Effectiveness of practices for improving the diagnostic accuracy of Non ST Elevation Myocardial Infarction in the Emergency Department: A Laboratory Medicine Best Practices™ systematic review

Abstract

Objectives This article presents evidence from a systematic review of the effectiveness of four practices (assay selection, decision point cardiac troponin (cTn) threshold selection, serial testing, and point of care testing) for improving the diagnostic accuracy for Non-ST-Segment Elevation Myocardial Infarction (NSTEMI) in the Emergency Department. Design and Methods The CDC-funded Laboratory Medicine Best Practices (LMBP™) Initiative systematic review A6 Method for Laboratory Best Practices was used. Results The current guidelines (e.g., ACC/AHA) recommend using cardiac troponin assays with a 99th percentile upper reference limit (URL) diagnostic threshold to diagnose NSTEMI. The evidence in this systematic review indicates that contemporary sensitive cTn assays meet the assay profile requirements (sensitivity, specificity, PPV, and NPV) to more accurately diagnose NSTEMI than alternate tests. Additional biomarkers did not increase diagnostic effectiveness of cTn assays. Sensitivity, specificity, and negative predictive value (NPV) were consistently high and low positive predictive value (PPV) improved with serial sampling. Evidence for use of cTn point of care testing (POCT) was insufficient to make recommendations, though some evidence suggests cTn POCT may result in reduction to patient length of stay and costs. Conclusions Two best practice recommendations emerged from the systematic review and meta-analysis of literature conducted using the LMBP™ A6 Method criteria: Testing with cardiac troponin assays, using the 99th percentile URL as the clinical diagnostic threshold for the diagnosis of NSTEMI and without additional biomarkers, is recommended. Also recommended is serial cardiac troponin sampling with one sample at presentation and at least one additional sample taken a minimum of 6 hours later to identify a rise or fall in the troponin level. Testing with high-sensitivity cardiac troponin assays, at presentation and again within 6 hours, is the recommended evidence-based best practice testing algorithm for optimized NSTEMI diagnosis.

Trends in Use of Biomarker Protocols for the Evaluation of Possible Myocardial Infarction

“…Adoption of the 99th percentile as a single cut point as recommended as a Laboratory Medicine Best Practice6 holds significant diagnostic and prognostic implications in the evaluation of AMI, given that it increases the diagnosis of AMI and identifies patients at greater risk for both readmission and recurrent AMI in comparison with higher cut points 4, 5. We found wide variation in the choice of diagnostic cut points by institution, with cumulatively less than half (49%) using the 99th percentile, although use did increase over time.…”

“…Importantly, use of the 99th percentile as the cut‐off value increases the frequency of AMI diagnosis, has been associated with improved outcomes, and is championed as a Laboratory Medicine Best Practice 4, 5, 6. Guidelines were updated in 2012, shortening the marker sampling interval to 3 to 6 hours, reflecting the improved cTn assay sensitivity 3.…”

Utilization of cardiac troponin assays in adult and pediatric populations: Guideline recommendations vs. reality

“…(7). We hypothesized that considerable variability existed in utilization and reporting of cTn across institutions and that there were likely additional differences in use of cTn between adult and pediatric hospitals.…”

“…A recent systematic review demonstrated evidence supporting serial cTn testing and analysis of acute changes to increase specificity and NPV, with a modest decrease in positive predictive value for diagnosis of NSTEMI(7). The timing protocol and definition for significance of change varied among the evidence base although it is clear that delta analysis should never be used for sensitivity or PPV.…”

Establishing consensus-based, assay-specific 99th percentile upper reference limits to facilitate proper utilization of cardiac troponin measurements

“…Currently, expert consensus and evidence-based documents strongly advocate the 99th percentile as the appropriate upper reference limit for cTn concentrations [12,30]. Clinical outcome studies solidified these recommendations; several retrospective and prospective studies have indicated that, in the context of acute coronary syndromes, a cTn concentration above this threshold portended worse outcomes.…”