Jes-Niels Boeckel1, Lars Palapies2, Tanja Zeller3, Sophia M Reis2, Beatrice von Jeinsen2, Stergios Tzikas4, Christoph Bickel5, Stephan Baldus6, Stefan Blankenberg3, Thomas Münzel7, Andreas M Zeiher8, Karl J Lackner9, Till Keller10. 1. Institute for Cardiovascular Regeneration, Center of Molecular Medicine and DZHK (German Centre for Cardiovascular Research), partner site Rhein-Main, Germany; 2. Division of Cardiology, Department of Medicine III, Goethe University Frankfurt, Frankfurt, Germany; 3. Clinic for General and Interventional Cardiology, University Heart Centre Hamburg, Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany; 4. Department of Medicine II, University Medical Center, Johannes Gutenberg University, Mainz, Germany; 3rd Department of Cardiology, Aristotle University of Thessaloniki, Ippokrateio Hospital, Thessaloniki, Greece. 5. Department of Internal Medicine, Federal Armed Forces Hospital, Koblenz, Germany; 6. Heart Center, University of Cologne, Cologne, Germany; 7. Department of Medicine II, University Medical Center, Johannes Gutenberg University, Mainz, Germany; DZHK (German Centre for Cardiovascular Research), partner site Rhein-Main, Germany; 8. Division of Cardiology, Department of Medicine III, Goethe University Frankfurt, Frankfurt, Germany; DZHK (German Centre for Cardiovascular Research), partner site Rhein-Main, Germany; 9. Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center, Johannes Gutenberg University, Mainz, Germany; 10. Division of Cardiology, Department of Medicine III, Goethe University Frankfurt, Frankfurt, Germany; DZHK (German Centre for Cardiovascular Research), partner site Rhein-Main, Germany; Till.Keller@kgu.de.
Abstract
BACKGROUND: The limit of detection (LoD) is the minimal amount of a substance that can be consistently detected. In the diagnosis of acute myocardial infarction (AMI) many patients present with troponin concentrations below the LoD of contemporary sensitive cardiac troponin I (cs-cTnI) assays. These censored values below the LoD influence the diagnostic performance of these assays compared to highly sensitive cTnI (hs-cTnI) assays. Therefore we assessed the impact of a new approach for interpolation of the left-censored data of a cs-cTnI assay in the evaluation of patients with suspected AMI. METHODS: Our posthoc analysis used a real world cohort of 1818 patients with suspected MI. Data on cs-cTnI was available in 1786 patients. As a comparator the hs-cTnI version of the assay was used. To reconstruct quantities below the LoD of the cs-cTnI assay, a gamma regression approach incorporating the GRACE (Global Registry of Acute Coronary Events) score variables was used. RESULTS: Censoring of cs-cTnI data below the LoD yielded weaker diagnostic information [area under the curve (AUC), 0.781; 95% CI, 0.731-0.831] regarding AMI compared to the hs-cTnI assay (AUC, 0.949; CI, 0.936-0.961). Use of our model to estimate cs-cTnI values below the LoD showed an AUC improvement to 0.921 (CI, 0.902-0.940). The cs-cTnI LoD concentration had a negative predictive value (NPV) of 0.950. An estimated concentration that was to be undercut by 25% of patients presenting with suspected AMI was associated with an improvement of the NPV to 0.979. CONCLUSIONS: Estimation of values below the LoD of a cs-cTnI assay with this new approach improves the diagnostic performance in evaluation of patients with suspected AMI.
BACKGROUND: The limit of detection (LoD) is the minimal amount of a substance that can be consistently detected. In the diagnosis of acute myocardial infarction (AMI) many patients present with troponin concentrations below the LoD of contemporary sensitive cardiac troponin I (cs-cTnI) assays. These censored values below the LoD influence the diagnostic performance of these assays compared to highly sensitive cTnI (hs-cTnI) assays. Therefore we assessed the impact of a new approach for interpolation of the left-censored data of a cs-cTnI assay in the evaluation of patients with suspected AMI. METHODS: Our posthoc analysis used a real world cohort of 1818 patients with suspected MI. Data on cs-cTnI was available in 1786 patients. As a comparator the hs-cTnI version of the assay was used. To reconstruct quantities below the LoD of the cs-cTnI assay, a gamma regression approach incorporating the GRACE (Global Registry of Acute Coronary Events) score variables was used. RESULTS: Censoring of cs-cTnI data below the LoD yielded weaker diagnostic information [area under the curve (AUC), 0.781; 95% CI, 0.731-0.831] regarding AMI compared to the hs-cTnI assay (AUC, 0.949; CI, 0.936-0.961). Use of our model to estimate cs-cTnI values below the LoD showed an AUC improvement to 0.921 (CI, 0.902-0.940). The cs-cTnI LoD concentration had a negative predictive value (NPV) of 0.950. An estimated concentration that was to be undercut by 25% of patients presenting with suspected AMI was associated with an improvement of the NPV to 0.979. CONCLUSIONS: Estimation of values below the LoD of a cs-cTnI assay with this new approach improves the diagnostic performance in evaluation of patients with suspected AMI.
Authors: Dieter Fischer; Friederike Remberg; Dirk Böse; Michael Lichtenberg; Philipp Kümpers; Pia Lebiedz; Hermann-Joseph Pavenstädt; Johannes Waltenberger; Frank Breuckmann Journal: Eur J Med Res Date: 2016-03-17 Impact factor: 2.175