Copeptin combined with either non-high sensitivity or high sensitivity cardiac troponin for instant rule-out of suspected non-ST segment elevation myocardial infarction.

BACKGROUND: Whether Copeptin combined with high sensitivity troponin below the respective decision cut-offs improves rule-out of NSTEMI and may predict all-cause death at 30-day is under debate. METHODS: Data on 10,329 patients from 5 trials were pooled to evaluate the diagnostic and prognostic performance of an initial Copeptin below decision cut-off in combination with a (hs)-cTn below the uppler limit of normal (ULN) compared to a) the initial (hs)-cTn alone in the standard serial sampling strategy based on the 99th percentile and b) a single marker strategy (SMS) based on hs-cTn < limit of detection. Endpoints were sensitivities and negative predictive values (NPV) for rule-out of NSTEMI, 30-day all-cause mortality and rates of eligibility for DMS or SMS. RESULTS: NPV for NSTEMI was higher for DMS than for the initial cTn, regardless assay sensitivity. The highest NPVs were observed with DMS vs. hs-cTn (99.4% [95% CI: 99.0%-99.6%] vs. 98.8% [98.4%-99.1%],) , and improved performance was consistent across all important subgroups including presentation <3 h, again irrespective of assay sensitivity. The point estimate of all NPVs for all-cause death exceeded 99.75%. In the label populations, DMS versus SMS demonstrated comparably high NPVs for rule-out of NSTEMI (99.4% [99.0%-99.6%] vs. 99.9% [99.2%-100.0%]), very low mortality after rule-out (0.1% [0.0%-0.4% vs. 0.0% [0.0%-1.2%]), but eligibility for rule-out was 2.4-fold higher (61.4% [59.9%-62.9%] vs. 25.3% [23.7%-26.9%]) with DMS than SMS. CONCLUSION: Findings from a large pooled cohort corroborate the safety of the dual marker strategy for instant rule-out of NSTEMI, extending evidence to hs-cTn. Copeptin below cut-off in combination with hs-cTn below ULN may be used in more than 2.4-times more patients presenting with suspected ACS than a single marker strategy based on very low hs-cTn, without the need to exclude very early presenters or other important subgroups.

Use of copeptin in emergency patients with cardiac chief complaints.

BACKGROUND: Combined testing of copeptin and troponin at presentation to the emergency department (ED) has been shown to possess a high negative predictive value (NPV) for ruling out acute myocardial infarction (AMI) in patients with suspected acute coronary syndrome. PURPOSE: The aim of this study was to evaluate the diagnostic performance of the combination of copeptin and troponin for the exclusion of AMI in emergency patients with acute cardiac chief complaints and to assess diagnoses and outcome in copeptin-positive patients. METHODS: In this prospective study, 537 consecutive patients with cardiac chief complaints were recruited from the ED. Blood samples were collected at admission. RESULTS: The overall incidence of AMI in the study sample was 14.2% (n=76). In troponin-negative patients, copeptin showed a sensitivity of 76.9% (95% confidence interval (CI) 46.2-95.0), a specificity of 64.2% (95% CI 59.2-69.0), a positive predictive value (PPV) of 6.9% (95% CI 3.3-12.2) and an NPV of 98.8% (95% CI 96.5-99.8). The highest copeptin values were observed in patients with chronic heart failure, followed by ST-elevation myocardial infarction (STEMI), acute heart failure (AHF), pneumonia and non-STEMI (NSTEMI). A copeptin-value of above 10 pmol/l increased the risk of death within three months significantly (hazard ratio (HR)=5.42 (1.81-16.21) p=0.003). CONCLUSION: Copeptin seems to be a promising biomarker for the initial evaluation of emergency patients with cardiac chief complaints. The study adds to the evidence that a single copeptin and troponin test at admission achieves a high NPV for ruling-out NSTEMI early in low-to-intermediate risk patients and thus--in combination with the clinical evaluation--seems to be of considerable relevance in emergency medicine.

Qualitative process analysis and modelling of emergency care workflow and interface management: identification of critical process steps.

OBJECTIVES: Over the past few years, the number of patients attending emergency services has increased steadily. As a result, emergency departments (EDs) worldwide face frequent crowding, with the risk of reduced treatment quality and impaired patient outcome, patient and staff dissatisfaction and inefficient use of ED resources. A qualitative process analysis and process modelling was used as a method to detect critical process steps in the ED with respect to time and efficiency. METHODS: The analysis was carried out by independent external process experts. Over a period of 1 week, the complete treatment process of 25 patients was recorded. The monitoring of overall activities, decision points, causalities and interfaces was based on the treatment of 100 additional patients and on interviews with nurses and physicians. The project was closed with the identification of the three most critical process steps and modelling of the standard emergency care process in an event-process chain (EPC). RESULTS: The most time-crucial steps detected by the analysis were the process of developing a tentative diagnosis, including consultation and advice seeking by inexperienced physicians, the interface to imaging diagnostics and the search of hospital beds for inpatients. The results were visualized by standardized modelling of an event-process chain (EPC). CONCLUSION: The process analysis helped to identify inefficient process steps in the ED. Modelling with EPC is a useful tool to visualize and to understand the complexity of the emergency medical care and to identify key performance indicators for effective quality management.

Chief complaints in medical emergencies: do they relate to underlying disease and outcome? The Charité Emergency Medicine Study (CHARITEM).

OBJECTIVES: To evaluate the relationship between chief complaints and their underlying diseases and outcome in medical emergency departments (EDs). METHODS: All 34 333 patients who attended two of the EDs of the Charité Berlin over a 1-year period were included in the analysis. Data were retrieved from the hospital information system. For study purposes, the chief complaint (chest pain, dyspnoea, abdominal pain, headache or 'none of these symptoms') was prospectively documented in an electronic file by the ED-physician. Documentation was mandatory. RESULTS: The majority of patients (66%) presented with 'none of these symptoms', 11.5% with chest pain, 11.1% with abdominal pain and 7.4% with dyspnoea. In total, 39.4% of all patients were admitted to the hospital. The leading diagnosis was acute coronary syndrome (50.7%) for chest pain in-patients and chronic obstructive pulmonary disease (16.5%) and heart failure (16.1%) for in-patients with dyspnoea. The causes of abdominal pain in in-patients were of diverse gastrointestinal origin (47.2%). In-hospital mortality of in-patients was 4.7%. Patients with chest pain had significantly lower in-hospital mortality (0.9%) than patients with dyspnoea (9.4%) and abdominal pain (5.1%). CONCLUSION: The majority of emergency patients lack diagnosis-specific symptoms. Chief complaints help preselect patients but must not be mistaken as disease specific. Mortality largely differs depending on the chief complaint. In chest pain patients, standardized processes may be one factor that explains the low mortality in this group.

Heparin strongly induces soluble fms-like tyrosine kinase 1 release in vivo and in vitro--brief report.

OBJECTIVE: Soluble fms-like tyrosine kinase 1 (sFlt1) is involved in the pathophysiology of preeclampsia and coronary artery disease. Because sFlt1 has a heparin-binding site, we investigated whether or not heparin releases sFlt1 from the extracellular matrix. METHODS AND RESULTS: We measured sFlt1 before and after heparin administration in 135 patients undergoing coronary angiography, percutanous coronary intervention, or both. sFlt1 was increased directly after heparin administration (from 254 to 13,440 pg/mL) and returned to baseline within 10 hours. Umbilical veins and endothelial cells treated with heparin released sFlt1. Heparinase I and III also increased sFlt1. Mice treated with heparin had elevated sFlt1 serum levels. Their serum inhibited endothelial tube formation. CONCLUSIONS: Heparin releases sFlt1 by displacing the sFlt1 heparin-binding site from heparan sulfate proteoglycans. Heparin could induce an antiangiogenic state.