Copeptin Levels Are Independent from Mild Therapeutic Hypothermia but Do Not Predict Infarct Size in Patients Presenting with ST-Segment Elevation Myocardial Infarction

Background: Mild therapeutic hypothermia (MTH) is a treatment adjunct in ST-segment elevation myocardial infarction (STEMI) that deserves investigation. Copeptin―a surrogate marker for vasopressin―is an early biomarker in STEMI. Data from cardiac arrest patients suggest a reduction of copeptin levels through MTH; however, copeptin levels have not been investigated in MTH during STEMI. Methods: We analyzed patients treated with MTH during STEMI in a sub-study of the STATIM trial (Testori, Heart 2019). Patients were randomized to normothermia or MTH with out-of-hospital initiation. Seven copeptin samples were collected from each patient. Primary endpoint was the difference in copeptin levels between the groups. As secondary endpoints, we defined differences in the kinetics between the sampling timepoints and the correlation between copeptin and the infarct size in relation to left ventricular myocardium. Results: We included 99 patients (MTH n = 47, control n = 52) in our intention to treat analysis. No differences in copeptin values at first medical contact between the MTH and normothermia groups were found. MTH showed no effect on copeptin levels, neither during cooling phase nor through the course. Copeptin peaked at first medical contact and hospital admission in both groups. No differences in kinetics between the timepoints were found. Copeptin showed no correlation with infarct size, neither at first medical contact nor hospital admission. Conclusions: Copeptin levels were not influenced by MTH in STEMI, suggesting the use of this biomarker also during temperature management. Furthermore, copeptin levels were not usable as a surrogate marker for infarct size at any timepoint.

Mild Therapeutic Hypothermia Alters Hemostasis in ST Elevation Myocardial Infarction Patients

Background and Rationale: Mild therapeutic hypothermia (MTH) is a concept to reduce infarct size and improve outcome after ST-segment elevation myocardial infarction (STEMI). In the STATIM trial, we investigated MTH as an additional therapy for STEMI patients. In the intention-to-treat set, 101 patients were included. No difference in primary and secondary endpoints measured by cardiac magnetic resonance imaging was found. Platelet activation and plasmatic coagulation are key in the pathophysiology of STEMI. In the present study, we investigated the effect of MTH on primary and secondary hemostasis in STEMI patients.Methods and Results: Platelet function and morphology were assessed by routine blood count, aggregometry testing, and flow cytometry. Soluble platelet markers were determined by enzyme-linked immunosorbent assay (ELISA) testing. Plasmatic coagulation was measured throughout the study. Platelet count remained unchanged, irrespective of treatment, whereas platelet size decreased in both patient groups. Platelet aggregometry indicated increased platelet reactivity in the MTH group. Furthermore, higher adenosine diphosphate (ADP) plasma levels were found in MTH patients. Expression of glycoprotein IIb/IIIa was increased on platelets of STEMI patients treated with MTH. Lower patient temperatures correlated with longer clotting times and resulted in reduced pH. Lower pH values were positively correlated with longer clotting times.Conclusion: Present data indicate longer clotting times and higher platelet reactivity in STEMI patients treated with MTH. These changes did not correspond to clinical bleeding events or larger infarct size.