title: Clinical impact of the 2010-2012 low-end shift of high-sensitivity cardiac troponin T.
abstract: BACKGROUND
  The clinical implications of the 2010-2012 low-end shift of high-sensitivity cardiac troponin T (hs-cTnT) regarding possible misdiagnosis of acute myocardial infarction are largely unknown.
  
  
  METHODS
  We aimed to quantify the impact of the 2010-2012 low-end shift and adjustment issue in 857 patients presenting to the emergency department with suspected acute myocardial infarction by comparing measurements performed with affected 2010-2012 lots with recalculated 2010-2012 values using a linear regression formula (provided by the manufacturer) and the corrected assay (re-measured in 2013). The final diagnosis was adjudicated by two independent cardiologists using all information including coronary angiography, echocardiography and serial hs-cTnT levels (with the corrected 2013 assay).
  
  
  RESULTS
  Acute myocardial infarction was the adjudicated diagnosis in 195 patients (22.7%). Median hs-TnT values were 8.5 ng/l for affected lots, 11.1 ng/l with recalculated and 10 ng/l with the corrected assay (P<0.001 for all comparisons). Spearman correlation coefficient was 0.937 (<0.001) for correct and affected respective correct and recalculated values. The Cusum test indicated significant deviation from linearity (P<0.01) for both correlations. Deviations nearly exclusively affected hs-cTnT levels below the 99th percentile (14 ng/L). Among the 195 patients with an adjudicated diagnosis of acute myocardial infarction, no patient was misclassified using affected lots if using conventional serial sampling. In contrast, misdiagnosis of acute myocardial infarction was significantly increased by affected lots if applying the novel ESC 0 h/1 h algorithm for the early rule-out of acute myocardial infarction (negative predictive value with affected lots 97.7% versus 99.7% with corrected lots).
  
  
  CONCLUSIONS
  The 2010-2012 hs-cTnT low-end shift affected nearly exclusively levels below the 99th percentile cut-off. While it did not affect the diagnosis of acute myocardial infarction when using conventional serial sampling as done in 2010-2012, it would impact on new early rule-out strategies using very low levels of hs-cTnT such as the ESC 0 h/1 h algorithm.
  
  
  BACKGROUND
  NCT0047058, NCT00470587.
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
authors.forename: Karin
authors.initials: K
authors.lastname: Wildi
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
authors.forename: Raphael
authors.initials: R
authors.lastname: Twerenbold
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
authors.forename: Cedric
authors.initials: C
authors.lastname: Jaeger
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland Pneumology Department, Parc de Salut Mar-IMIM-UPF, Spain Emergency Department, Parc de Salut Mar, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Rubini Giménez
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
authors.forename: Tobias
authors.initials: T
authors.lastname: Reichlin
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
authors.forename: Melanie
authors.initials: M
authors.lastname: Stoll
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
authors.forename: Petra
authors.initials: P
authors.lastname: Hillinger
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Puelacher
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
authors.forename: Jasper
authors.initials: J
authors.lastname: Boeddinghaus
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nestelberger
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
authors.forename: Karin
authors.initials: K
authors.lastname: Grimm
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland.
authors.forename: Maja
authors.initials: M
authors.lastname: Grob
authors.affiliation: Laboratory Medicine, University Hospital Basel, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Rentsch
authors.affiliation: Department of Internal Medicine, Kantonsspital Olten, Switzerland.
authors.forename: Christiane
authors.initials: C
authors.lastname: Arnold
authors.affiliation: Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, Switzerland christian.mueller@usb.ch.
authors.forename: Christian
authors.initials: C
authors.lastname: Mueller
mesh_terms: D000368:Aged; D000465:Algorithms; D015415:Biomarkers / Q000097:blood; D003951:Diagnostic Errors; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis*; D015588:Observer Variation; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D020107:Troponin T / Q000097:blood*
chemical_list: D015415:Biomarkers; D020107:Troponin T
keywords: High-sensitivity cardiac troponin T (hs-cTnT); clinical implication; diagnosis of acute myocardial infarction; low-end shift of hs-cTnT; recalculation of hs-cTnT