may therefore be a cost effective and widely available surrogate for the estimation of infarct size. Purpose To validate correlations between CE-MRI infarct mass and hs-cTnT values at different time points in patients with confirmed AMI. Methods Patients presenting with AMI and with available CE-MRI between January 1, 2018 and December 31, 2020 were included. Correlation coefficients between hs-cTnT on admission, after 24h, 48h, 72h, 96h and peak hs-cTnT values and CE-MRI infarct mass were calculated. Correlations between hs-cTnT and CE-MRI infarct mass were compared to those of a 3rd generation cTnT assay from a previously published study of our group. Results 137 patients were included for the present analysis. Median CE-MRI infarct mass was 12,5 g (95%CI: 9.8-16.2 g). Hs-cTnT values and infarct mass correlated well at all time points including admission (r=0.474, [95%CI: 0.331-0.560], p&amp;lt;0.0001), 24h (r=0.508, [95%CI: 0.370-0.625], p&amp;lt;0.0001), 48h (r=0.547, [95%CI: 0.404-0.664], p&amp;lt;0.0001), 72h (r=0.489, [95%CI: 0.320-0.628], p&amp;lt;0.0001), 96h (r=0.509, [95%CI: 0.330-0.653], p&amp;lt;0.001) including peak hs-cTnT values (r=0.547, [95%CI: 0.416-0.656], p&amp;lt;0.0001) and maximum absolute delta changes within 96h (r=0.507, [95%CI: 0.369-0.622], p&amp;lt;0.001). Correlations of the 3rd generation assay could be confirmed for hs-cTnT at all time points. A superior correlation with CE-MRI infarct mass was observed for hs-cTnT values on admission. Conclusions Hs-cTnT values at different time points correlate well with CE-MRI infarct mass. Correlations of admission hs-cTnT values are superior to those of a 3rd generation assay.

Frequencies of Anti-Troponin I vs Anti-Troponin T Autoantibodies and Degrees of Interference on Troponin Assays.

Presence of autoantibodies against troponin I (cTnI) or T (cTnT) has been reported to interfere with troponin assays. However, the extent of the interference with the measurement has not been explored sufficiently. The aims of this study were to examine the frequencies of autoantibodies against troponin I and troponin T and how much these antibodies would affect the measurement. The study comprised 52 subjects who visited Hokkaido University Hospital with suspected ischemic heart diseases. To evaluate the presence of autoantibodies, we calculated the recoveries of cTnI or cTnT after immunoglobulin G depletion, and the distributions of peaks reactive with cTnI or cTnT by high-performance liquid chromatography were examined. Autoantibodies against cTnI and cTnT were identified in 8 subjects (15.4%) and 1 subject (1.9%), respectively. Although the greatest difference between cTnI and cTnT was 32-fold, the distributions of cTnI-to-cTnT ratios in groups with and without anti-cTnI were not statistically different. Autoantibodies against cTnI were more frequent by several fold than those against cTnT. Their presence did not significantly expand the discrepancy between cTnI and cTnT assays.

The difference in prognostic value between high-sensitive cardiac troponin T and I for long-term major adverse cardiovascular events in hemodialysis patients

Abstract Background Previous studies using conventional cardiac troponin (cTn) assays have shown conflicting results in the predictability of major adverse cardiovascular events (MACEs) in hemodialysis patients. Objective We aimed to evaluate the prognostic values of high-sensitivity cTnT (hs-cTnT) and hs-cTnI assays for long-term MACEs in asymptomatic chronic hemodialysis patients. Methods A total of 198 asymptomatic patients undergoing regular hemodialysis (mean age 62.4±14.8 years) were enrolled in this study. Pre-dialysis hs-cTnT and hs-cTnI levels were measured at the time of study entry. The primary outcome was the prognostic value of hs-cTnT and hs-cTnI for all-cause mortality. Results At baseline, the median values of hs-cTnT and hs-cTnI were 61.1 ng/L (IQR 36.6–102.0 ng/L) and 18.4 ng/L (IQR 9.5–36.6 ng/L), respectively. During a median follow-up period of 408 days (IQR 343–415 days), 35 (17.7%) patients developed MACEs, and 20 (10.1%) patients died. The patients with hs-cTnT level above the highest quartile (&amp;gt;102 ng/L) had an increased risk of all-cause mortality (HR 3.34; 95% CI 1.39–8.04, P=0.007) and MACEs (HR 1.99; 95% CI 1.00–3.96, P=0.049), compared to those with lower hs-cTnT level. The association between hs-cTnT and all-cause mortality remained significant after adjustment for age, gender, and comorbidities. On the contrary, hs-cTnI level was not associated with long-term all-cause mortality and MACEs. Conclusions We demonstrated that level of hs-cTnT, but not hs-cTnI, was associated with higher risk of long-term mortality and MACEs. As a result, hs-cTnT may be a better prognostic factor than hs-cTnI in this population. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Faculty of Medicine Endowment Fund for medical research

Correlation of serial high-sensitivity cardiac Troponin T values to infarct mass determined by cardiac magnetic resonance imaging: a validation study.

To validate correlations between contrast-enhanced magnetic resonance imaging (CE-MRI) infarct mass and high-sensitivity cardiac Troponin T (hs-cTnT) values at different time points in patients with confirmed acute myocardial infarction (AMI). Patients presenting with AMI and with available CE-MRI between 1 January 2018 and 31 December 2020 were included. Correlation coefficients between hs-cTnT on admission, after 24, 48, 72, and 96 h, and peak hs-cTnT values and CE-MRI infarct mass were calculated. Correlations between hs-cTnT and CE-MRI infarct mass were compared with those of a third generation cTnT assay from a previously published study of our group. A total of 137 patients were included for the present analysis. Median CE-MRI infarct mass was 12,5 g [95% confidence interval (CI): 9.8-16.2 g]. Hs-cTnT values and infarct mass correlated well at all time points including admission (r = 0.474, 95% CI: 0.331-0.560, P < 0.0001), 24 h (r = 0.508, 95% CI: 0.370-0.625, P < 0.0001), 48 h (r = 0.547, 95% CI: 0.404-0.664, P < 0.0001), 72 h (r = 0.489, 95% CI: 0.320-0.628, P < 0.0001), 96 h (r = 0.509, 95% CI: 0.330-0.653, P < 0.001) including peak hs-cTnT values (r = 0.547, 95% CI: 0.416-0.656, P < 0.0001), and maximum absolute delta changes within 96 h (r = 0.507, 95% CI: 0.369-0.622, P < 0.001). Correlations of the third generation assay could be confirmed for hs-cTnT at all time points. A superior correlation with CE-MRI infarct mass was observed for hs-cTnT values on admission. Hs-cTnT values at different time points correlate well with CE-MRI infarct mass. Correlations of admission hs-cTnT values are superior to those of a third generation assay.

Age-specific reference values for the 5th generation cardiac troponin T assay in Chinese children.

The clinical use of the cardiac troponin T (cTnT) assay was limited to the adult population in the diagnosis and prognosis of myocardial injury. However, emerging studies indicated its significant value in the assessment of pediatric cardiology, and it has been routinely measured in most hospitals. Our study investigated the normative values of cTnT in Chinese children and reported the age-specific 99th percentile cut-off for them.A total of 1280 apparently healthy Chinese children were enrolled in our study. Serum levels of cTnT were analyzed on the Roche Elecsys Troponin T Gen 5 STAT assay. According to the Clinical and Laboratory Standards Institute C28-A3 guideline, the 99th percentile upper reference limits (URLs) with 90% confidence intervals (CIs) were calculated in different age subgroups.The 99th percentile URL was 38 (90%CI: 37.0-51.0) ng/L for 1 to <4months old, 26 (90%CI: 25.2-28.5) ng/L for 4 to ≤ 12months old, and 12 (90%CI: 11.1-12.9) ng/L for 1 to 18 years old, respectively. For subjects aged from 1 to 18years, boys had slightly higher cTnT levels than girls (P = .003), while our assay could not measure low cTnT concentrations (≥the limit of detection) in 50% girls.Our study provided age-specific URLs of cTnT for Chinese children, with the 5th generation cTnT assay from Roche Diagnostics. It had significant clinical implications in the interpretation and use of test results for pediatric cardiology.

High-sensitivity troponin T and I in patients suspected of acute myocardial infarction

Measurement of cardiac troponin (cTn) is the cornerstone in the diagnosis of myocardial infarction (MI). Potential disparities in concentrations of cTn, trajectories and mortality, following initial measurement warrant further investigation. Such data may guide clinicians treating patients suspected of MI. Plasma concentrations of cTnT and cTnI were measured in 503 consecutive patients at Aarhus University Hospital between June 13th and June 27th, 2019. cTnT was measured with the Roche cobas® E602 hs-cTnT assay, while cTnI was measured with the Siemens ADVIA Centaur® XPT hs-cTnI assay. Analytical agreement was determined based on assay-specific 99th percentiles. Medical records were reviewed for adjudication of the MI diagnosis. MI was the final diagnosis in 65 patients (12.9%) and the analytical agreement between cTnT and cTnI assays was 95.2%. For patients diagnosed with MI, cTnI reached higher peak concentrations in shorter time, compared to cTnT. All-cause mortality risk increased with increasing levels of both biomarkers. In this study, the analytical agreement of two cTn assays was high. However, some disparities in troponin trajectories were observed.

Implementation of more sensitive cardiac troponin T assay in a state-wide health service

AimsExplore the impact of deploying high-sensitivity (hs) cardiac troponin T (cTnT) assay across a state-wide health service. Methods and resultsPresentations to emergency departments of six tertiary hospitals between January 2008 and August 2019 were included; standard cTnT assay was superseded by hs-cTnT in June 2011 without changing the reference range (≥30 ng/L reported as elevated), despite cTnT level of 30 ng/L being equivalent to ∼44 ng/L with hs-cTnT. Clinical outcomes were captured using state-wide linked health records. Interrupted time series analyses were used adjusted for seasonality and multiple co-morbidities using propensity score matching allowing for correlation within hospitals.In total, 614,847 presentations had ≥1 troponin measurement. Clinical ordering of troponin decreased throughout the study with no increase in elevated measurements amongst those tested with hs-cTnT. Small but statistically significant changes in index myocardial infarction (MI) diagnosis (−0.36%/year, 95%CI [confidence interval]:–0.48, −0.24,p < 0.001) and invasive coronary angiography (0.12%/year,95%CI:0, 0.24,p = 0.02) were seen, with no impact on death/MI at 30 days or 3-year survival in episodes of care (EOCs) with elevated cTnT after hs-cTnT implementation. Length of stay (LOS) was shorter among those with an elevated hs-cTnT (−4.44 h/year, 95%CI:–5.27, −3.60, p < 0.001). Non-elevated cTnT EOCs demonstrated shorter total LOS and improved 3-year survival (adjusted hazard ratio:0.90, 95%CI:0.83, 0.97,p = 0.008) although death/MI at 30 days was unchanged using hs-cTnT. ConclusionWidespread implementation of hs-cTnT without altering clinical thresholds reported to clinicians provided significantly shorter LOS without a clinically significant impact on clinical outcomes. A safer cohort with non-elevated cTnT was identified by hs-cTnT compared to the standard cTnT assay.

The Elevated High-Sensitivity Cardiac Troponin T Pilot: Diagnoses and Outcomes

ObjectiveTo identify the diagnoses and outcomes associated with elevated high sensitivity cardiac troponin T (hs-cTnT) compared with the 4th-generation troponin T and to validate the Mayo Clinic hs-cTnT myocardial infarction algorithm cutoff values. Patients and MethodsConsecutive blood samples of patients presenting to the emergency department between July 2017 and August 2017, who had 4th-generation troponin T, were also analyzed using the hs-cTnT assay. Troponin T values, discharge diagnoses, comorbidities, and outcomes were assessed. In addition, analyses of sex-specific and hs-cTnT cutoff values were assessed. ResultsOf 830 patients, 32% had an elevated 4th-generation troponin T, whereas 64% had elevated hs-cTnT. With serial sampling, 4th-generation troponin missed a chronic myocardial injury pattern and acute myocardial injury pattern in 64% and 16% of patients identified with hs-cTnT, respectively. Many of these “missed” patients had discharge diagnoses associated with cardiovascular disease, infection, or were postoperative. Five of the 6 patients with unstable angina ruled in for myocardial infarction. ConclusionThere were many increases in hs-cTnT that were missed by the 4th-generation cTnT assay. Most new increases are not related to acute cardiac causes. They were more consistent with chronic myocardial injury. High-sensitivity cTnT did reclassify most patients with unstable angina as having non–ST-elevation myocardial infarction. Older age, more comorbidities, and lower hemoglobin were associated with elevated hs-cTnT. Our data also support the use of our sex-specific cutoff values.

Evaluation and Comparison with Other High-Sensitivity Methods of Analytical Performance and Measured Values of a New Laboratory Test for Cardiac Troponin I Assay.

The aim of this study was to evaluate both analytical characteristics and clinical results of a new chemiluminescent method for the measurement of cardiac troponin I (cTnI), named VITROS ® High Sensitivity Troponin I Assay, using the VITROS® 3600 automated platform. The results found with this new method were compared to those observed with hs-cTnI ARCHITECT and ECLIA hs-cTnT ELECSYS methods. For evaluation of analytical performance and comparison of clinical results, plasma samples (lithium-heparin), were collected from apparently healthy subjects and patients with cardiovascular diseases. The hs-cTnI VITROS method showed values for limit of blank (LoB 0.33 ng/L), limit of detection (LoD, 0.91 ng/L), limit of quantifications at 20% (LoQ 20% CV, 1.82 ng/L), and 10% (LoQ 10% CV, 4,74 ng/L), which are comparable to those previously reported for other hs-cTnI methods. Moreover, the clinical results of the hs-cTnI VITROS method were found to be closely correlated to those of hs-cTnI ARCHITECT (R = 0,9883, N = 198) and ECLIA hs-cTnT Elecsys (R = 0,9704, N = 293) methods. The hs-cTnI VITROS method shows analytical performance comparable to other cTnI and cTnT assay. The results of this study confirm that there are significant systematic differences among hs-cTnI methods. Further multicenter studies using larger reference populations are needed in order to obtain a better estimation, especially of the 99° percentile URL values categorized for sex and age of hs-cTnI and hs-cTnT methods.