Camille Chenevier-Gobeaux

Diagnostic accuracy of combined cardiac troponin and copeptin assessment for early rule-out of myocardial infarction: : a systematic review and meta-analysis

Aims: This systematic review aimed to investigate the diagnostic accuracy of combined cardiac troponin (cTn) and copeptin assessment in comparison to cTn alone for early rule-out of acute myocardial infarction (AMI). Methods: Primary studies were eligible if they evaluated diagnostic accuracy for cTn with and without copeptin in patients with symptoms suggestive of AMI. AMI was defined according to the universal definition, using detection of cTn as a marker for myocardial necrosis. Eligible studies were identified by searching electronic databases (Medline, EMBASE, Science Citation Index Expanded, CINAHL, Pascal, and Cochrane) from inception to March 2013, reviewing conference proceedings and contacting field experts and the copeptin manufacturer. Results: In 15 studies totalling 8740 patients (prevalence of AMI 16%), adding copeptin improved the sensitivity of cTn assays (from 0.87 to 0.96, p=0.003) at the expense of lower specificity (from 0.84 to 0.56, p<0.001). In 12 studies providing data for 6988 patients without ST-segment elevation, the summary sensitivity and specificity estimates were 0.95 (95% CI 0.89 to 0.98) and 0.57 (95% CI 0.49 to 0.65) for the combined assessment of cTn and copeptin. When a high-sensitivity cTnT assay was used in combination with copeptin, the summary sensitivity and specificity estimates were 0.98 (95% CI 0.96 to 1.00) and 0.50 (95% CI 0.42 to 0.58). Conclusion: Despite substantial between-study heterogeneity, this meta-analysis demonstrates that copeptin significantly improves baseline cTn sensitivity. Management studies are needed to establish the effectiveness and safety of measuring copeptin in combination with high-sensitivity cTnT for early rule-out of AMI without serial testing.

Can early cardiac troponin I measurement help to predict recent coronary occlusion in out-of-hospital cardiac arrest survivors?

Objective:Recent guidelines recommend the immediate performance of a coronary angiography when an acute myocardial infarction is suspected as a cause of out-of-hospital cardiac arrest. However, prehospital factors such as postresuscitation electrocardiogram pattern or clinical features are poorly sensitive in this setting. We searched to evaluate if an early measurement of cardiac troponin I can help to detect a recent coronary occlusion in out-of-hospital cardiac arrest. Design:Retrospective analysis of a prospective electronic registry database. Setting:University cardiac arrest center. Patients:Between January 2003 and December 2008, 422 out-of-hospital cardiac arrest survivors without obvious extra-cardiac cause have been consecutively studied. An immediate coronary angiography has been systematically performed. The primary outcome was the finding of a recent coronary occlusion. Intervention:First, blood cardiac troponin I levels at admission were analyzed to assess the optimum cutoff for identifying a recent coronary occlusion. Second, a logistic regression was performed to determine early predictive factors of a recent coronary occlusion (including cardiac troponin I) and their respective contribution. Measurements and Main Results:An ST-segment elevation was present in 127 of 422 patients (30%). During coronary angiography, a recent occlusion has been detected in 193 of 422 patients (46%). The optimum cardiac troponin I threshold was determined at 4.66 ng·mL−1 (sensitivity 66.7%, specificity 66.4%). In multivariate analyses, in addition of smoking and epinephrine initial dose, cardiac troponin I (odds ratio 3.58 [2.03–6.32], p < .001) and ST-segment elevation (odds ratio 10.19 [5.39–19.26], p < .001) were independent predictive factors of a recent coronary occlusion. Conclusions:In this large cohort of out-of-hospital cardiac arrest patients, isolated early cardiac troponin I measurement is modestly predictive of a recent coronary occlusion. Furthermore, the contribution of this parameter even in association with other factors does not seem helpful to predict recent occlusion. As a result and given the high benefit of percutaneous coronary intervention for such patients, the dosage of cardiac troponin I at admission could not help in the decision of early coronary angiogram.

Combined copeptin and troponin to rule out myocardial infarction in patients with chest pain and a history of coronary artery disease

PURPOSE The main objective of this multicentric study was to evaluate the additional value of copeptin to conventional cardiac troponin (cTn) for a rapid ruling out of acute myocardial infarction (AMI) in patients with acute chest pain and a previous history of coronary artery disease (CAD). PATIENTS AND METHOD Patients with a previous history of CAD presenting in the emergency department with acute chest pain lasting for 6 hours or less suggestive of non-ST-segment elevation AMI and negative cTn were selected. Levels of copeptin were blindly measured at presentation. The diagnosis was adjudicated by 2 independent experts using all available data including cTn. RESULTS A total of 451 patients were included (mean age, 67±14; 330 [73%] men). The adjudicated final diagnosis was AMI in 36 (8%) patients, unstable angina in 131 (29%), and other diagnosis in 284 (63%). A negative cTn combined with a copeptin value lower than 10.7 pmol/L at presentation was able to rule out AMI, with a negative predictive value of 98% (95% confidence interval, 95%-99%). CONCLUSION In triage patients with acute chest pain lasting for less than 6 hours and a previous history of CAD, the combination of copeptin and cTn allows for the ruling out AMI, with a negative predictive value greater than 95%.

High-sensitivity versus conventional troponin in the emergency department for the diagnosis of acute myocardial infarction

IntroductionRecently, newer assays for cardiac troponin (cTn) have been developed which are able to detect changes in concentration of the biomarker at or below the 99th percentile for a normal population. The objective of this study was to compare the diagnostic performance of a new high-sensitivity troponin T (HsTnT) assay to that of conventional cTnI for the diagnosis of acute myocardial infarction (AMI) according to pretest probability (PTP).MethodsIn consecutive patients who presented to our emergency departments with chest pain suggestive of AMI, levels of HsTnT were measured at presentation, blinded to the emergency physicians, who were asked to estimate the empirical PTP of AMI. The discharge diagnosis was adjudicated by two independent experts on the basis of all available data.ResultsA total of 317 patients were included, comprising 149 (47%) who were considered to have low PTP, 109 (34%) who were considered to have moderate PTP and 59 (19%) who were considered to have high PTP. AMI was confirmed in 45 patients (14%), 22 (9%) of whom were considered to have low to moderate PTP and 23 (39%) of whom were considered to have high PTP (P < 0.001). In the low to moderate PTP group, HsTnT levels ≥ 0.014 μg/L identified AMI with a higher sensitivity than cTnI (91%, 95% confidence interval (95% CI) 79 to 100, vs. 77% (95% CI 60 to 95); P = 0.001), but the negative predictive value was not different (99% (95% CI 98 to 100) vs. 98% (95% CI 96 to 100)). There was no difference in area under the receiver operating characteristic (ROC) curve between HsTnT and cTnI (0.93 (95% CI 0.90 to 0.98) vs. 0.94 (95% CI 0.88 to 0.97), respectively).ConclusionsIn patients with low to moderate PTP of AMI, HsTnT is slightly more useful than cTnI. Our results confirm that the use of HsTnT has a higher sensitivity than conventional cTnI.

Influence of Age and Renal Function on High-Sensitivity Cardiac Troponin T Diagnostic Accuracy for the Diagnosis of Acute Myocardial Infarction

Concerns have been raised about the performance of highly sensitive cardiac troponin assays to accurately detect acute myocardial infarction (AMI), particularly in non-ST 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 [1.2-3.9], 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.

Comparison of conventional and high-sensitivity troponin in patients with chest pain: A collaborative meta-analysis

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.

Midregional Pro–Atrial Natriuretic Peptide for the Diagnosis of Cardiac-Related Dyspnea according to Renal Function in the Emergency Department: A Comparison with B-Type Natriuretic Peptide (BNP) and N-Terminal ProBNP

BACKGROUND Although renal dysfunction influences the threshold values of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in diagnosis of cardiac-related dyspnea (CRD), its effects on midregional pro-atrial natriuretic peptide (MR-proANP) threshold values are unknown. We evaluated the impact of renal function on MR-proANP concentrations and compared our results to those of BNP and NT-proBNP. METHODS MR-proANP, BNP, and NT-proBNP concentrations were measured in blood samples collected routinely from dyspneic patients admitted to the emergency department. Patients were subdivided into tertiles based on their estimated glomerular filtration rate [eGFR, in mL · min(-1) · (1.73 m(2))(-1)]: tertiles 1 (<44.3), 2 (44.3-58.5), and 3 (≥58.6). RESULTS Of 378 patients studied, 69% (n = 260) had impaired renal function [<60 mL · min(-1) · (1.73 m(2))(-1)] and 30% (n = 114) had CRD. MR-proANP, BNP, and NT-proBNP concentrations were significantly increased in patients with impaired renal function. In each tertile, all peptides remained significantly increased in CRD patients by comparison with non-CRD patients. By ROC analysis, MR-proANP, BNP, and NT-proBNP threshold values for the diagnosis of CRD increased as eGFR decreased from tertile 3 to tertile 1. Areas under the ROC curve for all peptides were significantly lower in tertile 1. Using adapted thresholds, MR-proANP, BNP, and NT-proBNP remained independently predictive of CRD, even in tertile 1 patients. CONCLUSIONS Renal function influences optimum cutoff points of MR-proANP for the diagnosis of CRD. With use of an optimum threshold value adapted to the eGFR category, MR-proANP remains as effective as BNP and NT-proBNP in independently predicting a diagnosis of CRD in the emergency department.

Presepsin (sCD14-ST) in emergency department: The need for adapted threshold values?

Presepsin is elevated in patients developing infections and increases in a severity-dependent manner. We aimed to evaluate circulating values of this new biomarker in a population free of any acute infectious disorder. We recruited 144 consecutive patients presenting at the emergency department (ED) without acute infection or acute/unstable disorder, and 54 healthy participants. Presepsin plasmatic concentrations were measured on the PATHFAST point-of-care analyzer. The 95th percentile of presepsin values in the ED population is 750ng/L. Presepsin was significantly increased in patients aged ≥70years vs. younger patients (470 [380-601] ng/L vs. 300 [201-457] ng/L, p<0.001). Prevalence of elevated presepsin values was increased in patients in comparison to controls (80% vs.13%, p<0.001), and in patients aged ≥70years in comparison to younger patients (87% vs. 47%, p<0.001). Presepsin concentrations were significantly increased in patients with kidney dysfunction. Aging was an independent predictor of an elevated presepsin value. In conclusion, presepsin concentrations increase with age and kidney dysfunction. Therefore interpretation of presepsin concentrations might be altered in the elderly or in patients with impaired renal function. Adapted thresholds are needed for specific populations.

Presepsin (sCD14-ST), an innate immune response marker in sepsis

Innate immunity is the first barrier to fight off bacteria, and partly relies on the engagement of the membrane coreceptor CD14. A product of cleavage of CD14, the soluble subtype of CD14 (sCD14-ST) or presepsin, is released in circulation after activation of defense mechanisms. Presepsin can be detected by biochemical methods and therefore appears as an emergent biomarker of infection. Here we present the rationale for presepsin development and recent data supporting its use at bedside. Presepsin may be worthwhile for early diagnosis and prognostic assessment of patients with systemic infections. This biomarker shows high specificity, and results from experimental and clinical studies are reinforcing the proof of concept. Performances place presepsin at the level of PCT who is used as a comparator. Biomarkers of infection are futile to diagnose infection with direct access to bacteria (as urinary tract infection, meningitis), but their use can be advocated to ascertain unclear diagnosis. Future developments of presepsin will probably use clinical models with a Bayesian approach to ascertain the additional value of the biomarker at bedside.

Analytical evaluation of a high-sensitivity troponin T assay and its clinical assessment in acute coronary syndrome

Background The recently developed, highly sensitive cardiac troponin T (hs-cTnT) immunoassay improves the detection of acute myocardial infarction (AMI). However, this assay requires further analytical and clinical evaluation. Methods Imprecision, linearity, limits of quantification and interferences were evaluated; hs-cTnT was compared with a conventional cardiac troponin I assay (cTnI), performed on an X-pand®HM, in a population of patients with suspected AMI. Finally, the 99th percentile cut-off point for a reference population was explored in 213 healthy control subjects. Results Imprecision analysis demonstrated coefficients of variation (CVs) below 4%, linearity showed a 0.999 coefficient of correlation, with excellent recovery (99.9%) and a limit of quantification (10%CV) was found at 9.2 ng/L. A negative interference (>20%) with haemolysis was observed when supplemental haemoglobin was above 0.25 g/dL. Patients with suspected AMI more frequently displayed an increased hs-cTnT (83%) than an increased cTnI (55%, P < 0.01). Unstable angina was present in 63% of patients with an increased hs-cTnT associated with no increase in cTnI. The 99th percentile value for our reference population was 16.9 ng/L. In 213 healthy blood donors, hs-cTnT levels were significantly correlated with age (P < 0.0001), and were higher in men than in women (P < 0.0001). Conclusions The analytical performance of hs-cTnT complied with the international guidelines for AMI detection. Determining the degree of haemolysis in a sample is of paramount importance to the interpretation of hs-cTnT results. The 99th percentile value of our reference population was established.