title: Estimation of Values below the Limit of Detection of a Contemporary Sensitive Troponin I Assay Improves Diagnosis of Acute Myocardial Infarction.
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.
authors.affiliation: Institute for Cardiovascular Regeneration, Center of Molecular Medicine and DZHK (German Centre for Cardiovascular Research), partner site Rhein-Main, Germany;
authors.forename: Jes-Niels
authors.initials: JN
authors.lastname: Boeckel
authors.affiliation: Division of Cardiology, Department of Medicine III, Goethe University Frankfurt, Frankfurt, Germany;
authors.forename: Lars
authors.initials: L
authors.lastname: Palapies
authors.affiliation: Clinic for General and Interventional Cardiology, University Heart Centre Hamburg, Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany;
authors.forename: Tanja
authors.initials: T
authors.lastname: Zeller
authors.affiliation: Division of Cardiology, Department of Medicine III, Goethe University Frankfurt, Frankfurt, Germany;
authors.forename: Sophia M
authors.initials: SM
authors.lastname: Reis
authors.affiliation: Division of Cardiology, Department of Medicine III, Goethe University Frankfurt, Frankfurt, Germany;
authors.forename: Beatrice
authors.initials: B
authors.lastname: von Jeinsen
authors.affiliation: Department of Medicine II, University Medical Center, Johannes Gutenberg University, Mainz, Germany; 3rd Department of Cardiology, Aristotle University of Thessaloniki, Ippokrateio Hospital, Thessaloniki, Greece.
authors.forename: Stergios
authors.initials: S
authors.lastname: Tzikas
authors.affiliation: Department of Internal Medicine, Federal Armed Forces Hospital, Koblenz, Germany;
authors.forename: Christoph
authors.initials: C
authors.lastname: Bickel
authors.affiliation: Heart Center, University of Cologne, Cologne, Germany;
authors.forename: Stephan
authors.initials: S
authors.lastname: Baldus
authors.affiliation: Clinic for General and Interventional Cardiology, University Heart Centre Hamburg, Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany;
authors.forename: Stefan
authors.initials: S
authors.lastname: Blankenberg
authors.affiliation: Department of Medicine II, University Medical Center, Johannes Gutenberg University, Mainz, Germany; DZHK (German Centre for Cardiovascular Research), partner site Rhein-Main, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Münzel
authors.affiliation: Division of Cardiology, Department of Medicine III, Goethe University Frankfurt, Frankfurt, Germany; DZHK (German Centre for Cardiovascular Research), partner site Rhein-Main, Germany;
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University Medical Center, Johannes Gutenberg University, Mainz, Germany;
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Lackner
authors.affiliation: 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.
authors.forename: Till
authors.initials: T
authors.lastname: Keller
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D015331:Cohort Studies; D005260:Female; D006801:Humans; D057230:Limit of Detection; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis*; D011379:Prognosis; D012372:ROC Curve; D012044:Regression Analysis; D019210:Troponin I / Q000097:blood*
chemical_list: D019210:Troponin I