Original Investigation
Prospective Validation of the 0/1-h Algorithm for Early Diagnosis of Myocardial Infarction

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Abstract

Background

The safety of the European Society of Cardiology (ESC) 0/1-h algorithm for rapid rule-out and rule-in of non–ST-segment elevation myocardial infarction (NSTEMI) using high-sensitivity cardiac troponin (hs-cTn) has been questioned.

Objectives

This study aimed to validate the diagnostic performance of the 0/1-h algorithm in a large multicenter study.

Methods

The authors prospectively enrolled unselected patients in 6 countries presenting to the emergency department with symptoms suggestive of NSTEMI. Final diagnosis was centrally adjudicated by 2 independent cardiologists. Hs-cTnT and hs-cTnI blood concentrations were measured at presentation and after 1 h. Safety of rule-out was quantified by the negative predictive value (NPV) for NSTEMI, accuracy of rule-in by the positive predictive value (PPV), and overall efficacy by the proportion of patients triaged towards rule-out or rule-in within 1 h.

Results

Prevalence of NSTEMI was 17%. Among 4,368 patients with serial hs-cTnT measurements available, safety of rule-out (NPV 99.8%, 2,488 of 2,493), accuracy of rule-in (PPV 74.5%, 572 of 768), and overall efficacy were high by assigning three-fourths of patients either to rule-out (57%, 2,493 to 4,368) or rule-in (18%, 768 to 4,368). Similarly, among 3,500 patients with serial hs-cTnI measurements, safety of rule-out (NPV 99.7%, 1,528 of 1,533), accuracy of rule-in (PPV 62.3%, 498 of 800), and overall efficacy were high by assigning more than two-thirds of patients either to rule-out (44%, 1,533 of 3,500) or rule-in (23%, 800 of 3,500). Excellent safety was confirmed in multiple subgroup analyses including patients presenting early (≤3 h) after chest pain onset.

Conclusions

The ESC 0/1-h algorithm using hs-cTnT and hs-cTnI is very safe and effective in triaging patients with suspected NSTEMI. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587; and Biomarkers in Acute Cardiac Care [BACC]; NCT02355457)

Key Words

diagnosis of myocardial infarction
diagnostic algorithms
myocardial infarction
rule-in
rule-out
troponin

Abbreviations and Acronyms

CAD
coronary artery disease
cTn
cardiac troponin
ECG
electrocardiography
ED
emergency department
ESC
European Society of Cardiology
hs-cTn
high-sensitivity cardiac troponin
LR
likelihood ratio
MACE
major adverse cardiac event
MI
myocardial infarction
NPV
negative predictive value
NRI
net reclassification improvement
NSTEMI
non–ST-segment elevation myocardial infarction
PPV
positive predictive value
UA
unstable angina

Cited by (0)

The APACE study was supported by research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the KTI, the European Union, the Stiftung für kardiovaskuläre Forschung Basel; Abbott, Beckman Coulter, Biomerieux, Brahms, Roche, Siemens, and Singulex. The BACC study was supported by the German Center of Cardiovascular Research and an unrestricted grant from Abbott Diagnostics. The investigated high-sensitivity cardiac troponin T and I assays were partly donated by Roche and Abbott, who had no role in the design of the study, the analysis of the data, the preparation of the manuscript, or the decision to submit the manuscript for publication. Dr. Twerenbold has received research support from the Swiss National Science Foundation (P300PB_167803), the Swiss Heart Foundation, the University Hospital of Basel, the University of Basel, and the Cardiovascular Research Foundation Basel; and speaker honoraria/consulting honoraria from Roche Diagnostics, Abbott Diagnostics, Siemens, Singulex, Thermo Scientific, and Brahms. Dr. Neumann was supported by a grant from the German Heart Foundation/German Foundation of Heart Research and the Else Kröner Fresenius Stiftung; and has received consulting honoraria from Acarix. Dr. Rubini Giménez has received speaker honoraria from Abbott. Dr. Boeddinghaus has received speaker honoraria/consulting honoraria from Siemens. Dr. Wildi has received research funding from FAG Basel and the Gottfried and Julia Bangerter-Rhyner Foundation. Dr. Reichlin has received research grants from the Goldschmidt-Jacobson-Foundation, the Swiss National Science Foundation (PASMP3-136995), the Swiss Heart Foundation, the Professor Max Cloëtta Foundation, the Uniscientia Foundation Vaduz, the University of Basel, and the Department of Internal Medicine, University Hospital Basel; and has received speaker honoraria from Brahms and Roche. Dr. Blankenberg has received research funding from Abbott Diagnostics, Bayer, Boehringer Ingelheim, Siemens, Singulex, and Thermo Fisher; has received consulting honoraria from Bayer, Thermo Fisher, Roche Diagnostics, and Novartis; has received speaker honoraria from Abbott Diagnostics, Bayer, Boehringer Ingelheim, Siemens, Thermo Fisher, AstraZeneca, Medtronic, Pfizer, and Roche Diagnostics; and has served on advisory boards for Bayer, Boehringer Ingelheim, Thermo Fisher, Roche Diagnostics, and Novartis. Dr. Mueller has received research support from the Swiss National Science Foundation, the Swiss Heart Foundation, the KTI, the European Union, the Stiftung für Kardiovaskuläre Forschung Basel, Abbott, Alere, AstraZeneca, Beckman Coulter, Biomerieux, Brahms, Roche, Siemens, Singulex, Sphingotec, and the Department of Internal Medicine, University Hospital Basel; and has received speakers/consulting honoraria from Abbott, Alere, AstraZeneca, Biomerieux, Boehringer Ingelheim, BMS, Brahms, Cardiorentis, Novartis, Roche, Siemens, and Singulex. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The hs-cTnI and hs-cTnT assays were donated by Roche and Abbott, who had no role in the design of the study, the analysis of the data, the preparation of the manuscript, or the decision to submit the manuscript for publication.

Listen to this manuscript's audio summary by JACC Editor-in-Chief Dr. Valentin Fuster.

Drs. Twerenbold and Neumann have contributed equally to this work and should be considered first authors.

Drs. Westermann and Mueller have contributed equally to this work and should be considered senior authors.