One-hour rule-in and rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I Cedric Jaeger, MD, Karin Wildi, MD, Raphael Twerenbold,

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One-hour rule-in and rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I Cedric Jaeger, MD, Karin Wildi, MD, Raphael Twerenbold, MD, Tobias Reichlin, MD, Maria Rubini Gimenez, MD, Jean-Daniel Neuhaus, MD, Karin Grimm, MD, Jasper Boeddinghaus, MD, Petra Hillinger, MD, Thomas Nestelberger, MD, Helene Singeisen, MD, Mathias Gugala, MD, Gil Pretre, MD, Christian Puelacher, MD, Max Wagener, MD, Ursina Honegger, MSc, Carmela Schumacher, MSc, Zoraida Moreno Weidmann, MD, Philipp Kreutzinger, MD, Lian Krivoshei, MD, Michael Freese, RN, Claudia Stelzig, MS, Sebastian Dietsche, MS, Susanne Ernst, MD, Katharina Rentsch, PhD, Stefan Osswald, MD, Christian Mueller, MD American Heart Journal Volume 171, Issue 1, Pages 92-102.e5 (January 2016) DOI: 10.1016/j.ahj.2015.07.022 Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 1 Patients flow diagram. Patient flow diagram: *Patients with ST-segment elevation myocardial infarction (STEMI) as adjudicated final diagnosis were excluded because biomarkers are considered of limited clinical value in these patients. **Patients were also excluded if the final adjudication was not possible due to lack of late hs-cTnT samples (which were used for adjudication) or lack of detailed cardiac workup (eg, coronary angiography) due to extensive comorbidities and/or patient refusal. ┼ In 312 patients, the 1-hour algorithm could not be determined due to missing 1-hour study blood samples. The most common reasons for missing values after 1 hour were early transfer to the catheterization laboratory or coronary care unit and diagnostic procedures around the 1-hour window that precluded blood draw at 1 hour. No differences in baseline characteristics were found between patients with and without a blood sample after 1 hour (see online Appendix). American Heart Journal 2016 171, 92-102.e5DOI: (10.1016/j.ahj.2015.07.022) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 2 Performance of the 1-hour hs-cTnI algorithm. Performance of the 1-hour algorithm for the diagnosis of AMI using high-sensitivity cardiac troponin I (hs-cTnI). Results are displayed for the derivation (n = 750) and validation cohort (n = 750). High-sensitivity cardiac troponin I values are presented in nanograms per liter. 0h indicates hs-cTnI at presentation to the ED; Delta 1h, absolute change of hs-cTnI within the first hour. Abbreviations: Sens, Sensitivity; Spec, specificity. (See online Appendix for additional information). American Heart Journal 2016 171, 92-102.e5DOI: (10.1016/j.ahj.2015.07.022) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 3 Forest plot of the NPV in various subgroups. Forrest plot showing the NPV of various subgroups in the rule-out zone of the overall cohort. Abbreviation: CAD, Coronary artery disease. American Heart Journal 2016 171, 92-102.e5DOI: (10.1016/j.ahj.2015.07.022) Copyright © 2015 Elsevier Inc. Terms and Conditions

Figure 4 Mortality during 30 and 360 days. Kaplan-Meier curves for the cumulative mortality according to classification provided by the 1-h hs-cTnI algorithm. Kaplan-Meier curves display the cumulative mortality during 30 days of follow-up (A) and 1 year of follow-up (B) in all patients (n = 1,500) according to the classification into “rule-out” (n = 787), “observational zone”(n = 513), and “rule-in” (n = 200) provided by the hs-cTnT 1-hour algorithm. Differences in survival were assessed using the log-rank test. American Heart Journal 2016 171, 92-102.e5DOI: (10.1016/j.ahj.2015.07.022) Copyright © 2015 Elsevier Inc. Terms and Conditions

Supplementary Figure 1A This figure shows the head-to-head comparison of diagnostic accuracy for AMI between hs-cTnI (Siemens Vista) and hs-cTnT (Roche) of the baseline (0 hour) value as well as the 1-hour value in the overall cohort (n = 1,500). American Heart Journal 2016 171, 92-102.e5DOI: (10.1016/j.ahj.2015.07.022) Copyright © 2015 Elsevier Inc. Terms and Conditions

Supplementary Figure 1B this figure shows the head-to-head comparison of prognostic accuracy for 360-day mortality between hs-cTnI (Siemens Vista) and hs-cTnT (Roche) of the baseline (0 hour) value as well as the 1-hour value in the overall cohort (n = 1,500). American Heart Journal 2016 171, 92-102.e5DOI: (10.1016/j.ahj.2015.07.022) Copyright © 2015 Elsevier Inc. Terms and Conditions

Supplementary Figure 2 Sex-specific performance of the 0-/1-hour algorithm in the validation group. American Heart Journal 2016 171, 92-102.e5DOI: (10.1016/j.ahj.2015.07.022) Copyright © 2015 Elsevier Inc. Terms and Conditions