Acute Phase Response and Non-Reproducible Elevated Concentrations with a High-Sensitivity Cardiac Troponin I Assay

Abstract

High-sensitivity cardiac troponin (hs-cTn) testing has enabled physicians to make earlier diagnostic and prognostic decisions in the hospital setting than previous cardiac troponin assays. Analytical improvements have permitted one to measure cardiac troponin precisely in the nanogram per litre (ng/L) range with hs-cTn assays which has resulted in fast 0/1-h and 0/2-h algorithms for ruling-in and ruling-out myocardial infarction. Although analytical interferences that affect the reporting of hs-cTn are uncommon, not all hs-cTn assays are designed the same nor have undergone the same clinical and analytical validations. Here, after investigating an initial case of discrepant hs-cTnI results, we report that patients with an acute phase response (e.g., patients with inflammatory or infectious illnesses) can yield high and non-reproducible results with the Ortho Clinical Diagnostics hs-cTnI assay. Compared to Abbott Diagnostics hs-cTnI, Ortho Clinical Diagnostics hs-cTnI assay misclassifies biochemical injury in approximately 10% of the population being assessed for myocardial injury with imprecise results in approximately half of this population (i.e., 5%). In conclusion, caution is warranted in interpreting Ortho Clinical Diagnostics hs-cTnI alone in patients being evaluated for myocardial injury, especially in patients whose primary presentation is related to an acute phase response and not an acute coronary syndrome symptom.

Disagreement between Cardiac Troponin Tests Yielding a Higher Incidence of Myocardial Injury in the Emergency Setting

“…The findings from both studies reported here support recent clinical data indicating that the OCD hs-cTnI may misclassify biochemical injury in approximately 10% of the population being evaluated for myocardial injury [14][15][16]. Despite OCD using the same three antibodies in their cTnI ES (contemporary/conventional) assay and their hs-cTnI (high-sensitivity) assay [22], there is better agreement between the cTnI ES assay with the Abbott hs-cTnI assay as compared to the OCD hs-cTnI assay.…”

“…There were 469 samples (HGH = 137, JHCC = 150, SJH = 118, WLMH = 39, MUMC = 25) with sufficient volume for testing in the following order: Abbott ARCHITECT (Abbott Laboratories, Chicago, IL, USA) hs-cTnI, OCD (Ortho Clinical Diagnostics, Raritan, NJ, USA) VITROS XT 7600 hs-cTnI, OCD VITROS XT 7600 cTnI ES (run 1); then immediately retested in the following order except for cTnI ES (cTnI ES is OCD's contemporary/conventional assay and in run 2 only hs-cTnI was measured to maximize the number of samples for duplicate measurements for the hs-cTnI assays n = 411). Acceptable repeats were identified if the difference between results was ≤3 ng/L for average concentrations <15 ng/L or ≤20% for concentrations ≥15 ng/L, consistent with previous analyses [12,16]. The mean, coefficient of variations (CVs), and number of measurements for the QC for the assays during the testing were as follows: OCD cTnI ES: level 1 mean = 0.076 µg/L/CV = 3.6%/n = 8; level 2 mean = 0.654 µg/L/CV = 2.5%/n = 8; level 3 mean = 7.168 µg/L/CV = 1.9%/n = 8 | OCD hs-cTnI: level 1 mean = 6.3 ng/L/CV = 13.7%/n = 25; level 2 mean = 36.5 ng/L/CV = 11.8%/n = 27; level 3 mean = 8120.9 ng/L/CV = 7.5%/n = 27 | Abbott hs-cTnI level 1 mean = 12.4 ng/L/CV = 4.1%/n = 9; level 2 mean = 49.2 ng/L/CV = 4.7%/n = 9; level 3 mean = 14,094.4 ng/L/CV = 12.9%/n = 12.…”

“…Performed in real-time and after study 1, it was decided for patient safety that all OCD hs-cTnI requests from the EDs from the five sites would be performed in duplicate. Only duplicate results with acceptable repeats (≤3 ng/L or ≤20%) had the average result reported, with poor repeat measurements not reported for the OCD hs-cTnI assay with the sample sent immediately for testing with the Abbott hs-cTnI assay [12,16]. Samples yielding a concentration greater than the upper reference limit (URL; i.e., >99th percentile cutoff from a healthy population, which indicates myocardial injury) for the OCD hs-cTnI assay (female 99th percentile cutoff ≤9 ng/L and male 99th percentile cutoff ≤13 ng/L) were also sent/reflexed for Abbott hs-cTnI testing at the JHCC (inpatient hs-cTnI testing for all hospitals was also performed with the Abbott hs-cTnI assay at the JHCC with female 99th percentile ≤16 ng/L and male 99th percentile ≤34 ng/L) [2,10].…”

“…For study 2, sex-specific 99th percentiles were used to identify injury (as recommended by the Fourth Universal Definition of Myocardial Infarction) [6], with non-parametric analyses (i.e., Passing-Bablok, Spearman) performed with the 95% confidence intervals (CIs) derived for all estimates. Previous studies have documented that the OCD hs-cTnI assay yields lower concentrations (approximately 30% to 50% lower) as compared to the Abbott hs-cTnI assay [5,10], therefore, specific analyses were performed in the group where OCD hs-cTnI was higher than Abbott hs-cTnI; as this may indicate the presence of an interference [16]. Here, chart reviews were performed for those patients with normal Abbott hs-cTnI concentrations whose corresponding OCD hs-cTnI concentrations were higher than Abbott's values.…”

“…Within a month of the HRLMP transitioning from the Abbott hs-cTnI assay to the OCD hs-cTnI assay, one of its hospitals identified quality control (QC) failures with the OCD hs-cTnI assay [13]. Subsequent work at the JHCC (hospital and cancer centre) and WLMH (small community hospital) indicated that the OCD hs-cTnI assay yielded a higher incidence of false positive results, in part due to an acute phase response [14][15][16].…”