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      Is high-sensitivity troponin, alone or in combination with copeptin, sensitive enough for ruling out NSTEMI in very early presenters at admission? A post hoc analysis performed in emergency departments

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          Abstract

          Objectives

          Copeptin and high-sensitivity cardiac troponin (HS-cTn) assays improve the early detection of non-ST-segment elevation myocardial infarction (NSTEMI). Their sensitivities may, however, be reduced in very early presenters.

          Setting

          We performed a post hoc analysis of three prospective studies that included patients who presented to the emergency department for chest pain onset (CPO) of less than 6 hours.

          Participants

          449 patients were included, in whom 12% had NSTEMI. CPO occurred <2 hours from ED presentation in 160, between 2 and 4 hours in 143 and >4 hours in 146 patients. The prevalence of NSTEMI was similar in all groups (9%, 13% and 12%, respectively, p=0.281).

          Measures

          Diagnostic performances of HS-cTn and copeptin at presentation were examined according to CPO. The discharge diagnosis was adjudicated by two experts, including cardiac troponin I (cTnI). HS-cTn and copeptin were blindly measured.

          Results

          Diagnostic accuracies of cTnI, cTnI +copeptin and HS-cardiac troponin T (HS-cTnT) (but not HS-cTnT +copeptin) lower through CPO categories. For patients with CPO <2 hours, the choice of a threshold value of 14 ng/L for HS-cTnT resulted in three false negative (Sensitivity 80%(95% CI 51% to 95%); specificity 85% (95% CI 78% to 90%); 79% of correctly ruled out patients) and that of 5 ng/L in two false negative (sensitivity 87% (95% CI 59% to 98%); specificity 58% (95% CI 50% to 66%); 52% of correctly ruled out patients). The addition of copeptin to HS-cTnT induced a decrease of misclassified patients to 1 in patients with CPO <2 hours (sensitivity 93% (95% CI 66% to 100%); specificity 41% (95% CI 33% to 50%)).

          Conclusion

          A single measurement of HS-cTn, alone or in combination with copeptin at admission, seems not safe enough for ruling out NSTEMI in very early presenters (with CPO <2 hours).

          Trial registration number

          DC-2009–1052

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          Most cited references 29

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          Third universal definition of myocardial infarction.

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            Serial changes in highly sensitive troponin I assay and early diagnosis of myocardial infarction.

            Introduction of highly sensitive troponin assays into clinical practice has substantially improved the evaluation of patients with chest pain. To evaluate the diagnostic performance of a highly sensitive troponin I (hsTnI) assay compared with a contemporary troponin I (cTnI) assay and their serial changes in the diagnosis of acute myocardial infarction (AMI). A total of 1818 patients with suspected acute coronary syndrome were consecutively enrolled at the chest pain units of the University Heart Center Hamburg, the University Medical Center Mainz, and the Federal Armed Forces Hospital Koblenz, all in Germany, from 2007 to 2008. Twelve biomarkers including hsTnI (level of detection, 3.4 pg/mL) and cTnI (level of detection, 10 pg/mL) were measured on admission and after 3 and 6 hours. Diagnostic performance for AMI of baseline and serial changes in hsTnI and cTnI results at 3 hours after admission to the emergency department. Of the 1818 patients, 413 (22.7%) were diagnosed as having AMI. For discrimination of AMI, the area under the receiver operating characteristic (ROC) curve was 0.96 (95% CI, 0.95-0.97) for hsTnI on admission and 0.92 (95% CI, 0.90-0.94) for cTnI on admission. Both were superior to the other evaluated diagnostic biomarkers. The use of hsTnI at admission (with the diagnostic cutoff value at the 99th percentile of 30 pg/mL) had a sensitivity of 82.3% and a negative predictive value (for ruling out AMI) of 94.7%. The use of cTnI (with the diagnostic cutoff value at the 99th percentile of 32 pg/mL) at admission had a sensitivity of 79.4% and a negative predictive value of 94.0%. Using levels obtained at 3 hours after admission, the sensitivity was 98.2% and the negative predictive value was 99.4% for both hsTnI and cTnI assays. Combining the 99th percentile cutoff at admission with the serial change in troponin concentration within 3 hours, the positive predictive value (for ruling in AMI) for hsTnI increased from 75.1% at admission to 95.8% after 3 hours, and for cTnI increased from 80.9% at admission to 96.1% after 3 hours. Among patients with suspected acute coronary syndrome, hsTnI or cTnI determination 3 hours after admission may facilitate early rule-out of AMI. A serial change in hsTnI or cTnI levels from admission (using the 99th percentile diagnostic cutoff value) to 3 hours after admission may facilitate an early diagnosis of AMI.
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              Incremental value of copeptin for rapid rule out of acute myocardial infarction.

              The purpose of this study was to examine the incremental value of copeptin for rapid rule out of acute myocardial infarction (AMI). The rapid and reliable exclusion of AMI is a major unmet clinical need. Copeptin, the C-terminal part of the vasopressin prohormone, as a marker of acute endogenous stress may be useful in this setting. In 487 consecutive patients presenting to the emergency department with symptoms suggestive of AMI, we measured levels of copeptin at presentation, using a novel sandwich immunoluminometric assay in a blinded fashion. The final diagnosis was adjudicated by 2 independent cardiologists using all available data. The adjudicated final diagnosis was AMI in 81 patients (17%). Copeptin levels were significantly higher in AMI patients compared with those in patients having other diagnoses (median 20.8 pmol/l vs. 6.0 pmol/l, p < 0.001). The combination of troponin T and copeptin at initial presentation resulted in an area under the receiver-operating characteristic curve of 0.97 (95% confidence interval: 0.95 to 0.98), which was significantly higher than the 0.86 (95% confidence interval: 0.80 to 0.92) for troponin T alone (p < 0.001). A copeptin level <14 pmol/l in combination with a troponin T < or =0.01 microg/l correctly ruled out AMI with a sensitivity of 98.8% and a negative predictive value of 99.7%. The additional use of copeptin seems to allow a rapid and reliable rule out of AMI already at presentation and may thereby obviate the need for prolonged monitoring and serial blood sampling in the majority of patients. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587).
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                Author and article information

                Journal
                BMJ Open
                BMJ Open
                bmjopen
                bmjopen
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2044-6055
                2019
                16 June 2019
                : 9
                : 6
                Affiliations
                [1 ] departmentService de Diagnostic Biologique Automatisé , Hôpital Cochin, Hôpitaux Universitaires Paris Centre (HUPC), Assistance Publique des Hôpitaux de Paris (AP-HP) , Paris, France
                [2 ] departmentDépartement des Urgences , Hôpital Lapeyronie, CHU de Montpellier , Montpellier, France
                [3 ] departmentService de Cardiologie , Hôpital Avicenne, Hôpitaux Universitaires Paris Seine Saint Denis, Assistance Publique des Hôpitaux de Paris (AP-HP), Bobigny; Université Paris , Paris, France
                [4 ] departmentINSERM UMR S-942 , INSERM , Paris, France
                [5 ] departmentDépartement de Biochimie , Hôpital Lapeyronie – CHU Montpellier , Montpellier, France
                [6 ] Laboratoire de Biochimie et Hormonologie, Hôpital Tenon, Hôpitaux Universitaires Est Parisien, Assistance Publique des Hôpitaux de Paris (AP-HP) , Paris, France
                [7 ] Sorbonne Universités UPMC-University Paris , Biosfast, Paris
                [8 ] Urgences-SMUR, Centre Hospitalier Eure-Seine - Hôpital d’Evreux, Rue Léon Schwartzenberg , Évreux, France
                [9 ] Centre Régional Universitaire des Urgences, Hôpital François Mitterrand, 5 Boulevard Jeanne d’Arc , Dijon, France
                [10 ] Université de Bourgogne , Dijon, France
                Author notes
                [Correspondence to ] Dr Camille Chenevier-Gobeaux; camille.gobeaux@ 123456aphp.fr
                Article
                bmjopen-2018-023994
                10.1136/bmjopen-2018-023994
                6589015
                31209082
                © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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