BACKGROUND: Rapid diagnosis of acute coronary syndrome is a clinical and operational priority in busy emergency departments (ED). We examined the performance of an investigational troponin I (TnI) assay with 10-100-times greater sensitivity than current commercial assays. METHODS: Among patients with non-traumatic chest pain enrolled in the BWH-TIMI ED Chest Pain Study, we measured TnI (n=381) at baseline, 4-6 h, and 12-24 h with an investigational assay (S-TnI; Singulex, detection-limit 0.0002 µg/l, 99th percentile 0.009 µg/l) and a contemporary sensitive assay (TnI-Ultra; Siemens, detection-limit 0.006 µg/l, 99th percentile 0.04 µg/l). Final diagnosis was adjudicated using all diagnostic data and local hospital-based cardiac TnI (Siemens), blinded to investigational cardiac Tn. RESULTS: The adjudicated diagnosis was myocardial infarction (MI) in 96 patients, unstable angina in 41, and acute non-coronary cardiovascular conditions in 50 patients. Baseline S-TnI was highly sensitive for MI (97%, 95% CI 91-99%) with specificity 81% (95% CI 76-86%) and positive predictive value 63% (95% CI 55-71%). The negative predictive value with S-TnI was 99% (95% CI 96-100%). S-TnI had better diagnostic accuracy than the local assay (area under the curve 0.976 vs. 0.916, p=0.003). Among 20 patients with negative baseline TnI and diagnosis of MI, 19 had elevated baseline S-TnI. Compared to TnI-Ultra, S-TnI trended toward higher sensitivity (97 vs. 94%, p=NS) but did not differ significantly in negative predictive value (99 vs. 98%) or area under the curve (p=0.29). CONCLUSION: Current and investigational Tn assays substantially increased clinical sensitivity and improved diagnostic accuracy for MI, despite a decline in specificity. A contemporary sensitive assay delivered similar overall accuracy to the investigational test, suggesting that we have reached a point of maximum diagnostic return with increasing analytical sensitivity.
BACKGROUND: Rapid diagnosis of acute coronary syndrome is a clinical and operational priority in busy emergency departments (ED). We examined the performance of an investigational troponin I (TnI) assay with 10-100-times greater sensitivity than current commercial assays. METHODS: Among patients with non-traumatic chest pain enrolled in the BWH-TIMI ED Chest Pain Study, we measured TnI (n=381) at baseline, 4-6 h, and 12-24 h with an investigational assay (S-TnI; Singulex, detection-limit 0.0002 µg/l, 99th percentile 0.009 µg/l) and a contemporary sensitive assay (TnI-Ultra; Siemens, detection-limit 0.006 µg/l, 99th percentile 0.04 µg/l). Final diagnosis was adjudicated using all diagnostic data and local hospital-based cardiac TnI (Siemens), blinded to investigational cardiac Tn. RESULTS: The adjudicated diagnosis was myocardial infarction (MI) in 96 patients, unstable angina in 41, and acute non-coronary cardiovascular conditions in 50 patients. Baseline S-TnI was highly sensitive for MI (97%, 95% CI 91-99%) with specificity 81% (95% CI 76-86%) and positive predictive value 63% (95% CI 55-71%). The negative predictive value with S-TnI was 99% (95% CI 96-100%). S-TnI had better diagnostic accuracy than the local assay (area under the curve 0.976 vs. 0.916, p=0.003). Among 20 patients with negative baseline TnI and diagnosis of MI, 19 had elevated baseline S-TnI. Compared to TnI-Ultra, S-TnI trended toward higher sensitivity (97 vs. 94%, p=NS) but did not differ significantly in negative predictive value (99 vs. 98%) or area under the curve (p=0.29). CONCLUSION: Current and investigational Tn assays substantially increased clinical sensitivity and improved diagnostic accuracy for MI, despite a decline in specificity. A contemporary sensitive assay delivered similar overall accuracy to the investigational test, suggesting that we have reached a point of maximum diagnostic return with increasing analytical sensitivity.
Authors: Kristian Thygesen; Joseph S Alpert; Harvey D White; Allan S Jaffe; Fred S Apple; Marcello Galvani; Hugo A Katus; L Kristin Newby; Jan Ravkilde; Bernard Chaitman; Peter M Clemmensen; Mikael Dellborg; Hanoch Hod; Pekka Porela; Richard Underwood; Jeroen J Bax; George A Beller; Robert Bonow; Ernst E Van der Wall; Jean-Pierre Bassand; William Wijns; T Bruce Ferguson; Philippe G Steg; Barry F Uretsky; David O Williams; Paul W Armstrong; Elliott M Antman; Keith A Fox; Christian W Hamm; E Magnus Ohman; Maarten L Simoons; Philip A Poole-Wilson; Enrique P Gurfinkel; José-Luis Lopez-Sendon; Prem Pais; Shanti Mendis; Jun-Ren Zhu; Lars C Wallentin; Francisco Fernández-Avilés; Kim M Fox; Alexander N Parkhomenko; Silvia G Priori; Michal Tendera; Liisa-Maria Voipio-Pulkki; Alec Vahanian; A John Camm; Raffaele De Caterina; Veronica Dean; Kenneth Dickstein; Gerasimos Filippatos; Christian Funck-Brentano; Irene Hellemans; Steen Dalby Kristensen; Keith McGregor; Udo Sechtem; Sigmund Silber; Michal Tendera; Petr Widimsky; José Luis Zamorano; Joao Morais; Sorin Brener; Robert Harrington; David Morrow; Michael Lim; Marco A Martinez-Rios; Steve Steinhubl; Glen N Levine; W Brian Gibler; David Goff; Marco Tubaro; Darek Dudek; Nawwar Al-Attar Journal: Circulation Date: 2007-10-19 Impact factor: 29.690
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Authors: Christopher J Lindsell; Venkataraman Anantharaman; Deborah Diercks; Jin Ho Han; James W Hoekstra; Judd E Hollander; J Douglas Kirk; Swee-Han Lim; W Frank Peacock; Brian Tiffany; Eric K Wilke; W Brian Gibler; Charles V Pollack Journal: Ann Emerg Med Date: 2006-10-02 Impact factor: 5.721
Authors: John Todd; Bob Freese; Ann Lu; Douglas Held; Jennifer Morey; Richard Livingston; Philippe Goix Journal: Clin Chem Date: 2007-09-21 Impact factor: 8.327
Authors: W Frank Peacock; Deborah Diercks; Robert Birkhahn; Adam J Singer; Judd E Hollander; Richard Nowak; Basmah Safdar; Chadwick D Miller; Mary Peberdy; Francis Counselman; Abhinav Chandra; Joshua Kosowsky; James Neuenschwander; Jon Schrock; Elizabeth Lee-Lewandrowski; William Arnold; John Nagurney Journal: Ann Lab Med Date: 2016-09 Impact factor: 3.464