Multicenter Evaluation of a 0-Hour/1-Hour Algorithm in the Diagnosis of Myocardial Infarction With High-Sensitivity Cardiac Troponin T - 24/06/16

Doi : 10.1016/j.annemergmed.2015.11.013

Christian Mueller, MD ^a,^⁎ , Evangelos Giannitsis, MD ^b, Michael Christ, MD ^c, Jorge Ordóñez-Llanos, MD ^d, Christopher deFilippi, MD ^e, James McCord, MD ^g, Richard Body, MB ChB, PhD ^h, Mauro Panteghini, MD ⁱ, Tomas Jernberg, MD ^j, Mario Plebani, MD ^k, Franck Verschuren, PhD ^l, John French, PhD ^m, Robert Christenson, PhD ^f, Silvia Weiser, PhD ⁿ, Garnet Bendig, PhD ⁿ, Peter Dilba, Dipl Stat ⁿ, Bertil Lindahl, MD ^o
for the
TRAPID-AMI Investigators^{^†}
A list of additional contributors in the TRAPID-AMI study is provided in Table E1, available online at www.annemergmed.com.
Raphael Twerenbold, MD, Hugo A. Katus, MD, PhD, Steffen Popp, MD, Miquel Santalo-Bel, MD, PhD, Richard M. Nowak, MD, MBA, Daniel Horner, MD, Alberto Dolci, MD, Martina Zaninotto, Alessandro Manara, MD, Sylvie Menassanch-Volker, PhD, Jochen Jarausch, PhD, Christian Zaugg, PhD

^a Department of Cardiology and Cardiovascular Research Institute Basel, University Hospital Basel, Basel, Switzerland
^b University Hospital Heidelberg, Heidelberg, Germany
^c Department of Emergency and Critical Care Medicine, General Hospital, Paracelsus Medical University, Nuremberg, Germany
^d Department of Clinical Biochemistry, Institut d'Investigacions Biomèdiques Sant Pau, Barcelona, Spain
^e Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
^f Department of Pathology, University of Maryland School of Medicine, Baltimore, MD
^g Henry Ford Heart and Vascular Institute, Henry Ford Health System, Detroit, MI
^h Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK
ⁱ Department of Biomedical and Clinical Sciences “Luigi Sacco,” University of Milan Medical School, Milan, Italy
^j Department of Medicine, Karolinska Institutet, Huddinge, Sweden
^k Department of Laboratory Medicine, University Hospital of Padova, Padua, Italy
^l Department of Acute Medicine, Cliniques Universitaires St-Luc and Université Catholique de Louvain, Brussels, Belgium
^m Liverpool Hospital and University of New South Wales, Liverpool, NSW, Australia
ⁿ Roche Diagnostics Germany, Penzberg, Germany
^o Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden

^∗Corresponding Author.

Abstract

Study objective

We aim to prospectively validate the diagnostic accuracy of the recently developed 0-h/1-h algorithm, using high-sensitivity cardiac troponin T (hs-cTnT) for the early rule-out and rule-in of acute myocardial infarction.

Methods

We enrolled patients presenting with suspected acute myocardial infarction and recent (<6 hours) onset of symptoms to the emergency department in a global multicenter diagnostic study. Hs-cTnT (Roche Diagnostics) and sensitive cardiac troponin I (Siemens Healthcare) were measured at presentation and after 1 hour, 2 hours, and 4 to 14 hours in a central laboratory. Patient triage according to the predefined hs-cTnT 0-hour/1-hour algorithm (hs-cTnT below 12 ng/L and Δ1 hour below 3 ng/L to rule out; hs-cTnT at least 52 ng/L or Δ1 hour at least 5 ng/L to rule in; remaining patients to the “observational zone”) was compared against a centrally adjudicated final diagnosis by 2 independent cardiologists (reference standard). The final diagnosis was based on all available information, including coronary angiography and echocardiography results, follow-up data, and serial measurements of sensitive cardiac troponin I, whereas adjudicators remained blinded to hs-cTnT.

Results

Among 1,282 patients enrolled, acute myocardial infarction was the final diagnosis for 213 (16.6%) patients. Applying the hs-cTnT 0-hour/1-hour algorithm, 813 (63.4%) patients were classified as rule out, 184 (14.4%) were classified as rule in, and 285 (22.2%) were triaged to the observational zone. This resulted in a negative predictive value and sensitivity for acute myocardial infarction of 99.1% (95% confidence interval [CI] 98.2% to 99.7%) and 96.7% (95% CI 93.4% to 98.7%) in the rule-out zone (7 patients with false-negative results), a positive predictive value and specificity for acute myocardial infarction of 77.2% (95% CI 70.4% to 83.0%) and 96.1% (95% CI 94.7% to 97.2%) in the rule-in zone, and a prevalence of acute myocardial infarction of 22.5% in the observational zone.

Conclusion

The hs-cTnT 0-hour/1-hour algorithm performs well for early rule-out and rule-in of acute myocardial infarction.

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Plan

Introduction

Background

Importance

Goals of This Investigation

Materials and Methods

Study Design

Selection of Participants

Outcome Measures

Primary Data Analysis

Results

Characteristics of Study Subjects

Limitations

Discussion

	Please see page 77 for the Editor’s Capsule Summary of this article.
	Supervising editor: Judd E. Hollander, MD
	Author contributions: CM, SW, and BL designed the study. CM and BL reviewed the literature. CM wrote the article. CM, EG, MC, JO-L, CdF, JM, RB, M. Panteghini, TJ, M. Plebani, FV, and JF recruited patients and interpreted results. EG, MC, JO-L, CdF, JM, RB, M. Panteghini, TJ, M. Plebani, FV, JF, RC, SW, GB, PD, and BL critically reviewed the article. CM, EG, MC, JO-L, CdF, JM, RB, M. Panteghini, TJ, M. Plebani, FV, JF, and RC collected data. RC measured samples. SW and GB managed the study. CM, GB, PD, and BL analyzed and interpreted the study data. PD was the study statistician. All authors have read and approved the final article and take final responsibility for the decision to submit for publication in the present form. CM takes responsibility for the paper as a whole.
	Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The study was sponsored by Roche Diagnostics. Dr. Mueller has received research support from the European Union, the Swiss National Science Foundation, the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, Abbott, Alere, AstraZeneca, Beckman Coulter, BRAHMS, Critical Diagnostics, Roche, Siemens, Singulex, Sphingotec, and the Department of Internal Medicine, University Hospital Basel, as well as speaker and consulting honoraria or travel support from Abbott, Alere, AstraZeneca, Bayer, BG Medicine, bioMérieux, BRAHMS, Cardiorentis, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Radiometer, Roche, Siemens, and Singulex. Dr. Giannitsis has received honoraria for lectures from Roche Diagnostics, BRAHMS ThermoFisher, and Mitsubishi Chemical Europe; has received an institutional research grant from Roche Diagnostics; and serves as a consultant for Roche Diagnostics and BRAHMS ThermoFisher. Dr. Christ has received research support and speaking honoraria from Roche, ThermoFisher, and Novartis. Dr. Ordóñez-Llanos reports grants, personal fees, and nonfinancial support from Roche Diagnostics during the conduct of the study; grants, personal fees, and nonfinancial support from Abbott Diagnostics; personal fees and nonfinancial support from Alere Diagnostics; nonfinancial support from Critical Diagnostics; and other support from Stat Diagnostics and ThermoFisher outside the submitted work. Dr. deFilippi reports grants and personal fees from Roche Diagnostics during the conduct of the study, grants and personal fees from Critical Diagnostics, grants from BG Medicine, nonfinancial support from Alere, personal fees from Radiometer, personal fees from Siemens Healthcare, personal fees from Singulex, and personal fees from HDL outside the submitted work. In addition, Dr. deFilippi has patent 61/990,386 pending. Dr. McCord has received research support from Roche. Dr. Body has accepted travel and accommodation for conferences from Roche Diagnostics and Randox Laboratories, and has undertaken research supported by the donation of reagents by Roche Diagnostics, Siemens Healthcare Diagnostics, Randox Laboratories, Alere, and Abbott Laboratories. Dr. Panteghini received a research grant from Roche Diagnostics during the course of the study. Dr. Plebani reports an institutional research grant from Roche. Dr. French reports grants from The Medicines Company and other support from The Medicines Company, Boehringer Ingelheim, Eli Lilly, sanofi-aventis, Bayer, and AstraZeneca outside the submitted work. Dr. Christenson reports personal fees from Roche Diagnostics outside the submitted work. Drs. Weiser, Bendig, and Dilba are employees of Roche Diagnostics. Dr. Lindahl has served as a consultant for Roche Diagnostics, Beckman Coulter Inc., Siemens Healthcare Diagnostics, Radiometer Medical, bioMérieux Clinical Diagnostics, Philips Healthcare, and Fiomidiagnostics AB; has received a lecture fee from ThermoFisher; and has received research grants from Roche Diagnostics, Fiomidiagnostics AB, and bioMérieux Clinical Diagnostics. All other authors declare that they have no conflict of interest with this study. Alisa Davis and Steve Winter were supported by Roche Diagnostics.
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