die Bedeutung und Anwendbarkeit von Multimarkerstrategien und Point-of-Care Diagnostik zur schnellen Behandlung akuter kardiovaskulärer Erkrankungen in der Notaufnahme

Einleitung: Hochsensitive Troponin-Tests (hsTn) werden in der kardiovaskulären Diagnostik zunehmend eingesetzt, zum frühen Infarktausschluss ist jedoch wegen der zeitversetzten Freisetzung immer ein zweiter Wert erforderlich. Copeptin ist ein Marker der Vasopressinfreisetzung, der komplementär zum Troponin bereits unmittelbar nach Beginn eines Myokardinfarkts (MI) erhöht ist. Im Bereich der cerebrovaskulären Akutdiagnostik ist bisher kein Biomarker fest etabliert. Retrospektive Analysen haben gezeigt, daß die Bestimmung von Copeptin in Kombination mit Troponin insbesondere den Ausschluss eines Myokardinfarkts beschleunigen kann. Der Nutzen des hsTn in der klinischen Routine der Notaufnahme mit zahlreichen Patienten, die aus anderen Gründen als dem MI erhöhte Werte aufweisen, wird noch kontrovers diskutiert. Methodik und Ergebnisse: In zwei unabhängigen prospektiven Studien wurde die Verwendbarkeit von Copeptin für die Akutdiagnostik des Akuten Koronarsyndroms (ACS) und den sicheren Ausschluss eines Myokardinfarktes (Publikation 1), sowie eine Eignung zur Differenzierung des akuten Schlaganfalls und seiner Differentialdiagnosen insbesondere „stroke mimics“ (Publikation 2) evaluiert. Die sichere Verwendung bei Patienten mit niedrigem bis mittelhohem Risiko und Verdacht auf MI konnte unter Realbedingungen in der Notaufnahme gezeigt werden. Eine Eignung für die sichere Differenzierung beim V. a. Schlaganfall konnte allerdings nicht bestätigt werden. In einer dritten Studie (Publikation 3) wurde in einer unselektierten Population von Notfallpatienten mit Troponin-Anforderung ein Troponin-Test auf Point of Care (PoC)-Basis verglichen mit einem laborbasierten hochsensitiven Troponin-Assay. In der Studie konnte eine vergleichbare diagnostische Wertigkeit der verschiedenen Systeme gezeigt werden, sowie keine signifikanten Unterschiede bezüglich eines sicheren Nicht-ST-Hebungsinfarkt-Ausschlusses (NSTEMI). Bei Verwendung der 99. Perzentilen zeigt der PoC-Assay eine höhere Genauigkeit, die höchste Sensitivität hingegen konnte für den hsTnT-Assay an der 99. Perzentile berechnet werden. Schlussfolgerung: Die klinische Sicherheit und Machbarkeit einer Multimarkerstrategie von Copeptin und Troponin für die ACS-Akut-Diagnostik und die Gleichwertigkeit von PoC-Geräten im notfallmedizinischen Alltag konnte gezeigt werden und bieten im zeitkritischen Kontext der Notfallmedizin eine sichere Alternative zum gegenwärtig definierten Standard serieller Troponinmessungen. Die zuverlässige Differenzierung zwischen Schlaganfall, Transitorische Ischämische Attacke (TIA) und stroke mimics gelingt mittels Copeptin nicht.Introduction: The use of high-sensitive troponin testing (hsTn) in cardiovascular diagnostics is increasing but due to time-dependent release of troponin a second measurement is needed for early rule-out of myocardial infarction (MI). Copeptin is a marker of Vasopressin release and correlates to rising troponin levels immediately after the start of MI. Regarding diagnostics of acute cerebrovascular diseases, no such biomarker could be established yet. Retrospective analyses have shown that the combined use of copeptin and troponin-testing led to reduced turnaround times in the rule-out of MI. The use of hsTn in the clinical emergency routine in patients with elevated values based on other reasons than MI is still discussed controversially. Methods and Results: In two independent prospective studies the usability of Copeptin was evaluated regarding the diagnosis of Acute Coronary Syndrome (ACS) and myocardial infarction (publication 1) and the value of Copeptin in differentiating ischemic stroke and its differential diagnoses including stroke mimics (publication 2). The safety utilizing Copeptin in suspected ACS and MI patients with low to intermediate risk could be shown under real life conditions in the Emergency Department. The safe use of copeptin in differentiating suspected acute stroke could not be confirmed. In a third study (publication 3) a Point of Care-based (PoC) troponin assay was compared to a lab-based high-sensitive troponin assay in regards to diagnostic performance in an unselected population of acute patients with a troponin testing order. The study results showed a comparable diagnostic accuracy of the different systems used. No significant differences were detected in the safe rule-out of Non-ST-elevation myocardial infarction (NSTEMI). Looking at the 99th percentile, the highest Negative Predictive Value (NPV) and sensitivity were achieved using hsTnT while PoC-TnT showed higher accuracy. Conclusion: The safe use of a multimarker-strategy of Copeptin and Troponin in ACS diagnosis and the equivalence of PoC-testing in the acute setting was successfully shown under routine and real-life conditions. Facing the time-critical conditions of an emergency, the new process can be seen as a safe alternative to the current standard of serial troponin testing. The safe differentiation of suspected ischemic stroke, Transitoric Ischemic Attack (TIA) and its differential diagnoses using copeptin failed

Early discharge using single cardiac troponin and copeptin testing in patients with suspected acute coronary syndrome (ACS): a randomized, controlled clinical process study

Aims This randomized controlled trial (RCT) evaluated whether a process with single combined testing of copeptin and troponin at admission in patients with low-to-intermediate risk and suspected acute coronary syndrome (ACS) does not lead to a higher proportion of major adverse cardiac events (MACE) than the current standard process (non-inferiority design). Methods and results A total of 902 patients were randomly assigned to either standard care or the copeptin group where patients with negative troponin and copeptin values at admission were eligible for discharge after final clinical assessment. The proportion of MACE (death, survived sudden cardiac death, acute myocardial infarction (AMI), re-hospitalization for ACS, acute unplanned percutaneous coronary intervention, coronary artery bypass grafting, or documented life threatening arrhythmias) was assessed after 30 days. Intention to treat analysis showed a MACE proportion of 5.17% [95% confidence intervals (CI) 3.30-7.65%; 23/445] in the standard group and 5.19% (95% CI 3.32-7.69%; 23/443) in the copeptin group. In the per protocol analysis, the MACE proportion was 5.34% (95% CI 3.38-7.97%) in the standard group, and 3.01% (95% CI 1.51-5.33%) in the copeptin group. These results were also corroborated by sensitivity analyses. In the copeptin group, discharged copeptin negative patients had an event rate of 0.6% (2/362). Conclusion After clinical work-up and single combined testing of troponin and copeptin to rule-out AMI, early discharge of low- to intermediate risk patients with suspected ACS seems to be safe and has the potential to shorten length of stay in the ED. However, our results need to be confirmed in larger clinical trials or registries, before a clinical directive can be propagate

Early discharge using single cardiac troponin and copeptin testing in patients with suspected acute coronary syndrome (ACS): a randomized, controlled clinical process study

Aims: This randomized controlled trial (RCT) evaluated whether a process with single combined testing of copeptin and troponin at admission in patients with low-to-intermediate risk and suspected acute coronary syndrome (ACS) does not lead to a higher proportion of major adverse cardiac events (MACE) than the current standard process (non-inferiority design). Methods and results: A total of 902 patients were randomly assigned to either standard care or the copeptin group where patients with negative troponin and copeptin values at admission were eligible for discharge after final clinical assessment. The proportion of MACE (death, survived sudden cardiac death, acute myocardial infarction (AMI), re-hospitalization for ACS, acute unplanned percutaneous coronary intervention, coronary artery bypass grafting, or documented life threatening arrhythmias) was assessed after 30 days. Intention to treat analysis showed a MACE proportion of 5.17% [95% confidence intervals (CI) 3.30–7.65%; 23/445] in the standard group and 5.19% (95% CI 3.32–7.69%; 23/443) in the copeptin group. In the per protocol analysis, the MACE proportion was 5.34% (95% CI 3.38–7.97%) in the standard group, and 3.01% (95% CI 1.51–5.33%) in the copeptin group. These results were also corroborated by sensitivity analyses. In the copeptin group, discharged copeptin negative patients had an event rate of 0.6% (2/362). Conclusion: After clinical work-up and single combined testing of troponin and copeptin to rule-out AMI, early discharge of low- to intermediate risk patients with suspected ACS seems to be safe and has the potential to shorten length of stay in the ED. However, our results need to be confirmed in larger clinical trials or registries, before a clinical directive can be propagated

Copeptin: Limited Usefulness in Early Stroke Differentiation?

Background. Stroke can be a challenging diagnosis in an emergency-setting. We sought to determine whether copeptin may be a useful biomarker to differentiate between ischemic stroke (IS), transient ischemic attack (TIA), and stroke-mimics. Methods. In patients with suspected stroke arriving within 4.5 hours of symptom-onset, copeptin-levels were measured in initial blood-samples. The final diagnosis was adjudicated by vascular neurologists blinded to copeptin-values. Results. Of all 36 patients with available copeptin-values (median age 71 years, IQR: 54–76; 44% female), 20 patients (56%) were diagnosed with IS, no patient was diagnosed with hemorrhagic stroke, nine patients (25%) were diagnosed with TIA, and seven patients (19%) were stroke-mimics. Copeptin-levels (in pmol/L) tended to be higher in patients with IS [19.1 (11.2–48.5)] compared to TIA [9.4 (5.4–13.8)]. In stroke-mimics the range of values was extremely broad [33.3 (7.57–255.7)]. The diagnostic accuracy of copeptin for IS was 63% with a sensitivity of 80% and a positive predictive value of 64%. Conclusion. In this cohort of patients copeptin-levels within 4.5 hours of symptom onset were higher in patients with IS compared to TIA but the broad range of values in stroke-mimics limits diagnostic accuracy. This trial is registered with UTN: U1111-1119-7602

High-sensitivity cardiac troponin T for diagnosis of NSTEMI in the elderly emergency department patient: a clinical cohort study

<p><b>Purpose:</b> The aim of this study is to evaluate the impact of age on the diagnostic performance of high-sensitivity troponin T (hsTnT) under routine conditions.</p> <p><b>Materials and methods:</b> Data of 4118 consecutive emergency department (ED) patients who underwent a routine TnT measurement between 11 October 2012 and 30 November 2013 were analysed. Diagnostic accuracy of hsTnT was compared in four age categories (<50, 50–64, 65–74, ≥75 years of age) for different cut-off values. Primary endpoint was a main hospital diagnosis of NSTEMI.</p> <p><b>Results:</b> The median age of the study population (<i>n</i> = 4118) was 61 years (IQR: 45–75 years). NSTEMI was diagnosed in 3.3% (<i>n</i> = 136) of all patients. There were significant differences in hsTnT concentrations between age-groups (<i>p</i> < 0.001) in all patients, but not in NSTEMI patients (<i>p</i> = 0.297). 72.2% of all patients ≥75 years of age (583/808) without NSTEMI had hsTnT concentrations above the 99th percentile of a healthy reference population. Specificity at 14 ng/L was 93.6% (95% CI: 92.12–94.87) in patients below 50 years of age and 27.9% (95% CI: 24.78–31.08) in patients 75 years of age and older.</p> <p><b>Conclusions:</b> Patients’ age needs to be considered at least one influencing factor on hsTnT concentrations at admission and should be included in the clinical interpretation of hsTnT concentrations for further clinical workup beneath other influencing factors like comorbidities and symptom onset time. The implementation of age-specific cut-off values could be considered for single troponin testing at admission but is associated with an increased risk of underdiagnosis of NSTEMI.</p

Sex differences of troponin test performance in chest pain patients

Background: Current guidelines recommend troponin as the preferred biomarker to diagnose acute myocardial infarction (AMI) irrespective of the patient's sex. Recent reports have shown that sex-specific cut-offs should be considered but studies investigating sex-differences in the diagnostic accuracy of cardiac troponins are sparse.\ud \ud Objective: To evaluate whether the diagnostic performance of cardiac troponin at admission (cTn) under routine conditions is influenced by patient's sex.\ud \ud Methods: Between 15th of February 2009 and 15th of February 2010, women (n = 1648) and men (n = 2305) who presented to the emergency department with chest pain (n = 3954) were enrolled. The diagnostic performance of the routine, contemporary sensitive cTn assays (TnI; Stratus® CS, Siemens and TnT; Roche Diagnostics) at baseline for the diagnosis of non-ST-elevation myocardial infarction (NSTEMI) was analyzed.\ud \ud Results: NSTEMI was diagnosed in 7.3% (n = 287) of all patients. Men were more likely to be diagnosed with NSTEMI (8.8%; n = 202) as compared to women (5.2%; n = 85; p < 0.001). Sensitivity was 56.1% (95% CI: 44.7–67.0%) in women and 70.1% (95% CI: 63.1–76.4%) in men. Specificity was 96.8% (95% CI: 95.6–97.7%) in women and 94.5% (95% CI: 93.3–95.6%) in men. This resulted in a lower positive predictive value (PPV) for women (53.5%; 95% CI: 42.4–64.3) as compared to men (60.8%; 95% CI: 54.1–67.2) and a slightly higher negative predictive value (NPV) for women: 97.1% (95% CI: 96.0–97.9) vs. 96.3% (95% CI: 95.2–97.2) in men.\ud \ud Conclusions: The findings of this study underline that the performance of cTn for the diagnosis of NSTEMI depends on a patient's sex, with a lower sensitivity and NPV in women. The definition and implementation of sex-specific cut-off values for cTn into clinical routine seems to be highly recommendable