cTn Concentrations Research Articles

Temporal Release of High-Sensitivity Cardiac Troponin T and I and Copeptin After Brief Induced Coronary Artery Balloon Occlusion in Humans.

Cardiac troponins (cTns) are the cornerstone of diagnosing acute myocardial infarction. There is limited knowledge on the duration of ischemia necessary to induce a measurable release of cTns or the very-early-release kinetics of cTns after an ischemic event. Copeptin may have a supplementary role in ruling out myocardial infarction early. We investigated the release of cTns and copeptin in the first hours after experimental balloon-induced ischemia in humans. Thirty-four patients (median age, 60 years [interquartile range, 51-64]; 15 men, 43%) with angiographically normal coronary arteries were randomly assigned into 4 groups with different durations of induced myocardial ischemia (0, 30, 60, 90 s). Ischemia was induced by inflating a balloon in the left anterior descending artery between the first and second diagonal branch. Blood was collected before balloon inflation (baseline) every 15 minutes for the first 3 hours, and every 30 minutes for the next 3 hours. The cTns were analyzed by 3 high-sensitivity (hs) cTn assays: hs-cTnT (Roche), hs-cTnI (Siemens), and hs-cTnI (Abbott). Copeptin was analyzed by a sandwich immunoluminometric assay. None of the patients had any complications. Increased cTn concentrations were detected by all 3 assays, and the magnitude of the increase was associated with the duration of ischemia. Increased hs-cTnI (Siemens) concentrations were first detectable 15 minutes after 90-s ischemia (median 43.7% increase) and increased more steeply and had a higher peak than the other assays. Copeptin levels did not significantly change. Using the cTnT, hs-cTnI (Siemens), and hs-cTnI (Abbott) concentrations at 0 and 180 minutes, 1 (11%), 0, and 0 patients from the 60-s ischemia group and 5 (63%), 2 (25%), and 1 (11%) from the 90-s ischemia group, respectively, fulfilled criteria for a biochemical myocardial infarction. This study is the first to report the early-release kinetics of cTn concentrations after different durations of experimental coronary balloon occlusion in humans. All assays detected a cTn increase after only 30 s of ischemia. hs-cTnI (Siemens) rose faster and reached a higher peak. Copeptin levels did not change significantly. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03203057.

Myocardial Injury in Adults Hospitalized With COVID-19.

Myocardial Injury in Adults Hospitalized With COVID-19.

Interpretacja stężeń troponin sercowych w świetle czwartej uniwersalnej definicji zawału serca z 2018 roku

Cardiac troponin (cTn) is a laboratory test routinely used in patients with suspected acute coronary syndrome (ACS). Unfortunately, wide variety of laboratory assays and different cut-off values regarding gender may result in difficulties with diagnosis and delay the treatment. Troponin I and less specific troponin T are used to diagnose ACS. Dynamic changes in cTn concentration are required to confirm the diagnosis of myocardial infarction (MI). The fourth universal definition of myocardial infarction defines five major types of MI — atherosclerotic plaque disruption, imbalance between myocardial oxygen supply and demand unrelated to acute coronary atherothrombosis, cardiac death with symptoms suggestive of myocardial ischaemia and new ischaemic electrocardiographic changes, MI connected with percutaneous coronary intervention or coronary bypass grafting. Considering this definition, increased cTn concentrations are not always related to abnormal findings in coronary angiography and can be associated with many conditions. Increased high sensitivity cTn values in healthy individuals can be induced by intense physical activity, which is confirmed by studies performed in marathoners. While elevated cTn levels are observed in 20–60% of patients with acute ischemic stroke and are associated with an increased long-term mortality, acute MI is diagnosed only in 3,5% of patients. Elevated cTn levels often accompany chronic kidney disease, however changes in serial testing are obligatory for acute MI diagnosis. Deterioration of kidney function is more connected with elevated TnT rather than TnI levels. Regardless of the reason, increased cTn concentration is a negative predictive factor. Patients with elevated cTn levels need further diagnosis, risk stratification and a long-term follow-up.

Short- and long-term biological variation of cardiac troponin I in healthy individuals, and patients with end-stage renal failure requiring haemodialysis or cardiomyopathy.

Objectives High-sensitivity (hs) cardiac troponin (cTn) assays can quantitate small fluctuations in cTn concentration. Determining biological variation allows calculation of reference change values (RCV), to define significant changes. We assessed the short- and long-term biological variation of cardiac troponin I (cTnI) in healthy individuals and patients with renal failure requiring haemodialysis or cardiomyopathy. Methods Plasma samples were collected hourly for 4h and weekly for seven further weeks from 20 healthy individuals, 9 renal failure patients and 20 cardiomyopathy patients. Pre- and post-haemodialysis samples were collected weekly for 7weeks. Samples were analysed using a hs-cTnI assay (Abbott Alinity ci-series). Within-subject biological variation (CVI), analytical variation (CVA) and between-subject biological variation (CVG) was used to calculate RCVs and index of individuality (II). Results For healthy individuals, CVI, CVA, CVG, RCV and II values were 8.8, 14.0, 43.1, 45.8% and 0.38 respectively for short-term, and 41.4, 14.0, 25.8, 121.0% and 1.69 for long-term. For renal failure patients, these were 2.6, 5.8, 50.5, 17.6% and 0.30 respectively for short-term, and 19.1, 5.8, 11.2, 55.2% and 1.78 for long-term. For cardiomyopathy patients, these were 4.2, 10.0, 65.9, 30.0% and 0.16 respectively for short-term, and 17.5, 10.0, 63.1, 55.8% and 0.32 for long-term. Mean cTnI concentration was lower post-haemodialysis (15.2 vs. 17.8ng/L, p<0.0001), with a 16.9% mean relative change. Conclusions The biological variation of cTnI is similar between end-stage renal failure and cardiomyopathy patients, but proportionately greater in well-selected healthy individuals with very low baseline cTnI concentrations.

Epinephrine Exacerbates Myocyte Injury in a Porcine Model of Cardiac Arrest

ObjectiveAlthough circulating cardiac troponin (cTn) concentrations are often elevated in patients following resuscitation from cardiac arrest (CA), this finding is commonly attributed to myocyte injury caused by ongoing myocardial infarction (MI) and/or defibrillation during resuscitation. To determine whether measurable cTn elevations occur independently of these factors, we employed serial sampling of systemic and coronary venous blood to quantify cTn release in a porcine model of CA devoid of ongoing MI or multiple defibrillation attempts. In light of recent concerns regarding potential detrimental effects of epinephrine (EPI) in CA, cTn levels were compared in animals that were resuscitated with vs. without exogenous EPI.MethodsSwine (n=41) were subjected to 7 min CA via electrical induction of ventricular fibrillation (VF) followed by cardiopulmonary resuscitation (CPR) with manual chest compressions and mechanical ventilation for up to 20 min. Biphasic defibrillation (200 J) was performed 1 min after the start of CPR and a subset of animals (n=10) received intravenous EPI (0.015 mg/kg) 1 min later. After return of spontaneous circulation (ROSC; defined as unassisted systolic blood pressure &gt;80 mmHg for 1 min), animals were followed for up to 4 hours with serial blood sampling from the jugular vein and coronary sinus for assessment of cTnI via a porcine‐specific ELISA.ResultsAmong the entire cohort, 1.2±0.1 defibrillator shocks were required to terminate VF, ROSC was achieved 175±7 seconds after the initiation of CPR, and 15 animals (38%) survived for the entire 4‐hour recovery period (2/10 with EPI, 13/31 without EPI). Despite the absence of ongoing MI or prolonged resuscitation efforts, a significant 5‐fold rise in coronary sinus (from 106±17 to 526±74 ng/L, p&lt;0.01) and systemic (from 67±14 to 350±54 ng/L, p&lt;0.01) cTnI concentrations was observed 15 min post‐ROSC (trans‐coronary cTnI gradient from 39±7 to 176±29 ng/L, p&lt;0.01). Widening of the trans‐coronary cTnI gradient continued throughout the recovery period, reaching 795±164 ng/L 4 hours post‐ROSC and leading to a 16‐fold increase in circulating cTnI concentrations at this timepoint (1087±208 ng/L, p&lt;0.01 vs. baseline). Exogenous EPI exacerbated myocyte injury, as EPI‐treated animals exhibited a significantly higher trans‐coronary cTnI gradient 30 min post‐ROSC that persisted throughout the recovery period and led to significantly higher circulating cTnI concentrations vs. animals resuscitated without EPI at each timepoint (Figure ).ConclusionsThese results demonstrate that resuscitation from CA is associated with measurable elevations in cTnI as early as 15 min post‐ROSC, even in the absence of ongoing MI or prolonged CPR with multiple defibrillator shocks. Thus, assessment of circulating cTnI following resuscitation from CA is unlikely to accurately identify patients suffering from an acute coronary syndrome. Administration of exogenous EPI during resuscitation exacerbates the extent of myocyte injury, which may contribute to poor long‐term outcomes.Support or Funding InformationFunding SourcesNIH, AHA, ZOLL Foundation, Pro‐Al Medico Technologies, Inc., UB CAT, NCATS, and the Dept. of Veterans Affairs.Figure 1

Combining serum calcitonin, carcinoembryonic antigen, and neuron-specific enolase to predict lateral lymph node metastasis in medullary thyroid carcinoma.

BackgroundThis study aimed to investigate the clinical application of combined detection of serum calcitonin (Ctn), carcinoembryonic antigen (CEA), and neuron‐specific enolase (NSE) in predicting lateral lymph node metastasis (LLNM) in medullary thyroid carcinoma (MTC).MethodsSeventy‐four consecutive patients with MTC were enrolled. The relationship between serum Ctn, CEA, and NSE and LLNM was retrospectively analyzed by univariate analysis and logistic regression analysis. Furthermore, the clinical application of serum Ctn, CEA, and NSE combined detection in prediction of LLNM in MTC was also evaluated.ResultsThe rate of LLNM in this study was 48.64% (36/74).The expression levels of serum Ctn, CEA, and NSE in MTC with LLNM were significantly higher than those without LLNM (all P < .01). The area under the curve (AUC) predicted by serum Ctn, CEA, and NSE for LLNM in MTC patients was 0.867, 0.831, and 0.726, respectively, and the AUC of serum Ctn, CEA, and NSE combined detection was up to 0.890, higher than using a single biomarker. The sensitivity and specificity of serum Ctn, CEA, and NSE combined detection in prediction of LLNM were 88.89% and 81.57%, respectively.ConclusionsThe concentrations of serum Ctn, CEA, and NSE are closely related to LLNM in MTC, and the combined detection of all three biomarkers has a higher clinical value in the evaluation of MTC patients with LLNM. With more perspective study in the future, it would be an indicator of influencing personalized surgical strategy for different MTC patients.

Laboratory-related issues in the measurement of cardiac troponins with highly sensitive assays.

A number of assay-related issues can affect the performance of cardiac troponin (cTn) measurement in everyday practice. In this respect, it is vital that all information on cTn assays is known and that the performance characteristics of assays are objectively assessed and adequately described. The advent of the latest generation of more sensitive cTn assays has heralded a new wave of information about low concentrations of cTn in blood. These recent generation assays have improved analytical sensitivity and corresponding performance at low cTn concentrations when compared to their predecessors, providing a convincing goal for laboratory medicine in helping clinicians in the diagnosis of acute myocardial infarction. Crucial to the clinical utility of highly sensitive cTn assays is the laboratorians' role in closely scrutinizing proposed assays and defining their value in relation to available evidence. Analytical, as well as pre-analytical and post-analytical, aspects must be documented. In this review, we describe what laboratory professionals should know about their cTn assay performance characteristics and the pre-analytical prerequisites for robustness to ensure optimal post-analytical reporting.

Impact of comorbidities on peak troponin levels and mortality in acute myocardial infarction

ObjectivesTo characterise peak cardiac troponin levels, in patients presenting with acute myocardial infarction (AMI), according to their comorbid condition and determine the influence of peak cardiac troponin (cTn) levels on...

Early kinetic profiles of troponin I and T measured by high-sensitivity assays in patients with myocardial infarction

The early concentration kinetic profiles of cardiac troponin in patients with non-ST-elevated myocardial infarction (NSTEMI) measured by high-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) assays have not been described.In intermediate-to-high-risk of NSTEMI patients we measured serial cTn concentrations on ED arrival, at 1, 2, 3, 6–12, 24 and 48-hours with hs-cTnI and hs-cTnT assays. Log-normal curves were fitted to concentrations from time from symptom onset, and the time to rule-out decision thresholds estimated (hs-cTnI: 2 ng/L and 5 ng/L; hs-cTnT: 5 ng/L).Among 164 patients there were 58 NSTEMI. The hs-cTnI to hs-cTnT ratio increased linearly over the first 6–12 h following symptom onset. The estimated times from symptom onset to the 2 ng/L and 5 ng/L thresholds for hs-cTnI were 1.8 (0.1–3.1) and 1.9 (1.1–3.5) hours, and to the 5 ng/L threshold for hs-cTnT 1.9 (1.1–3.8) hours. The estimated time to exceed 5 ng/L was ≥3 hours in 32.6% (95%CI: 20.0% to 48.1%) cases for hs-cTnI and 33.3% (19.6% to 50.0%) for hs-cTnT.cTnI concentrations increased at a much more rapid rate than cTnT concentrations in patients with NSTEMI. Concentrations of a high proportion of patients took longer than 3 hours from symptom onset to exceed the 5 ng/L rule-out decision threshold.

Evaluation of the Relationship between Early Troponin Clearance and Short-Term Mortality in Patients with Chronic Renal Failure

Objective In patients with CKD, cTn concentrations may be elevated in the absence of AMI, which is a predicted finding caused by chronic structural heart disease rather than acute injury. The increase in troponin level observed in noncardiac conditions provides conflicting results when predicting mortality. Low lactate clearance was associated with increased mortality. Lactate clearance is calculated as follows: (early lactate − late lactate/early lactate) ∗ 100. We aimed to investigate whether troponin clearance calculated according to this formula had an effect on short-term mortality. Methods The study included 300 patients with chronic renal failure who had a sepsis-related organ failure assessment (SOFA) score ≥3. By taking the baseline troponin at the time of emergency presentation as reference and comparing them with the fourth-hour troponin values, troponin clearance was investigated in the evaluation of mortality among hospitalized patients with CKD within the first month after discharge. The data obtained were analyzed using the SPSS data analysis software version 20.0. Student's t-test was used for the parametric data, and the Chi-squared test for the nonparametric data. Results Of the 300 patients evaluated, 189 patients survived (mean age 66.20 ± 14.597 years), and 111 died (mean age 74.81 ± 12.916 years). Troponin clearance was detected in 40 of the 111 patients in the mortality group and 119 of the 189 patients in the survival group. Troponin clearance was significantly more frequent in surviving patients (P=0.0000083). Conclusion Troponin clearance can be considered as a valuable leading indicator of survival, but higher levels of troponin clearance did not lead to higher survival rates.

Study of the 99th-percentile reference value for sensitive cardiac troponin I assays in Egyptian population

<br><b>Background</b><br>To establish the 99^th-percentile cutoff for sensitive cardiac troponin-I (cTnI) assay in Egyptian population.<br><b>Patients and methods</b><br>A sample size of 400 volunteers were divided into two groups [group A, including 200 participants without cardiovascular risk factors (CVRF), and group B, including 200 participants with more than 1 CVRF]. These two groups were used to create cardiac troponin-I (cTnI) 99^th-percentile cutoffs, which were implied later on a third group of 100 patients suspected as myocardial infarction (MI) to illustrate the effect of the calculated values and to assess their precision in the diagnosis of MI.<br><b>Results</b><br>After calculation of the 99^th percentile of each group, the present data revealed that the exclusion of CVRFs resulted in lowering of the calculated cutoffs from 0.05 to 0.038 ng/ml for group B and group A, respectively. Additionally, it has been clear that sex and age are important factors influencing the cTn concentrations. These lower values have predicted more patients at risk of having acute MI. There were correlations of troponin I with age, sex, and traditional risk factors.<br><b>Conclusion</b><br>Troponin-I concentrations in apparently healthy individuals rely on cardiac risk factors, sex, and age. Using the lower cutoff values after exclusion of risk factors led to prediction of more patients at risk compared with higher thresholds at the expense of specificity.<br>

Research on the effects of CPAP for OSA combined CHD long-term prognosis

Objective:To investigate the effects of CPAP for obstructive sleep apnea（OSA） combined CHD（coronary heart disease） long-term prognosis. Method:One hundred and twenty cases of OSA combind CHD in gansu province people's hospital sleep center were randomly divided into two groups according to apnea hypopnea index（AHI）, group A（light, medium OSA and CHD） 60 cases, group B（severe OSA and CHD） 60 cases. Contrast analysis and comparison between two groups PSG（Polysomnography） parameters, and the differences between the degree of coronary artery lesions and CPAP therapy effect on coronary long-term prognosis. Result:Compared group B with A, AHI, BMI, LSaO2, Epworth sleepiness scale（ESS） score, the amino acid homocysteine, the prevalence of hypertension, type 2 diabetes, the prevalence of acute myocardial infarction（ami） and vascular lesions and SYNTAX score increased significantly（P<0.05）. The ejection fraction decreased significantly（P<0.05）. The BNP（Brain natriuretic peptide） and cTNT（cardiac troponin, cTn） concentration there was no significant difference between the two groups（P>0.05）. CPAP treatment（30.0±4.2） months later, Group B: CAPA + conventional treatment group, compared with the simple routine LSaO2, ejection fraction increased significantly（P<0.05）, AHI, cardiovascular adverse events, vascular lesions, SYNTAX score, the BNP and TNT concentration significantly reduced（P<0.05）; Group A: AHI, decreased significantly（P<0.05）, LSaO2increased significantly（P<0.05）, ejection fraction, cardiovascular adverse events, vascular lesions, SYNTAX score, there was no significant difference between the BNP and TNT concentration; Survival analysis showed that: Group A CPAP+conventional treatment group cumulative survival rate higher than the conventional treatment group, but there was no statistically significant difference（P=0.260）. Group B: CPAP+conventional treatment group total survival rate was significantly higher than that of the conventional treatment group（P<0.001）; Conclusion:With the increase of the severity of OSA, OSA merge CHD coronary artery pathological changes degree aggravating, CPAP therapeutic benefit the long-term prognosis of CHD.

Can Emergency Physician Gestalt "Rule In" or "Rule Out" Acute Coronary Syndrome: Validation in a Multicenter Prospective Diagnostic Cohort Study.

Chest pain is a common problem presenting to the emergency department (ED). Many decision aids and accelerated diagnostic protocols have been developed to help clinicians differentiate those needing admission from those who can be safely discharged. Some early evidence has suggested that clinician judgment or gestalt alone could be sufficient. Our aim was to externally validate whether emergency physician's gestalt could "rule in" or "rule out" acute coronary syndromes (ACS). We performed a multicenter prospective diagnostic accuracy study including consenting patients presenting to the ED in whom the physician suspected ACS. At the time of arrival, clinicians recorded their perceived probability of ACS using a 5-point Likert scale. The primary outcome was a diagnosis of ACS, defined as acute myocardial infarction or major adverse cardiac events within 30 days. A total of 1,391 patients were included; 240 (17.3%) had ACS. Overall, gestalt had fair diagnostic accuracy with a C-statistic of 0.75 (95% confidence interval= 0.72 to 0.79). If ACS was "ruled out" in the 60 (4.3%) patients where clinicians perceived that the diagnosis was "definitely not" ACS, a sensitivity of 98.0% and negative predictive value of 95.0% could have been achieved. If ACS was only ruled out in patients who also had no electrocardiographic (ECG) ischemia and a normal initial cardiac troponin (cTn) concentration, 100.0% sensitivity and NPV could be achieved. However, this strategy only applied to 4.1% of patients. If patients with "probably not" ACS who had normal ECG and cTn were also ruled out (n=418, 30.8%), sensitivity fell to 86.2% with 99.2% NPV. Using gestalt "definitely" ACS to rule in ACS gave a specificity of 98.5% and positive predictive value of 71.2%. Clinician gestalt is not sufficiently accurate or safe to either rule in or rule out ACS as a decision-making strategy. This study will enable emergency physicians to understand the limitations of our clinical judgment.

Fast 0/1-h algorithm for detection of NSTEMI: are current high-sensitivity cardiac troponin assays fit for purpose? An EQA-based evaluation.

Background High-sensitivity cardiac troponin T/I (hs-cTnT/I) assays have improved analytical sensitivity for the detection of myocardial infarction (MI). To gain clinical specificity and sensitivity, interpretation of changes in cTn concentrations over time is crucial. The 2015 ESC NSTEMI guideline defines absolute delta values as additional rule-in and rule-out criteria for MI. A critical assumption for application of this rule is that total analytical imprecision within the delta period, including inter-instrument bias, is comparable to analytical imprecision in the validation studies. Methods Data from the Dutch External Quality Assessment Scheme (EQAS) were used to calculate inter-instrument bias and estimate imprecision for the measuring range where the proposed delta values are relevant: for Roche Elecsys hs-cTnT, 5-52 and 5-12 ng/L; for Abbott Architect hs-cTnI, 2-52 and 2-5 ng/L for rule-in and rule-out, respectively. Results For Elecsys, the median inter-instrument bias is 0.3 ng/L (n = 33 laboratories), resulting in reference change values (RCVs) of 3.0 and 1.7 ng/L, respectively, for rule-in and rule-out with imprecision as claimed by the manufacturer. With RCVs smaller than the guideline's delta thresholds, 100% of the laboratories have adequate specifications. RCVs for rule-in/rule-out increased to 4.6 ng/L/2.5 ng/L, respectively, with individual imprecisions as estimated from EQA data, resulting in 64% and 82% of laboratories with adequate specifications. For Architect, 40% of instruments (n = 10) might falsely qualify the result as clinically relevant; hence, inter-instrument bias could not be determined. Conclusions We advise laboratories that use the fast 0/1-h algorithm to introduce stringent internal quality procedures at the relevant/low concentration level, especially when multiple analyzers are randomly used.

Skeletal myopathies as a non-cardiac cause of elevations of cardiac troponin concentrations.

Skeletal myopathies have been suggested as a non-cardiac cause of elevations of cardiac troponin (cTn), particularly cardiac troponin T (cTnT). This is of major clinical relevance and concern as cTn plays a major role in the early diagnosis of myocardial infarction (MI). While both the incidence as well as the true pathophysiology (cardiac versus non-cardiac) underlying elevations in cTn in skeletal myopathies remain largely unknown, re-expression of cTnT in regenerating adult skeletal muscle has been suggested as a possible contributor. However, unequivocal protein characterization in skeletal muscle and quantification of the relative amounts of this possible signal versus the cTn signal derived from true cardiomyocyte injury remains elusive. Alternatively, minor cross-reactivity of the cTnT (and possibly at times also cTnI) detection and capture antibodies used in current monoclonal immunoassays with the skeletal troponin T or I isoform may be considered. Both would represent "false positive" elevations from a clinical perspective and would need to be reliably differentiated from "true positive elevations" from subclinical cardiomyocyte injury not detectable by currently available imaging techniques such as echocardiography and contrast enhanced magnetic resonance imaging (MRI), which have at least a 5 times lower sensitivity for cardiomyocyte injury. This review aims to explore the currently available data, its methodological limitations and provide guidance to clinicians to avoid misinterpretation of cTn concentrations.

Postoperative Cardiac Troponin I Thresholds Associated With 1-Year Cardiac Mortality After Adult Cardiac Surgery: An Attempt to Link Risk Stratification With Management Stratification in an Observational Study

Cardiac troponin (cTn) concentrations are measured routinely in some centers after cardiac surgery as part of risk stratification, but there are no data on how increased cTn concentrations could change patients' management. The aim of this study was to estimate relevant cTnI thresholds and identify potential interventions (additional monitoring/therapeutic interventions) that could be part of management changes of patients with cTnI greater than relevant thresholds. Retrospective, single-center, observational study. Bichat-Claude Bernard Hospital, Paris, France, between January 1, 2009, and December 31, 2012. Consecutive adult patients undergoing cardiac surgery. cTnI was measured on the 20th postoperative hour. Causes of death and possible interventions were determined by analysis of individual medical records. cTnI thresholds for 1-year cardiac mortality with a specificity >80% were calculated. For this study, 3,228 procedures were analyzed; 129 deaths occurred (4%), 83 of which (2.6%) were cardiac deaths. Threshold cTnI values were 4.2 µg/L for coronary artery bypass grafting (95% confidence interval [CI] 3.9-4.5) and 10.7 µg/L for non-coronary artery bypass grafting (95% CI 10.0-11.3). In multivariable analysis, the EuroSCORE II (odds ratio 1.1 [95% CI 1.06-1.13]; p < 0.001) and cTnI concentrations greater than the thresholds (odds ratio 5.62 [95% CI 3.37-9.37]; p < 0.001) were associated with significantly increased risk of death. The additive and absolute Net Reclassification Index were 0.288% and 14.1%, respectively, for a logistic model including cTnI and EuroSCORE II (area under the curve C-index 0.82 [95% CI 0.77-0.87]) compared with a model including only EuroSCORE II (area under the curve C-index 0.80 [95% CI 0.75-0.84]). Fifty-three of the 83 patients who experienced cardiac death (64%) had a cTnI concentration greater than the threshold, and an intervention was deemed possible in 47 of those 53 (89%) (mostly patients with mild postoperative cardiac dysfunction). For noncardiac deaths, 28% of patients had a cTnI concentration greater than the threshold and no interventions were deemed possible. In an attempt to evolve from risk to management stratification, this study's results identified a subgroup of patients with mild cardiac dysfunction and a cTnI concentration greater than the threshold who could be the target for interventions in future validation studies concerning changes in patient management.

Occult obstructive coronary artery disease is associated with prolonged cardiac troponin elevation following strenuous exercise

Sudden cardiac death among middle-aged recreational athletes is predominantly due to myocardial ischaemia. This study examined whether measuring cardiac troponin I and T (cTnI and cTnT) after strenuous exercise could identify occult obstructive coronary artery disease. Prospective observational study. Subjects were recruited from 1002 asymptomatic recreational cyclists completing a 91-km mountain bike race (North Sea Race Endurance Exercise Study). No subject had known cardiovascular disease or took cardiovascular medication. Blood samples were collected within 24 h before and 3 h and 24 h after the race. Coronary computed tomography angiography was performed in 80 participants with the highest post-exercise cTnI and in 40 reference subjects with moderately elevated cTnI values. Study subjects (N = 120) were 45 (36-52) years old and 74% were male. There were similar demographics in the High-cTnI group and the Reference group. The cTn concentrations were highest at 3 h post-race: cTnI, 224 (125-304) ng/L; cTnT, 89 (55-124) ng/L. Nine subjects had obstructive coronary artery disease on coronary computed tomography angiography, eight of whom were High-cTnI responders. Two subjects had myocardial bridging, both High-cTnI responders. Troponin concentrations at 24 h post-race were higher in subjects with obstructive coronary artery disease than in the rest of the cohort (n = 109): cTnI, 151 (72-233) ng/L vs. 24 (19-82) ng/L, p = 0.005; cTnT, 39 (25-55) ng/L vs. 20 (14-31) ng/L, p = 0.002. The areas under the receiver operating characteristic curves for predicting obstructive coronary artery disease were 0.79, p = 0.005 (cTnI) and 0.82, p = 0.002 (cTnT). In subjects with occult obstructive coronary artery disease there was a prolonged elevation of cTn following strenuous exercise.

Prognostic value of high-sensitive cardiac troponin I in asymptomatic chronic hemodialysis patients.

Increased levels of cardiac troponins (cTn) are a hallmark of acute myocardial infarction (AMI), along with symptoms and electrocardiographic (ECG) changes. Stably elevated cTn concentrations are frequently observed in asymptomatic patients with chronic kidney disease (CKD) and/or on hemodialysis (HD); the meaning of this elevation, as assessed by conventional techniques, remains unclear. Aim of our study was to evaluate the clinical significance of cTnI levels in asymptomatic HD patients by employing a newer high-sensitive cTnI (hs-cTnI) assay. We enrolled 49 patients undergoing regular HD treatment for more than 3months; all patients were asymptomatic for chest pain and had no history of acute coronary syndrome in the past 2months. For every patient we measured hs-cTnI, cTnI and brain natriuretic peptide (BNP) before initiation of one HD session at baseline (T0), after 3 (T1) and 9months (T2). Demographic, anamnestic, dialytic and echocardiographic characteristics of the examined population were evaluated. We also recorded the number of cardiovascular events from T0 to 12months after T2. Fifteen patients were lost to follow-up: 6 died, 2 underwent kidney transplantation, 7 did not match the inclusion criteria later during observation. At T0 (49 patients) we observed 14 hs-cTnI positive patients vs. 4 standard c-TnI positive patients (28,5% vs 8,1%); at T1 (40 patients) 16 vs 3 (26.4% vs 7.5%); at T2 (34 pz) 9 vs 0 (26.4% vs 0%). During the study we recorded 10 cardiovascular events, 8 of which in patients that were hs-cTNI positive, leading to death in 3. Hs-cTnI levels were predictive of cardiovascular events at all times and predictive of cardiovascular mortality at T0 and T1 (p < 0.001). In a multivariate analysis, a history of coronary artery disease (CAD) was an independent variable of high hs-cTnI levels at T0 (p < 0.04) and T1 (p < 0.03). Our study shows that a novel sensitive assay detects more asymptomatic HD patients compared to previously used methods, being at the same time predictive of cardiovascular mortality and morbidity. The only independent variable of high hs-cTnI concentrations was a positive history of cardiovascular disease, suggesting a possible role of hs-cTnI in identifying a high-risk subset of patients.

Predicting Acute Myocardial Infarction with a Single Blood Draw.

We desired to determine cardiac troponin (cTn) concentrations necessary to achieve a positive predictive value (PPV) of ≥75% for acute myocardial infarction (AMI) to justify immediate admission of patients to a monitored unit and, in general, early coronary angiography. In a prospective multicenter diagnostic study enrolling patients presenting to the emergency department with symptoms suggestive of AMI, final diagnoses were adjudicated by 2 independent cardiologists based on clinical information including cardiac imaging. cTn concentrations were measured using 5 different sensitive and high-sensitivity cTn (hs-cTn) assays in a blinded fashion at presentation and serially thereafter. The diagnostic end point was PPV for rule-in of AMI of initial cTn concentrations alone and in combination with early changes. Among 3828 patients, 616 (16%) had an AMI. At presentation, 7% to 14% of patients had cTnT/I concentrations associated with a PPV of ≥75%. Adding absolute or relative changes did not significantly further increase the PPV. PPVs increased from 46.5% (95% CI, 43.6-49.4) for hs-cTnT at presentation >14 ng/L to 78.9% (95% CI, 74.7-82.5) for >52 ng/L (P < 0.001), whereas PPVs in higher hs-cTnT strata remained largely unchanged [e.g., 82.4% (95% CI, 77.5-86.7) for >80 ng/L vs 83.9% (95% CI, 76.0-90.1) for >200 ng/L (P = 0.72)]. The addition of early changes in hs-cTnT further increased the PPV up to 60 ng/L, but not for higher concentrations. Serial sampling does not seem necessary for predicting AMI and concurrent decision-making in about 10% of patients, as it only marginally increases the PPV for AMI and not in a statistically or clinically significant way. NCT00470587.

Revisiting the Biological Variability of Cardiac Troponin: Implications for Clinical Practice.

The diagnosis of acute myocardial injury requires a rise and/or fall of cardiac troponin (cTn) on serial testing, with at least one concentration above the 99th percentile value of a normal reference population according to the recently published Fourth Universal Definition of Myocardial Infarction.1 However, the magnitude of change in cTn that constitutes a significant rise and/or fall was again not specified in detail. High-sensitivity cardiac troponin (hs-cTn) assays can measure ten-fold lower concentrations of cTn with more precision than older assays, and can accurately quantify cTn in more than 50% of healthy individuals with a coefficient of variation of less than 10% at the 99th percentile. These hs-cTn assays are also able to detect the normal variations in cTn results that are due to biological variability. Understanding and quantifying the normal variations in cTn is important as this would allow significant changes to be better defined. Numerous studies have sought to investigate the biological variability of cTn over the last ten years. Such studies are usually conducted in healthy individuals, however individuals with chronic cardiac disease or chronic renal failure have also been examined. These studies have yielded varying results in regards to significant change values for cTn. In light of the recent redefinition for myocardial infarction, the purpose of this mini-review is to revisit the biological variability of cTn. In particular, we outline concepts for determining a significant change value, review the results of previous studies on the biological variation of cTn and discuss potential considerations for clinical practice.