• Joan Walter, Jeanne du Fay de Lavallaz, Luca Koechlin, Tobias Zimmermann, Jasper Boeddinghaus, Ursina Honegger, Ivo Strebel, Raphael Twerenbold, Melissa Amrein, Thomas Nestelberger, Desiree Wussler, Christian Puelacher, Patrick Badertscher, Michael Zellweger, Gregor Fahrni, Raban Jeger, Christoph Kaiser, Tobias Reichlin, and Christian Mueller.
• Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.).
• Ann. Intern. Med. 2020 Feb 4; 172 (3): 175-185.

BackgroundThe optimal noninvasive method for surveillance in symptomatic patients with stable coronary artery disease (CAD) is unknown.ObjectiveTo 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.DesignProspective diagnostic cohort study. (ClinicalTrials.gov: NCT01838148).SettingUniversity hospital.Patients1896 consecutive patients with CAD referred with symptoms possibly related to inducible myocardial ischemia.MeasurementsPresence 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).ResultsOverall, 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%).LimitationData were generated in a large single-center diagnostic study using central adjudication.ConclusionIn 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 SourceEuropean 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.

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