Misdiagnosis of Myocardial Infarction Related to Limitations of the Current Regulatory Approach to Define Clinical Decision Values for Cardiac Troponin
Background—Misdiagnosis of acute myocardial infarction (AMI) may significantly harm patients and may result from inappropriate clinical decision values (CDV) for cardiac troponin (cTn) due to limitations in the current regulatory process.
Methods and Results—In an international prospective multicenter study we quantified the incidence of inconsistencies in the diagnosis of AMI using fully characterized and clinically available high-sensitivity cTn assays (hs-cTnI Abbott and hs-cTnT Roche) among 2300 consecutive patients with suspected AMI. We hypothesized that the approved CDV for the two assays are not biologically equivalent and might therefore contribute to inconsistencies in the diagnosis of AMI. Findings were validated using gender-specific CDV as well as with parallel measurements of other hs-cTnI assays. AMI was the adjudicated diagnosis in 473 patients (21%). Among these, 86 patients (18.2%) had inconsistent diagnoses using the approved uniform CDV. Using gender-specific CDV, 14.1 % of female and 22.7% of male AMI patients had inconsistent diagnoses. Using biologically equivalent CDV reduced inconsistencies to 10% (p<0.001). These findings were confirmed with parallel measurements of other hs-cTn assays. The incidence of inconsistencies was only 7.0% for assays with CDV that were nearly biologically equivalent. Patients with inconsistent AMI had comparable long-term mortality as compared to patients with consistent diagnoses (p=ns), and a trend to higher long-term mortality than patients diagnosed with unstable angina (p=0.05).
Conclusions—Currently approved CDV are not biologically equivalent and contribute to major inconsistencies in the diagnosis of AMI. One out of five AMI patients will receive a diagnosis other than AMI if managed with the alternative hs-cTn assay.
Clinical Trial Registration Information—http://clinicaltrials.gov/. Identifier:NCT00470587.
- Received November 7, 2014.
- Revision received March 20, 2015.
- Accepted April 2, 2015.
Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDervis License (http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.