title: Misdiagnosis of Myocardial Infarction Related to Limitations of the Current Regulatory Approach to Define Clinical Decision Values for Cardiac Troponin.
abstract: BACKGROUND
  Misdiagnosis of acute myocardial infarction (AMI) may significantly harm patients and may result from inappropriate clinical decision values (CDVs) for cardiac troponin (cTn) owing to limitations in the current regulatory process.
  
  
  RESULTS
  In an international, prospective, multicenter study, we quantified the incidence of inconsistencies in the diagnosis of AMI using fully characterized and clinically available high-sensitivity (hs) cTn assays (hs-cTnI, Abbott; hs-cTnT, Roche) among 2300 consecutive patients with suspected AMI. We hypothesized that the approved CDVs for the 2 assays are not biologically equivalent and might therefore contribute to inconsistencies in the diagnosis of AMI. Findings were validated by use of sex-specific CDVs and parallel measurements of other hs-cTnI assays. AMI was the adjudicated diagnosis in 473 patients (21%). Among these, 86 patients (18.2%) had inconsistent diagnoses when the approved uniform CDV was used. When sex-specific CDVs were used, 14.1% of female and 22.7% of male AMI patients had inconsistent diagnoses. Using biologically equivalent CDV reduced inconsistencies to 10% (P<0.001). These findings were confirmed with parallel measurements of other hs-cTn assays. The incidence of inconsistencies was only 7.0% for assays with CDVs that were nearly biologically equivalent. Patients with inconsistent AMI had long-term mortality comparable to that of patients with consistent diagnoses (P=NS) and a trend toward higher long-term mortality than patients diagnosed with unstable angina (P=0.05).
  
  
  CONCLUSIONS
  Currently approved CDVs are not biologically equivalent and contribute to major inconsistencies in the diagnosis of AMI. One of 5 AMI patients will receive a diagnosis other than AMI if managed with the alternative hs-cTn assay.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587.
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Karin
authors.initials: K
authors.lastname: Wildi
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Maria Rubini
authors.initials: MR
authors.lastname: Gimenez
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Raphael
authors.initials: R
authors.lastname: Twerenbold
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Tobias
authors.initials: T
authors.lastname: Reichlin
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Cedric
authors.initials: C
authors.lastname: Jaeger
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Amely
authors.initials: A
authors.lastname: Heinzelmann
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Christiane
authors.initials: C
authors.lastname: Arnold
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Berit
authors.initials: B
authors.lastname: Nelles
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Sophie
authors.initials: S
authors.lastname: Druey
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Philip
authors.initials: P
authors.lastname: Haaf
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Petra
authors.initials: P
authors.lastname: Hillinger
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Nicolas
authors.initials: N
authors.lastname: Schaerli
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Philipp
authors.initials: P
authors.lastname: Kreutzinger
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Yunus
authors.initials: Y
authors.lastname: Tanglay
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Thomas
authors.initials: T
authors.lastname: Herrmann
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Zoraida
authors.initials: Z
authors.lastname: Moreno Weidmann
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Lian
authors.initials: L
authors.lastname: Krivoshei
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Michael
authors.initials: M
authors.lastname: Freese
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Claudia
authors.initials: C
authors.lastname: Stelzig
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Christian
authors.initials: C
authors.lastname: Puelacher
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Katharina
authors.initials: K
authors.lastname: Rentsch
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.).
authors.forename: Stefan
authors.initials: S
authors.lastname: Osswald
authors.affiliation: From Department of Cardiology and Cardiovascular Research Institute Basel (K.W., M.R.G., R.T., T.R., C.J., A.H., S.D., P.H., P.H., N.S., P.K., Y.T., T.H., Z.M.W., L.K., M.F., C.S., C.P., S.O., C.M.) and Laboratory Medicine (K.R.), University Hospital Basel, Switzerland; Servicio de Urgencias y Pneumologia, CIBERES ISC III, Hospital del Mar-Institut Municipal d'Investigació Mèdica, Barcelona, Spain (M.R.G.); and Department of Internal Medicine, Kantonsspital Olten, Switzerland (C.A.). Christian.Mueller@usb.ch.
authors.forename: Christian
authors.initials: C
authors.lastname: Mueller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003951:Diagnostic Errors / Q000706:statistics & numerical data*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007391:International Cooperation; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D009206:Myocardium / Q000378:metabolism*; D011446:Prospective Studies; D012016:Reference Values; D012737:Sex Factors; D015996:Survival Rate; D019210:Troponin I / Q000097:blood*; D020107:Troponin T / Q000097:blood*
chemical_list: D015415:Biomarkers; D019210:Troponin I; D020107:Troponin T
keywords: acute cardiac care; biological markers; myocardial infarction; troponin