hs-TnT Measurements Research Articles

High-sensitivity troponin T and risk of stroke in persons with suspected acute coronary syndrome

Abstract Background Serial high-sensitivity troponin (hsTn) concentrations are associated with the risk of recurrent ischemic events and death from any cause. Higher hsTn levels may suggest greater infarct size and possibly, a more pronounced risk of non-coronary atherosclerotic events. Purpose To examine the association between single and serial hsTnT levels and the risk of incident stroke in individuals presenting with suspected acute coronary syndrome. Methods In this Danish nationwide registry-based study, we identified individuals without a history of stroke who presented for myocardial infarction, unstable angina, suspected myocardial infarction, or chest pain from 2013 through 2019, and who underwent serial hsTnT (Roche Diagnostics, Rotkreuz, Switzerland; 99th percentile upper reference limit: 13.5 ng/l) measurements 1-7 hours apart. Subjects were stratified according to their hsTnT level pattern from first to second measurement (main groups: normal, rising, persistently elevated, or falling) and the magnitude of hsTnT level change (secondary groups: <20%, >20 to 50%, or >50% in either direction). Additionally, they were grouped into quartiles based on the initial hsTnT measurement (<=9 ng/l, 10-16 ng/l, 17-68 ng/l, >=69 ng/l). The standardized risk of stroke was computed using multivariable logistic regression with average treatment effect modeling. Results The final study sample consisted of 26867 persons, of whom 10407 (38.7%) were diagnosed with myocardial infarction, 1404 (5.2%) with unstable angina, and 15056 (56.0%) with suspected myocardial infarction or chest pain. Median age was 64.3 years, and 40.1% were women. The prevalences of known cardiovascular disease were as follows: coronary artery disease, 20.2%; prior coronary revascularization, 8.4%; heart failure, 6.4%; and atrial fibrillation, 8.9%. At 30 days, 69 individuals had been diagnosed with a stroke, and an additional 185 individuals were diagnosed from days 31 through 365. The standardized risk of stroke at 30 days was <=0.31% in all main groups and did not meaningfully differ from each other. The risk remained low between days 31-365 (<=0,79%), with no significant between-group difference. The magnitude of hsTnT change within each group did not affect stroke risk, nor did hsTnT quartile based on the first measurement. Conclusions Persons with suspected acute coronary syndrome had a very low overall risk of incident stroke. Single or serial hsTnT levels at presentation did not seem helpful in identifying individuals at an increased risk of stroke.

High-Sensitivity Troponin-T and heart failure risk in individuals with suspected acute coronary syndrome

Abstract Background In individuals with suspected acute coronary syndrome (ACS), serial assessments of high-sensitivity cardiac troponin-T (hsTnT) levels demonstrate associations with both short- and long-term mortality and recurrent ischemic events. Nonetheless, the relationship with subsequent heart failure remains inadequately characterized. Purpose We investigated the association between single and serial hsTnT levels and subsequent hospitalization or outpatient medical encounters related to heart failure in individuals presenting with suspected ACS. Methods Utilizing Danish national registries from 2012 to 2019, we identified individuals without known heart failure who underwent dual hsTnT assessments ( 99th percentile upper reference limit: 13.5 ng/l), spaced 1-7 hours apart during hospitalization for myocardial infarction (MI), unstable angina, observation for suspected MI, or chest pain. Participants were categorized based on their hsTnT concentration patterns from the first to the second measurement (primary groups: normal, rising, persistently elevated, or falling) and the extent of hsTnT concentration alterations (secondary groups: <20%, >20 to 50%, or >50% in either direction). Additionally, they were grouped into quartiles based on the initial hsTnT measurement (<=9 ng/l, 10-15 ng/l, 16-66 ng/l, >=67 ng/l) to assess whether heightened hsTnT concentrations correlated with an increased risk of heart failure. Standardized risks of hospitalization or outpatient contacts for heart failure were computed using multivariable logistic regression with average treatment effect modeling. Results The study encompassed 26,835 individuals, of whom 38.9% received discharge diagnoses of MI, 5.1% were diagnosed with unstable angina, and 56.1% with observation for suspected MI or chest pain. Median age was 64.2 years, with 59.5% males. Prevalence of known cardiovascular disease included coronary disease in 18.1% of cases, prior revascularization in 7.2%, atrial fibrillation or flutter in 7.9%, and a history of stroke in 6.3%. Within the initial 30 days, 628 persons received a heart failure diagnosis, with an additional 960 diagnosed between days 31-365. Subjects displaying two normal hsTnT values exhibited the lowest standardized absolute risk (0.39% in days 0-30; 0.58% in days 31-365), while those with persistently elevated concentrations demonstrated the highest risk (6.45% in days 0-30; 7.05% in days 31-365) (Figure). Notably, the magnitude of hsTnT within each primary group did not affect heart failure risk. Conversely, heart failure risk exhibited a positive association with hsTnT concentrations measured in the initial sample. Conclusions In individuals presenting with suspected ACS, subjects with a sustained elevation in hsTnT levels showed the highest risk of subsequent heart failure events. Moreover, a dose-response association was observed between hsTnT concentrations and heart failure risk.Figure

External Validation of the Recalibrated HEART Score for Evaluation of Possible Acute Coronary Syndrome

A single high-sensitivity troponin-T (hs-TnT) measurement may be sufficient to risk-stratify emergency department (ED) patients with possible acute coronary syndrome (ACS) using the recalibrated History, Electrocardiogram, Age, Risk Factors, Troponin (rHEART) score. We sought to validate this approach in a multiethnic population of United States patients and investigate gender-specific differences in performance. We conducted a secondary analysis of a prospective cohort study of adult ED patients with possible ACS at a single, urban, academic hospital. We investigated the diagnostic performance of rHEART for the incidence of type-1 acute myocardial infarction (AMI) and other major adverse cardiac events (MACE) at 30 days, using both single (19 ng/L) and gender-specific (14 ng/L for women, 22 ng/L for men) 99th percentile hs-TnT thresholds. The 821 patients included were 54% women, 57% Hispanic, and 26% Black. Overall, 4.6% of patients had MACE, including 2.4% with AMI. Single-threshold rHEART ≤3 had a sensitivity of 94.4% (95% confidence interval 81% to 99%) and negative predictive values of 99.3% (98% to 100%) for MACE; gender-specific thresholds performed nearly identically. Sensitivity and negative predictive values for AMI were 90.0% (67% to 98%) and 99.3% (97% to 100%). Excluding patients presenting <3 hours from symptom onset improved sensitivity for MACE and AMI to 97.0% (84% to 100%) and 94.1% (71% to 100%). Logistic regression demonstrated odds of MACE increased with higher rHEART scores at a similar rate for men and women. In conclusion, a single initial hs-TnT and rHEART score can be used to risk-stratify male and female ED patients with possible ACS, especially when drawn >3 hours after symptom onset.

Preoperative N-terminal Pro-B-type Natriuretic Peptide and High-sensitivity Cardiac Troponin T and Outcomes after Major Noncardiac Surgery: A Prospective Cohort Study.

Patients undergoing noncardiac surgery have varying risk of cardiovascular complications. This study evaluated preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T to enhance cardiovascular events prediction for major noncardiac surgery. This prospective cohort study included adult patients with cardiovascular disease or risk factors undergoing elective major noncardiac surgery at four hospitals in China. Blood samples were collected within 30 days before surgery for NT-proBNP and high-sensitivity troponin T (hs-TnT) measurements. The primary outcome was a composite of any cardiovascular events within 30 days after surgery. Logistic regression models were used to assess associations, and the predictive performance was evaluated primarily using area under the receiver operating characteristics curve (AUC) and fraction of new predictive information. Between June 2019 and September 2021, a total of 2,833 patients were included, with 435 (15.4%) experiencing the primary outcome. In the logistic regression model that included clinical variables and both biomarkers, the odds ratio for the primary outcome was 1.68 (95% CI, 1.37 to 2.07) when comparing the 75th percentile to the 25th percentile of NT-proBNP distribution, and 1.91 (95% CI, 1.50 to 2.43) for hs-TnT. Each biomarker enhanced model discrimination beyond clinical predictors, with a change in AUC of 0.028 for NT-proBNP and 0.029 for high-sensitivity cardiac troponin T, and a fraction of new information of 0.164 and 0.149, respectively. The model combining both biomarkers demonstrated the best discrimination, with a change in AUC of 0.042 and a fraction of new information of 0.219. Preoperative NT-proBNP and hs-TnT both improved the prediction for cardiovascular events after noncardiac surgery in addition to clinical evaluation, with their combination providing maximal predictive information.

High-sensitivity troponin-T concentrations and long-term risk of death in patients with acute pulmonary embolism

Abstract Background Cardiac troponin elevation is associated with adverse short-term prognosis in patients with pulmonary embolism (PE). However, it is unknown whether high-sensitivity troponin concentrations predict long-term outcomes and whether serial measurements offer additional prognostic information in this setting. Purpose To determine short- and long-term prognostic implications of high-sensitivity troponin-T (hsTnT) concentrations and their changes from baseline, in patients with acute PE. Methods Retrospective cohort study based on Danish national registries. We identified all patients discharged from the hospital with a PE from 2013 through 2019 and merged them with all records of at least one hsTnT (99th percentile upper reference limit, 13.5 ng/l) measurement obtained during the same hospitalization. Absolute and relative risks for death from any cause at days 0-30 and 31-365 were calculated through multivariable logistic regression with average treatment effect modeling. Moreover, we tested whether hsTnT changes (in those who had a second measurement available ≥1 hour and ≤7 hours after the first measurement) were associated with additional prognostic information. Results At least one hsTnT measurement was available in 4611 individuals. Median age (25th-75th percentile) was 70.8 (58.6-79.5) years, and 2312 (50.1%) were women. One-hundred and forty-one (3.1%) patients had a prior venous thromboembolic event, 731 (15.9%) had known coronary artery disease, and 1001 (21.7%) had a history of cancer. Median baseline hsTnT was 29 (25th-75th percentile, 14-79) ng/l, and 1082 (76.5%) had an elevated concentration. Four-hundred and thirty-one (9.3%) individuals had died at 30 days, while an additional 614 (14.7% of 30-day survivors) died between days 31-365. hsTnT concentration displayed a significant, non-linear association with death (P&amp;lt;0.001). Figure 1 shows the unadjusted 30-day risk of death stratified for hsTnT quartiles, while Figure 2 shows the risk at days 31-365 (with 0 on the x-axis representing day 30 from the index event). Upon multivariable adjustment (including absence or presence of acute cor pulmonale), the risk of death at both timepoints remained significantly higher among individuals in each of quartiles 3 and 4 versus quartile 1 (P&amp;lt;0.05), with quartile 2 showing a trend (P=0.06 and P=0.07 for short- and long-term death, respectively). In 1247 subjects with two hsTnT measurements available, absolute and relative changes from baseline did not appear to carry additional prognostic information, nor did switching from normal to elevated hsTnT or vice versa, though the latter was only observed in very few persons. Conclusions In patients with acute PE, elevated hsTnT concentrations were associated with both short- and long-term mortality, but unlike in acute coronary syndromes, the utility of drawing a second sample appeared limited.Figure 1Figure 2

Assay of macrotroponin I not complexed with troponin T: effect on the performance of troponin T to predict myocardial infarction

Abstract Background Cardiac troponin-immunoglobulin (Ig) complexes (macrotroponin) can interfere with cardiac troponin (cTn) test performance. However, the role of this interference has not been fully explored. We developed a specific, novel, 2-hour prototype immunoassay of monomer IgG-bound TnI (bTnI-IgG). Using this assay, our purpose was to examine the potential contribution of cTnT binding to macro-TnI, and report its effects on the clinical diagnostic and predictive performance of highly sensitive TnT (hs-TnT) and TnI (hs-TnI) assays. Methods Using the bTnI-IgG assay, we evaluated EDTA blood samples taken at presentation (t=0) from two ED acute chest pain studies; SPACE (n=1066) and FAST-TRAC (n=1440), with statistical analysis (logistic regression, ROC curves), to AMI and 1-year outcomes, alone and in combination, with hsTnT (Roche) and hsTnI (Abbott/Beckmann) tests. Pathway analysis was used to identify if single bTnI-IgG measurements improve risk stratification in low and high AMI risk. Results In individual and combined study datasets, bTnI-IgG concentrations in patients with adjudicated acute MI (n=336) were lower than all other diagnoses (p&amp;lt;0.001). Singularly, and in multivariable models containing hs-TnT or hs-TnI concentrations, bTnI-IgG was an independent predictor of MI. Amongst all patients with MI not ruled-out on presentation (hs-TnT &amp;gt;5ng/L) and not high-risk (hsTnT&amp;lt;14ng/L), the addition of bTnI-IgG to a model containing hs-TnT, HxMI and sex improved discrimination (AUC increase of 0.014 (95%CI: 0.004 to 0.025) from 0.788 to 0.802, p=0.009). Within a diagnostic pathway analyses of n=2126 matched patient data points, adding presentation bTnI-IgG measurement alone to an MI risk stratification model consisting of hs-TnT ≤URL, HxMI and sex yielded 14% more low risk patients identified (n=586 v 667 patients) through improved specificity (77% to 88%) whilst maintaining an overall sensitivity of &amp;gt;99%. bTnI-IgG also predicted 1-year mortality and new stroke in all patients (Odds Ratios 0.292 [95%CI 0.130 to 0.654] p=0.009) and 0.255 ([95%CI 0.078 to 0.834] p=0.024), respectively. Conclusions Measurement of bTnI-IgG that is free from cTnT could potentially improve ED presentation diagnostic test performance and risk stratification of MI patients using criteria that includes hs-TnT. No effects upon hs-TnI assays were observed. This data suggests current hs-TnT test design and measurements may be impacted by binding interactions between TnT and TnI. Finally, bTnI-IgG can independently predict mortality and stroke outcomes within 1 year of index presentation.

Mortality prediction using high-sensitivity troponin after coronary artery bypass surgery

Abstract Introduction Recommendations regarding the threshold levels of cardiac troponin elevations for the definition of peri-operative myocardial infarction and clinically important peri-procedural myocardial injury in patients undergoing cardiac surgery range widely (&amp;gt;10 to ≥70x the upper limit of normal (ULN)) (1,2). Limited evidence is available to support these recommendations. In a recent multicentre cohort study, Devereaux and colleagues (3) characterised appropriate thresholds of high-sensitivity troponin-I (hs-TnI) for defining myocardial injury within 3 days after cardiac surgery. The threshold associated with an increased risk of 30-day mortality after coronary artery bypass grafting (CABG) was 218 xULN (95% confidence interval (CI), 40-318) of the hs-TnI assay. There have been no large studies assessing this threshold using high-sensitivity troponin-T (hs-TnT). Furthermore, the long-term prognostic value of troponin following CABG is unknown. Purpose The aim of our study was to assess the threshold associated with an increased risk of 30-day and 5-year mortality using hs-TnI assays, and to compare these thresholds to those using hs-TnT assays. Methods A retrospective cohort study was carried out using the National Institute for Health Research Health Informatics Collaborative Cardiovascular dataset (4,5) of all consecutive patients who had a troponin measured at five hospitals between 2010 and 2017. Patients who had a troponin measurement within three days following CABG were identified. Results were analysed using multivariable adjusted restricted cubic spline Cox regression. All hazard ratios were adjusted for the following components of the European System for Cardiac Operative Risk Evaluation II (EuroSCORE II); age, gender, renal impairment, poor mobility, chronic lung disease, diabetes, left ventricular function, and pulmonary hypertension. Analyses on troponin were performed using the peak troponin level, which was the highest troponin level measured within the first three days following CABG. All troponin measurements were high-sensitivity and were standardised by using the ratio of the observed troponin value divided by the ULN for each troponin assay. The reference for hazard ratios was a troponin level of 1 xULN. Results A total of 1055 patients (median age 72 years (interquartile range 63 to 78), 79% male) had a troponin measured within three days post-CABG at the five centres between 2010 and 2017. The threshold for hs-TnI associated with an increased mortality risk was 196xULN (95%CI, 42-494) for predicting 30-day mortality (Figure 1A) and 157xULN (95%CI, 32-409) for 5-year mortality (Figure 1B). The thresholds were similar for hs-TnT assays (Figure 1C and 1D). Conclusion The currently recommended troponin thresholds for diagnosing significant myocardial injury following cardiac surgery (&amp;gt;10 to ≥70xULN) are too low. There was good correlation between hs-TnI and hs-TnT measurements for predicting both short- and long-term mortality.Figure 1

High-sensitivity cardiac troponin-T concentrations and their prognostic implications in paroxysmal supraventricular tachycardia: A nationwide study

Abstract Introduction Paroxysmal supraventricular tachycardia (PSVT) may mimic symptoms and electrocardiographic findings compatible with acute coronary syndromes. As a result, cardiac troponin concentrations are frequently measured upon presentation. Although PSVT may increase troponin concentrations, the expected magnitude and prognostic clinical value of high-sensitivity troponin (hs-TnT) concentrations remain uncertain. Purpose The purpose of this study was to examine whether elevated hs-TnT concentrations in PSVT patients were associated with a higher risk of death from any cause. Methods We used Danish nationwide registry data from January 2013 through December 2019. PSVT was defined as all supraventricular tachycardias except atrial fibrillation and atrial flutter. The inclusion criteria were de novo PSVT and at least one measured hs-TnT level during hospitalization. Exclusion criteria were a history of cardiovascular disease (coronary artery disease, atrial fibrillation or flutter, or heart failure) or absence of hemoglobin or creatinine measurement within one day of the hs-TnT measurement. Elevated hs-TnT was defined as a value of ≥14 ng/l (the conventional 99th percentile upper reference limit). The primary outcome was death from any cause evaluated at 0-30 and 31-365 days, using multivariable Cox regression with average treatment effect, rendering standardized absolute and relative risks. Results A total of 1029 patients were included. Median age was 58 years (25th to 75th percentile: 45-71), and 45% were male. Elevated hs-TnT level was observed in 674 (65.5%) patients, who also had a higher prevalence of cardiovascular comorbidities. The median hs-TnT level was 16 ng/l (25th to 75th percentile: 10-35). The standardized mortality risk at 30 days was significantly higher in patients with elevated hs-TnT compared with patients with normal hs-TnT concentrations (2.38% [95% confidence interval (CI): 1.38 to 3.37] versus &amp;lt;0.01% [95% CI: &amp;lt;0.01 to &amp;lt;0.01]) (Figure 1). The relative risk was 58722906 (95% CI: 23126570 to 94319242), p = 0.001. At 31-365 days, the standardized risk of death was 1.51% (95% CI: 0 to 3.28) in individuals with a normal hs-TnT and 4.23% (95% CI: 2.81 to 5.66) in those with an elevated hs-TnT (Figure 2), resulting in a relative risk of 2.81 (95% CI: 0 to 6.32), p = 0.31. Conclusion In patients without prior cardiovascular disease, an elevated hs-TnT concentration during the first episode of PSVT was only associated with an increased early mortality risk. Long-term mortality was not affected by elevated hs-TnT.Figure 1Figure 2

Abstract 18862: Optimal High Sensitivity Troponin “Delta” for Prediction of 30-Day Mace

Introduction: High-sensitivity troponin (hsTnT) values are used extensively in clinical practice to determine acute myocardial infarction (MI). Most hsTnT algorithms use an accelerated diagnostic protocol based on ranges of hsTnT and time-based changes within those ranges. Little is known about the performance of a protocol based on absolute change with time regardless of absolute values. Research question: Is there a level of hsTnT change (dTnT) that can be used as a single decision factor in the triage of chest pain? Goals/Aims: To assess the diagnostic value of dTnT in ruling out 30-day MI or 30-day death and to identify optimal cut-off values. Methods: Retrospective review of patients with chest pain (CP) who presented to the ED of a single tertiary medical center between September 2017 to September 2019. Patients were included if they had at least 2 hsTnT measurements. dTnT was calculated using the difference between the first and second readings. Presence or absence of MI or death at 30 days from this ED presentation was also recorded from chart review. ROC analysis was performed to determine cut-off values for predicting each event. Statistical analysis was performed using SPSS. Results: dTnT was available in 488 patients and predicted 30-day MI (4/488) with a high AUC of 0.864 (p=0.01). The Cut-off value range of 12.5 to 20.5% had a similar sensitivity of 75% but the specificity increased as the cut-off increased to 20.5%, highest specificity being 87%.dTnT was not sensitive in predicting 30-day death, the AUC was 0.524 (p=0.9). Conclusion: Without compromising on sensitivity, the specificity of this test may increase as the cut-off value is increased. The use of troponin change as a risk marker for MACE in pts with CP has optimal sensitivity and good specificity in predicting 30-day MI and its diagnostic utility should be evaluated further.

Very early risk modeling in patients with chest pain based on the pattern on admission ECG.

The aim was to investigate the prognostic accuracy of admission ECG and its usefulness in determining the population at the highest risk of worse outcomes. Fast and accurate assessment of chest pain patients remains a challenge for clinicians. Electrocardiogram (ECG) is performed in each case of suspicion of the cardiac origin of chest pain. Consecutive adult chest pain patients with suspicion of acute myocardial infarction (AMI) were enrolled in the study. The prognostic value of admission ECG changes alone and in combination with other clinical variables (cardiac troponin, diagnosis of AMI) were analyzed for the incidence of major adverse cardiac events (MACE) in a one‑year observation. The ischemic pattern on admission ECG was a single risk factor of MACE (HR 2.996 95% CI 1.31-6.86, p = 0.009), contrary to the single admission high-sensitivity cardiac troponin T assay (hs-cTnT) (HR 1.79 95% CI 0.695-4.61). The highest risk of MACE was identified in case of the presence of both ischemic-ECG and positive hs-cTnT (HR 3.19 95% CI 1.496-6.81, p = 0.003). The presence of ischemic changes in ECG in chest pain population with AMI suspicion increases the risk of MACE. The group at highest risk of MACE can by identified by the additional stratification with the admission single hs-TnT measurement (Tab. 2, Fig. 4, Ref. 40). Text in PDF www.elis.sk Keywords: acute coronary syndromes, cardiac troponin, electrocardiogram, emergency department, chest pain.

The Predictive Power of the 14-51 Ng/L High Sensitive Troponin T (hsTnT) Values for Predicting Cardiac Revascularization in a Clinical Setting.

Background: high sensitive Troponin T (hsTnT) values between 14−50 ng/L represent a challenge in diagnosing acute coronary syndrome (ACS) at the Emergency Department (ED). The European Society for Cardiology (ESC) recommends a second hsTnT measurement 3 h later to distinguish between ACS and other causes depending on the Δ hsTnT. Our study aims to evaluate the predictive power this approach in a clinical setting by following patients presenting at the ED with hsTnT values 14−51 ng/L. Materials and methods: patients presenting with chest pain or dyspnea and a hsTnT value between 14 and 50 ng/L at the Erasmus MC ED in 2012−2013 were included and retrospectively monitored for 90 days after initial presentation for the occurrence of a cardiac revascularization. Patient records were reviewed according to the standing protocol, which depended on the Δ hsTnT. The “event-group” consists of patients receiving cardiac revascularization within 90 days after the ED visit, whereas the “no event-group” consisted of patients without revascularization. Results: a total of 889 patients patient records were reviewed. After excluding out-of-hospital-cardia-arrests (60), non-cardiological chest pain (373) and incomplete follow-up (100), 356 patients remained for final analysis. In 207 patients, a second hsTnT was actually performed (58%). From these 207 patients, 68 (33%) had a Δ hsTnT ≥7 ng/L. In these patients, 37 (54%) experienced an event within 90 days. In the 139 patients with a Δ hsTnT < 7 ng/L, 23 (17%) presented with an event within 90 days. Conclusion: our study demonstrated a sensitivity of 62%, a specificity of 79%, a positive predicted value (PPV) of 54% and a negative predictive value (NPV) of 83% for using a 3-h Δ hsTnT ≥7 ng/L cut-off, related to risk of an event in 90 days following ED presentation.

Abstract 9438: Serial Troponin T and Long-Term Risks of Myocardial Infarction and Revascularization in Patients With Suspected Acute Coronary Syndrome

Introduction: Long-term prognostic implications of serial high-sensitivity troponin concentrations in patients with suspected myocardial infarction (MI) are unknown. Hypothesis: To determine short- and long-term risks of MI and revascularization (PCI or CABG) according to high-sensitivity troponin T (hsTnT) concentrations and their changes from baseline, in patients with suspected acute coronary syndrome. Methods: Retrospective cohort study based on Danish national registries. We identified all patients discharged from the hospital with either MI, unstable angina, suspected MI, or chest pain from January 2012 through December 2019 and merged them with records of two serial hsTnT measurements obtained 1-7 hours apart. Absolute risks of MI and revascularization were calculated through multivariable logistic regression with average treatment effect modeling (G-formula), with patients stratified in groups according to normal and elevated concentrations and relative changes of 20% and 50% from baseline. Results: Complete data were available in 28,902 individuals (median age [25 th -75 th percentile] 65.2 [53.4-75.4] years, 11,632 [40.2%] women). The standardized risk of MI was highest in individuals with two elevated hsTnT concentrations (0-30 days: 54.1%, 31-365 days: 9.7%) and lowest in those with two normal values (0-30 days: 2.5%, 31-365 days: 0.4%). In the latter group, the risk of MI did not appear to depend on the relative hsTnT change between samples while in persons with two elevated hsTnT concentrations, the risks at both 0-30 days and 31-365 days increased in a stepwise fashion with more pronounced hsTnT rises. Individuals with a &gt;20% to 50% fall also had a higher risk of MI than those with a less pronounced change while results were not significant for those with a &gt;50% fall. Finally, individuals who went from a normal to an elevated hsTnT level and had a concomitant &gt;50% rise had a significantly higher risk of MI at days 0-30 than those with a less pronounced rise. The standardized likelihood of undergoing coronary revascularization according to serial hsTnT concentrations followed the same pattern. Conclusions: Serial hsTnT measurements identify patients at long-term risk for both MI and revascularization.

Serial troponin-T and long-term outcomes in suspected acute coronary syndrome.

Long-term prognostic implications of serial high-sensitivity troponin concentrations in subjects with suspected acute coronary syndrome are unknown. Individuals with a first diagnosis of myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019 who underwent two high-sensitivity troponin-T (hsTnT) measurements 1-7 h apart were identified through Danish national registries. Absolute and relative risks for death at days 0-30 and 31-365, stratified for whether subjects had normal or elevated hsTnT concentrations, and whether these concentrations changed by <20%, > 20 to 50%, or >50% in either direction from first to second measurement, were calculated through multivariable logistic regression with average treatment effect modeling. Of the 28 902 individuals included, 2.8% had died at 30 days, whereas 4.9% of those who had survived the first 30 days died between days 31-365. The standardized risk of death was highest among subjects with two elevated hsTnT concentrations (0-30 days: 4.3%, 31-365 days: 7.2%). In this group, mortality was significantly higher in those with a > 20 to 50% or >50% rise from first to second measurement, though only at 30 days. The risk of death was very low in subjects with two normal hsTnT concentrations (0-30 days: 0.1%, 31-365 days: 0.9%) and did not depend on relative or absolute changes between measurements. Individuals with suspected acute coronary syndrome and two consecutively elevated hsTnT concentrations consistently had the highest risk of death. Mortality was very low in subjects with two normal hsTnT concentrations, irrespective of changes between measurements.

High-sensitive Troponin T is not associated with the progression of asymptomatic mild to moderate aortic stenosis: a post hoc substudy of the SEAS trial

Abstract Background Aortic stenosis (AS) and coronary artery disease (CAD) share pathophysiological pathways, as reflected by frequent concomitant revascularization in patients undergoing aortic valve replacement (AVR). High-sensitive Troponin T (hsTnT) is a proven biomarker of cardiomyocyte overload and injury, and predicts postoperative mortality after AVR. However, it is unknown if hsTnT can predict AVR, mortality or ischemic coronary events (ICE) in asymptomatic AS patients. Purpose To investigate the hypothesis that increased hsTnT is associated with more severe AS and a higher risk of adverse outcomes in asymptomatic AS patients without overt CAD. Methods hsTnT concentrations were examined at baseline and after 1-year follow-up in 1739 asymptomatic AS patients enrolled in the randomized, double-blind Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. The main inclusion criteria were: left ventricular (LV) ejection fraction &amp;gt;55%, transaortic maximal velocity between 2.5–4.0 m/s, and no history of CAD. The primary exposure variable was increased hsTnT (&amp;gt;14 pg/mL according to the assay manufacturer, Roche). This study's primary endpoint was a composite of competing risk outcomes: all-cause mortality as the first event, AVR without revascularization, and ICE (defined as myocardial infarction before AVR, PCI before or combined with AVR, or any CABG). Multivariable regression examined associations between hsTnT and clinical variables. Cox proportional hazards regression models were adjusted for age, sex, creatinine, LV mass index, mean aortic pressure gradient (Pmean) and stratified by center and lipid-lowering treatment. We analyzed outcomes during 5-year follow-up from baseline. Results At baseline, 453 (26.0%) patients had increased hsTnT and 302 (17.4%) had moderate-severe AS with a mean (SD) aortic valve area of 0.8 (0.2) cm2 and Pmean of 33.2 (8.8) mmHg. The median annual hsTnT change from baseline to year 1 was 0.8 pg/mL (IQR, −0.4 to 2.3), regardless of AS severity (P=0.08). In adjusted models, log(hsTnT at baseline) was associated with age, sex, creatinine, and LV mass index (all P&amp;lt;0.05), but not with AS severity (P=0.36). The incidence rate ratio for ICE (Figure 1) in patients with increased vs normal baseline hsTnT concentrations was 2.32 (95% CI, 1.72–3.11, P&amp;lt;0.001). In adjusted Cox regression, increased hsTnT was associated with an increased 5-year ICE risk (HR 1.64; 95% CI, 1.18–2.29, P=0.003), but neither with AVR without revascularization nor death (Figure 1). Conclusion In these asymptomatic AS patients without overt CAD, hsTnT is often normal and remains stable during 1 year of follow-up regardless of AS severity. Increased hsTnT is associated with CAD-related events, but neither to AS severity nor AVR without concomitant revascularization. This analysis does not support routine hsTnT measurement in asymptomatic AS to predict AVR related to AS progression, although hsTnT could improve the risk assessment for ICE. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Main sponsor (SEAS): Merck &amp; Co Inc, Whitehouse Station, New JerseyBlood analysis sponsor: Roche Diagnostics International Ltd, Switzerland

Serial high-sensitivity troponin T concentrations and long-term outcomes in patients with suspected acute coronary syndrome

Abstract Background High-sensitivity troponin assays allow for accurate and rapid rule-in or rule-out of myocardial infarction (MI) among patients with acute-onset chest pain. However, prognostic implications of serial high-sensitivity troponin concentrations are unknown. Purpose To determine short- and long-term prognostic implications of high-sensitivity troponin T (hsTnT) concentrations and their changes from baseline, in patients with suspected acute coronary syndrome. Methods Retrospective cohort study based on Danish national registries. We identified all patients discharged from the hospital with either MI, unstable angina, suspected MI, or chest pain from January 2012 through December 2019 and merged these individuals with all records of two serial hsTnT measurements obtained ≤7 hours apart during the same hospitalization. The primary outcome was death at days 0–30 and 31–365. Prognostic implications of serial hsTnT were examined in accordance with the 2012 ESC algorithm stratifying patients for normal baseline concentrations and relative changes of 20% and 50% from baseline. In case of a normal baseline concentration, 20% and 50% of the upper reference level (14 ng/l) were used as thresholds instead, i.e., 3 ng/l and 7 ng/l, respectively. Absolute risks were calculated through multivariable logistic regression with average treatment effect modeling (G-formula). Results Complete data were available in 28,902 individuals (median age [25th-75th percentile] 65.2 [53.4–75.4] years, 11,632 [40.2%] women). Of these, 11,116 (38.5%) had a final diagnosis of MI, 1518 (5.3%) of unstable angina, and 16,268 (56.3%) of either suspected MI or chest pain. Median baseline hsTnT was 18 ng/l (25th-75th percentile, 10–69), second hsTnT 21 ng/l (25th-75th percentile, 10–248), relative hsTnT change 3.6% (25th-75th percentile, 0–66.7), and time between samples 4.0 hours (25th-75th percentile, 3.2–5.4). Most patients had either two normal hsTnT concentrations (9483, 32.8%) or two elevated hsTnT concentrations (18,235, 63.1%). At 30 days, 796 (2.8%) individuals had died, while an additional 1287 (4.6% of 30-day survivors) died between days 31–365. Baseline hsTnT and the relative hsTnT change both displayed a significant, non-linear association with death and interacted with each other (P&amp;lt;0.001). Tables 1 and 2 show the standardized, absolute risks of death (with 95% confidence intervals) from days 0–30 and from days 31–365, respectively. Patients with two normal hsTnT concentrations had very low mortality rates, irrespective of the magnitude of relative change. Conversely, patients with two elevated hsTnT concentrations consistently had high mortality rates. Conclusions This is the first study to assess both short- and long-term outcomes as a function of both baseline hsTnT and its change from first to second measurement. In general, patients with two normal hsTnT concentrations have an excellent prognosis while those with two elevated concentrations require scrutiny. Funding Acknowledgement Type of funding sources: None.

Not T too! False elevations in high-sensitivity cardiac troponin T (hs-TnT) following specimen transport

Though false elevations attributed to preanalytical specimen handling have been widely reported for Troponin I (TnI), Troponin T (TnT) has appeared more robust to falsely elevated Tn. We describe reproducible false elevations in high sensitivity TnT (hs-TnT) in specimens after courier transport in plasma separator tubes (PST) off-site for testing.Hs-TnT was measured under 5 different conditions: 1) at collection location (N = 24); 2) after transport upright in racks (N = 66); 3) after transport with no control over tube agitation (N = 69); 4) on transported aliquots (N = 84); or 5) immediately after transport with no control over tube agitation (N = 16), followed by keeping the specimen upright and re-measuring at 1hr, 2hr, 4hr, and 20-24hrs (N = 6). To assess the degree of discrepancy, plasma from the original PST was aliquotted, re-centrifuged, potential debris removed, and hs-TnT re-measured.43% of PST specimens collected offsite and transported with no control over tube agitation had clinically significant false elevations of hs-TnT which subsequently decreased following aliquotting and re-centrifugation (median decrease = 9.9 ng/L). Onsite testing or transported aliquots demonstrated no discrepancy. After being kept upright, discrepant specimens were not different from re-centrifuged aliquots by 4hrs (p = 0.6141, repeated measures ANOVA with Dunn’s multiple comparisons).Clinically significant false elevations of hs-TnT occurred in approximately 40% of separated PSTs that were transported in containers where specimens are transported with no control over tube agitation. This interference does not occur if plasma is aliquoted or if hs-TnT is tested at the collection site. In order to prevent these false elevations, and their potential patient impact on the diagnosis of acute myocardial infarction, specimens for hs-TnT measurement should be aliquoted at the collection location prior to transport.

Distribution and specificity of high-sensitivity cardiac troponin T in older adults without acute cardiac conditions: cross-sectional results from the population-based AugUR study

ObjectiveEuropean guidelines recommended a uniform upper reference limit of high-sensitivity cardiac troponin T (hsTnT) to rule out non-ST segment elevation myocardial infarction. Our study aimed to provide a hsTnT reference...

Does high sensitivity troponin add prognostic value to validated risk scores to predict in-hospital mortality in patients with acute heart failure?

Troponin elevation correlates with an increased short and long-term mortality in patients with acute decompensated heart failure (AHF). However, it has not been included in the development of multiple validated predictive models of mortality. We aim to determine whether the addition of high-sensitivity troponin T (hs-TnT) to clinical risk scores improves the prediction of in-hospital mortality in patients with AHF. A retrospective analysis of a prospective and consecutive cohort was performed. Adult patients hospitalized between 2015 and 2019 with a primary diagnosis of AHF were included. Hs-TnT was measured on admission. OPTIMIZE-HF, GWTG-HF, and ADHERE risks score were calculated for each patient. The primary endpoint was all-cause in-hospital mortality. Discrimination of isolated hs-TnT and the risk scores with and without the addition of hs-TnT were evaluated using the area under the ROC curve (AUC-ROC). A subanalysis was performed according to left ventricular ejection fraction (LVEF). Of 712 patients, 562 (79%) had hs-TnT measurement upon admission, and was elevated in 91%. In-hospital mortality was 8.7% (n = 49). The AUC-ROC was 0.70 (95% CI 0.63-0.77) for isolated hs-TnT, and 0.80 (0.74-0.87), 0.79 (0.72 -0.86) and 0.79 (0.71-0.86) for the OPTIMIZE-HF, GWTG-HF and ADHERE scores, respectively. The addition of hs-TnT to the models did not increase the AUC: 0.72 (0.66-0.79) for the OPTIMIZE-HF + hs-TnT score (difference between AUC - 0.08 p = 0.04), 0.74 (0.68-0.80) for GWTG-HF (difference between AUC-0.04, p = 0.2) and 0.7 (0.63-0.77) for ADHERE (difference between AUC - 0.085 p = 0.07). The models presented good calibration (p > 0.05). In the sub-analysis, no differences were found between risk scores with the addition of hs-TnT in the population with LVEF < 40% and ≥ 40%. Elevated hs-TnT on admission was frequent and its incorporation into the validated risk scores did not prove an incremental prognostic benefit in patients hospitalized for AHF, regardless of LVEF. Isolated hs-TnT had a modest ability to predict hospital mortality. Additional prospective studies are needed to validate these findings.

Importance of myocardial ischemia detected with protocol-based measurements of high-sensitivity troponin, ECG and echocardiography in critically ill patients without acute coronary syndrome—a prospective study

Elevated cardiac troponin is detected in the majority of critically ill patients. This study aimed to evaluate the prognostic value of protocol-guided detection of myocardial ischemia (MI) (serial 12-lead electrocardiograms (ECG), high-sensitivity troponin T (hsTnT) measurements, and echocardiography) and compare it with a retrospective cohort with only clinically driven detection of MI. In a prospective observational study, 95 patients hospitalized ≥48 hours for reasons other than acute coronary syndrome in medical or surgical intensive-care unit (ICU) were enrolled. A protocol-based approach, with regular 12-lead ECG recordings, hsTnT measurements and admission echocardiography was conducted. All events possibly indicating MI were documented, and ECG, hsTnT, echocardiography were repeated. The protocol-based approach was compared to a retrospective group with only clinically driven detection of MI. In the prospective group, 95.8% of patients had at least one elevated hsTnT value. A hsTnT ＞70 ng/L was associated with the use of inotropes (OR 3.35 (95% CI: 1.184, 9.472), p = 0.022), left ventricular ejection fraction &lt;30% (OR 9.65 (95% CI: 1.172, 76.620), p = 0.035), regional wall motion abnormalities (OR 3.87 (95% CI: 1.032, 14.533), p = 0.045), ICU mortality (OR 8.38 (95% CI: 1.004, 69.924), p = 0.0495), hospital mortality (OR 3.05 (95% CI: 1.133, 8.230), p = 0.027) and 1-year mortality (OR: 5.43 (95% CI: 2.1099, 13.971), p = 0.005). The incidence of MI was higher in the prospective, as compared to the retrospective group (22.1% vs 5.3%; p = 0.001). MI, compared to the high “hsTnT positive only” group, predicted hospital mortality (OR 3.33 (95% CI: 1.190, 9.329), p = 0.02) and 1-year mortality (OR 4.66 (95% CI: 1.647, 13.222), p = 0.0037). A protocol-based compared to a clinically driven approach for the detection of MI reveals more patients with MI. The majority of critically ill patients have elevated hsTnT levels. Detected MI additionally stratifies patients with elevated hsTnT to higher hospital and 1-year mortality.

The ESC algorithm for serial high-sensitivity troponin T changes and long-term outcomes in patients with suspected acute coronary syndrome

Abstract Background The fourth universal definition of myocardial infarction (MI) consensus paper suggests that patients with changing troponins not reaching concentrations greater than the 99th percentile may be at high risk and deserve close scrutiny. Purpose To determine long-term prognostic implications of high-sensitivity troponin T (hs-TnT) levels and their relative change (Δ) from baseline in subjects with suspected acute coronary syndrome (ACS). Methods We conducted a retrospective cohort study through individual participant-level linkage between Danish national registries, including subjects with a final discharge diagnosis of acute MI, unstable angina, suspected MI, or chest pain from March 2013 through December 2016 who had a record of at least two serial hs-TnT measurements during hospitalization. Individuals were followed for 12 months, until the occurrence of an event, or censoring due to emigration. Kaplan-Meier analysis and Cox regression, incorporating the competing risk of death, were used to examine the prognostic implications of serial hs-TnT. Subjects were categorized according to whether their first and second hs-TnT were normal/elevated as well as Δhs-TnT and its direction, the latter employing a modified version of the 0/3-hour diagnostic algorithm proposed by ESC, i.e., using cut-offs for Δhs-TnT of 20% and 50%. The primary outcome was a composite of presumed death from cardiovascular causes, recurrent MI, or repeat revascularization (i.e., not including the index event unless the patient died) within 12 months. Results A total of 13,494 individuals (mean age 63.4 years, 39.5% women) were included. Of these, 6129 (45.4%) had a final diagnosis of MI, 941 (7.0%) of unstable angina, and 6414 (47.5%) of either suspected MI or chest pain. Median baseline hs-TnT was 20 ng/l (72.1% elevated), second hs-TnT 27 ng/l (74.6% elevated), Δhs-TnT 4.8%, and time between samples 5.4 hours. At 12 months, 1055 (7.8%) had experienced a primary event. Baseline hs-TnT and Δhs-TnT both displayed a significant association with the primary outcome (P&amp;lt;0.001 for both overall trends and for non-linearity vs. linearity). The Figure shows the prognostic implications of serial hs-TnT. Overall, subjects with two consecutively elevated hs-TnT had the highest 12-month event risk (10.0%), followed by those who went from an elevated to a normal hs-TnT (8.6%), those who went from a normal to an elevated hs-TnT (6.3%), and those with two normal hs-TnT levels (1.6%). The majority either had non-significant Δhs-TnT (−20% to 20%: 56.8%) or a large positive Δhs-TnT (&amp;gt;50%: 30.6%). Individuals with a positive Δhs-TnT (&amp;gt;20%) had a worse prognosis than those without. Conclusions An elevated hs-TnT at any time and Δhs-TnT were both determinants of poorer prognosis in subjects with suspected ACS. Individuals with two normal hs-TnT had a good prognosis, irrespective of their Δhs-TnT. Figure 1 Funding Acknowledgement Type of funding source: None