Two-Hour Algorithm for Rapid Triage of Suspected Acute Myocardial Infarction Using a High-Sensitivity Cardiac Troponin I Assay

Abstract

BACKGROUND We aimed to derive and externally validate a 0/2-h algorithm using the high-sensitivity cardiac troponin I (hs-cTnI)-Access assay. METHODS We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI) in 2 prospective diagnostic studies using central adjudication. Two independent cardiologists adjudicated the final diagnosis, including all available medical information including cardiac imaging. hs-cTnI-Access concentrations were measured at presentation and after 2 h in a blinded fashion. RESULTS AMI was the adjudicated final diagnosis in 164 of 1131 (14.5%) patients in the derivation cohort. Rule-out by the hs-cTnI-Access 0/2-h algorithm was defined as 0-h hs-cTnI-Access concentration <4 ng/L in patients with an onset of chest pain >3 h (direct rule-out) or a 0-h hs-cTnI-Access concentration <5 ng/L and an absolute change within 2 h <5 ng/L in all other patients. Derived thresholds for rule-in were a 0-h hs-cTnI-Access concentration ≥50 ng/L (direct rule-in) or an absolute change within 2 h ≥20 ng/L. In the derivation cohort, these cutoffs ruled out 55% of patients with a negative predictive value (NPV) of 99.8% (95% CI, 99.3–100) and sensitivity of 99.4% (95% CI, 96.5–99.9), and ruled in 30% of patients with a positive predictive value (PPV) of 73% (95% CI, 66.1–79). In the validation cohort, AMI was the adjudicated final diagnosis in 88 of 1280 (6.9%) patients. These cutoffs ruled out 77.9% of patients with an NPV of 99.8% (95% CI, 99.3–100) and sensitivity of 97.7% (95% CI, 92.0–99.7), and ruled in 5.8% of patients with a PPV of 77% (95% CI, 65.8–86) in the validation cohort. CONCLUSIONS Safety and efficacy of the l hs-cTnI-Access 0/2-h algorithm for triage toward rule-out or rule-in of AMI are very high. TRIAL REGISTRATION APACE, NCT00470587; ADAPT, ACTRN1261100106994; IMPACT, ACTRN12611000206921.

Myocardial Infarction Can Be Safely Excluded by High‐sensitivity Troponin I Testing 3 Hours After Emergency Department Presentation

“…The high NPV obtained with LoQ-based strategy did result in a poor PPV (26.7%, 95% CI = 22.8% to 31.1%) requiring further 13,18 In fact, in this study four patients within Hi-Hi cohort were diagnosed with MI. While earlier international publications on using Access hsTnI for rapid rule-out algorithms allowed only the consideration of the baseline hsTnI, 15 our suggested approach is fully consistent with the fourth universal definition of MI and current U.S. guidelines for NSTEMI, 19 because it relies on the sequential draws and considers patients with at least one value above URL as high risk.…”

“…The amount of analyte in the sample is determined from a stored, multipoint calibration curve, the analytical performance of which has been previously described. [8][9][10][11][12][13][14][15] Data Analysis For this analysis, the URL for both sexes was defined as 17.9 ng/L and was derived from data that served as part of the FDA submission for this assay, as is documented in the package insert. 7,16 The appropriate sample size was a priori determined for the FDA submission, but not for this secondary analysis.…”

Prognosis, Prognosis, Wherefore Art Thou Prognosis?

“…data where absolute deltas with this assay that exceed predefined thresholds of 4 ng/L at 1 hour 2 and 5 ng/L 3 at 2 hours, even among those with low initial troponins, were associated with acute MI. This may be attributable to the cohort enrolled by Peacock et al, where the prevalence of MI was lower (11.2% vs. 15.4% 2 and 14.5% 3 ) and the time from symptom onset to first blood draw which exceeded 3 hours for the vast majority of enrolled patients. From a care delivery perspective, demonstration that the 10% CV cut‐point provides acceptable safety is key as it enables rule‐out in more than twice as many people (58% vs. 24%) compared to the LoQ.…”

Critical appraisal of the 2020 ESC guideline recommendations on diagnosis and risk assessment in patients with suspected non-ST-segment elevation acute coronary syndrome

“…Five publications [33][34][35][36][37] were discussed to support this recommendation. Neumann et al [33] prospectively evaluated individual patient-level data from 15 studies including 23,327 patients who presented to the emergency department with suspected acute myocardial infarction (AMI).…”