High-sensitivity cTn Research Articles

Cardiac troponin elevation in intracerebral hemorrhage patients may rather reflect acute myocardial damage than acute myocardial infarction

Abstract Background Patients with acute ischemic stroke (AIS) and elevated cardiac troponin (cTn) have worse functional and mortality-related outcome. While elevated cTn is also frequently observed in patients with intracerebral hemorrhage (ICH), routine invasive coronary angiography should not be performed on these patients. Existing data on correlation of cTn elevation with patient outcome and the underlying causes in this specific patient group are sparse and largely heterogeneous. Purpose To investigate the clinical variables that predict cTn elevation in patients with ICH and the impact of cTn elevation on intrahospital mortality and functional outcome. Methods Our long-term Stroke Database was screened for ICH patients with high-sensitivity (hs) cTn measurement on admission (from 2015 onwards). Baseline characteristics, intrahospital mortality and functional outcome at discharge were compared between the groups with and without cTn elevation (hs-cTnI > vs. ≤0.045 µg/L). In addition, clinical variables with suspected significance for cTn elevation were analyzed for their predictive value. Results A total of 93/498 patients with ICH (18.7%; mean age 73±15 years, 53.8% females) were found to have a cTn elevation. Regarding etiology, 38.7% had an ICH occurring after AIS and 31.2% had a hypertensive ICH (each p=NS between groups). Patients with cTn elevation did not have a more pronounced cardiovascular risk profile and had a comparably low prevalence of coronary artery disease (CAD; 18.5%, p=NS). However, they were significantly less likely to be on oral anticoagulation at the time of the bleeding event (7.5 vs. 18.0%, p=0.013). CTn elevation had no negative impact on intrahospital mortality (21.5 vs. 20.5%, p=NS) or functional outcome at discharge (NIHSS score 10 (2; 26) vs. 9 (2; 22) points, mRS 5 (3; 5) vs. 5 (3; 5) points, each p=NS). Increasing NIHSS score on admission (p=0.021, OR 1.084 [1.012-1.160]), mRS ≥4 on admission (p=0.005, OR 2.207 [1.180-2.826]), infratentorial bleeding localization (p=0.034, OR 4.899 [1.132-21.207]) and aortic valve stenosis ≥ intermediate (p<0.001, OR 8.435 [2.429-29.294]) predicted cTn elevation. In contrast, severely impaired left ventricular function, CAD, atrial fibrillation, intraventricular hemorrhage or ICH occurring after AIS had no predictive value. Conclusions Almost one fifth of patients with ICH had an elevated cTn. Unlike in AIS, in ICH cTn elevation was not associated with a worse functional or mortality-related intrahospital outcome. In particular, severe functional impairment on admission, reflecting severe ICH, or infratentorial hemorrhage localization, thought to affect the autonomic nervous system, was predictive of concomitant myocardial cell damage. CAD was rare overall. This could indicate that the cTn elevation in connection with ICH is primarily related to acute myocardial damage along the brain-heart axis and less to myocardial infarction.

Comparison of multiple high sensitivity cardiac troponin assays for early low risk rule out of myocardial infarction: SCORECARD

Abstract Background/Introduction The use of a single low high-sensitivity cardiac troponin measurement to rule out myocardial infarction (MI) at presentation is advocated by international guidelines. Studies have not systematically compared high-sensitivity cardiac troponin (hs-cTn) I and T assays to determine which values should be used to rule out MI in patients with suspected acute coronary syndrome. Methods In a pooled analysis from three prospective observational cohort studies the lowest cTn concentration was determined that gave a negative predictive value (NPV) of ≥99.5% for MI or death at 30 days on presentation to the emergency department. EDTA or lithium heparin plasma or serum samples collected at presentation were measured using five hs-cTnI assays (Abbott ARCHITECT i2000, Beckman Coulter Access 2, Siemens Atellica IM, Ortho-Clinical Diagnostics VITROS 5600, LSI Medience PATHFAST) and one hs-cTnT assay (Roche Cobas e411). The diagnostic outcome of MI or death at 30 days was adjudicated according to the Fourth Universal Definition of MI. Optimal thresholds were determined to identify the highest proportion of patients that could be considered for discharge for a NPV of ≥99.5% for each assay. Results Among 941 patients, MI or death at 30 days occurred in 113 (12%). Optimized thresholds varied between assays ranging from <2 to <7 ng/L (Table) that identified between 22% and 60% of patients as low risk (0-1%) for MI or death at 30 days. Conclusions Our data identify differences in the effectiveness of thresholds between hs-cTnI and hs-cTnT assays for the same safety performance to rule out MI on presentation using a single measurement. In some cases, these thresholds differ from those used in clinical practice. Due to lack of assay standardization, optimal decision thresholds should be defined and validated for each high sensitivity cTn assay.

Prognostic importance of persistent elevations in high-sensitivity troponin T in the early convalescent phase (two weeks) following high-risk myocardial infarction: insights from the PARADISE-MI trial

Abstract Introduction Myocardial infarction (MI) is defined by a rise and fall in cardiac troponin (cTn) with clinical evidence of acute myocardial ischemia. How often cTn remains elevated in high-risk patients stabilized following MI and the relation between convalescent cTn levels and subsequent clinical outcomes in these patients is unknown. Aims To evaluate the prognostic importance of high-sensitivity cTn T (hs-cTnT) in the early convalescent phase of a MI for a range of cardiovascular (CV) outcomes in patients enrolled in the Prospective ARNI vs ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI). Methods Patients ≥18 years without prior heart failure (HF) (n=5661) were randomized to sacubitril/valsartan or ramipril within 0.5 to 7 days of MI complicated by transient pulmonary congestion, LVEF ≤40%, or both. Hs-cTnT was measured using the Roche Elecsys Troponin T-high-sensitive assay in 1093 patients two weeks after randomization (median 2.6 weeks after the index MI). Associations between log (2)-transformed hs-cTnT and clinical outcomes were investigated in landmark analyses using Cox regression models adjusted for clinical covariates of known prognostic importance and NT-proBNP (Figure). Results Median week 2 hs-cTnT concentration was 34 ng/L [IQR 17-94 ng/L] and exceeded the 99th percentile upper reference limit in 69% of patients. Patients with persistently elevated hs-cTnT concentrations (n=753) were older, more likely men, more commonly had atrial fibrillation and lower estimated glomerular filtration rate and less likely had a prior MI. They more commonly had presented with ST-segment elevation MI and pulmonary congestion and had higher concentrations of NT-proBNP. Rates of primary reperfusion were similar. Log(2)-transformed hs-cTnT was only weakly correlated with LVEF (rho = -0.15, p<0.001), irrespective of the type of MI. hs-cTnT was independently and linearly associated with the primary composite outcome of CV death or incident HF (adj HR 1.17 per doubling; 95% CI, 1.03 – 1.34), all-cause death (adj HR 1.20; 95% CI, 1.01 – 1.44) and CV death (adj HR 1.25; 95% CI, 1.02 – 1.52) but not with non-CV death (adj HR 1.04; 95% CI, 0.70-1.54). hs-cTnT was not significantly associated with recurrent fatal or non-fatal MI (adj HR 1.00; 95% CI, 0.85-1.18) (Figure). Concentrations of week 2 hs-cTnT were not altered by sacubitril/valsartan relative to ramipril (+4%; 95% CI, -8% to 18%). Conclusions Persistent elevations in hs-cTnT during the early convalescent phase following high-risk MI are common and are associated with heightened risk of all-cause death, CV death and incident HF but not of recurrent MI or non-CV death. hs-cTnT measured ~2.5 weeks after high-risk MI provides incremental prognostic information beyond traditional risk factors and NT-proBNP.

Exercise-induced cardiac troponins in long-distance walkers: a preliminary observation.

Abstract Background Elevated concentrations of cardiac troponin (cTnT and cTnI), the preferred biomarker to diagnose myocardial infarction, can be detected in other (cardiac) conditions and even post-exercise. Whether these exercise-induced elevations reflect a (patho)physiological process, as well as their clinical implications, is unknown. In this preliminary study, pre- and post-exercise high-sensitivity cTn (hs-cTnT and hs-cTnI) concentrations were investigated in long-distance walkers. Purpose Gain insight of elevated cTnT and cTnI concentrations post-exercise in long-distance walkers. Methods From 478 participants, walking 30-50 km on the first day of the 4Daagse 2023, blood-samples were collected pre- and <6h post-exercise. In addition, health and exercise questionnaires were conducted. Hs-cTnT (Roche) and hs-cTnI (Abbott) concentrations were determined and the unisex, female and male Upper Reference Limit (URL) were according to package inserts (Roche: 14 ng/L, 9 ng/L, 16 ng/L, Abbott: 26 ng/L, 16 ng/L, 34 ng/L). Results Participants (51% female) were 57±7.6 years (mean±SD). At baseline, median [IQR] hs-cTnT and hs-cTnI were 5.9 [4.5-8.0] and 1.7 [1.1-2.9] ng/L, which increased significantly post-exercise to 8.7 [6.4-12.4] ng/L (P<0.001) and 5.2 [3.1-9.5] ng/L (P<0.001). Pre-exercise, the unisex-URL for hs-cTnT was exceeded by 4.4% walkers and for sex-specific URLs, this resulted in 6.6% females and 3.8% males. For hs-cTnI, the unisex-URL was exceeded by 0.6%, as for sex-specific URLs, 0.8% females and 1.3 % males surpassed. Post-exercise, hs-cTnT URLs were exceeded by 18.2%, 35.1%, 16.5% and as for hs-cTnI post-exercise, 7.3%, 11.6%, 3.8% for unisex, female and male. Alternatively, the absolute median delta difference was 2.4 [0.9-4.6] ng/L for hs-cTnT and 3.0 [1.6-5.7] ng/L hs-cTnI. Conclusion Post-exercise long-distance walkers had significantly increased hs-cTnT and hs-cTnI concentrations, in particular in women when using sex-specific cutoffs. In order to understand clinical implications of these findings, status of cardiac vascular diseases, risk-factors and exercise characteristics will be analyzed in the future.

Temporal trends in concordance between ICD-coded and cardiac biomarker-classified hospitalisation rates for acute coronary syndromes: a linked hospital and biomarker data study

BackgroundSince 2000, the definition of myocardial infarction (MI) has evolved with reliance on cardiac troponin (cTn) tests. The implications of this change on trends of acute coronary syndrome (ACS) subtypes...

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

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.

Pre-hospital evaluation of chest pain patients using the modified HEART-score: rationale and design.

Background: This study assesses how ambulance paramedics using the modified HEART-score with a point-of-care cardiactroponin (cTn) compare to the emergency physicians using the modified HEART-score with a high-sensitive cTn (hs-cTn) in patients with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS), focusing on interobserver agreement and diagnostic performance. Methods: In this prospective multicenter cohort, we compare four cTntesting strategies (serial point of care and hs-cTn cTn measurement) with and without the HEART-score. Outcomes include the HEART-score's interobserver agreement, NSTE-ACS at discharge, major adverse cardiovascular events (MACE) after 30days, and diagnostic accuracy of the different strategies. Conclusion: The POPular HEART study aims to improve NSTE-ACS diagnostic pathways, promoting pre-hospital detection and ruling out of NSTE-ACS to minimize unnecessary hospitalizations and associated costs.Clinical Trial Registration: NCT04851418 (ClinicalTrials.gov).

Implementation of high sensitivity troponin into routine clinical practice - results of the extended CARdiac MArkers guideline uptake in Europe group (CARMAGUE) survey

BackgroundMeasurement of cardiac troponin (cTn) by a high sensitivity method is now the recommended strategy for the detection of myocardial injury. An international survey was undertaken to assess how this has been implemented. MethodsA questionnaire based around 14 domains on cardiac biomarkers was distributed electronically with the aid of professional societies accessed by a web link within the invitation. Results were returned electronically then extracted into a relational database for analysis. ResultsResponses were obtained from 663 laboratories across 76 countries ranging from 1 to 69 largest country. The majority of responses (79.6%) came from the European area. Responses were grouped into broad geographic areas for analysis. Most responses came from hospitals providing a local and regional service of which the majority provided angioplasty. cTn measurement was the dominant biomarker. The majority of laboratories include creatine kinase (CK) in their cardiac profile and approximately 50% also offer the MB isoenzyme of CK. The majority of laboratories (91.9%) measure cTn by a high sensitivity method. Sex specific reference ranges were typically implemented for cardiac troponin I but not for cardiac troponin T. The preferred unit of measurement was nanograms/L. A structured decision-making pathway utilising high sensitivity cTn measurement was used by 83.3% of laboratories who responded. Single sample rule out is common but the majority used serial sampling strategy based on measurement on admission and three hours. ConclusionsMeasurement of cTn by a high sensitivity method is now well established internationally, the use of rapid diagnostic protocols lags behind.

Exercise-induced cardiac troponin release in athletes with versus without coronary atherosclerosis.

The magnitude of exercise-induced cardiac troponin (cTn) elevations is dependent on cardiovascular health status, and previous studies have shown that occult coronary atherosclerosis is highly prevalent among amateur athletes. We tested the hypothesis that middle-aged and older athletes with coronary atherosclerosis demonstrate greater cTn elevations following a controlled endurance exercise test compared with healthy peers. We included 59 male athletes from the Measuring Athletes' Risk of Cardiovascular events 2 (MARC-2) study and stratified them as controls [coronary artery calcium score (CACS) = 0, n = 20], high CACS [≥300 Agatston units or ≥75th Multi-Ethnic Study of Atherosclerosis (MESA) percentile, n = 20] or significant stenosis (≥50% in any coronary artery, n = 19). Participants performed a cycling test with incremental workload until volitional exhaustion. Serial high-sensitivity cTn (hs-cTn) T and I concentrations were measured (baseline, after 30-min warm-up, and 0, 30, 60, 120, and 180 min postexercise). There were 58 participants (61 [58-69] yr) who completed the exercise test (76 ± 14 min) with a peak heart rate of 97.7 [94.8-101.8]% of their estimated maximum. Exercise duration and workload did not differ across groups. High-sensitivity cardiac troponin T (Hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) concentrations significantly increased (1.55 [1.33-2.14]-fold and 2.76 [1.89-3.86]-fold, respectively) over time, but patterns of cTn changes and the incidence of concentrations >99th percentile did not differ across groups. Serial sampling of hs-cTnT and hs-cTnI concentrations during and following an exhaustive endurance exercise test did not reveal differences in exercise-induced cTn release between athletes with versus without coronary atherosclerosis. These findings suggest that a high CACS or a >50% stenosis in any coronary artery does not aggravate exercise-induced cTn release in middle-aged and older athletes.NEW & NOTEWORTHY Exercise-induced cardiac troponin (cTn) release is considered to be dependent on cardiovascular health status. We tested whether athletes with coronary atherosclerosis demonstrate greater exercise-induced cTn release compared with healthy peers. Athletes with coronary atherosclerosis did not differ in cTn release following exercise compared with healthy peers. Our findings suggest that a high CACS or a >50% stenosis in any coronary artery does not aggravate exercise-induced cTn release in middle-aged and older athletes.

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.

A randomized clinical trial of sex and population-specific troponin cutoffs for ruling out acute MI - the danish study of sex and population-specific cutoffs of troponin (DANSPOT)

Abstract Background Measurements of high-sensitivity cardiac troponin (cTn) T/I are used as the gold standard and are the preferred biomarkers to diagnose acute myocardial infarction (MI) in conjugation with symptoms and changes in the ECG. The URL is based on the 99th percentile of troponin concentrations in a healthy reference population. Currently, a sex-uniform manufacturer provided 99th percentile URL of troponin is utilized at Danish hospitals as a diagnostic cutoff for acute MI for both men and women. Reportedly, healthy men have twofold the troponin level compared to healthy women, suggesting that the use of a uniform URL for troponins may lead to the under-diagnostication of acute MI in women and potentially over-diagnostication in men. Purpose The purpose of the DANSPOT study is to evaluate the clinical effect on diagnosis, treatment and outcomes in men and women presenting with acute MI of implementing international guidelines recommended sex-specific 99th percentile URLs for troponin into clinical practice. Methods First, to determine the sex-specific 99th percentile URLs of troponins (table) based on a healthy Danish reference population, blood samples from Danish blood donors, were analyzed using five high-sensitivity (hs) cTn assays (Siemens Atellica and Vista hs-cTnI, Roche hs-cTnT, Abbott Alinity hs-cTnI and Orthos VITROS hs-cTnI). Second, the DANSPOT study is a nationwide cluster-randomized trial with "stepped-wedge" design (figure) with participation of 22 Danish hospital center. With one-month intervals, each of the 22 centers have been randomized to shift from the presently applied sex-uniform 99th percentile URL of troponin to the population and sex-specific 99th percentiles URLs. First center started implementing the new 99th percentiles URLs on April 1, 2022, and the last center is planned to enroll on January 1, 2024. Patients are followed up in Danish registries for 12 months after index admission. The primary endpoint is a composite of myocardial infarction, unplanned revascularization (after index admission) and all-cause mortality and is calculated for the cohort of women and men with ≥2 measurements of troponin within the first 24 hours of admission with maximal troponin level between the new sex-specific 99th percentile URLs and the old sex-uniform 99th percentile URL. Perspective The clinical significance of sex-specific 99th percentile URLs of troponin is poorly investigated and for the same reason not yet implemented in Denmark or many other countries. With the implementation of population and sex-specific 99th URLs of troponin, we expect to detect significantly more women with acute MI, theoretically resulting in a more accurate diagnosis and treatment of women and men with acute MI. This would be guideline-defining for implementing sex-specific cutoffs for troponin in Denmark as well as internationally as recommended in guidelines by professional cardiological societies.Schematic presentation of study designTable of the new 99th percentiles of cTn

Postoperative Myocardial Injury and Inflammatory Biomarkers in Patients Undergoing Vascular Surgery: A Subanalysis of the Platelet Reactivity and Postoperative Myocardial Injury after Major Vascular Surgery (PROMISE) Study

BackgroundPostoperative myocardial injury (PMI) is associated with morbidity and mortality, but the aetiology remains unclear. We studied whether PMI is associated with perioperative systemic inflammation. ObjectiveTo examine the relationship between inflammatory biomarkers (Interleukin 6[IL-6], C-reactive protein [CRP]) and PMI, detected by elevated cardiac troponin (cTn), in patients undergoing elective open abdominal aortic surgery. MethodsThis prospective, single-centre, observational, cohort study included 54 patients undergoing elective open abdominal aortic surgery between March 2018 and April 2021. Patients were routinely treated with aspirin. IL-6 and CRP were measured pre-operatively, directly after surgery, 24h and 48h post-operative. The primary outcome was cTn release assessed by a fifth generation high-sensitive cTn assay. Multivariable generalized linear regression models were used to evaluate the association between inflammatory biomarkers and cTn concentrations. ResultsFifteen patients (27.8%) developed PMI. IL-6 directly and 24h post-operatively was associated with elevated cTn concentrations (1.28 [1.07-1.54], p=0.009)) and 1.75 [1.18-2.59], p=0.006, respectively). Also, CRP directly and 24h post-operatively was associated with elevated cTn concentrations (1.25 [1.06-1.47], p=0.009)) and 1.61 [1.1-2.33], p=0.013, respectively). No association was found between IL-6 or CRP and cTn concentrations when measured at 48h post-surgery. ConclusionBiomarkers of inflammation are associated with elevated post-operative cTn concentrations in the early postoperative period in patients undergoing elective open abdominal aortic surgery.

A-014 Analytical Outlier Occurrence and False Positivity Rate of the Beckman Coulter Access High-sensitivity Cardiac Troponin I Assay

Abstract Background Cardiac troponin (cTn) is the preferred biomarker for the diagnosis of acute myocardial infarction due to its high sensitivity and specificity relative to other available cardiac markers. Accurate measurement is therefore paramount to proper risk stratification of patients. Analytical outliers and false positive results have been previously reported on various platforms though the exact cause remains unknown. These false positive test results may pose a risk for the misclassification of patients and lead to adverse clinical outcomes. We evaluated the performance of the Beckman Coulter Access high-sensitivity cTn I method by measuring the occurrence of analytical outliers between duplicate results and the false positivity rate (i.e., fliers). Methods We tested 2535 samples from 1879 patients in duplicate on the Beckman Coulter Access hs-cTn I assay. These specimens had initial troponin measurements above the gender-specific 99th percentile of the upper reference limit (URL) cutoff and were immediately aliquoted, re-centrifuged, and re-tested. Non-reproducible results (outliers) were defined as having a concentration difference between the replicates exceeding 10%. Critical outliers were defined as duplicate results with concentrations that differed by greater than 10% from the initial result and the second result was classified in a lower risk stratification category than the original result. Results Approximately 12% (305) of the positive samples tested in duplicate had a percent difference that was >10% and therefore did not meet the recommended precision requirements of the assay. Of these specimens, 33 (10.8%) were classified as critical outliers because the repeat test result crossed a critical decision limit threshold. For sixteen samples the risk classification for the patient was downgraded from high (>50 ng/L) to moderate risk (13–50 ng/L (F); 20–50 ng/L (M)). Seventeen false positive results were identified in which the patients were downgraded from the high to low risk category (<13 ng/L (F); <20 ng/L (M)). Nearly 85% of the samples identified as outliers were lithium heparinized plasma. Conclusion We evaluated the reproducibility of the Beckman Coulter Access hs-cTn I method across 11 hospitals in an integrated healthcare network to characterize the occurrence of analytical outliers and false positive results. Our data indicated an outlier rate of 12% (305/2535) for positive hs-cTn I results; however, the risk category only changed for 1.3% (33/2535) of positive troponin results upon repeat analysis. Overall the false positivity rate was determined to be <0.1% (n = 55 560).

High-Sensitivity Cardiac Troponin Assays: Ready for Prime Time!

Rapid and accurate triage of patients presenting with chest pain to an emergency department (ED) is critical to prevent ED overcrowding and unnecessary resource use in individuals at low risk of acute myocardial infarction (AMI) and to efficiently and effectively guide patients at high risk to definite therapy. The use of biomarkers for rule-out or rule-in of suspected AMI has evolved substantially over the last several decades. Previously well-established biomarkers have been replaced by cardiac troponin (cTn). High-sensitivity cTn (hs-cTn) assays represent the newest generation of cTn assays and offer tremendous advantages, including improved sensitivity and precision. Still, implementation of these assays in the United States lags behind several other areas of the world. Within this educational review, we discuss the evolution of biomarker testing for detection of myocardial injury, address the specifics of hs-cTn assays and their recommended use within triage algorithms, and highlight potential challenges in their use. Ultimately, we focus on implementation strategies for hs-cTn assays, as they are now clearly ready for prime time.

The Clinical Validation of a Common Analytical Change Criteria for Cardiac Troponin for Ruling in an Acute Cardiovascular Outcome in Patients Presenting with Ischemic Chest Pain Symptoms.

Serial cardiac troponin (cTn) testing on patients with symptoms suggestive of acute coronary syndrome (ACS) is primarily to identify those patients with evolving myocardial injury. With the improved analytical performance of the high-sensitivity cTn (hs-cTn) assays, different change criteria have been proposed that are mostly assay dependent. Here, we developed and compared a new Common Change Criteria (3C for the combined criteria of >3 ng/L, >30%, or >15% based on the initial cTn concentration of <10 ng/L, 10 to 100 ng/L, or >100 ng/L, respectively) method, versus the 2 h assay-dependent absolute change criteria endorsed by the European Society of Cardiology (ESC), versus the common relative >20% change criterion. These different analytical change criteria were evaluated in 855 emergency department (ED) patients with symptoms of ACS and who had two samples collected 3 h apart. The cTn concentrations were measured with four different assays (Abbott hs-cTnI, Roche hs-cTnT, Ortho cTnI-ES, and Ortho hs-cTnI). The outcomes evaluated were myocardial infarction (MI) and a composite outcome (MI, unstable angina, ventricular arrhythmia, heart failure, or cardiovascular death) within 7 days of ED presentation. The combined change criteria (3C) method yielded higher specificities (range: 93.9 to 97.2%) as compared to the >20% criterion (range: 42.3 to 88.1%) for all four assays for MI. The 3C method only yielded a higher specificity estimate for MI for the cTnI-ES assay (95.9%) versus the absolute change criteria (71.7%). Similar estimates were obtained for the composite outcome. There was also substantial agreement between hs-cTnT and the different cTnI assays for MI with the 3C method, with the percent agreement being ≥95%. The Common Change Criteria (3C) method combining both absolute and different percent changes may be used with cTnI, hs-cTnT, and different hs-cTnI assays to yield similar high-specificity (rule-in) estimates for adverse cardiovascular events for patients presenting to the ED with ACS symptoms.

Development and validation of nomogram models to discriminate between acute aortic syndromes and non-ST-elevation myocardial infarction during troponin-blind period.

Blood-test-based methods of distinguishing between acute aortic syndromes (AASs) and non-ST-elevation myocardial infarction (NSTEMI) during the troponin-blind period of <2-3 h of symptom onset have not been studied previously. We aimed to explore whether routine biomarkers might facilitate differential diagnosis. Data were retrospectively collected from 178 patients with AASs and 460 patients with NSTEMI within 3 h of onset. Differential risk factors related to AASs were identified by univariate and multivariate logistic regression analyses for patients with onset <2 h and onset ≥2 h, respectively, in the cardiac troponin (cTn) cohort. Nomograms were established in the cTn cohort as a training set and validated in the high-sensitivity cTn cohort. To assess the utility of the models in clinical practice, decision curve analyses were performed. D-dimer, fibrinogen, and age were identified as differential risk factors for AASs with the onset of <2 h. D-dimer at an optimal cutoff level of 281 ng/mL for AASs had a sensitivity of 86.4% and a specificity of 91.3%. A nomogram was developed and validated with areas under the curve (AUC) of 0.934 (95% CI: 0.880-0.988) and 0.952 (95% CI: 0.874-1.000), respectively. D-dimer, neutrophil, bilirubin, and platelet were the differential risk factors for AASs with the onset of ≥2 h. D-dimer at an optimal cutoff level of 385 ng/mL has a sensitivity of 91.8% and a specificity of 91.3%. The AUC of the second nomogram in the training set and the validation set were 0.965 (95% CI: 0.942-0.988) and 0.974 (95% CI: 0.944-1.000), respectively. Time-dependent quality of D-dimer should be considered for discriminating AASs from NSTEMI. Both nomogram models may have a clinical utility for evaluating the probability of AASs.

Abstract 12766: Tropsensor: A Rapid Non-Invasive Transdermal Solution For Troponin Measurement

Introduction: Early identification of Acute Myocardial Injury can prompt rapid triage and appropriate interventions to improve clinical outcomes. Over 10 million patients present at the ED with chest-pain, with the majority due to non-cardiac causes, resulting in unnecessary burdens for Emergency Departments (ED). An instant non-invasive method to measure cardiac troponin (cTn) would therefore be of great benefit. Identified need: All Guidelines recommend the use of high sensitivity (HS) cTn for the diagnosis of acute coronary syndromes (ACS). Current biochemical biomarker testing relies on labeling the cTn with turnaround times often an hour or more. Point-of-care solutions reduce the test time, but still depend on the proper handling of samples and blood processing techniques that could lead to difficulties. Tropsensor provides a non-invasive alternative to standard of care (SOC) hs-cTn measurements without the need for a blood draw. The molecular infrared spectroscopy-based transdermal device provides a cTn readout within 5 minutes and allows for serial measurements without any of the delays or complications of blood draws. Methods: A 26-patient (consented and IRB approved) study was conducted at Zuckerberg San Francisco General Hospital with recruitment based on ACS-related presenting symptoms at the ED. Wrist-worn Tropsensor was used on the patients while the corresponding troponin was determined using a high sensitivity (SOC) assay (Siemens ADVIA Centaur) via a blood draw. Results and conclusions: A Pearson’s correlation of 82% with the hs-cTnI was observed. AMI diagnosis sensitivity was 100%, Specificity=50%, PPV=81.8%, NPV=100% and accuracy=84.6%. The Tropsensor modality seems to provide data similar to that of a hs-cTn assay. If so, it would accelerate the assessment of patients presenting with chest pain. By not requiring a blood draw, the Tropsensor could provide a rapid, safe, standardized and reliable source for cTn while allowing bedside serial trending. It thus has the potential to streamline cardiac care workflow by ruling-out many non-cardiac patients and identifying those with high values who are at risk. Such an approach has the potential to facilitate appropriate patient triage towards early discharge of emergent treatment.

Postoperative myocardial injury and platelet reactivity in patients undergoing vascular surgery: The platelet reactivity and postoperative myocardial injury after major vascular surgery (PROMISE) study

BackgroundPostoperative myocardial injury (PMI) after major vascular surgery, detected by elevated cardiac troponin (cTn), has been associated with morbidity and mortality. It is unclear whether the pathophysiology of PMI is determined by increased platelet activity. ObjectiveTo examine the relationship between platelet activation (P-selectin expression) and PMI in patients undergoing elective open abdominal aortic surgery. MethodsThis prospective, single-centre, observational, cohort study included 33 patients undergoing elective open abdominal aortic surgery between March 2018 and April 2021. Patients were routinely treated with aspirin. Unstimulated platelet activation was measured by platelet bound P-selectin expression (range 0–100 %). Explorative coagulation measurements were: stimulated platelet aggregation measured with the VerifyNow® assay (aspirin cartridge), with the Multiplate® analyzer (ASPI, ADP and TRAP) and stimulated coagulation status evaluated by the TEG® Hemostasis Analyzer System (global hemostasis cartridge). The primary outcome was cTn release assessed by the fifth generation high-sensitive cTn assay. Multivariable generalized linear mixed models were used to evaluate the association between platelet function and cTn concentrations over time. ResultsTen patients (30.3 %) developed PMI. Increased P-selectin expression directly after surgery was associated with the cTn concentrations over 48 h (β = 1.39 (1.1–1.75), P = 0.0064). No association was found between P-selectin measured later after surgery (at 24 h or 48 h) and cTn concentrations. Furthermore, there was no association between the explorative coagulation parameters and cTn release. ConclusionPlatelet reactivity, assessed by P-selectin expression measured directly after surgery is associated with PMI, assessed by elevated cTn concentrations in the early postoperative period in patients undergoing elective open abdominal aortic surgery.

Frequency histograms of three high-sensitivity cardiac troponin assays in a reference population.

BackgroundCardiac troponin (cTn) values above the 99th percentile upper reference limit (URL) indicate myocardial injury. We established 99th percentile URLs for three high‐sensitivity cTn (hs‐cTn) assays (Beckman Coulter Access hs‐cTnI, Abbott STAT hs‐cTnI, and Roche Elecsys hs‐cTnT) using a healthy population in Korea.MethodsEach cTn value was measured by three assays and analyzed by dividing by gender and age.ResultsThe frequency histograms of log‐transformed cTn values for Beckman and Abbott assays exhibited a bell‐shaped distribution. The 99th percentile URLs were 9.8, 17.4, and 17.3 ng/L in the total population; 10.9/9.0, 18.9/17.0, and 18.9/17.7 ng/L in the male/female population (p < 0.001 for all three assays); and 11.2/7.2, 19.9/14.5, and 22.7/9.3 ng/L in the older/younger population (p < 0.001 for all three assays) for Beckman, Abbott, and Roche assays, respectively.ConclusionAmong the three assays, bell‐shaped distributions were observed in a frequency histogram of log‐transformed cTn values for healthy population in Beckman and Abbott assays. Also, our findings show that the 99th percentile URLs for cTn levels vary not only by gender but age.