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Cardiac troponin (cTn) assays have quickly gained in analytical sensitivity to become what are termed 'high-sensitivity cardiac troponin' (hs-cTn) assays, bringing a flurry of dense yet incomplete literature data. The net result is that cTn assays are not yet standardized and there are still no consensus-built data on how to use and interpret cTn assay results. To address these issues, the authors take cues and clues from multiple disciplines to bring responses to frequently asked questions. In brief, the effective use of hs-cTn hinges on knowing: specific assay characteristics, particularly precision at the 99th percentile of a reference population; factors of variation at the 99th percentile value; and the high-individuality of hs-cTn assays, for which the notion of individual kinetics is more informative than straight reference to 'normal' values. The significance of patterns of change between two assay measurements has not yet been documented for every hs-cTn assay. Clinicians need to work hand-in-hand with medical biologists to better understand how to use hs-cTn assays in routine practice., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: Multiple studies have evaluated the diagnostic and prognostic performance of conventional troponin (cTn) and high-sensitivity troponin (hs-cTn). We performed a collaborative meta-analysis comparing cTn and hs-cTn for diagnosis of acute myocardial infarction (AMI) and assessment of prognosis in patients with chest pain., Methods: MEDLINE/PubMed, Cochrane CENTRAL, and EMBASE were searched for studies assessing both cTn and hs-cTn in patients with chest pain. Study authors were contacted and many provided previously unpublished data., Results: From 17 included studies, there were 8,644 patients. Compared with baseline cTn, baseline hs-cTn had significantly greater sensitivity (0.884 vs 0.749, P < .001) and negative predictive value (NPV; 0.964 vs 0.935, P < .001), whereas specificity (0.816 vs 0.938, P < .001) and positive predictive value (0.558 vs 0.759, P < .001) were significantly reduced. Based on summary receiver operating characteristic curves, test performance for the diagnosis of AMI was not significantly different between baseline cTn and hs-cTn (0.90 [95% CI 0.85-0.95] vs 0.92 [95% CI 0.90-0.94]). In a subanalysis of 6 studies that alternatively defined AMI based on hs-cTn, cTn had lower sensitivity (0.666, P < .001) and NPV (0.906, P < .001). Elevation of baseline hs-cTn, but negative baseline cTn, was associated with increased risk of death or nonfatal myocardial infarction during follow-up (P < .001) compared with both negative., Conclusion: High-sensitivity troponin has significantly greater early sensitivity and NPV for the diagnosis of AMI at the cost of specificity and positive predictive value, which may enable early rule in/out of AMI in patients with chest pain. Baseline hs-cTn elevation in the setting of negative cTn is also associated with increased nonfatal myocardial infarction or death during follow-up., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Measurements of cardiac troponins (cTn) are yet considered the gold standard method in patients with chest pain. Very recently, high-sensitivity (hs)cTn emerged and allow to measure very low concentrations of cTn. The aim of these assays was the better detection of patients with acute myocardial infarction (AMI). The threshold value should be the 99th percentile of the method, which corresponds to the concentration obtained from 99% of a reference population. These assays improve the detection of patients with elevated cTn concentrations. All patients with increased hs-cTn concentration above the 99th percentile should be considered at high risk of future clinical event when compared to patients with lower concentration. However, these elevated concentrations are not necessarily related to AMI due to coronary artery plaque rupture and superimposed thrombus. In order to understand adequately cTn measurement, the physician should base his interpretation on the context, the cTn concentration, variations during serial sampling, and the possible existence of a coexistent disease characterized by increased cTn concentrations.

Background: Failure to identify patients with acute coronary syndrome (ACS) is a serious clinical problem. The incidence, characteristics, and outcome of ACS patients with normal high-sensitivity cardiac troponin T (hs-cTnT) levels at presentation are unknown., Methods: In a prospective multicenter study, hs-cTnT was determined in a blinded fashion in 1181 consecutive patients presenting with acute chest pain to the emergency department. The final diagnosis of ACS was adjudicated by 2 independent cardiologists. Patients were followed for 12 months., Results: ACS was the adjudicated diagnosis in 351 patients (30%), including 187 patients with acute myocardial infarction (AMI) and 164 patients with unstable angina (UA). At presentation, hs-cTnT was normal (<.014 ug/L) in 112 ACS patients (32%), including 11 patients (6%) with AMI and 101 patients (62%) with UA (P <.001). Multivariable analysis revealed previous statin treatment, younger age, preserved renal function, and the absence of ST deviation on the electrocardiogram as independently associated with normal hs-cTnT levels. Mortality rates in ACS patients with normal hs-cTnT level were 0.0% at 30 days, 0.0% at 90 days, and 2.0% (95% confidence interval, 0.5-7.9) at 360 days, which was significantly lower than in ACS patients with elevated hs-cTnT level at presentation (17.5% at 360 days, P <.001). Conversely, AMI rates at 360 days was higher in ACS patients with normal versus elevated hs-cTnT levels (P=.004)., Conclusion: Almost one third of ACS patients have normal hs-cTnT levels at presentation, mostly patients with UA. ACS patients with normal hs-cTnT have a very low mortality, but an increased rate of AMI during the subsequent 360 days., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To compare the accuracy of the GRACE score, a strong prognosticator in acute coronary syndrome (ACS) that is calculated using conventional cardiac troponin (cTn) assays, with that calculated with high-sensitivity cTn (hs-cTn) and with the combination of the GRACE score with hs-cTn or B-type natriuretic peptide (BNP)., Design: Prospective international cohort. Settings University Hospital., Patients: Patients enrolled in the Predictors of Acute Coronary Syndromes Evaluation prospective study with proven ACS. Main outcome measured The capacity to predict in-hospital mortality, 1-year mortality and combined death/acute myocardial infarction (AMI) at 1 year., Results: 370 patients were enrolled (173 with unstable angina and 197 with AMI). In-hospital mortality was 4.1%; 1-year mortality was 12.5%. The GRACE score was significantly higher in patients who died than in those discharged alive (200 (174-222) vs 125 (98-155); p<0.001), and in those who died than in those who survived for 1 year (151 (133-169) vs 104 (85-125); p<0.001). The area under the curve of the GRACE score was 0.87 regarding in-hospital mortality and 0.88 for 1-year mortality; if calculated with hs-cTn, it was 0.87 and 0.88, respectively (p=NS for all comparisons). The addition of hs-cTn to the GRACE score resulted in no increased value, whereas the addition of BNP tended to improve 1-year mortality prediction (p=0.058)., Conclusion: The GRACE score is accurate for determining both in-hospital and long-term mortality in patients with ACS in the era of hs-cTn. The addition of hs-cTn or BNP to the GRACE score does not significantly improve risk prediction.

Background Recent 2015 ESC recommendations for the management of patients with suspected acute myocardial infarction (AMI) support that a single value of high-sensitivity cardiac troponin (HS-cTn) measured at presentation could rule out AMI if below the limit of blank (LoB) or detection (LoD). Objectives We aimed to evaluate whether an undetectable HS-cTnT at presentation safely rules out NSTEMI in unselected patients with chest pain. Patients and methods This is a post hoc analysis of two prospective cohorts with similar design that included patients suspected of AMI at three French university hospitals. Patients were followed-up during one month, before the adjudication of a final diagnosis. Results 413 patients (mean age 58 ± 17 years) were analyzed; 45 (11%) had a final diagnosis of NSTEMI, and 26 (6%) had STEMI. The sensitivity of HS-cTnT value at 3 ng/L (LoB) for NSTEMI was 97.8% [95% CI: 86.8–99.9], yielding a negative predictive value (NPV) of 99.3% [95% CI: 95.4–100.0]. Proportion of patients ruled out for NSTEMI was 32% when applying the LoB. The sensitivity of HS-cTnT value at 5 ng/L (LoD) was 97.8% [95% CI: 86.8–99.9] yielding a NPV of 99.5% [95% CI: 96.5–100.0]. Proportion of patients ruled out for NSTEMI was 43% when applying the LoD. One patient (delay between onset of chest pain and presentation < 3 h) had NSTEMI and HS-cTnT < LoB at presentation. Conclusion The NPV of a single measurement of HS-cTnT below the LoD is high in unselected patients, but not enough to rule out safely NSTEMI for very early presenters. [ABSTRACT FROM AUTHOR]

Abstract: Background: The introduction of high-sensitivity cardiac troponin (hs-cTn) assays allows the assessment of clinical decision values below the 99th percentile. Methods: Final diagnosis and one-year mortality were adjudicated in a multicenter, prospective cohort of 1181 patients presenting with acute chest pain to the emergency department. Hs-cTnT (Roche) and cTnI-ultra (Siemens) were measured in a blinded fashion. Results: At presentation hs-cTnT and cTnI-ultra were below the limit of blank (LOB) in 201 (17%) and 549 (47%) patients, below the 75th percentile in 379 (32%) and 623 (53%) patients, below the 95th percentile in 603 (51%) and 808 (68%), and below the 99th percentile in 748 (63%) and 913 (77%), respectively. Sensitivities for the diagnosis of AMI were 100.0% and 96.8% respectively for hs-cTnT and cTnI-ultra (LOB as cut-off value), 99.5% and 96.2% (75th percentile), 96.8% and 93.0% (95th percentile), and 94.1% and 88.1% (99th percentile). The proportion of patients correctly classified as having or not AMI increased from 32.9% (LOB as cut-off value) to 47.8% (75th percentile), 65.9% (95th percentile) and 77.3% (99th percentile) for hs-cTnT and from 61.2% to 67.3%, 81.9% and 89.3% respectively for cTnI-ultra. At 1year, all-cause mortality was very low and similar for patients below all of these cut-off levels (between 0.7% and 1.5%, p=0.748 for all-groups comparison). Conclusion: cTn should be considered as a continuous variable. Decision values below the 99th percentile (e.g. the 75th percentile) are associated with a very high NPV for the diagnosis of AMI, but have a lower accuracy than the 99th percentile. [Copyright &y& Elsevier]

Abstract: Background: Patients with acute chest pain having serial undetectable cardiac troponin (cTn) levels, as measured with conventional assays, are considered at very low risk. The aim of this multicenter study was to determine the accuracy of multiple biomarkers in these patients. Methods: We enrolled 1247 consecutive patients with suspected AMI. Of these, 325 had undetectable levels of cTnT (Roche, 4th generation assay) at presentation and at 6h. Fourteen novel markers quantifying cardiomyocyte damage, inflammation and/or plaque rupture, and neurohormonal activation were measured at presentation. The occurrence of death or acute myocardial infarction (AMI) (primary end point) and unplanned coronary revascularization (secondary endpoint) were recorded during long-term follow-up. Results: During a mean follow-up of 668±241days, death/AMI occurred in 23 patients (7%), unplanned revascularization in 46 (14%). Among all biomarkers, high-sensitive cTnT (hs-cTnT), Midregional pro-adrenomedullin (MR-proADM) and growth differentiation factor-15 (GDF-15) were independently associated with future death/AMI; hs-cTnT was 0.013 (0.008–0.017) μg/l versus 0.006 (0.003–0.010) μg/l, MR-proADM was 0.78 (0.66–1.09) nmol/l versus 0.60 (0.18–0.80) nmol/l and GDF-15 was 1800 (1600–2200) ng/l versus 1100 (800–1700) ng/l in patients with versus without death/AMI during follow-up (p <0.001 each). The area under the receiver-operating characteristics curve to predict death/AMI was 0.73 (95%CI 0.63–0.83) for hs-cTnT, 0.71 (95% CI 0.62–0.81) for MR-proADM and 0.78 (95%CI 0.71–0.86) for GDF-15. Conclusion: Patients with serial undetectable levels of cTnT using the contemporary 4th generation assay are at low but not negligible risk of future cardiac events. Hs-cTnT, MR-proADM and/or GDF-15 might help to further improve risk-stratification in this group. [Copyright &y& Elsevier]

Concerns have been raised about the performance of highly sensitive cardiac troponin assays to accurately detect acute myocardial infarction (AMI), particularly in noneST segment elevation (NSTEMI), in elderly patients, and in patients with renal failure. We evaluated whether increased age and low estimated glomerular filtration rate (eGFR) alter diagnostic performance of high-sensitivity cardiac troponin T (HScTnT). In a prospective multicentric study, HScTnT levels were measured blindly at presentation in patients with acute chest pain. Three hundred and sixty-seven patients were enrolled, including 84 patients ≽70 years. Final diagnosis was AMI for 57 patients (16%) and NSTEMI for 43 patients (12%). NSTEMI was more frequent in elderly patients (p = 0.008). Sensitivity and specificity of HScTnT >14 ng/L at admission for AMI were 96% and 51% in patients 70 years versus 91% (NS) and 88% (p <0.0001) in younger patients; the same observations were done for the diagnosis of NSTEMI. Given an HScTnT >53.5 ng/L for the diagnosis of AMI and NSTEMI, respective sensitivities were 87% and 84% and respective specificities were 87% and 87% in elderly patients. Using a cutoff at 35.8 ng/L (for AMI) or 43.2 ng/L (for NSTEMI), sensitivities were 94% and 92%, and specificities were 86% and 88% in patients with low eGFR. Older age, but not low eGFR, was an independent predictive factor of an elevated HScTnT at admission (odds ratio 2.2 [1.2e3.9], p = 0.007). In conclusion, adapted thresholds of HScTnT are required for an accurate diagnosis of AMI/NSTEMI in patients aged ≽70 and in those with low eGFR. [ABSTRACT FROM AUTHOR]

We hypothesized that midregional pro–A-type natriuretic peptide (MR-proANP), the stable midregional epitope of proANP, might be useful in the early diagnosis and risk stratification of patients with suspected acute myocardial infarction (AMI). In this multicenter study we measured MR-proANP, cardiac troponin T (cTnT), and high-sensitive cTnT (hs-cTnT) at presentation in 675 consecutive patients presenting to the emergency department with suspected AMI. The final diagnosis was adjudicated by 2 independent cardiologists. Patients were followed 360 days for mortality and AMI. AMI was the final diagnosis in 119 patients (18%). Median MR-proANP levels at presentation were significantly higher in patients with AMI (189 pmol/L, interquartile range 97 to 341) versus patients with another final diagnosis (83 pmol/L, 49 to 144, p <0.001). However, neither the combination of MR-proANP with cTnT nor its combination with hs-cTnT significantly improved diagnostic accuracy as quantified by area under the receiver operating characteristic curve (0.91 vs 0.89 for cTnT alone, p = 0.086; 0.95 vs 0.96 for hs-cTnT, respectively, p = 0.02). Cumulative 360-day mortality/AMI rates were 2.4% in the first, 3.6% in the second, 9.5% in the third, and 18.8% in the fourth quartiles of MR-proANP (p <0.001). MR-proANP (area under the curve 0.76) predicted mortality/AMI independently of and more accurately than cTnT (area under the curve 0.62), hs-cTnT (area under the curve 0.71), and Thrombolysis In Myocardial Infarction risk score (area under the curve 0.72). Net reclassification improvements offered by the additional use of MR-proANP were 0.388 (p <0.001), 0.425 (p <0.001), and 0.217 (p = 0.007), respectively. In conclusion, MR-proANP improves risk prediction for 360-day mortality/AMI but does not seem to help in the early diagnosis of AMI. [Copyright &y& Elsevier]

The article discusses a study that quantifies cardiac hemodynamic stress and cardiomyocyte damage in ischemic and nonischemic acute heart failure (AHF). It is stated that hemodynamic cardiac stress is quantified by B-type natriuretic peptide (BNP) while cardiomyocyte damage is quantified by cardiac troponin. The results showed that patients with ischemic AHF at the emergency department exhibited extensive hemodynamic cardiac stress and cardiomyocyte damage than patients with nonischemic AHF.

A letter to the editor on a new algorithm using high-sensitivity cardiac troponins for the rapid rule-out of non ST-segment elevation myocardial infarction (NSTEMI) is presented.

Multiple studies have evaluated copeptin, a surrogate for arginine vasopressin, in the diagnosis of acute myocardial infarction (AMI) with mixed results. A systematic review and collaborative meta-analysis were performed for diagnosis of AMI and assessment of prognosis in patients presenting to the emergency department with chest pain. MEDLINE/ PubMed, Cochrane CENTRAL, and EMBASE were searched for studies assessing copeptin in such patients. Study investigators were contacted, and many provided previously unpublished data. Random-effects methods were used to compare the data for copeptin, troponin, and their combination. There were a total of 9,244 patients from the 14 included studies. Mean age was 62 years; 64% were men; and 18.4% were ultimately diagnosed with AMI. Patients with AMI had a higher presentation copeptin level than those without AMI (22.8 vs 8.3 pmol/L, respectively, p <0.001). Although troponin had better diagnostic accuracy than copeptin for AMI, the combination of copeptin and troponin significantly improved the sensitivity (0.905 [0.888 to 0.921] vs 0.686 [0.661 to 0.710], respectively, p <0.001) and negative predictive value (0.97 [0.964 to 0.975] vs 0.93 [0.924 to 0.936], respectively, p <0.001) compared with troponin alone. Elevation in copeptin carried a similar risk of all-cause mortality to an elevation in troponin (odds ratio 5.84 vs 6.74, respectively, p = 0.67). In conclusion, copeptin not only identifies patients at risk of all-cause mortality, but its addition to troponin improved the sensitivity and negative likelihood ratio for diagnosis of AMI compared with troponin alone. Thus, copeptin may help identify patients who may be safely discharged early from the emergency department. [ABSTRACT FROM AUTHOR]

Background--We hypothesized that high-sensitivity cardiac troponin (hs-cTn) and its early change are useful in distinguishing acute myocardial infarction (AMI) from acute cardiac noncoronary artery disease. Methods and Results--In a prospective, international multicenter study, hs-cTn was measured with 3 assays (hs-cTnT, Roche Diagnostics; hs-cTnl, Beckman-Coulter; hs-cTnl Siemens) in a blinded fashion at presentation and serially thereafter in 887 unselected patients with acute chest pain. Accuracy of the combination of presentation values with serial changes was compared against a final diagnosis adjudicated by 2 independent cardiologists. AMI was the adjudicated final diagnosis in 127 patients (15%); cardiac noncoronary artery disease, in 124 (14%). Patients with AMI had higher median presentation values of hs-cTnT (0.113 &mgr;g/L [interquartile range, 0.049-0.246 &mgr;g/L] versus 0.012 &mgr;g/L [interquartile range, 0.006-0.034 &mgr;g/L]; P<0.001) and higher absolute changes in hs-cTnT in the first hour (0.019 &mgr;g/L [interquartile range, 0.007-0.067 &mgr;g/L] versus 0.001 &mgr;g/L [interquartile range, 0-0.003 &mgr;g/L]; P<0.001) than patients with cardiac noncoronary artery disease. Similar findings were obtained with the hs-cTnl assays. Adding changes of hs-cTn in the first hour to its presentation value yielded a diagnostic accuracy for AMI as quantified by the area under the receiver-operating characteristics curve of 0.94 for hs-cTnT (0.92 for both hs-cTnl assays). Algorithms using ST-elevation, presentation values, and changes in hs-cTn in the first hour accurately separated patients with AMI and those with cardiac noncoronary artery disease. These findings were confirmed when the final diagnosis was readjudicated with the use of hs-cTnT values and validated in an independent validation cohort. Conclusion--The combined use of hs-cTn at presentation and its early absolute change excellently discriminates between patients with AMI and those with cardiac noncoronary artery disease. [ABSTRACT FROM AUTHOR]

Abstract: Background: It is unknown to what extent noncardiac causes, including renal dysfunction, may contribute to high-sensitivity cardiac troponin T levels. Methods: In an observational international multicenter study, we enrolled consecutive patients presenting with acute chest pain to the emergency department. Of 1181 patients enrolled, 572 were adjudicated by 2 independent cardiologists to have a noncardiac cause of chest pain. Multiple linear regression analyses were used to determine the important predictors of log-transformed high-sensitivity cardiac troponin T. Kaplan-Meier curve was used to assess the prognostic significance of high-sensitivity cardiac troponin T>0.014 μg/L (99th percentile). Results: A total of 88 patients (15%) had high-sensitivity cardiac troponin T>0.014 μg/L. Less than 50% of cardiac troponins could be explained by known cardiac or noncardiac diseases. In decreasing order of importance, age, estimated glomerular filtration rate, hypertension, previous myocardial infarction, and chronic kidney disease (adjusted r 2 0.44) emerged as significant factors in linear regression analysis to predict high-sensitivity cardiac troponin T. High-sensitivity cardiac troponin T was best explained by a linear curve with age as≤0.014 μg/L. Patients with high-sensitivity cardiac troponin T levels>0.014 μg/L were at increased risk for all-cause mortality (hazard ratio 3.0; 95% confidence interval, 0.8-10.6; P=.02) during follow-up. Conclusion: Among the known covariates, age and not renal dysfunction is the most important determinant of high-sensitivity cardiac troponin T. Because known cardiac and noncardiac factors, including renal dysfunction, explain less than 50% of high-sensitivity cardiac troponin T levels among patients with a noncardiac cause of chest pain, unknown or underestimated cardiac involvement during the acute presenting condition seems to be the major cause of elevated high-sensitivity cardiac troponin T. [Copyright &y& Elsevier]