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Abstract
Background
Cardiac troponins I (cTnI) and T (cTnT) have received international endorsement as the standard biomarkers for detection of myocardial injury, for risk stratification in patients suspected of acute coronary syndrome, and for the diagnosis of myocardial infarction. An evidence-based clinical database is growing rapidly for high-sensitivity (hs) troponin assays. Thus, clarifications of the analytical principles for the immunoassays used in clinical practice are important.
Content
The purpose of this mini-review is (a) to provide a background for the biochemistry of cTnT and cTnI and (b) to address the following analytical questions for both hs cTnI and cTnT assays: (i) How does an assay become designated hs? (ii) How does one realistically define healthy (normal) reference populations for determining the 99th percentile? (iii) What is the usual biological variation of these analytes? (iv) What assay imprecision characteristics are acceptable? (v) Will standardization of cardiac troponin assays be attainable?
Summary
This review raises important points regarding cTnI and cTnT assays and their reference limits and specifically addresses hs assays used to measure low concentrations (nanograms per liter or picograms per milliliter). Recommendations are made to help clarify the nomenclature. The review also identifies further challenges for the evolving science of cardiac troponin measurement. It is hoped that with the introduction of these concepts, both laboratorians and clinicians can develop a more unified view of how these assays are used worldwide in clinical practice.
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References
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 | Fig. 1.Cardiac troponin I epitopes that are prone to interference. Ada pted from HyTest Ltd. [28]. |
Table 1.
Analytical characteristics of contemporary sensitive and point-of-care cardiac troponin assays.
| Company/platform/assay | Cardiac troponin concentration at: | Amino acid residues of epitopes recognized by capture (C) and detection (D) MAbs | ||
|---|---|---|---|---|
| LoD (μg/L) | 99th Percentile (μg/L, CV)∗ | 10% CV concentration (μg/L) | ||
| Abbott AxSYM ADV | 0.02 | 0.04 (14) | 0.16 | C: 87–91, 41–49; D: 24–40 |
| Abbott ARCHITECT | 0.009 | 0.028 (14) | 0.032 | C: 87–91, 24–40; D: 41–49 |
| Abbott i-STAT | 0.02 | 0.08 (16.5) | 0.10 | C: 41–49, 88–91; D: 28–39, 62–78 |
| Alere Triage | 0.05 | <0.05 (NA) | NA | C: NA; D: 27–40 |
| Alere Triage Cardio3† | 0.01 | 0.02 (17) | NA | C: 27–39; D: 83–93, 190–196 |
| Beckman Access AccuTnI | 0.01 | 0.04 (14) | 0.06 | C: 41–49; D: 24–40 |
| bioMérieux Vidas Ultra | 0.01 | 0.01 (27.7) | 0.11 | C: 41–49, 22–29; D: 87–91, MAb 7B9 |
| Mitsubishi Pathfast | 0.008 | 0.029 (5.0) | 0.014 | C: 41–49; D: 71–116, 163–209 |
| Ortho Vitros ECi ES | 0.012 | 0.034 (10) | 0.034 | C: 24–40, 41–49; D: 87–91 |
| Radiometer AQT90 cTnI | 0.009 | 0.023 (17.7) | 0.039 | C: 41–49, 190–196; D: 137–149 |
| Radiometer AQT90 cTnT | 0.008 | 0.017 (15.2) | 0.026 | C: 125–131; D: 136–147 |
| Response RAMP | 0.03 | <0.01 (18.5 at 0.05) | 0.21 | C: 85–92; D: 26–38 |
| Roche cobas h232 Cardiac T†,‡ | 0.05 | NA | NA | C: 125–131; D: 136–147 |
| Roche Elecsys TnT Gen 4 | 0.01 | <0.01 | 0.030 | C: 136–147; D: 125–131 |
| Roche Elecsys TnI | 0.16 | 0.16 (10) | 0.30 | C: 87–91, 190–196; D: 23–29, 27–43 |
| Roche Cardiac Reader cTnT§ | 0.03 | NA | NA | C: 125–131; D: 136–147 |
| Siemens Centaur Ultra | 0.006 | 0.04 (8.8) | 0.03 | C: 41–49, 87–91; D: 27–40 |
| Siemens Dimension RxL | 0.04 | 0.07 (20) | 0.14 | C: 27–32; D: 41–56 |
| Siemens Immulite 2500 | 0.1 | 0.2 (NA) | 0.42 | C: 87–91; D: 27–40 |
| Siemens Stratus CS | 0.03 | 0.07 (10) | 0.06 | C: 27–32; D: 41–56 |
| Siemens Vista | 0.015 | 0.045 (10) | 0.04 | C: 27–32; D: 41–56 |
| Tosoh AIA | 0.06 | <0.06 (NA) | 0.09 | C: 41–49; D: 87–91 |
Table 2.
Analytical characteristics of hs cardiac troponin assays.
| Company/ platform/assay | Cardiac troponin concentration at: | Amino acid residues of epitopes recognized by capture (C) and detection (D) MAbs | ||
|---|---|---|---|---|
| LoD (ng/L) | 99th Percentile (ng/L, CV)∗ | 10% CV concentration (ng/L) | ||
| hs-cTnI | ||||
| Abbott ARCHITECT† | 1.2 | 16 (5.6) | 3.0 | C: 24–40; D: 41–49 |
| Beckman Access† | 2–3 | 8.6 (10) | 8.6 | C: 41–49; D: 24–40 |
| Nanosphere MTP† | 0.2 | 2.8 (9.5) | 0.5 | C: 136–147; D: MAb PA1010 |
| Singulex Erenna† | 0.09 | 10.1 (9.0) | 0.88 | C: 41–49; D: 27–41 |
| Siemens Vista† | 0.5 | 9 (5.0) | 3 | C: 30–35; D: 41–56, 171–190 |
| hs-cTnT | ||||
| Roche Elecsys‡ | 5.0 | 14 (8) | 13 | C: 136–147; D: 125–131 |
Table 3.
Short-term analytical and biological variation by hs-cTnI assays.
| Abbott∗ | Beckman∗ | Roche (E170)† | Siemens∗ | Singulex‡ | |
|---|---|---|---|---|---|
| CV-A (%) | 13.8 | 14.5 | 7.8 | 13.0 | 8.3 |
| CV-I (%) | 15.2 | 6.1 | 15.0 | 12.9 | 9.7 |
| CV-G (%) | 70.5 | 34.8 | NA | 12.3 | 57 |
| Index of individuality | 0.22 | 0.46 | NA | 0.11 | 0.21 |
| RCV (%)§ | NA | NA | 47.0 | NA | NA |
| RCV increase (%)II | 69.3 | 63.8 | NA | 57.5 | 46.0 |
| RCV decrease (%)II | –40.9 | –38.9 | NA | –36.5 | –32 |
| Within-individual mean (ng/L) | 3.5 | 4.9 | NA | 5.5 | 2.8 |
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