Navigating the Observation Zone: Do Risk Scores Help Stratify Patients With Indeterminate High-Sensitivity Cardiac Troponins?
Authors: Nicklaus P. Ashburn, James K. McCord, Anna C. Snavely, Robert H. Christenson, Fred S. Apple, Richard M. Nowak, William F. Peacock, Christopher R. deFilippi, Simon A. Mahler
Journal: Circulation (2023)

European Society of Cardiology 0/1-hour algorithm is a cardiac troponin-only accelerated diagnostic protocol designed to rapidly rule out or rule in myocardial infarction (MI).However, when the algorithm was applied to the HIGH-US (High-Sensitivity Cardiac Troponin I Assays in the United States) cohort, 37% were risk stratified into the observation zone, indicating diagnostic uncertainty and the need for further evaluation. 1 It is unclear how best to evaluate observation zone patients who are without an ischemic ECG.The 2022 American College of Cardiology Expert Consensus on Chest Pain in the Emergency Department 2 suggests using risk scores to further stratify these patients.However, it is unknown whether the modified Thrombolysis in Myocardial Infarction (mTIMI) score; History, ECG, Age, and Risk factors (HEAR) score; or simplified Emergency Department Assessment of Chest Pain Score (sEDACS) can identify a subgroup with ≥99% negative predictive value (NPV) for index MI that can be safely discharged from the Emergency Department without additional testing, such as additional serial troponin measures, stress testing, or coronary angiography.To address this evidence gap, we conducted a secondary analysis of the HIGH-US study that prospectively enrolled 2505 patients with possible MI at 29 US hospitals from April 2015 to April 2016.Study procedures are described elsewhere. 1,3,4In brief, Emergency Department patients ≥22 years of age with possible MI were consented, had blood drawn at 0-and 1-hour after Emer-gency Department arrival for high-sensitivity cardiac troponin (hs-cTnI) measurement at a central laboratory (Siemens Atellica IM TnIH assay; Erlangen, Germany; Limit of Quantitation of 2.5 ng/L; 10% coefficient of variation at 6 ng/L; 99th percentile 53 ng/L for men and 34 ng/L for women), an ECG performed, and risk scores (mTIMI, HEAR, and sEDACS) documented. 1 Each element of the risk scores was obtained by research personnel by medical record review, patient interview, or query of the Emergency Department physician.Troponin measures were not incorporated into the calculation of any risk scores.Patients in the European Society of Cardiology 0/1-hour hs-cTnI algorithm observation zone (0-hour hs-cTnI value 6-119 ng/L and/or 1-hour delta of 3-11 ng/L) without an ischemic ECG were included.An ischemic ECG was defined as ST elevation ≥1 mm or ST depression ≥0.5 mm in the absence of ECG findings of left ventricular hypertrophy, left bundle-branch block, or ventricular-paced rhythm.Index and 30-day MI were adjudicated after reviewing relevant clinical information and local hospital standard cardiac troponin results.MI was defined using the Third Universal Definition of MI.The 5 adjudicators were blinded to investigational hs-cTnI measures.Death was determined by medical record review, querying the Social Security Death Index, and obituary searching.Telephone follow-up and electronic medical record review achieved 99.5% retention.Each risk score was evaluated at its traditional cut point (alone and in combination with hs-cTnI) and optimized cut