Using High-Sensitivity Cardiac Troponin for the Exclusion of Inducible Myocardial Ischemia in Symptomatic Patients: A Cohort Study.

Walter, Joan; du Fay de Lavallaz, Jeanne; Koechlin, Luca; Zimmermann, Tobias; Boeddinghaus, Jasper; Honegger, Ursina; Strebel, Ivo; Twerenbold, Raphael; Amrein, Melissa; Nestelberger, Thomas; Wussler, Desiree; Puelacher, Christian; Badertscher, Patrick; Zellweger, Michael; Fahrni, Gregor; Jeger, Raban; Kaiser, Christoph; Reichlin, Tobias; Mueller, Christian (2020). Using High-Sensitivity Cardiac Troponin for the Exclusion of Inducible Myocardial Ischemia in Symptomatic Patients: A Cohort Study. Annals of internal medicine, 172(3), pp. 175-185. American College of Physicians 10.7326/M19-0080

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The optimal noninvasive method for surveillance in symptomatic patients with stable coronary artery disease (CAD) is unknown.


To apply a novel approach using very low concentrations of high-sensitivity cardiac troponin I (hs-cTnI) for exclusion of inducible myocardial ischemia in symptomatic patients with CAD.


Prospective diagnostic cohort study. ( NCT01838148).


University hospital.


1896 consecutive patients with CAD referred with symptoms possibly related to inducible myocardial ischemia.


Presence of inducible myocardial ischemia was adjudicated using myocardial perfusion imaging with single-photon emission computed tomography, as well as coronary angiography and fractional flow reserve measurements where available. Staff blinded to adjudication measured circulating hs-cTn concentrations. An hs-cTnI cutoff of 2.5 ng/L, derived previously in mostly asymptomatic patients with CAD, was assessed. Predefined target performance criteria were at least 90% negative predictive value (NPV) and at least 90% sensitivity for exclusion of inducible myocardial ischemia. Sensitivity analyses were based on measurements with an hs-cTnT assay and an alternative hs-cTnI assay with even higher analytic sensitivity (limit of detection, 0.1 ng/L).


Overall, 865 patients (46%) had inducible myocardial ischemia. The hs-cTnI cutoff of 2.5 ng/L provided an NPV of 70% (95% CI, 64% to 75%) and a sensitivity of 90% (CI, 88% to 92%) for exclusion of inducible myocardial ischemia. No hs-cTnI cutoff reached both performance characteristics predefined as targets. Similarly, using the alternative assays for hs-cTnI or hs-cTnT, no cutoff achieved the target performance: hs-cTnT concentrations less than 5 ng/L yielded an NPV of 66% (CI, 59% to 72%), and hs-cTnI concentrations less than 2 ng/L yielded an NPV of 68% (CI, 62% to 74%).


Data were generated in a large single-center diagnostic study using central adjudication.


In symptomatic patients with CAD, very low hs-cTn concentrations, including hs-cTnI concentrations less than 2.5 ng/L, do not generally allow users to safely exclude inducible myocardial ischemia.

Primary Funding Source

European Union, Swiss National Science Foundation, Kommission für Technologie und Innovation (Innosuisse), Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University of Basel, University Hospital Basel, Roche, Abbott, and Singulex.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiology

UniBE Contributor:

Reichlin, Tobias Roman


600 Technology > 610 Medicine & health




American College of Physicians




Daria Vogelsang

Date Deposited:

30 Nov 2020 10:42

Last Modified:

30 Nov 2020 10:51

Publisher DOI:


PubMed ID:





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