Objective To derive and validate a hybrid algorithm for rule-out and rule-in of acute myocardial infarction based on measurements at presentation and after 2 hours with a novel cardiac troponin I (cTnI) assay.
Methods The algorithm was derived and validated in two cohorts (605 and 592 patients) from multicentre studies enrolling chest pain patients presenting to the emergency department (ED) with onset of last episode within 12 hours. The index diagnosis and cardiovascular events up to 30 days were adjudicated by independent reviewers.
Results In the validation cohort, 32.6% of the patients were ruled out on ED presentation, 6.1% were ruled in and 61.3% remained undetermined. A further 22% could be ruled out and 9.8% ruled in, after 2 hours. In total, 54.6% of the patients were ruled out with a negative predictive value (NPV) of 99.4% (95% CI 97.8% to 99.9%) and a sensitivity of 97.7% (95% CI 91.9% to 99.7%); 15.8% were ruled in with a positive predictive value (PPV) of 74.5% (95% CI 64.8% to 82.2%) and a specificity of 95.2% (95% CI 93.0% to 96.9%); and 29.6% remained undetermined after 2 hours. No patient in the rule-out group died during the 30-day follow-up in the two cohorts.
Conclusions This novel two-step algorithm based on cTnI measurements enabled just over a third of the patients with acute chest pain to be ruled in or ruled out already at presentation and an additional third after 2 hours. This strategy maximises the speed of rule-out and rule-in while maintaining a high NPV and PPV, respectively.
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Contributors All coauthors have approved the manuscript and the submission to Heart. BL and TJ were mainly responsible for the design of the FASTEST study. CM for the doing the APACE study. BL has been mainly responsible for analysing the data and writing the report. All other authors have contributed with enrolment of patients and/or analyses of the blood samples. All authors have also provided intellectual contribution to the manuscript.
Funding Both the FASTEST and APACE studies are academically initiated and driven studies. The FASTEST study has received research funding from the European Commission Seventh Framework Programme (BestAgeing), Research funding (ALF) from the Swedish government, Fiomi Diagnostics, bioMérieux and Radiometer. The APACE study has received research funding from the Swiss National Science Foundation, the Swiss Heart Foundation, the European Union, Abbott, Alere, Astra Zeneca, Beckman Coulter, bioMérieux, Brahms, Nanosphere, Roche, Siemens, Singulex, Sphingotec, 8sense, and the Department of Internal Medicine, University Hospital Basel.
Competing interests BL has received research support from Fiomi diagnostics, Radiometer and bioMérieux and has served as consultant for Fiomi Diagnostics, bioMérieux, Roche Diagnostics, Philips, Thermo-Fischer. KME has received honoraria from Abbott Laboratories and AstraZeneca, and has served as consultant for Abbott Laboratories and Fiomi Diagnostics. MRG received speakers honoraria from Abbott. DM has received honoraria from Roche Diagnostics. TR 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 as well as speaker honoraria from Brahms and Roche. TT received speakers honoraria from BRAHMS and Roche. KW received a travel grant from Pfizer. CM has received research support from the Swiss National Science Foundation, the Swiss Heart Foundation, the European Union, Abbott, Alere, Astra Zeneca, Beckman Coulter, bioMérieux, Brahms, Nanosphere, Roche, Siemens, Singulex, Sphingotec, 8sense, and the Department of Internal Medicine, University Hospital Basel, as well as speaker/consulting honoraria/travel support from Abbott, Alere, Astra Zeneca, Bayer, BG medicine, BioMérieux, Boehringer, BMS, Brahms, Cardiorentis, Daiichi Sankyo, Novartis, Roche, Sanofi, Siemens, and Singulex.
Ethics approval Regional Ethics Review Board Stockholm, Sweden (FASTEST), and for the APACE study by the local ethics committees for each participating centre.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The study protocol of the FASTEST and the APACE studies can be provided by the corresponding author.