Fabian Holert

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.

Diagnostic performance of a high-sensitive troponin T assay and a troponin T point of care assay in the clinical routine of an Emergency Department: A clinical cohort study

BACKGROUND A point of care test (POCT) for troponin T (TnT) in the Emergency Department (ED) was compared to a high-sensitivity TnT (hsTnT) central laboratory test (CLT) to determine the influence of test system and different cut-off values on the diagnostic performance in patients with suspected acute coronary syndrome (ACS) under routine conditions. METHODS All patients with routine TnT testing in the ED were enrolled. Only internal medicine patients without STEMI and with both troponin values were analyzed. TnT was measured with a contemporary sensitive POCT assay in the ED and with a hs-assay in the central laboratory. The diagnostic performance was analyzed at two different cut-off points (99th percentile and conventional rule-in cut-offs). Primary endpoint was the diagnosis of NSTEMI. RESULTS Of all patients (n=3423), 3.6% had a diagnosis of NSTEMI (n=124). For the hsTnT assay, 28.4% of all values were at or below the lower limit of detection (LOD) as compared to 75.7% of the POC-TnT-values. The area under the receiver operating curves did not differ significantly between the assays (hsTnT: 0.912(95%-CI: 0.884-0.940); POC-TnT: 0.896(95%-CI: 0.859-0.933)). The diagnostic performance was very similar for both assays: the positive predictive value was below 50% for troponin values below 100ng/L and hardly increased for values between 100 and 600ng/L for hs and conventional assays. CONCLUSIONS In our cohort of emergency patients, the diagnostic performance of conventional POC-testing was comparable to hsTnT. A 99th percentile cut-off may be useful for rule-out of NSTEMI, but seems limited for routine rule-in strategies.

Soluble fms-like tyrosine kinase-1 (sFLT-1) predicts post-percutaneous coronary intervention (PCI) myocardial infarction (MI type 4a)

Context: Acute myocardial infarction (AMI) related to percutaneous coronary intervention (PCI) (MI type 4a) occurs in up to 26% of elective patients. Objective: To evaluate if sFLT-1 helps to predict MI type 4a in troponin negative patients with elective PCI. Materials and methods: We enrolled 135 patients, 106 had a PCI. sFLT-1 levels were assessed at five time points before and after PCI. Results: MI type 4a occurred in 22.1% of patients. sFLT-1 levels at admission above 251 pg/mL indicated a significant relative risk for MI type 4a of 2.83. Conclusion and discussion: Increased sFLT-1 levels at baseline might indicate unstable atherosclerosis and risk for microembolization and thus be predictive of MI type 4a.

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

Abstract Purpose: 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. Materials and methods: 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. Results: The median age of the study population (n = 4118) was 61 years (IQR: 45–75 years). NSTEMI was diagnosed in 3.3% (n = 136) of all patients. There were significant differences in hsTnT concentrations between age-groups (p < 0.001) in all patients, but not in NSTEMI patients (p = 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. Conclusions: 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.