Application of High-Sensitivity Troponin in Suspected Myocardial Infarction

Johannes T Neumann; Raphael Twerenbold; Francisco Ojeda; Nils A Sörensen; Andrew R Chapman; Anoop S V Shah; Atul Anand; Jasper Boeddinghaus; Thomas Nestelberger; Patrick Badertscher; Arash Mokhtari; John W Pickering; Richard W Troughton; Jaimi Greenslade; William Parsonage; Matthias Mueller-Hennessen; Tommaso Gori; Tomas Jernberg; Niall Morris; Christoph Liebetrau; Christian Hamm; Hugo A Katus; Thomas Münzel; Ulf Landmesser; Veikko Salomaa; Licia Iacoviello; Marco M Ferrario; Simona Giampaoli; Frank Kee; Barbara Thorand; Annette Peters; Rossana Borchini; Torben Jørgensen; Stefan Söderberg; Susana Sans; Hugh Tunstall-Pedoe; Kari Kuulasmaa; Thomas Renné; Karl J Lackner; Andrew Worster; Richard Body; Ulf Ekelund; Peter A Kavsak; Till Keller; Bertil Lindahl; Philipp Wild; Evangelos Giannitsis; Martin Than; Louise A Cullen; Nicholas L Mills; Christian Mueller; Tanja Zeller; Dirk Westermann; Stefan Blankenberg; COMPASS-MI Study Group

doi:10.1056/NEJMoa1803377

Application of High-Sensitivity Troponin in Suspected Myocardial Infarction

N Engl J Med. 2019 Jun 27;380(26):2529-2540. doi: 10.1056/NEJMoa1803377.

Authors

Johannes T Neumann¹, Raphael Twerenbold¹, Francisco Ojeda¹, Nils A Sörensen¹, Andrew R Chapman¹, Anoop S V Shah¹, Atul Anand¹, Jasper Boeddinghaus¹, Thomas Nestelberger¹, Patrick Badertscher¹, Arash Mokhtari¹, John W Pickering¹, Richard W Troughton¹, Jaimi Greenslade¹, William Parsonage¹, Matthias Mueller-Hennessen¹, Tommaso Gori¹, Tomas Jernberg¹, Niall Morris¹, Christoph Liebetrau¹, Christian Hamm¹, Hugo A Katus¹, Thomas Münzel¹, Ulf Landmesser¹, Veikko Salomaa¹, Licia Iacoviello¹, Marco M Ferrario¹, Simona Giampaoli¹, Frank Kee¹, Barbara Thorand¹, Annette Peters¹, Rossana Borchini¹, Torben Jørgensen¹, Stefan Söderberg¹, Susana Sans¹, Hugh Tunstall-Pedoe¹, Kari Kuulasmaa¹, Thomas Renné¹, Karl J Lackner¹, Andrew Worster¹, Richard Body¹, Ulf Ekelund¹, Peter A Kavsak¹, Till Keller¹, Bertil Lindahl¹, Philipp Wild¹, Evangelos Giannitsis¹, Martin Than¹, Louise A Cullen¹, Nicholas L Mills¹, Christian Mueller¹, Tanja Zeller¹, Dirk Westermann¹, Stefan Blankenberg¹; COMPASS-MI Study Group

Collaborators

COMPASS-MI Study Group:
Sally J Aldous, A. Mark Richards, Chris J Pemberton, Remzi Anadol

Affiliation

¹ From the University Heart Center Hamburg (J.T.N., R.T., F.O., N.A.S., T.Z., D.W., S.B.), German Center for Cardiovascular Research (DZHK) Partner Site Hamburg-Kiel-Lübeck (J.T.N., N.A.S., T.Z., D.W., S.B.), and the Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf (T.R.), Hamburg, the Department of Cardiology, Heidelberg University Hospital (M.M.-H., H.A.K., E.G.), and DZHK Partner Site Heidelberg-Mannheim (M.M.-H., H.A.K., E.G.), Heidelberg, Cardiology I (T.G., T.M.) and Preventive Cardiology and Preventive Medicine (P.W.), Center for Cardiology, and the Center for Thrombosis and Hemostasis (P.W.), University Medical Center of Johannes Gutenberg University Mainz, and the Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz (K.J.L.), Mainz, DZHK Partner Site Rhine-Main and the Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim (C.L., C.H., T.K.), the Department of Cardiology, Justus Liebig University of Giessen and Marburg, Giessen (C.L., C.H.), the Department of Cardiology, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin Institute of Health, and DZHK Partner Site Berlin, Berlin (U.L.), and the Institute of Epidemiology, Helmholtz Zentrum, German Research Center for Environmental Health (B.T., A.P.), and DZHK Partner Site Munich Heart Alliance (A.P.), Munich - all in Germany; the Cardiovascular Research Institute Basel and the Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland (R.T., J.B., T.N., P.B., C.M.); the British Heart Foundation Centre for Cardiovascular Science (A.R.C., A.S.V.S., A.A., N.L.M.) and the Usher Institute of Population Health Sciences and Informatics (A.S.V.S., N.L.M.), University of Edinburgh, Edinburgh, the University of Manchester and Manchester University Foundation Trust, Manchester (N.M., R. Body), U.K. Clinical Research Collaboration for Public Health, Queens University of Belfast, Belfast (F.K.), and the Cardiovascular Epidemiology Unit, Institute of Cardiovascular Research, University of Dundee, Dundee (H.T.-P.) - all in the United Kingdom; the Department of Internal and Emergency Medicine, Lund University, Skåne University Hospital, Lund (A.M., U.E.), the Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm (T. Jernberg), the Department of Public Health and Clinical Medicine, and Heart Center, Cardiology, Umeå University, Umeå (S. Söderberg), and the Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Uppsala (B.L.) - all in Sweden; the Department of Medicine, University of Otago Christchurch, and Emergency Department, Christchurch Hospital, Christchurch, New Zealand (J.W.P., R.W.T., M.T.); the Departments of Emergency Medicine (J.G., L.A.C.) and Cardiology (W.P.), Royal Brisbane and Women's Hospital, Herston, QLD, and the Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove (J.G., W.P., L.A.C.) - all in Australia; the National Institute for Health and Welfare, Helsinki, Finland (V.S., K.K.); the Department of Epidemiology and Prevention, Istituto di Ricovero e Cura a Carattere Scientifico Neuromed, Pozzilli (L.I.), the Department of Medicine and Surgery, Research Center in Epidemiology and Preventive Medicine, University of Insubria, Varese (L.I., M.M.F., R. Borchini), and the Department of Cardiovascular, Dysmetabolic, and Aging-Associated Diseases, National Institutes of Health, Rome (S.G.) - all in Italy; the Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen (T. Jørgensen), the Research Center for Prevention and Health, Capital Region of Denmark, Glostrup (T. Jørgensen), and the Medical Faculty, Aalborg University, Aalborg (T. Jørgensen) - all in Denmark; the Catalan Department of Health, Barcelona (S. Sans); and the Division of Emergency Medicine (A.W.) and the Department of Pathology and Molecular Medicine (P.A.K.), McMaster University, Hamilton, ON, Canada.

PMID: 31242362
DOI: 10.1056/NEJMoa1803377

Abstract

Background: Data regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes.

Methods: In 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days.

Results: Among 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set.

Conclusions: A risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes. (Funded by the German Center for Cardiovascular Research [DZHK]; ClinicalTrials.gov numbers, NCT00470587, NCT02355457, NCT01852123, NCT01994577, and NCT03227159; and Australian New Zealand Clinical Trials Registry numbers, ACTRN12611001069943, ACTRN12610000766011, ACTRN12613000745741, and ACTRN12611000206921.).

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't
Validation Study

MeSH terms

Adult
Aged
Biomarkers / blood
Cohort Studies
Emergency Service, Hospital
Female
Humans
Male
Middle Aged
Myocardial Infarction / blood*
Myocardial Infarction / diagnosis*
Prognosis
Risk Assessment / methods*
Sensitivity and Specificity
Troponin / blood*
Troponin I / blood

Substances

Biomarkers
Troponin
Troponin I

Associated data

ClinicalTrials.gov/NCT00470587
ClinicalTrials.gov/NCT02355457
ClinicalTrials.gov/NCT01852123
ClinicalTrials.gov/NCT01994577
ClinicalTrials.gov/NCT03227159
ANZCTR/ACTRN12611001069943
ANZCTR/ACTRN12610000766011
ANZCTR/ACTRN12613000745741
ANZCTR/ACTRN12611000206921

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding