• Jasper Boeddinghaus, Thomas Nestelberger, Raphael Twerenbold, Karin Wildi, Patrick Badertscher, Janosch Cupa, Tobias Bürge, Patrick Mächler, Sydney Corbière, Karin Grimm, Giménez Maria Rubini MR From Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland (J.B., T.N., Christian Puelacher, Samyut Shrestha, Flores Widmer Dayana D From Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland (J.B., T.N.,, Jakob Fuhrmann, Petra Hillinger, Zaid Sabti, Ursina Honegger, Nicolas Schaerli, Nikola Kozhuharov, Katharina Rentsch, Òscar Miró, Beatriz López, F Javier Martin-Sanchez, Esther Rodriguez-Adrada, Beata Morawiec, Damian Kawecki, Eva Ganovská, Jiri Parenica, Jens Lohrmann, Wanda Kloos, Andreas Buser, Nicolas Geigy, Dagmar I Keller, Stefan Osswald, Tobias Reichlin, and Christian Mueller.
• From Cardiovascular Research Institute Basel and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland (J.B., T.N., R.T., K.W., P.B., J.C., T.B., P.M., S.C., K.G., M.R.G., C.P., S.S., D.F.W., J.F., P.H., Z.S., U.H., N.S., N.K., J.L. W.K., S.O., T.R., C.M.); Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland (J.B., T.N., K.G., P.H., N.S.); GREAT Network (J.B., T.N., R.T., K.W., P.B., J.C., S.C., K.G., M.R.G., C.P., S.S., D.F.W., P.H., Z.S., U.H., N.S., N.K., O.M., B.L., E.G., J.P., T.R., C.M.); Emergency Department, University Hospital Zurich, Switzerland (T.B., P.M., D.I.K.); Laboratory Medicine, University Hospital Basel, Switzerland (K.R.); Emergency Department, Hospital Clinic, Barcelona, Catalonia, Spain (O.M., B.L.); Servicio de Urgencias, Hospital Clínico San Carlos, Madrid, Spain (F.J.M.-S., E.R.-A.); 2nd Department of Cardiology, Medical University of Silesia, Zabrze, Poland (B.M., D.K.); Department of Cardiology, University Hospital Brno, Czech Republic and Medical Faculty, Masaryk University (E.G., J.P.); Blood Transfusion Centre, Swiss Red Cross, Basel, Switzerland and Department of Hematology, University Hospital Basel (A.B.); and Emergency Department, Kantonsspital Liestal, Switzerland (N.G.).
• Circulation. 2017 Apr 25; 135 (17): 1597-1611.

BackgroundFour strategies for very early rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I (hs-cTnI) have been identified. It remains unclear which strategy is most attractive for clinical application.MethodsWe prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. Hs-cTnI levels were measured at presentation and after 1 hour in a blinded fashion. We directly compared all 4 hs-cTnI-based rule-out strategies: limit of detection (LOD, hs-cTnI<2 ng/L), single cutoff (hs-cTnI<5 ng/L), 1-hour algorithm (hs-cTnI<5 ng/L and 1-hour change<2 ng/L), and the 0/1-hour algorithm recommended in the European Society of Cardiology guideline combining LOD and 1-hour algorithm.ResultsAmong 2828 enrolled patients, acute myocardial infarction was the final diagnosis in 451 (16%) patients. The LOD approach ruled out 453 patients (16%) with a sensitivity of 100% (95% confidence interval [CI], 99.2%-100%), the single cutoff 1516 patients (54%) with a sensitivity of 97.1% (95% CI, 95.1%-98.3%), the 1-hour algorithm 1459 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%-99.2%), and the 0/1-hour algorithm 1463 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%-99.2%). Predefined subgroup analysis in early presenters (≤2 hours) revealed significantly lower sensitivity (94.2%, interaction P=0.03) of the single cutoff, but not the other strategies. Two-year survival was 100% with LOD and 98.1% with the other strategies (P<0.01 for LOD versus each of the other strategies).ConclusionsAll 4 rule-out strategies balance effectiveness and safety equally well. The single cutoff should not be applied in early presenters, whereas the 3 other strategies seem to perform well in this challenging subgroup.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587.© 2017 American Heart Association, Inc.

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