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Letters to the Editor |
1
1st Lab. Clin. Chem., Clin. Chem. and Enzymol. Section,
2
Div. of Cardiol., Spedali Civili, 25125 Brescia, Italy
a Author for correspondence.
To the Editor:
The aim of this study was to validate a new automated cardiac troponin I (cTnI) assay developed by Sanofi Diagnostic Pasteur (Marnes la Coquette, France) on the Access immunoassay system from the same manufacturer, and to evaluate its diagnostic sensitivity for early detection of myocardial damage. The assay is a two-site sandwich, immuno-chemiluminometric ELISA using two monoclonal antibodies that recognize different epitopes unique to the human cTnI isoform (1). Pipetting, incubations, measurements, and data-reduction steps are performed on the Access analyzer, which produces the first test result in 20 min.
The minimum detectable cTnI concentration, assessed by 10 replicate measurements in a single run of the zero calibrator serum supplied with the kit and defined as the cTnI value corresponding to the signal 3 SD greater than the mean found for this calibrator, was estimated as 0.01 µg/L. The assay measured cTnI in serum and EDTA-anticoagulated plasma in the same way: Fresh specimens collected at the same time from subjects (n = 24) with an increased concentration of cTnI gave similar results for serum and EDTA-plasma (0.49 ± 0.78 vs 0.46 ± 0.74 µg/L, respectively; P = 0.48). Assay reproducibility was tested by assaying three control materials (from Sanofi) containing human cTnI at 0.28, 6.6, and 25.4 µg/L plus two samples of pooled fresh serum (0.07 and 0.30 µg/L, respectively). Within-run CVs (n = 30) were between 3.8% and 12.5%, and between-run CVs (n = 10) ranged between 4.3% and 15.7%. Correlation studies were conducted with two alternative techniques for cTnI: Sanofi Diagnostics Pasteur ELISA manual assay and Opus immunometric assay (Behring Diagnostics, Westwood, MA), performed according to the manufacturers' current protocols (2)(3). Linear regression equations were as follows: Access = 1.43 Pasteur - 0.08 µg/L (Sy|x = 0.19, r = 0.948, n = 44), and Access = 0.09 Opus + 0.05 µg/L (Sy|x = 0.48, r = 0.952, n = 81). In particular, the Opus assay led to ~10-fold higher values than the two Sanofi assays.
We used the Access assay to measure concentrations of cTnI in sera from subjects in five groups: (a) 105 apparently healthy people, ages 22–84 years; (b) 44 patients with a typical history of myocardial infarction (MI) of <8 h duration; (c) 8 patients with severe muscular damage [total creatine kinase (CK) values 10 240 to 29 000 U/L] but no apparent cardiac injury; (d) 20 consecutive dialysis patients with no evidence of myocardial injury; and (e) 22 patients with unstable angina (diagnosis based on typical electrocardiogram changes during episodes of chest pain together with coronary arteriography, performed within 72 h of admission). Procedures followed were in accordance with the Helsinki Declaration of 1975, as revised in 1983.
We found that cTnI concentrations in 99% of the apparently healthy
subjects were 
0.03 µg/L and in 88% were 0.01 µg/L, the
detection limit of the assay as defined above and determined with the
zero calibrator. The highest value for cTnI in these samples was 0.063
µg/L. To evaluate the diagnostic sensitivity of the Access cTnI in
the early phase of MI, we analyzed a single peripheral venous blood
sample obtained in our MI patients immediately after admission to the
hospital before any revascularization treatment, e.g., thrombolysis
(median time after the onset of chest pain, 210 min; range, 30–450
min). For comparison, we also measured myoglobin and CK-MB mass. All
three assays were performed on a single Access analyzer at the same
time. The cutoff values were as follows: myoglobin, 60 µg/L; CK-MB,
5.0 µg/L; and cTnI, 0.03 µg/L. In this population, the Access cTnI
showed the same diagnostic sensitivity (29 positive of 44 MI patients,
66%) as myoglobin (28 of 44, 64%), the classical early cardiac
marker, whereas the sensitivity of CK-MB mass determination was
significantly lower (19 of 44, 43%) (
2 = 4.58,
P = 0.032).
cTnI values were normal (<0.03 µg/L) in all but one of the patients
with skeletal muscle damage or chronic renal failure. One
polytraumatized individual had a cTnI concentration of 0.12 µg/L;
clinical evaluation, however, revealed no evidence of myocardial
injury. In patients with unstable angina, blood samples were collected
at admission to the hospital and every 4 h thereafter for 2 days.
These patients were separated into two subgroups, based on their cTnI
values: those with cTnI <0.03 µg/L (n = 15), and those with
cTnI >0.03 µg/L in at least one sample obtained after admission
(n = 7) (Table 1
). In the latter group, the first positive cTnI results were
already identified at admission (range 0.04–0.19 µg/L), and the peak
values (range 0.04–0.24 µg/L) were obtained no more than 24 h
later (mean 7.4 h; range 0–24 h). Although the two groups did not
differ with respect to clinical characteristics and quantitative degree
of coronary disease at angiography, the type of lesion morphology was
significantly different (2 = 6.36, P =
0.041), with ulcerated lesion or thrombus formation present in all
cTnI-positive patients. Regardless of the relatively small number of
patients studied, the incidence of MI (defined according to WHO
diagnostic criteria) during the following hospitalization was
significantly related to the presence of increased serum cTnI at
admission. Of the seven patients who were positive for cTnI, two had
non-Q-wave MI within 10 days after hospitalization. In contrast, none
of the 15 patients who were negative for cTnI had an in-hospital MI
(2 = 4.71, P = 0.03). In light of these
results, we propose the implementation of cTnI determination in
patients with suspected unstable angina so as to identify early the
subjects at greater risk of cardiac events. A few samples, i.e., two or
three, collected in the first 12–24 h after admission, are probably
enough to obtain this information.
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Acknowledgments
We thank Sanofi Diagnostics Pasteur for loan of Access apparatus and gifts of Access cTnI, myoglobin, and CK-MB reagents. To ensure against a potential conflict of interest, Sanofi was in no way involved in the collection of data, its analysis, or interpretation.
References
The following articles in journals at HighWire Press have cited this article:
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  J.-P. Quenot, G. Le Teuff, C. Quantin, J.-M. Doise, M. Abrahamowicz, D. Masson, and B. Blettery Myocardial Injury in Critically Ill Patients: Relation to Increased Cardiac Troponin I and Hospital Mortality Chest, October 1, 2005; 128(4): 2758 - 2764. [Abstract] [Full Text] [PDF]
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 I. Giuliani, J.-P. Bertinchant, C. Granier, M. Laprade, S. Chocron, G. Toubin, J.-P. Etievent, C. Larue, and S. Trinquier Determination of Cardiac Troponin I Forms in the Blood of Patients with Acute Myocardial Infarction and Patients Receiving Crystalloid or Cold Blood Cardioplegia Clin. Chem., February 1, 1999; 45(2): 213 - 222. [Abstract] [Full Text] [PDF]
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A. H. B. Wu, Y.-J. Feng, R. Moore, F. S. Apple, P. H. McPherson, K. F. Buechler, G. Bodor, f. t. A. A. for, and C. C. S. o. c. Standardization Characterization of cardiac troponin subunit release into serum after acute myocardial infarction and comparison of assays for troponin T and I Clin. Chem., June 1, 1998; 44(6): 1198 - 1208. [Abstract] [Full Text] [PDF]
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