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Aims: Concentrations of high‐sensitivity cardiac troponin T (hs‐cTnT) are frequently elevated in stable patients with confirmed muscle dystrophies. However, sparse information is available on the interpretation of serial concentration changes. Methods: Hs‐cTnT was collected in 35 stable outpatients with confirmed skeletal muscle dystrophies at 0 and 1 h and after 6–12 months during scheduled outpatient visits. We simulated the effectiveness of the European Society of Cardiology (ESC) 0/1 h algorithm and assessed biological variation at 6–12 months using two established methods: reference change value (RCV) and minimal important difference (MID). Results: Median baseline hs‐cTnT concentrations were 34.4 ng/L [inter‐quartile range (IQR): 17.5–46.2], and values > 99th percentile upper limit of normal were present in 34 of 35 patients. All patients were stable without cardiovascular adverse events during a follow‐up of 6.6 months (IQR: 6–7). Median concentration change was 1.9 ng/L (IQR: 0.7–3.2) and 0.8 ng/L (IQR: 0–7.0) at 60 min and 6–9 months, respectively. Applying the criteria of the ESC 0/1 h algorithm for triage of suspected acute coronary syndrome (ACS) showed poor overall effectiveness of baseline hs‐cTnT values. No patient would qualify for rule‐out based on hs‐cTnT less than the limit of detection, whereas five cases would qualify for rule‐in based on hs‐cTnT ≥ 52 ng/L. Biological variabilities at 6–12 months per MID and RCV were 1.2 ng/L [95% confidence interval (CI): 0.7–2.1] and 28.6% (95% CI: 27.9–29.6), respectively. A total of 8 (22.9%) and 25 (71.4%) cases exceeded the biological variation range, suggesting some additional myocardial damage. Conclusions: The high prevalence of elevated hs‐cTnT could negatively impact the effectiveness of rule‐out and rule‐in strategies based on a single hs‐cTnT value. Knowledge of the physiological and biological variation of hs‐cTnT after 6–12 months is helpful to detect the progression of cardiac involvement or to search for cardiac complications including but not limited to arrhythmias that may trigger acute or chronic myocardial damage. [ABSTRACT FROM AUTHOR]

Cardiac biomarkers, especially high-sensitivity cardiac troponin C or I (hs-cTnC or hs-cTnI, respectively), are vital for diagnosing acute myocardial infarction (AMI). Despite the specificity of hs-cTn as a biomarker, the creatine kinase-myocardial band (CK-MB) is commonly used alongside hs-cTn in emergency departments (EDs). We analyzed 23,771 simultaneous hs-cTn (hs-cTnT or hs-cTnI) and CK-MB requests for 17,185 patients in tertiary hospital ED in 2022. The objective of this study was to assess their practical value in diagnosing AMI in real-world settings. Among all 17,185 patients tested, 98.0% underwent hs-cTnT and CK-MB tests, and substantially fewer underwent hs-cTnI testing. We observed concordance between the initial hs-cTn and CK-MB results in 71.3% of patients. Of 131 AMI cases, 57 were positive for both biomarkers, 63 for hs-cTn only, and none for CK-MB alone. CK-MB positivity was often found in the absence of AMI. Discrepancies between the hscTnT and hs-cTnI results occurred in 30.0% of patients. Indiscriminate CK-MB testing for diagnosing AMI in EDs should be reconsidered. Efficient use of CK-MB is important for reducing costs and ensuring optimal patient care. [ABSTRACT FROM AUTHOR]

Kidney disease is linked to the development of cardiovascular disorders, further increasing morbidity and mortality in this high-risk population. Thus, early detection of myocardial damage is imperative in order to prevent devastating cardiovascular complications within this patient group. Over the years, cardiac biomarkers have been identified and are now widely used in everyday clinical practice. More specifically, available data suggest that cardiac troponin and its regulatory subunits (TnT, TnI, and TnC) reflect the injury and necrosis of myocardial tissue. While cTnC is identical in cardiac and skeletal muscle, TnT and TnI constitute cardiac-specific forms of troponin, and, as such, they have been established by international societies as biomarkers of cardiac damage and diagnostic indicators for acute myocardial infarction. Elevations in the levels of both cardiac troponins (cTnT and cTnI) have been also reported in asymptomatic patients suffering from chronic kidney disease. Therefore, if abnormal, they often generate confusion among clinicians regarding the interpretation and clinical significance of their numerical values in emergency settings. The aim of this review is to explore the reasons behind elevated troponin levels in patients with chronic kidney disease and identify when these elevated levels of biomarkers indicate the need for urgent intervention, considering the high cardiovascular risk in this patient group. [ABSTRACT FROM AUTHOR]

Background: Pulmonary hypertension (PH) can lead to cardiac failure, thereby significantly affecting life expectancy and quality of life. Due to inadequate disease surveillance and risk assessment, clinical challenges persist despite advances in diagnosis and treatment. We aimed to review the potential of high-sensitivity cardiac troponin (hs-cTn) as a biomarker for predicting outcomes in PH patients. Methods: A thorough examination of the PubMed and Google Scholar databases was conducted through March 2023. Studies involving adult PH patients and hsTn as a prognostic indicator of outcomes such as mortality, hospitalization, and disease progression were included, after screening their titles and abstracts. Two independent evaluators extracted data, with the quality assessed using the JBI critical appraisal tool. Results: This review uncovered eight studies that examined the prognostic value of hs-cTn in PH patients. Higher hs-cTn levels were associated with increased mortality and hospitalization rates, according to the studies. The severity of PH, cardiac dysfunction, right ventricular function, and systolic dysfunction were associated with hs-cTn. Multiple studies have demonstrated that hsTn has the potential to identify high-risk PH patients who could benefit from targeted therapies and increased clinical monitoring. Conclusions: This review suggests that hsTn may be a biomarker for PH risk stratification and prognosis. Across PH subtypes, elevated hsTn levels predict poor outcomes. However, large-scale prospective studies are needed to confirm hs-cTn's function in diagnosing pulmonary hypertension and determine its potential value in treatment. [ABSTRACT FROM AUTHOR]

Background: The high‐sensitivity HEART pathway (hs‐HP) risk stratifies emergency department (ED) patients with chest pain. It is unknown if its safety and effectiveness vary by sex or race. Methods: We conducted a subgroup analysis of the hs‐HP implementation study, a pre−post interrupted time series at five US EDs. The pre‐implementation period (January 2019 to April 2020) utilized the traditional HEART pathway with contemporary troponin (Siemens) and the post‐implementation period (November 2020 to February 2022) used the hs‐HP using hs‐cTnI (Beckman Coulter). Patients were risk‐stratified using the hs‐HP to rule‐out, observation, and rule‐in groups. Safety and effectiveness outcomes were 30‐day all‐cause mortality or myocardial infarction (MI) and 30‐day hospitalization. Results: Twenty‐six thousand and one hundred twenty‐six patients were accrued (12 317 pre‐ and 13 809 post‐implementation), of which 35.3% were non‐White and 52.7% were female. Among 9703 patients with complete hs‐HP assessments, 48.6% of White and 55.4% of non‐White patients were ruled‐out (p < 0.001). Additionally, 47.3% of males and 54.4% of females were ruled‐out (p < 0.001). Among rule‐out patients, 0.3% of White versus 0.3% of non‐White patients (p = 0.98) and 0.3% of females versus males 0.3% (p = 0.90) experienced 30‐day death or MI. Post‐implementation, 30‐day hospitalization decreased 17.2% among White patients (aOR 0.49, 95% CI: 0.45−0.52), 14.1% among non‐White patients (aOR 0.53, 95% CI: 0.48−0.59), 15.6% among females (aOR 0.50, 95% CI: 0.46−0.54), and 16.6% among males (aOR 0.51, 95% CI: 0.47−0.56). The interactions for 30‐day hospitalization between hs‐HP implementation and race (p = 0.10) and sex (p = 0.69) were not significant. Conclusions: The hs‐HP safely decreases 30‐day hospitalizations regardless of sex or race. However, it classifies more non‐White patients and women to the rule‐out group. [ABSTRACT FROM AUTHOR]

Abstract Aims Concentrations of high‐sensitivity cardiac troponin T (hs‐cTnT) are frequently elevated in stable patients with confirmed muscle dystrophies. However, sparse information is available on the interpretation of serial concentration changes. Methods Hs‐cTnT was collected in 35 stable outpatients with confirmed skeletal muscle dystrophies at 0 and 1 h and after 6–12 months during scheduled outpatient visits. We simulated the effectiveness of the European Society of Cardiology (ESC) 0/1 h algorithm and assessed biological variation at 6–12 months using two established methods: reference change value (RCV) and minimal important difference (MID). Results Median baseline hs‐cTnT concentrations were 34.4 ng/L [inter‐quartile range (IQR): 17.5–46.2], and values > 99th percentile upper limit of normal were present in 34 of 35 patients. All patients were stable without cardiovascular adverse events during a follow‐up of 6.6 months (IQR: 6–7). Median concentration change was 1.9 ng/L (IQR: 0.7–3.2) and 0.8 ng/L (IQR: 0–7.0) at 60 min and 6–9 months, respectively. Applying the criteria of the ESC 0/1 h algorithm for triage of suspected acute coronary syndrome (ACS) showed poor overall effectiveness of baseline hs‐cTnT values. No patient would qualify for rule‐out based on hs‐cTnT less than the limit of detection, whereas five cases would qualify for rule‐in based on hs‐cTnT ≥ 52 ng/L. Biological variabilities at 6–12 months per MID and RCV were 1.2 ng/L [95% confidence interval (CI): 0.7–2.1] and 28.6% (95% CI: 27.9–29.6), respectively. A total of 8 (22.9%) and 25 (71.4%) cases exceeded the biological variation range, suggesting some additional myocardial damage. Conclusions The high prevalence of elevated hs‐cTnT could negatively impact the effectiveness of rule‐out and rule‐in strategies based on a single hs‐cTnT value. Knowledge of the physiological and biological variation of hs‐cTnT after 6–12 months is helpful to detect the progression of cardiac involvement or to search for cardiac complications including but not limited to arrhythmias that may trigger acute or chronic myocardial damage.

Background: Emergency department (ED) presentations after a ground‐level fall (GLF) are common. Falls were suggested to be another possible presenting feature of a myocardial infarction (MI), as unrecognized MIs are common in older adults. Elevated high‐sensitivity cardiac troponin (hs‐cTn) concentrations could help determine the etiology of a GLF in ED. We investigated the prevalence of both MI and elevated high‐sensitivity cardiac troponin T (hs‐cTnT) and I (hs‐cTnI), as well as the diagnostic accuracy of hs‐cTnT and hs‐cTnI regarding MI, and their prognostic value in older ED patients presenting after a GLF. Methods: This was a prospective, international, multicenter, cohort study with a follow‐up of up to 1 year. Patients aged 65 years or older presenting to the ED after a GLF were prospectively enrolled. Two outcome assessors independently reviewed all discharge records to ascertain final gold standard diagnoses. Hs‐cTnT and hs‐cTnI levels were determined from thawed samples for every patient. Results: In total, 558 patients were included. Median (IQR) age was 83 (77–89) years, and 67.7% were female. Elevated hs‐cTnT levels were found in 384 (68.8%) patients, and elevated hs‐cTnI levels in 86 (15.4%) patients. Three patients (0.5%) were ascertained the gold standard diagnosis MI. Within 30 days, 18 (3.2%) patients had died. Nonsurvivors had higher hs‐cTnT and hs‐cTnI levels compared with survivors (hs‐cTnT 40 [23–85] ng/L in nonsurvivors and 20 [13–33] ng/L in survivors; hs‐cTnI 25 [14–54] ng/L in nonsurvivors and 8 [4–16] ng/L in survivors; p < 0.001 for both). Conclusions: A majority of patients (n = 364, 68.8%) presenting to the ED after a fall had elevated hs‐cTnT levels and 86 (15.4%) elevated hs‐cTnI levels. However, the incidence of MI in these patients was low (n = 3, 0.5%). Our data do not support the opinion that falls may be a common presenting feature of MI. We discourage routine troponin testing in this population. However, hs‐cTnT and hs‐cTnI were both found to have prognostic properties for mortality prediction up to 1 year. [ABSTRACT FROM AUTHOR]

Aims We aimed to test the hypothesis if combining coronary artery calcium score (Ca-score) as a quantitative anatomical marker of coronary atherosclerosis with high-sensitivity cardiac troponin as a quantitative biochemical marker of myocardial injury provided incremental value in the detection of functionally relevant coronary artery disease (fCAD) and risk stratification. Methods and results Consecutive patients undergoing myocardial perfusion single-photon emission computed tomography (MPS) without prior CAD were enrolled. The diagnosis of fCAD was based on the presence of ischaemia on MPS and coronary angiography; fCAD was centrally adjudicated in the diagnostic and prognostic domain. Diagnostic accuracy was evaluated using the area under the receiver-operating characteristic curve (AUC). The composite of cardiovascular death and non-fatal acute myocardial infarction (AMI) within 730 days was the primary prognostic endpoint. Among 1715 patients eligible for the diagnostic analysis, 399 patients had fCAD. The combination of Ca-score and high-sensitivity cardiac troponin T (hs-cTnT) had good diagnostic accuracy for the diagnosis of fCAD (AUC 0.79, 95% confidence interval (CI) 0.77–0.81), but no incremental value compared with the Ca-score alone (AUC 0.79, 95% CI 0.77–0.81, P = 0.965). Similar results were observed using high-sensitivity cardiac troponin I (AUC 0.80, 95% CI 0.77–0.82) instead of hs-cTnT. Among 1709 patients (99.7%) with available follow-up, 59 patients (3.5%) suffered the composite primary prognostic endpoint (non-fatal AMI, n = 34; CV death, n = 28). Both Ca-score and hs-cTnT had independent prognostic value. Increased risk was restricted to patients with elevation in both markers. Conclusion The combination of the Ca-score with hs-cTnT increases the prognostic accuracy for future events but does not provide incremental value vs. the Ca-score alone for the diagnosis of fCAD. Study registration Clinical trial registration: NCT00470587. [ABSTRACT FROM AUTHOR]

The Siemens Point-of-Care Testing (POC) Atellica® VTLi high-sensitivity troponin I (hsTnI) device has been previously validated. Verification independently provides evidence that an analytical procedure fulfils concordance with laboratory assays, imprecision, and hemolysis interference requirements.Five whole blood samples spanning the measuring interval were analysed 20 times in succession. Hemolysis interference was assessed at three troponin concentrations by spiking five hemolysate concentrations to plasma to achieve free hemoglobin concentrations 35–1,000 mg/dL. Concordance between whole blood (VTLi) and plasma on laboratory analysers (Beckman, Roche, Siemens) was assessed by Pearson correlation and kappa statistics at the (LOQ) and upper reference limit (URL). This was repeated for frozen plasma samples.Coefficients of variation for whole blood were <10 % for whole blood troponin concentrations of 9.2 and 15.9 ng/L, thus below the URL. Hemolysis positively interfered; at 250 mg/dL affecting the low troponin sample (+3 ng/L; +60 %) and high troponin sample (+37 ng/L; +24 %). Correlation coefficients were 0.98, 0.90 and 0.97 between VTLi and Beckman, Roche and Siemens assays respectively. Corresponding kappa statistics were 0.80, 0.73 and 0.84 at the LOQ and 0.70, 0.44 and 0.67 at the URL.Concordances between VTLi and laboratory assays were at least non-inferior to those between laboratory assays. Imprecision met manufacturer claims and was consistent with a high sensitivity assay. There is potential for hemolysis interference, highlighting the need for quality samples. The results support performance characteristics previously reported in validation studies, and the device offers acceptable performance for use within intended medical settings. [ABSTRACT FROM AUTHOR]

A 78-year-old male was seen in the emergency department (ED) with chest pain. Fifteen months earlier, he had presented to the ED with shoulder and elbow pain. High-sensitivity cardiac troponin I (hs-cTnI) testing was conducted at that time, which produced normal results of 10 and 13 ng/L (cutoff <48 ng/L). During the current admission, his electrocardiogram was unremarkable, with a borderline prolonged PR interval noted. The patient's hs-cTnI results were 25, 47, and 254 ng/L at 0, 1, and 7 hours, respectively. He was diagnosed with demand ischemia and admitted to the hospital. The detection of acute myocardial infarction in this case was made during the first sample collection (t = 0), despite the fact that this result was well within the normal range. [ABSTRACT FROM AUTHOR]

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

Background: The GRACE risk score is generically recommended by guidelines for timing of invasive coronary angiography without stating which score should be used. The aim was to determine the diagnostic performance of different GRACE risk scores in comparison to the ESC 0/1 h-algorithm using high-sensitivity cardiac troponin (hs-cTn). Methods: Prospectively enrolled patients presenting with symptoms suggestive of myocardial infarction (MI) in two large studies testing biomarker diagnostic strategies were included. Five GRACE risk scores were calculated. The amount of risk reclassification and the theoretical impact on guideline-recommended timing of invasive coronary angiography was studied. Results: Overall, 8,618 patients were eligible for analyses. Comparing different GRACE risk scores, up to 63.8% of participants were reclassified into a different risk category. The proportion of MIs identified (i.e., sensitivity) dramatically differed between GRACE risk scores (range 23.8–66.5%) and was lower for any score than for the ESC 0/1 h-algorithm (78.1%). Supplementing the ESC 0/1 h-algorithm with a GRACE risk score slightly increased sensitivity (P < 0.001 for all scores). However, this increased the number of false positive results. Conclusion: The substantial amount of risk reclassification causes clinically meaningful differences in the proportion of patients meeting the recommended threshold for pursuing early invasive strategy according to the different GRACE scores. The single best test to detect MIs is the ESC 0/1 h-algorithm. Combining GRACE risk scoring with hs-cTn testing slightly increases the detection of MIs but also increases the number of patients with false positive results who would undergo potential unnecessarily early invasive coronary angiography. [ABSTRACT FROM AUTHOR]

Summary: Background: Guidelines recommend high-sensitivity cardiac troponin to risk stratify patients with possible myocardial infarction and identify those eligible for discharge. Our aim was to evaluate adoption of this approach in practice and to determine whether effectiveness and safety varies by age, sex, ethnicity, or socioeconomic deprivation status. Methods: A multi-centre cohort study was conducted in 13 hospitals across the United Kingdom from November 1st, 2021, to October 31st, 2022. Routinely collected data including high-sensitivity cardiac troponin I or T measurements were linked to outcomes. The primary effectiveness and safety outcomes were the proportion discharged from the Emergency Department, and the proportion dead or with a subsequent myocardial infarction at 30 days, respectively. Patients were stratified using peak troponin concentration as low (sex-specific 99th percentile). Findings: In total 137,881 patients (49% [67,709/137,881] female) were included of whom 60,707 (44%), 42,727 (31%), and 34,447 (25%) were stratified as low-, intermediate- and high-risk, respectively. Overall, 65.8% (39,918/60,707) of low-risk patients were discharged from the Emergency Department, but this varied from 26.8% [2200/8216] to 93.5% [918/982] by site. The safety outcome occurred in 0.5% (277/60,707) and 11.4% (3917/34,447) of patients classified as low- or high-risk, of whom 0.03% (18/60,707) and 1% (304/34,447) had a subsequent myocardial infarction at 30 days, respectively. A similar proportion of male and female patients were discharged (52% [36,838/70,759] versus 54% [36,113/67,109]), but discharge was more likely if patients were

Kidney disease is linked to the development of cardiovascular disorders, further increasing morbidity and mortality in this high-risk population. Thus, early detection of myocardial damage is imperative in order to prevent devastating cardiovascular complications within this patient group. Over the years, cardiac biomarkers have been identified and are now widely used in everyday clinical practice. More specifically, available data suggest that cardiac troponin and its regulatory subunits (TnT, TnI, and TnC) reflect the injury and necrosis of myocardial tissue. While cTnC is identical in cardiac and skeletal muscle, TnT and TnI constitute cardiac-specific forms of troponin, and, as such, they have been established by international societies as biomarkers of cardiac damage and diagnostic indicators for acute myocardial infarction. Elevations in the levels of both cardiac troponins (cTnT and cTnI) have been also reported in asymptomatic patients suffering from chronic kidney disease. Therefore, if abnormal, they often generate confusion among clinicians regarding the interpretation and clinical significance of their numerical values in emergency settings. The aim of this review is to explore the reasons behind elevated troponin levels in patients with chronic kidney disease and identify when these elevated levels of biomarkers indicate the need for urgent intervention, considering the high cardiovascular risk in this patient group.

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

Acute myocardial infarction (AMI) is a leading cause of mortality globally, highlighting the need for timely and accurate diagnostic strategies. Cardiac troponin has been the biomarker of choice for detecting myocardial injury. A dynamic change in concentrations supports the diagnosis of AMI in the setting of evidence of acute myocardial ischemia. The new generation of high-sensitivity cardiac troponin (hs-cTn) assays has significantly improved analytical sensitivity but at the expense of decreased clinical specificity. As a result, sophisticated algorithms are required to differentiate AMI from non-AMI patients. Establishing optimal hs-cTn cutoffs for these algorithms to rule out and rule in AMI has been the subject of intensive investigations. These efforts have evolved from examining the utility of the hs-cTn 99th percentile upper reference limit, comparing the percentage versus absolute delta thresholds, and evaluating the performance of an early European Society of Cardiology-recommended 3 h algorithm, to the development of accelerated 1 h and 2 h algorithms that combine the admission hs-cTn concentrations and absolute delta cutoffs to rule out and rule in AMI. Specific cutoffs for individual confounding factors such as sex, age, and renal insufficiency have also been investigated. At the same time, concerns such as whether the small delta thresholds exceed the analytical and biological variations of hs-cTn assays and whether the algorithms developed in European study populations fit all other patient cohorts have been raised. In addition, the accelerated algorithms leave a substantial number of patients in a non-diagnostic observation zone. How to properly diagnose patients falling in this zone and those presenting with elevated baseline hs-cTn concentrations due to the presence of confounding factors or comorbidities remain open questions. Here we discuss the developments described above, focusing on criteria and underlying considerations for establishing optimal cutoffs. In-depth analyses are provided on the influence of biological variation, analytical imprecision, local AMI rate, and the timing of presentation on the performance metrics of the accelerated hs-cTn algorithms. Developing diagnostic strategies for patients who remain in the observation zone and those presenting with confounding factors are also reviewed. [ABSTRACT FROM AUTHOR]

Objectives. There is a paucity of data regarding the association between the use of high-sensitivity troponin (hs-cTn) compared with conventional troponin (cTn) and outcomes in chest pain patients in emergency departments (EDs). This study examined the impact of hs-cTnT on prognosis in chest pain patients in EDs. Design. In an observational cohort study, we included chest pain patients visiting the EDs of 14 hospitals in Sweden from 2011 to 2016. The study population was retrieved from each hospital, and information on characteristics and outcomes was collected from nationwide registries. Cox regression was used to estimate adjusted hazard ratios with 95% confidence intervals (HR, 95% CI) for (1) 1-year all-cause mortality, (2) missed acute coronary syndromes (ACSs), (3) use of coronary angiography, and (4) revascularizations within 30 days. Results. We included 170461 patients with chest pain where 62669 patients were tested with cTn while 107792 patients were tested with hs-cTnT. We found 4149 (4.6%) deaths in the cTn group and 6087 (3.7%) deaths in the hs-cTnT group. Patients in the hs-cTnT group had 9% lower mortality (0.91, 0.87–0.94), and were 14% more likely to undergo coronary angiography (1.14, 1.10–1.17), and 12% more likely to be revascularized (1.12, 1.08–1.17) than patients in the cTn group. Conclusions. Patients with chest pain visiting EDs using hs-cTnT had lower mortality and a higher likelihood of undergoing coronary angiographies and revascularizations than those using cTn. There may be a survival benefit of being tested with hs-cTnT compared with cTn in patients seeking medical attention for chest pain. [ABSTRACT FROM AUTHOR]

Background. High-sensitivity cardiac troponin (hs-cTn) is associated with cardiovascular outcomes in the general population, but the prognostic value of hs-cTn in the diabetic population remains inconclusive. This study aimed to systematically review current evidence regarding the association between hs-cTn and the prognosis of diabetic patients. Methods. MEDLINE, Embase, and the Cochrane Database were searched from inception to May, 2023. Observational studies that investigated the prognostic value of hs-cTn in diabetic patients were included in this meta-analysis. Studies were excluded if they did not report outcomes of interest, or urine hs-cTn were measured. Two independent investigators extracted and analyzed the data according to the PRISMA guidelines. The primary outcome was long-term major adverse cardiovascular events (MACE). Results. We included 30 cohort studies of 62,419 diabetic patients. After a median follow-up of 5 (4.1-9.5) years, the pooled results suggested elevation of hs-cTn was associated with a significantly increased risk of MACE (adjusted hazard ratio (HR) per standard deviation (SD) change 1.15, 95% CI [1.06-1.25], I² = 0%) and heart failure (adjusted HR per SD change 1.33, 95% CI [1.08-1.63], I² = 0%) in patients with diabetes. No significant association was found regarding the association between elevation of hs-cTn and risk of all-cause mortality (adjusted HR per SD change 1.24, 95% CI [0.98-1.57], I² = 0%). The results of sensitivity analyses were similar in prospective cohort studies, high-quality studies, or population without major cardiovascular comorbidities at baseline. hs-cTn may represent a strong and independent predictor of MACE and heart failure in diabetic patients. Future research is warranted to determine the appropriate cutoff value for hs-cTn with different comorbidities, for instance, diabetic nephropathy, peripheral artery diseases, etc. [ABSTRACT FROM AUTHOR]

The study aims to develop a decision pathway based on HEAR score and 0 h high-sensitivity cardiac troponin T (hs-cTnT) to safely avoid a second troponin test for suspected non-ST elevation myocardial infarction (NSTEMI) in emergency departments. A HEAR score consists of history, electrocardiogram, age, and risk factors. A HEAR pathway is established using a Bayesian approach based on a predefined safety threshold of NSTEMI prevalence in the rule-out group. In total, 7131 patients were retrospectively enrolled, 582 (8.2%) with index visit NSTEMI and 940 (13.2%) with 180-day major adverse cardiovascular events (MACE). For patients with a low-risk HEAR score (0 to 2) and low 0 h hs-cTnT (<14 ng/L), the HEAR pathway recommends early discharge without further testing. After the HEAR pathway had been applied to rule out NSTEMI, the negative predictive value of index visit NSTEMI was 100.0% (95% CI, 99.8% to 100.0%) and false-negative rate of 180-day MACE was 0.40% (95% CI, 0.18% to 0.87%). Compared with the 0 h hs-cTnT < limit of detection (LoD) strategy (<5 ng/L), the HEAR pathway could correctly reclassify 1298 patients without MACE as low risk and lead to a 18.2% decrease (95% CI, 17.4–19.1%) in the need for a second troponin test. The HEAR pathway may lead to a substantial and safe reduction in repeated troponin test for emergency department patients with suspected NSTEMI. [ABSTRACT FROM AUTHOR]

Aims The present acute myocardial infarction (AMI) rule-out strategies are challenged by the late temporal release of cardiac troponin. Copeptin is a non-specific biomarker of endogenous stress and rises early in AMI, covering the early period where troponin is still normal. An accelerated dual-marker rule-out strategy combining prehospital copeptin and in-hospital high-sensitivity troponin T could reduce length of hospital stay and thus the burden on the health care systems worldwide. The AROMI trial aimed to evaluate if the accelerated dual-marker rule-out strategy could safely reduce length of stay in patients discharged after early rule-out of AMI. Methods and results Patients with suspected AMI transported to hospital by ambulance were randomized 1:1 to either accelerated rule-out using copeptin measured in a prehospital blood sample and high-sensitivity troponin T measured at arrival to hospital or to standard rule-out using a 0 h/3 h rule-out strategy. The AROMI study included 4351 patients with suspected AMI. The accelerated dual-marker rule-out strategy reduced mean length of stay by 0.9 h (95% confidence interval 0.7–1.1 h) in patients discharged after rule-out of AMI and was non-inferior regarding 30-day major adverse cardiac events when compared to standard rule-out (absolute risk difference −0.4%, 95% confidence interval −2.5 to 1.7; P -value for non-inferiority = 0.013). Conclusion Accelerated dual marker rule-out of AMI, using a combination of prehospital copeptin and first in-hospital high-sensitivity troponin T, reduces length of hospital stay without increasing the rate of 30-day major adverse cardiac events as compared to using a 0 h/3 h rule-out strategy. [ABSTRACT FROM AUTHOR]

Recent guidelines recommend the use of a short 0-1h high sensitive cardiac troponin (hs-cTn) algorithm in patients presenting with chest pain at the emergency department (ED). This retrospective observational study evaluates the safety and effectiveness of the new 0-1h hs-cTn I protocol in comparison with the standard 0-3h cTn I protocol for the diagnosis of acute myocardial infarction (AMI). A total of two times 100 consecutive chest pain patients presenting at the ED in November/December 2018 (standard 0-3h cTn I group) and in November/December 2020 (short 0-1h hs-cTn I group) were enrolled. Decision making was based upon validated assay-specific cut-off values. The new 0-1h hs-cTn I protocol had a sensitivity of 100% (95% CI 83.2–100) and a negative predictive value of 100% to rule out AMI. The accuracy of rule-in was slightly lower with a specificity of 92.5% (95% CI 84.4–97.2). The overall protocol accuracy was 94% (95% CI 87.4–97.8) in the short 0-1h hs-cTn I group compared to 88% (95% CI 80.0–93.6) in the standard 0-3h cTn I group (p-value 0.14). The 0-1h hs-cTn I protocol was associated with a numerically higher rate of early hospital discharge compared to the conventional 0-3h cTn I protocol (47% versus 59%; p-value 0.09) and with a shorter median length of stay for those patients (mean 316 min versus 289 min; p-value 0.09). The abbreviated protocol based on the 0-1h hs-cTn I assays is effective and safe for the exclusion of AMI at the ED. [ABSTRACT FROM AUTHOR]

Abstract Background The majority of patients with suspected acute coronary syndrome presenting to the emergency department will be discharged once myocardial infarction has been ruled out, although a proportion will have unrecognised coronary artery disease. In this setting, high-sensitivity cardiac troponin identifies those at increased risk of future cardiac events. In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been ruled out, this trial aims to investigate whether outpatient computed tomography coronary angiography (CTCA) reduces subsequent myocardial infarction or cardiac death. Methods TARGET-CTCA is a multicentre prospective randomised open label with blinded endpoint parallel group event driven trial. After myocardial infarction and clear alternative diagnoses have been ruled out, participants with intermediate cardiac troponin concentrations (5 ng/L to 99th centile upper reference limit) will be randomised 1:1 to outpatient CTCA plus standard of care or standard of care alone. The primary endpoint is myocardial infarction or cardiac death. Secondary endpoints include clinical, patient-centred, process and cost-effectiveness. Recruitment of 2270 patients will give 90% power with a two-sided P value of 0.05 to detect a 40% relative risk reduction in the primary endpoint. Follow-up will continue until 97 primary outcome events have been accrued in the standard care arm with an estimated median follow-up of 36 months. Discussion This randomised controlled trial will determine whether high-sensitivity cardiac troponin-guided CTCA can improve outcomes and reduce subsequent major adverse cardiac events in patients presenting to the emergency department who do not have myocardial infarction. Trial registration ClinicalTrials.gov Identifier: NCT03952351. Registered on May 16, 2019.

Objectives: This study sought to derive and validate a simple model combining traditional clinical risk factors with biomarkers and imaging indicators easily obtained from routine preoperative examinations to predict functionally significant coronary artery disease (CAD) in Chinese populations. Methods: We developed five models from a derivation cohort of 320 patients retrospective collected. In the derivation cohort, we assessed each model discrimination using the area under the receiver operating characteristic curve (AUC), reclassification using the integrated discrimination improvement (IDI) and net reclassification improvement (NRI), calibration using the Hosmer-Lemeshow test, and clinical benefit using decision curve analysis (DCA) to derive the optimal model. The optimal model was internally validated by bootstrapping, and external validation was performed in another cohort including 96 patients. Results: The optimal model including 5 predictors (age, sex, hyperlipidemia, hs-cTnI and LVEF) achieved an AUC of 0.807 with positive NRI and IDI in the derivation cohort. Moreover, the Hosmer-Lemeshow test showed a good fit, and the DCA demonstrated good clinical net benefit. The C-statistic calculated by bootstrapping internal validation was 0.798, and the calibration curve showed adequate calibration (Brier score = 0.179). In the external validation cohort, the optimal model performance was acceptable (AUC = 0.704; Brier score = 0.20). Finally, a nomogram based on this model was constructed to facilitate its use in clinical practice. Conclusions: A simple model combined clinical risk factors with hs-cTnI and LVEF improving the prediction of functionally significant CAD in Chinese populations. This attractive model may be a choice for clinicians to risk stratification for CAD.

The relevance of perioperative myocardial injury (PMI) after cardiac surgery for 30-day mortality and long-term survival remains to be determined. This study assessed the association of PMI after cardiac surgery, reflected by postoperative troponin release, with 30-day mortality and long-term survival after: 1) coronary artery bypass grafting (CABG); 2) isolated aortic valve replacement (AVR) surgery; and 3) all other cardiac surgeries. A consecutive cohort of 8,292 patients undergoing cardiac surgery with serial perioperative high-sensitivity cardiac troponin T (hs-cTnT) measurements was retrospectively analyzed. The relationship between postoperative hs-cTnT release and 30-day mortality or 5-year mortality was analyzed after adjustment with EuroSCORE II using a Cox proportional hazards model. hs-cTnT thresholds for 30-day and 5-year mortality were determined for isolated CABG (32.3%), AVR (14%), and other cardiac surgery (53.8%). High postoperative hs-cTnT levels were associated with higher 30-day mortality but not 5-year mortality. In CABG, median peak concentration of postoperative hs-cTnT was 1,044 ng/L, in AVR it was 502 ng/L, and in other cardiac surgery it was 1,110 ng/L. hs-cTnT thresholds defining mortality-associated PMI were as follows: for CABG, 2,385 ng/L (170× the upper reference limit of normal in a seemingly healthy population [URL]); for AVR, 568 ng/L (41× URL); and for other cardiac procedures, 1,873 ng/L (134× URL). hs-cTnT levels above the cutoffs resulted in an HR for 30-day mortality for CABG of 12.56 (P < 0.001), for AVR of 4.44 (P = 0.004), and for other cardiac surgery of 3.97 (P < 0.001). PMI reflected by perioperative hs-cTnT release is associated with the expected 30-day mortality but not 5-year mortality. Postoperative hs-cTnT cutoffs to identify survival-relevant PMI are higher than suggested in current definitions. [Display omitted] [ABSTRACT FROM AUTHOR]

Aims Cardiac troponin T and I can be measured using a number of high-sensitivity (hs) assays. This study aimed to characterize correlations between four such assays and test their comparative associations with mortality. Methods and results Among adults without cardiovascular disease in the 1999–2004 National Health and Nutrition Examination Survey, hs-troponin T was measured using one assay (Roche) and hs-troponin I using three assays (Abbott, Siemens, and Ortho). Cox regression was used to estimate associations with all-cause and cardiovascular mortality. Pearson's correlation coefficients comparing concentrations from each assay ranged from 0.53 to 0.77. There were 2188 deaths (488 cardiovascular) among 9810 participants. Each hs-troponin assay [log-transformed, per 1 standard deviation (SD)] was independently associated with all-cause mortality: hazard ratio (HR) 1.20 [95% confidence interval (CI) 1.13–1.28] for Abbott hs-troponin I; HR 1.10 (95% CI 1.02–1.18) for Siemens hs-troponin I; HR 1.23 (95% CI 1.14–1.33) for Ortho hs-troponin I; and HR 1.31 (95% CI 1.21–1.42) for Roche hs-troponin T. Each hs-troponin assay was also independently associated with cardiovascular mortality (HR 1.44 to 1.65 per 1 SD). Associations of hs-troponin T and all-cause and cardiovascular mortality remained significant after adjusting for hs-troponin I. Furthermore, associations of hs-troponin I remained significant after mutually adjusting for hs-troponin I from the other individual assays: e.g. cardiovascular mortality HR 1.46 (95% CI 1.19–1.79) for Abbott after adjustment for the Siemens assay and HR 1.29 (95% CI 1.09–1.53) for Abbott after adjustment for the Ortho assay. Conclusion This study demonstrates only modest correlations between hs-troponin T and three hs-troponin I assays and that hs-troponin I assays can provide distinct risk information for mortality in the general population. [ABSTRACT FROM AUTHOR]

Background Elevated levels of high-sensitivity cardiac troponin (hs-cTn) are suggestive of myocardial cell injury and coronary artery disease. We explored the association between hs-cTn and subclinical arteriosclerosis using coronary artery calcification (CAC) scoring among 337 virally suppressed patients with human immunodeficiency virus (HIV) who were ≥50 years old and without evidence of known coronary artery disease. Methods Noncontrast cardiac computed tomography and blood sampling for hs-cTn, both subunit I (hs-cTnI) and subunit T (hs-cTnT), were performed. The relationship between CAC (Agatston score) and serum hs-cTn levels was analyzed using Spearman correlation and logistic regression models. Results The patients, of whom 62% were male, had a median age of 54 years and had been on antiretroviral therapy for a median of 16 years; the CAC score was >0 in 50% of patients and ≥100 in 16%. Both hs-cTn concentrations were positively correlated with the Agatston score, with correlation coefficients of 0.28 and 0.27 (P <.001) for hs-cTnI and hs-cTnT, respectively. hs-cTnI and hs-cTnT concentrations of ≥4 and ≥5.3 pg/mL, respectively, provided the best performance for discriminating patients with Agatston scores ≥100, with a sensitivity and specificity of 76% and 60%, respectively, for hs-cTnI and 70% and 50% for hs-cTnT. In multivariable logistic regression analysis, each log unit increase in hs-cTnI level was independently associated with increased odds of having an Agatston score ≥100 (odds ratio, 2.83 [95% confidence interval, 1.69–4.75]; P <.001). Although not an independent predictor, hs-cTnT was also associated with an increased odds of having an Agatston score ≥100 (odds ratio, 1.58 [95% confidence interval,.92–2.73]; P =.10). Conclusions Among Asians aged ≥50 years with well-controlled HIV infection and without established cardiovascular disease, 50% had subclinical arteriosclerosis. Increasing hs-cTnI and hs-cTnT concentrations were associated with an increased risk of severe subclinical arteriosclerosis, and hs-cTn may be a potential biomarker to detect severe subclinical arteriosclerosis. [ABSTRACT FROM AUTHOR]

Background: The majority of patients with suspected acute coronary syndrome presenting to the emergency department will be discharged once myocardial infarction has been ruled out, although a proportion will have unrecognised coronary artery disease. In this setting, high-sensitivity cardiac troponin identifies those at increased risk of future cardiac events. In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been ruled out, this trial aims to investigate whether outpatient computed tomography coronary angiography (CTCA) reduces subsequent myocardial infarction or cardiac death. Methods: TARGET-CTCA is a multicentre prospective randomised open label with blinded endpoint parallel group event driven trial. After myocardial infarction and clear alternative diagnoses have been ruled out, participants with intermediate cardiac troponin concentrations (5 ng/L to 99th centile upper reference limit) will be randomised 1:1 to outpatient CTCA plus standard of care or standard of care alone. The primary endpoint is myocardial infarction or cardiac death. Secondary endpoints include clinical, patient-centred, process and cost-effectiveness. Recruitment of 2270 patients will give 90% power with a two-sided P value of 0.05 to detect a 40% relative risk reduction in the primary endpoint. Follow-up will continue until 97 primary outcome events have been accrued in the standard care arm with an estimated median follow-up of 36 months. Discussion: This randomised controlled trial will determine whether high-sensitivity cardiac troponin-guided CTCA can improve outcomes and reduce subsequent major adverse cardiac events in patients presenting to the emergency department who do not have myocardial infarction. Trial registration: ClinicalTrials.gov Identifier: NCT03952351. Registered on May 16, 2019. [ABSTRACT FROM AUTHOR]

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• Pre-analytical factors can affect high-sensitivity cardiac troponin (hs-cTn) assays. • Different sample types/matrices may result in different troponin concentrations. • Knowing storage and matrix effects may help in hs-cTn discordant investigations. The current definition of high-sensitivity cardiac troponin (hs-cTn) assays is laboratory-based and their analytical attributes and characteristics have drawn significant attention in the literature at least partly due to the lower concentration cut-offs and changes in concentrations (i.e., deltas) employed in different algorithms and pathways to manage patient care. We propose that pre-analytical conditions such as sample type, storage conditions, and other interferences may also have a significant impact on hs-cTn concentrations and clinical management. The purpose of this literature review is to provide a summary of important pre-analytical and interference studies affecting hs-cTn concentrations. A breakdown of the literature for the major diagnostic companies providing core laboratory instrumentation (i.e., Abbott, Beckman, Ortho, Roche, and Siemens) is also provided. Finally, three cases are highlighted where knowledge of pre-analytical factors aids the hs-cTn clinically discordant investigations. This review highlights the importance of pre-analytical variables, especially storage condition, sample handling, and blood tubes used (i.e., sample type) when interpreting hs-cTn assays. Additional studies are needed to further elaborate on pre-analytical variables (i.e., centrifugation, sample type, stability) and interferences for all hs-cTn assays in clinical use, as knowledge of these variables may aid in hs-cTn clinically discordant investigations. [ABSTRACT FROM AUTHOR]

Background: In light of overlapping symptoms, discrimination between non-ST-elevation (NSTE) acute coronary syndrome (ACS) and acute heart failure (HF) is challenging, particularly in patients with equivocal clinical presentation for suspected ACS. We sought to evaluate the diagnostic and prognostic properties of copeptin in this scenario. Methods: Data from 1088 patients from a single-center observational registry were used to test the ability of serial high sensitivity cardiac troponin T (hs-cTnT)—compared to copeptin, or a combination of copeptin with hs-cTnT—to discriminate acute HF from uncomplicated non-ST-elevation myocardial infarction (NSTEMI) and to evaluate all-cause mortality after 365 days. Patients with STEMI, those with unstable angina and either normal or undetectable hs-cTnT concentrations were excluded. The findings were validated in an independent external NSTE-ACS cohort. Results: A total of 219 patients were included in the analysis. The final diagnosis was acute HF in 56 and NSTE-ACS in 163, with NSTEMI in 78 and unstable angina having stable elevation of hs-cTnT >ULN in 85. The rate of all-cause death at 1 year was 9.6% and occurred significantly more often in acute HF than in NSTE-ACS (15 vs. 6%, p < 0.001). In the test cohort, the area under the receiver operator curve (AUC) for the discrimination of acute HF vs. NSTE-ACS without HF was 0.725 (95% confidence interval [CI] 0.625–0.798) for copeptin and significantly higher than for hs-cTnT at 0 h (AUC = 0.460, 0.370–0.550) or at 3 h (AUC = 0.441, 0.343–0.538). Copeptin and hs-cTnT used either as continuous values or at cutoffs optimized to yield 90% specificity for acute HF were associated with significantly higher age- and sex-adjusted risk for all-cause mortality at 365 days. The findings from the test cohort were consistently replicated in the independent external NSTE-ACS validation cohort. Conclusions: High concentrations of copeptin in patients with suspected NSTE-ACS and equivocal clinical presentation suggest the presence of acute HF compared to uncomplicated NSTE-ACS and are associated with higher rates of all-cause death at 365 days. [ABSTRACT FROM AUTHOR]

BackgroundFew studies explored the association between high-sensitive cardiac troponin T (hs-cTnT) and long-term mortality for patients after surgery. This study was conducted to assess the association of hs-cTnT with long-term mortality and to investigate the extent to which this association is mediated via myocardial injury after noncardiac surgery (MINS).MethodsThis retrospective cohort study included all patients with hs-cTnT measurements who underwent non-cardiac surgery at Sichuan University West China Hospital. Data were collected from February 2018 and November 2020, with follow-up through February 2022. The primary outcome was all-cause mortality within 1 year. As secondary outcomes, MINS, length of hospital stay (LOS), and ICU admission were analyzed.ResultsThe cohort included 7,156 patients (4,299 [60.1%] men; 61.0 [49.0–71.0] years). Among 7,156 patients, there were 2,151 (30.05%) with elevated hs-cTnT(>14 ng/L). After more than 1 year of follow-up, more than 91.8% of mortality information was available. During one-year follow-up after surgery, there were 308 deaths (14.8%) with a preoperative hs-cTnT >14 ng/L, compared with 192 deaths (3.9%) with a preoperative hs-cTnT

Background High‐sensitivity cardiac troponin (hs‐cTn)‐based diagnostic algorithms are recommended for the management of patients with suspected myocardial infarction (MI) without ST elevation. Although mirroring different phases of myocardial injury, falling and rising troponin patterns (FPs and RPs, respectively) are equally considered by most algorithms. We aimed to compare the performance of diagnostic protocols for RPs and FPs, separately. Methods and Results We pooled 2 prospective cohorts of patients with suspected MI and stratified patients to stable, FP, and RP during serial sampling separately for hs‐cTnI and hs‐cTnT and applied the European Society of Cardiology 0/1‐ and 0/3‐hour algorithms comparing the positive predictive values to rule in MI. Overall, 3523 patients were included in the hs‐cTnI study population. The positive predictive value for patients with an FP was significantly reduced compared with patients with an RP (0/1‐hour: FP, 53.3% [95% CI, 45.0–61.4] versus RP, 76.9 [95% CI, 71.6–81.7]; 0/3‐hour: FP, 56.9% [95% CI, 42.2–70.7] versus RP, 78.1% [95% CI, 74.0–81.8]). The proportion of patients in the observe zone was larger in the FP using 0/1‐hour (31.3% versus 55.8%) and 0/3‐hour (14.6% versus 38.6%) algorithms. Alternative cutoffs did not improve algorithm performances. Compared with stable hs‐cTn, the risk for death or MI was highest in those with an FP (adjusted hazard ratio [HR], hs‐cTnI 2.3 [95% CI, 1.7–3.2]; RP adjusted HR, hs‐cTnI 1.8 [95% CI, 1.4–2.4]). Findings were similar for hs‐cTnT tested in 3647 patients overall. Conclusions The positive predictive value to rule in MI by the European Society of Cardiology 0/1‐ and 0/3‐hour algorithms is significantly lower in patients with FP than RP. These are at highest risk for incident death or MI. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02355457, NCT03227159.

[Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Aims To evaluate echocardiographic and biomarker changes during chemotherapy, assess their ability to early detect and predict cardiotoxicity and to define the best time for their evaluation. Methods and results Seventy‐two women with breast cancer (52 ± 9.8 years) treated with anthracyclines (26 also with trastuzumab), were evaluated for 14 months (6 echocardiograms/12 laboratory tests). We analysed: high‐sensitivity cardiac troponin T, NT‐proBNP, global longitudinal strain (GLS), left ventricle end‐systolic volume (LVESV), left ventricle end‐diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF). Cardiotoxicity was defined as a reduction in LVEF>10% compared with baseline with LVEF

[Display omitted] [ABSTRACT FROM AUTHOR]

Cardiac biomarkers, especially high-sensitivity cardiac troponin C or I (hs-cTnC or hs-cTnI, respectively), are vital for diagnosing acute myocardial infarction (AMI). Despite the specificity of hs-cTn as a biomarker, the creatine kinase-myocardial band (CK-MB) is commonly used alongside hs-cTn in emergency departments (EDs). We analyzed 23,771 simultaneous hs-cTn (hs-cTnT or hs-cTnI) and CK-MB requests for 17,185 patients in tertiary hospital ED in 2022. The objective of this study was to assess their practical value in diagnosing AMI in real-world settings. Among all 17,185 patients tested, 98.0% underwent hs-cTnT and CK-MB tests, and substantially fewer underwent hs-cTnI testing. We observed concordance between the initial hs-cTn and CK-MB results in 71.3% of patients. Of 131 AMI cases, 57 were positive for both biomarkers, 63 for hs-cTn only, and none for CK-MB alone. CK-MB positivity was often found in the absence of AMI. Discrepancies between the hs-cTnT and hs-cTnI results occurred in 30.0% of patients. Indiscriminate CK-MB testing for diagnosing AMI in EDs should be reconsidered. Efficient use of CK-MB is important for reducing costs and ensuring optimal patient care.

Background: Point-of-care (POC) high-sensitivity troponin (hs-cTn) assays within a clinical pathway may safely reduce length of stay (LoS) for patients presenting to the emergency department (ED) with possible acute myocardial infarction (AMI). In this early-report we present the first evaluation of a POC hs-cTn in real-life care., Methods: In adult patients presenting to ED investigated for possible AMI we compared the LoS in patients assessed with a troponin in the 8-weeks before (usual-care phase) and the 8-weeks following introduction of the Siemens Atellica VTLi POC hs-cTnI for decision-making (intervention phase). The VTLi replaced the laboratory (Beckman Coulter) assay as the default hs-cTn test within the clinical pathway. This was the only change to the pathway process. The safety outcome was first event AMI or cardiac death within 30-days., Results: There were 2376 presentations in the usual-care phase with 188 individuals with AMI and 2392 in the intervention phase with 198 AMI. In the intervention phase there was a mean (95% CI) reduction in LoS of 32 minutes (22 mins to 41 mins) compared with the usual-care phase. This represents 21.4 fewer patient-hours in the ED each day (1196 in the 8-week period). In both phases the pathway correctly identified all cases of AMI at index attendance. There were four follow-up events (2 usual-care, 2 intervention) within 30d., Conclusion: The deployment of a hs-cTn POC analyser into a large ED safely reduced length of stay. If translatable to other EDs this could represent an important advancement to patient care., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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., Competing Interests: Declaration of competing interest Edward Suh reports a relationship with Roche Diagnostics that includes: funding grants. Bryn Mumma reports a relationship with Roche Diagnostics that includes: consulting or advisory. Marc Probst reports a relationship with Roche Diagnostics that includes: non-financial support. Andrew Einstein reports a relationship with Ionetix that includes: speaking and lecture fees. Andrew Einstein reports a relationship with WL Gore and Associates that includes: consulting or advisory and funding grants. Andrew Einstein reports a relationship with Canon Medical Systems Corporation that includes: consulting or advisory and funding grants. Lauren Ranard reports a relationship with Boston Scientific Corporation that includes: funding grants. Andrew Einstein reports a relationship with Attralus, Inc. that includes: funding grants. Andrew Einstein reports a relationship with BridgeBio that includes: funding grants. Andrew Einstein reports a relationship with GE Healthcare that includes: funding grants. Andrew Einstein reports a relationship with Intellia Therapeutics Inc that includes: funding grants. Andrew Einstein reports a relationship with Ionis Pharmaceuticals Inc that includes: funding grants. Andrew Einstein reports a relationship with Neovasc Inc that includes: funding grants. Andrew Einstein reports a relationship with Roche Medical Systems that includes: funding grants. Andrew Einstein reports a relationship with Pfizer that includes: funding grants. Co-author, AJE, has recieved authorship fees from Wolters Kluwer Healthcare - UpToDate. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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

Abstract Background Although some emergency department risk stratification tools consider non‐specific ECG findings as an aid in disposition decisions, their clinical value in patients with an initially low high‐sensitivity cardiac troponin I (hsTnI) is unclear. Objective Our purpose was to determine if non‐specific ECG (ns‐ECG) findings are associated with 30‐day major adverse cardiac events (MACE) in ED patients presenting with suspected acute coronary syndromes (ACS) who have a low initial hsTnI. Methods Using the prospective Siemens Atellica hsTnI Food and Drug Administration submission observational database, we conducted a retrospective cohort study of the association between ns‐ECG findings (defined as left bundle branch block [LBBB], ST depression [STD], or T‐wave inversions [TWI]) and 30‐day MACE (death, myocardial infarction, heart failure hospitalization, or coronary revascularization). Eligible patients presented with suspected ACS to one of 29 US EDs from April 2015 to April 2016, had stable vital signs, a blood sample for hsTnI (Siemen's Atellica, Siemens Healthineers, Inc, Malvern, PA) obtained at 1, 3, and 6 hours after ED presentation, and were followed for 30 days. The relationship between 30‐day outcome, initial hsTnI, and ns‐ECG was evaluated using chi‐square testing. Results Of 2676 enrolled, 1313 patients met the inclusion criteria and are included in the analysis. Median (interquartile range) age was 62 years (54, 72), 54% were male, with 56% white, and 39% African American. Median (interquartile range) times from symptom onset to presentation and presentation to specimen collection were 92 (0, 216) and 146 (117, 177) minutes, respectively. The most common presenting symptoms were chest pain (84%), followed by dyspnea (9%). ECG findings were categorized as T‐wave inversion or non‐specific T wave changes (42%), ST depression ns‐ECG ST changes (16%), or LBBB (2%). Thirty‐day MACE occurred in 72 (5.5%) patients, with coronary revascularization (35 patients, 2.7%) and heart failure (25 patients, 1.9%) being the most frequent outcomes. In patients with an initial hsTnI below the limit of quantitation (LOQ) of 2.5 ng/L (n = 449), there was no association between ns‐ECG changes and 30‐day MACE (P = 0.42). If the hsTnI was ≥LOQ (2.5 ng/L), there were increased rates of 30‐day MACE and ns‐ECG findings (P = 0.01). Conclusion In ED suspected ACS patients without unstable vital signs, and an initial hsTnI less than the LOQ (2.5 ng/L), ns‐ECG findings are not associated with 30‐day major adverse cardiac events. The use of ns‐ECG findings in ACS disposition should be considered in the context of hsTnI levels.

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 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.

Increased inflammation and myocardial injury can be observed in the absence of myocardial infarction or obstructive coronary artery disease (CAD). The authors determined whether biomarkers of inflammation and myocardial injury—interleukin (IL)-6 and high-sensitivity cardiac troponin (hs-cTn)—were associated with the presence and extent of CAD and were independent predictors of major adverse cardiovascular events (MACEs) in stable chest pain. Using participants from the PROMISE trial, the authors measured hs-cTn I and IL-6 concentrations and analyzed computed tomography angiography (CTA) images in the core laboratory for CAD characteristics: significant stenosis (≥70%), high-risk plaque (HRP), Coronary Artery Disease Reporting and Data System (CAD-RADS) categories, segment involvement score (SIS), and coronary artery calcium (CAC) score. The primary endpoint was a composite MACE (death, myocardial infarction, or unstable angina). The authors included 1,796 participants (age 60.2 ± 8.0 years; 47.5% men, median follow-up 25 months). In multivariable linear regression adjusted for atherosclerotic cardiovascular disease (ASCVD) risk, hs-cTn was associated with HRP, stenosis, CAD-RADS, and SIS. IL-6 was only associated with stenosis and CAD-RADS. hs-cTn above median (1.5 ng/L) was associated with MACEs in univariable analysis (HR: 2.1 [95% CI: 1.3-3.6]; P = 0.006), but not in multivariable analysis adjusted for ASCVD and CAD. IL-6 above median (1.8 ng/L) was associated with MACEs in multivariable analysis adjusted for ASCVD and HRP (HR: 1.9 [95% CI: 1.1-3.3]; P = 0.03), CAC (HR: 1.9 [95% CI: 1.0-3.4]; P = 0.04), and SIS (HR: 1.8 [95% CI: 1.0-3.2]; P = 0.04), but not for stenosis or CAD-RADS. In participants with nonobstructive CAD (stenosis 1%-69%), the presence of both hs-cTn and IL-6 above median was strongly associated with MACEs (HR: 2.5-2.7 after adjustment for CAD characteristics). Concentrations of hs-cTn and IL-6 were associated with CAD characteristics and MACEs, indicating that myocardial injury and inflammation may each contribute to pathways in CAD pathophysiology. This association was most pronounced among participants with nonobstructive CAD representing an opportunity to tailor treatment in this at-risk group. (PROspective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550) [Display omitted] [ABSTRACT FROM AUTHOR]

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To validate the analytical performance and diagnostic accuracy for non-ST-segment elevation myocardial infarction (NSTEMI) with a new high-sensitivity cardiac troponin I (hs-cTnI) assay on the automated light-initiated chemiluminescent assay (LiCA®) platform. Comprehensive analytical validations were performed, and the 99th percentile upper reference limit (URL) from apparently healthy individuals were established. We evaluated the diagnostic performance of the assay for NSTEMI. The limit of quantitation (LoQ) were 1.9 ng/L (20% CV) and 5.1 ng/L (10% CV). The sex-specific 99th percentile URLs were 17.6 ng/L (4.2% CV) for men (age 20–79y) and 14.2 ng/L (4.9% CV) for women (age 19–89y) in serum, 14.4 ng/L (4.9% CV) for men (age 19–88y) and 12.9 ng/L (5.2% CV) for women (age 19–87y) in plasma, respectively. Detection rates in healthy individuals were from 98.7 to 99.1%. The correlation coefficient and median bias between LiCA and Architect were 0.985 and 0.1% (−2.0–2.9%) in full analytical range of serum specimens. In lower range (<100 ng/L), LiCA had an overall positive bias 6.7% (−1.6–13.3%), R=0.949. At the specific medical decision levels (15.2, 26.2 and 64.0 ng/L), assay difference was estimated to be <10%. No significant differences on AUC, sensitivity and specificity, NPV and PPV were found between LiCA and Architect for the diagnosis of NSTEMI. LiCA hs-cTnI is a precise, highly sensitive and specific assay that meets the requirement of a 3rd generation (level 4) high-sensitivity method. The diagnostic accuracy of LiCA assay for NSTEMI is comparable to the established Architect hs-cTnI assay. [ABSTRACT FROM AUTHOR]

Aims Current troponin cut-offs suggested for the post-operative workup of patients following coronary artery bypass graft (CABG) surgery are based on studies using non-high-sensitive troponin assays or are arbitrarily chosen. We aimed to identify an optimal cut-off and timing for a proprietary high-sensitivity cardiac troponin I (hs-cTnI) assay to facilitate post-operative clinical decision-making. Methods and results We performed a retrospective analysis of all patients undergoing elective isolated CABG at our centre between January 2013 and May 2019. Of 4684 consecutive patients, 161 patients (3.48%) underwent invasive coronary angiography after surgery, of whom 86 patients (53.4%) underwent repeat revascularization. We found an optimal cut-off value for peak hs-cTnI of >13 000 ng/L [>500× the upper reference limit (URL)] to be significantly associated with repeat revascularization within 48 h after surgery, which was internally validated through random repeated sampling with 1000 iterations. The same cut-off also predicted 30-day major adverse cardiovascular events and all-cause mortality after a median follow-up of 3.1 years, which was validated in an external cohort. A decision tree analysis of serial hs-cTnI measurements showed no added benefit of hs-cTnI measurements in patients with electrocardiographic or echocardiographic abnormalities or haemodynamic instability. Likewise, early post-operative hs-cTnI elevations had a low yield for clinical decision-making and only later elevations (at 12–16 h post-operatively) using a threshold of 8000 ng/L (307× URL) were significantly associated with repeat revascularization with an area under the curve of 0.92 (95% confidence interval 0.88–0.95). Conclusion Our data suggest that for hs-cTnI, higher cut-offs than currently recommended should be used in the post-operative management of patients following CABG. [ABSTRACT FROM AUTHOR]

Keywords: bias; cardiac surgery; high-sensitivity cardiac troponin; reagent lot-to-lot EN bias cardiac surgery high-sensitivity cardiac troponin reagent lot-to-lot e105 e107 3 05/31/23 20230601 NES 230601 To the Editor, Badrick, Ward and Hickman aptly highlight in their review article the importance of immunoassay curve fitting and its impact on bias [[1]]. Here, the patient bias was -2.9% while the QC bias was 7.6%, thus reinforcing the need to analyze patient samples when performing lot-to-lot evaluations. [[1]] This redesign might be helpful for hospital laboratories whose clinicians only order hs-cTn in the emergency setting for patients with possible acute coronary syndrome; however, there are other patient populations where hs-cTn measurements provide equally important risk-stratification information [[6]], [[7]], [[8]], [[9]]. [Extracted from the article]