Julia Searle

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

Abstract 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.

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. Conclusion—Heparin releases sFlt1 by displacing the sFlt1 heparin-binding site from heparan sulfate proteoglycans. Heparin could induce an antiangiogenic state.

Autoantibodies against cardiac troponin I in patients with congestive heart failure

In this randomized, double‐blind clinical study, we investigated the relationship between autoantibodies against cardiac troponin I (cTnI) and disease severity in elderly congestive heart failure (CHF) patients before and after titration of beta‐blocker therapy.

Prognostic Value of Undetectable hs Troponin T in Suspected Acute Coronary Syndrome

BACKGROUND The search for improved strategies for safe and early discharge of patients with suspected acute coronary syndrome in emergency departments is ongoing. This Biomarkers in Cardiology (BIC)-8 biomarker substudy evaluated the usefulness of high-sensitivity troponin T (hsTnT) below or above the limit of detection (LoD) in low-to-intermediate-risk patients with suspected acute coronary syndrome in the emergency department. METHODS Patients were categorized into hsTnT ≥ the 99th percentile, between the 99th percentile and LoD, or undetectable hsTnT (<LoD). HsTnT and copeptin were measured at admission, using a copeptin cut-off of 10 pmol/L. The primary endpoint was death and myocardial infarction within 90 days after admission. RESULTS Of 882 patients with all biomarker results, 577 (65.4%) had detectable hsTnT levels (≥LoD). Among the 305 patients (34.6%) with undetectable hsTnT, no myocardial infarctions or deaths occurred within 90 days. In patients with detectable hsTnT at admission (≥LoD but ≤99th percentile), the combined endpoint occurred in 1.5% (6/410) of the copeptin-negative patients and in 6.3% (6/96) of copeptin-positive patients within 90 days (hazard ratio 4.39; 95% confidence interval, 1.42-13.61; P = .01). In patients with an initially elevated hsTnT (≥14 ng/L), 9.7% (3/31) of the copeptin-negative patients and 15.4% (4/26) of the copeptin-positive patients experienced the combined endpoint (hazard ratio 1.61; 95% confidence interval, 0.36-7.17; P = .536). CONCLUSIONS In low-to-intermediate-risk patients with suspected acute coronary syndrome, undetectable hsTnT values at admission allow a safe discharge without occurrence of death or myocardial infarction within 90 days.

Temporal Release Pattern of Copeptin and Troponin T in Patients With Suspected Acute Coronary Syndrome and Spontaneous Acute Myocardial Infarction

BACKGROUND The release pattern of copeptin during the initial 36 h of spontaneous acute myocardial infarction (AMI) has received relatively little investigation but may provide important information on optimal timing of diagnostic measurements. METHODS We investigated the release pattern of copeptin and cardiac troponin T in patients with suspected acute coronary syndrome (ACS). Blood samples were collected in the ambulance, at admission, and after 2, 4, 6, and 12-36 h. Copeptin and high-sensitivity cardiac troponin T (hs-cTnT) were measured in heparin plasma samples. RESULTS Of 93 patients studied, 37 (39.8%) had ST-elevation myocardial infarction (STEMI), 20 (21.5%) non-STEMI, 20 (21.5%) unstable angina pectoris (UAP), and 16 (17.2%) non-ACS diagnoses. Peak copeptin concentrations were detected during ambulance transport for NSTEMI patients [median 94.0 pmol/L, interquartile range (IQR) 53.3-302.1 pmol/L] and at admission for patients with STEMI (70.0 pmol/L, 22.0-144.8 pmol/L). In patients with AMI, copeptin decreased significantly over time (P < 0.0001). This was true for patients with STEMI (P = 0.005) and non-STEMI (P = 0.021). The diagnostic performance during ambulance transport was similar for hs-cTnT (area under the ROC curve 0.75, 95% CI 0.62-0.88) and copeptin (0.81, 0.69-0.92). In early presenters (n = 52), no patient with AMI was initially (in ambulance or at admission) negative for copeptin, resulting in an area under the ROC curve of 0.963 for ambulance values and a negative predictive value of 100%. In late presenters, the negative predictive value of copeptin was 50% in ambulance and at admission. CONCLUSIONS Our analysis is the first to show a consistent early increase in copeptin at first medical contact in the ambulance and a decrease to routine values within 12-36 h in patients presenting early with spontaneous AMI.

[Exploring Patient Motives to Use Emergency Departments for Non-urgent Conditions: A Qualitative Study].

Background: The increasing utilization of Emergency Departments (ED) by outpatients with acute but non-urgent conditions contributes to ED crowding. This study aims to explore the motives of patients categorized as non-urgent for visiting the ED. Methods: A qualitative study based on semi-structured interviews was conducted at 2 EDs at Charité Berlin. A total of 40 patients categorized as non-urgent were interviewed. Data were analyzed using Qualitative Content Analysis. Results: In addition to unavailable appointments or having to wait a long time for an appointment with general practitioners and specialists, patients stated better time-flexibility, the University Hospitals quality of care and the availability of multidisciplinary care as reasons to seek medical care in the ED. Because of the 24/7 availability of EDs, some patients seem to make little effort to seek an appointment with a GP or a specialist outside the hospital. Conclusion: Our interview data indicate an independent function of EDs in outpatient care. It must be assumed that even a full coverage of service guarantee by the association of statuary health insurance physicians would not reduce ED utilization to cases of medical urgency only. To ensure sustainable medical quality for urgent as well as non-urgent medical care seekers, EDs need appropriate resources to cover the demand.

The role of myeloperoxidase (MPO) for prognostic evaluation in sensitive cardiac troponin I negative chest pain patients in the emergency department

Background: The diagnostic work-up of patients with acute chest pain in the emergency department (ED) is a challenging task. Serial troponin testing is required to rule-out acute myocardial infarction. Objective: To evaluate the value of myeloperoxidase (MPO) testing in sensitive cardiac troponin I (cTnI) negative patients with suspected acute coronary syndromes (ACS) in the routine setting of an ED. Methods: MPO was assessed in 432 consecutive patients presenting to the ED with ACS. In 266 patients, serial blood samples were available. After 6 weeks, major adverse cardiac events (MACE) were assessed. MPO and cTnI were measured in all available samples. For cTnI, a sensitive assay was used. Cut-off values were derived from an independent sample of 300 healthy volunteers. Results: Incidence of MACE in our population was 13%. MPO levels revealed sensitivity (Sens) of 82.1% and specificity (Spec) of 37.2% for MACE compared with 60.7% Sens and 61.4% Spec for sensitive cTnI. In serial sensitive cTnI negative patients (n=218), MACE incidence was 6.4%. MPO continued to demonstrate significant discriminatory power for the prognosis of MACE. Multivariate analyses confirmed these findings. Conclusion: MPO has an independent prognostic value overall and most notably in patients tested negative with a higher sensitive cardiac troponin I assay. MPO could be a promising biomarker for the initial evaluation of patients in chest pain units and is worth further investigation.

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.

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 patients 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. OBJECTIVE To evaluate whether the diagnostic performance of cardiac troponin at admission (cTn) under routine conditions is influenced by patients sex. 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. 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. CONCLUSIONS The findings of this study underline that the performance of cTn for the diagnosis of NSTEMI depends on a patients 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.