Validation of high-sensitivity troponin I in a 2-hour diagnostic strategy to assess 30-day outcomes in emergency department patients with possible acute coronary syndrome

TY - JOUR

T1 - Validation of high-sensitivity troponin I in a 2-hour diagnostic strategy to assess 30-day outcomes in emergency department patients with possible acute coronary syndrome

AU - Cullen, Louise

AU - Mueller, Christian

AU - Parsonage, William A.

AU - Wildi, Karin

AU - Greenslade, Jaimi H.

AU - Twerenbold, Raphael

AU - Aldous, Sally

AU - Meller, Bernadette

AU - Tate, Jillian R.

AU - Reichlin, Tobias

AU - Hammett, Christopher J.

AU - Zellweger, Christa

AU - Ungerer, Jacobus P.J.

AU - Rubini Gimenez, Maria

AU - Troughton, Richard

AU - Murray, Karsten

AU - Brown, Anthony F.T.

AU - Mueller, Mira

AU - George, Peter

AU - Mosimann, Tamina

AU - Flaws, Dylan F.

AU - Reiter, Miriam

AU - Lamanna, Arvin

AU - Haaf, Philip

AU - Pemberton, Christopher J.

AU - Richards, A. Mark

AU - Chu, Kevin

AU - Reid, Christopher M.

AU - Peacock, William Frank

AU - Jaffe, Allan S.

AU - Florkowski, Christopher

AU - Deely, Joanne M.

AU - Than, Martin

N1 - Funding Information: Funded by Queensland Emergency Medicine Research Foundation, Christchurch Heart Institute and Health Research Council and Heart Foundation of New Zealand, Christchurch Emergency Care Foundation, Abbott Diagnostics, Alere, Swiss National Science Foundation, University Basel, Swiss Heart Foundation, Roche, Siemens, and University Hospital Basel . Dr. Cullen has received funding from the Queensland Emergency Medical Research Foundation for chest pain clinical trials; from Abbott Diagnostics, Roche, Alere, Siemens, and Radiometer Pacific for clinical trials; and from Alere, Boehringer-Ingelheim, Pfizer, AstraZeneca, Abbott Diagnostics, and Radiometer Pacific for speaking and education. Prof. Mueller has received research grants from the Swiss National Science Foundation, University Basel, Swiss Heart Foundation, Stiftung für kardiovaskuläre Forschung Basel, 8sense, Abbott, Alere, Brahms, Critical Diagnostics, Nanosphere, Roche, Siemens, and the Department of Internal Medicine ; and honoraria to speak from Abbott, Alere, Brahms, Novartis, Roche, and Siemens. Dr. Parsonage has received funding from the Queensland Emergency Medicine Research Foundation, Abbott Diagnostics, Roche, Alere, and Beckmann Coulter for research on diagnostic protocols; and honoraria, travel expenses, and consultancy fees from Abbott, AstraZeneca, Hospira, and Sanofi-Aventis. Dr. Aldous has received funding from the National Heart Foundation (New Zealand) for cardiac research. Dr. Reichlin has received research grants from the Swiss National Science Foundation ( PASMP3-136995 ), Swiss Heart Foundation, University of Basel, Professor Max Cloetta Foundation , and the Department of Internal Medicine, University Hospital Basel ; and honoraria to speak from Brahms and Roche. Dr. Hammett has received consultancy fees from Lilly and Bayer; speaker fees from AstraZeneca, Lilly, Bayer, and Boehringer-Ingelheim; and travel grants from Abbott, AstraZeneca, Bayer, Boehringer-Ingelheim, Boston Scientific, Cordis, Lilly, Medtronic, Pfizer, Sanofi, and Schering-Plough . Dr. Ungerer has received funding from Pathology Queensland Study, Research and Education Trust Fund for unrelated research. Dr. Brown has received funding from AstraZeneca, Boehringer-Ingelheim, Aventis, and Roche to attend educational meetings; honoraria from Boehringer-Ingelheim and Roche for educational material; is on the Board of the Queensland Emergency Medical Research Foundation and received funding from this body as a co-investigator; and has been an Expert Medical Witness by the Queensland, Victorian, NT Coroner, and various legal companies . Peter George has received funding from Abbott, Beckman Coulter, and Roche for speaking. Dr. Flaws has received support from Alere to travel to meetings. Dr. Pemberton has received funding from the Health Research Council of New Zealand for studies investigating novel diagnostic markers of acute coronary syndromes. Dr. Richards has received speaker honoraria and funds from Roche Diagnostics and Alere for research support. Dr. Chu has received funding from the Queensland Emergency Medicine Research Foundation for unrelated research. Dr. Reid has received funding from the National Health & Medical Research Council (Australia) for Cardiovascular Research. Dr. Peacock has received research grants from Abbott, Alere, Brahms, Novartis, Roche, and The Medicines Company ; has been a consultant for Abbott, Alere, Lily, and The Medicines Company; and has been a speaker for Bureau Abbott, and Alere. Dr. Deely has received funding from the Emergency Care Foundation for medical writing and Health Research Council (New Zealand) for unrelated research. Dr. Than has received funding from the Health Research Council (New Zealand) for two chest pain random clinical trials, the New Zealand National Heart Foundation for analysis of blood troponins from a chest pain clinical trial, and the Canterbury Community Trust for a diagnostic for unrelated research, and is Chair of the Emergency Care Foundation. All other authors have reported they have no relationships relevant to the contents of this paper to disclose.

PY - 2013/10/1

Y1 - 2013/10/1

N2 - Objectives The study objective was to validate a new high-sensitivity troponin I (hs-TnI) assay in a clinical protocol for assessing patients who present to the emergency department with chest pain. Background Protocols using sensitive troponin assays can accelerate the rule out of acute myocardial infarction in patients with low-risk (suspected) acute coronary syndrome (ACS). Methods This study evaluated 2 prospective cohorts of patients in the emergency department with ACS in an accelerated diagnostic pathway integrating 0- and 2-h hs-TnI results, Thrombolysis In Myocardial Infarction (TIMI) risk scores, and electrocardiography. Strategies to identify low-risk patients incorporated TIMI risk scores = 0 or ≤1. The primary endpoint was a major adverse cardiac event (MACE) within 30 days. Results In the primary cohort, 1,635 patients were recruited and had 30-day follow-up. A total of 247 patients (15.1%) had a MACE. The finding of no ischemic electrocardiogram and hs-TnI ≤26.2 ng/l with the TIMI = 0 and TIMI ≤1 pathways, respectively, classified 19.6% (n = 320) and 41.5% (n = 678) of these patients as low risk; 0% (n = 0) and 0.8% (n = 2) had a MACE, respectively. In the secondary cohort, 909 patients were recruited. A total of 156 patients (17.2%) had a MACE. The TIMI = 0 and TIMI ≤1 pathways classified 25.3% (n = 230) and 38.6% (n = 351), respectively, of these patients as low risk; 0% (n = 0) and 0.8% (n = 1) had a MACE, respectively. Sensitivity, specificity, and negative predictive value for TIMI = 0 in the primary cohort were 100% (95% confidence interval [CI]: 98.5% to 100%), 23.1% (95% CI: 20.9% to 25.3%), and 100% (95% CI: 98.8% to 100%), respectively. Sensitivity, specificity, and negative predictive value for TIMI ≤1 in the primary cohort were 99.2 (95% CI: 97.1 to 99.8), 48.7 (95% CI: 46.1 to 51.3), and 99.7 (95% CI: 98.9 to 99.9), respectively. Sensitivity, specificity, and negative value for TIMI ≤1 in the secondary cohort were 99.4% (95% CI: 96.5 to 100), 46.5% (95% CI: 42.9 to 50.1), and 99.7% (95% CI: 98.4 to 100), respectively. Conclusions An early-discharge strategy using an hs-TnI assay and TIMI score ≤1 had similar safety as previously reported, with the potential to decrease the observation periods and admissions for approximately 40% of patients with suspected ACS. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study, NCT00470587; A 2hr Accelerated Diagnostic Protocol to Assess patients with chest Pain symptoms using contemporary Troponins as the only biomarker [ADAPT]: A prospective observational validation study, ACTRN12611001069943)

AB - Objectives The study objective was to validate a new high-sensitivity troponin I (hs-TnI) assay in a clinical protocol for assessing patients who present to the emergency department with chest pain. Background Protocols using sensitive troponin assays can accelerate the rule out of acute myocardial infarction in patients with low-risk (suspected) acute coronary syndrome (ACS). Methods This study evaluated 2 prospective cohorts of patients in the emergency department with ACS in an accelerated diagnostic pathway integrating 0- and 2-h hs-TnI results, Thrombolysis In Myocardial Infarction (TIMI) risk scores, and electrocardiography. Strategies to identify low-risk patients incorporated TIMI risk scores = 0 or ≤1. The primary endpoint was a major adverse cardiac event (MACE) within 30 days. Results In the primary cohort, 1,635 patients were recruited and had 30-day follow-up. A total of 247 patients (15.1%) had a MACE. The finding of no ischemic electrocardiogram and hs-TnI ≤26.2 ng/l with the TIMI = 0 and TIMI ≤1 pathways, respectively, classified 19.6% (n = 320) and 41.5% (n = 678) of these patients as low risk; 0% (n = 0) and 0.8% (n = 2) had a MACE, respectively. In the secondary cohort, 909 patients were recruited. A total of 156 patients (17.2%) had a MACE. The TIMI = 0 and TIMI ≤1 pathways classified 25.3% (n = 230) and 38.6% (n = 351), respectively, of these patients as low risk; 0% (n = 0) and 0.8% (n = 1) had a MACE, respectively. Sensitivity, specificity, and negative predictive value for TIMI = 0 in the primary cohort were 100% (95% confidence interval [CI]: 98.5% to 100%), 23.1% (95% CI: 20.9% to 25.3%), and 100% (95% CI: 98.8% to 100%), respectively. Sensitivity, specificity, and negative predictive value for TIMI ≤1 in the primary cohort were 99.2 (95% CI: 97.1 to 99.8), 48.7 (95% CI: 46.1 to 51.3), and 99.7 (95% CI: 98.9 to 99.9), respectively. Sensitivity, specificity, and negative value for TIMI ≤1 in the secondary cohort were 99.4% (95% CI: 96.5 to 100), 46.5% (95% CI: 42.9 to 50.1), and 99.7% (95% CI: 98.4 to 100), respectively. Conclusions An early-discharge strategy using an hs-TnI assay and TIMI score ≤1 had similar safety as previously reported, with the potential to decrease the observation periods and admissions for approximately 40% of patients with suspected ACS. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] Study, NCT00470587; A 2hr Accelerated Diagnostic Protocol to Assess patients with chest Pain symptoms using contemporary Troponins as the only biomarker [ADAPT]: A prospective observational validation study, ACTRN12611001069943)

KW - acute myocardial infarction

KW - ADAPT

KW - APACE

KW - chest pain

KW - high-sensitivity troponin I

KW - TIMI

UR - http://www.scopus.com/inward/record.url?scp=84881480711&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2013.02.078

DO - 10.1016/j.jacc.2013.02.078

M3 - SCORING: Journal article

C2 - 23583250

AN - SCOPUS:84881480711

VL - 62

SP - 1242

EP - 1249

JO - J AM COLL CARDIOL

JF - J AM COLL CARDIOL

SN - 0735-1097

IS - 14

ER -