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Evaluation of a Point-of-Care System for Quantitative Determination of

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Clin Chem Lab Med 2000; 38(6):567–574 © 2000 by Walter de Gruyter · Berlin · New York
Evaluation of a Point-of-Care System for Quantitative
Determination of Troponin T and Myoglobin
Margit Müller-Bardorff1, Christer Sylvén2, Gundars
Rasmanis2, Bo Jørgensen3, Paul O. Collinson4, Ulla
Waldenhofer5, Michael M. Hirschl5, Anton N.
Laggner5, Willie Gerhardt6, Gerd Hafner7, Irene
Labaere8, Robert Leinberger8, Rainer Zerback8 and
Hugo A. Katus1
1
Medizinische Klinik II, Medizinische Universität zu Lübeck,
Lübeck, Germany
2 Department of Cardiology, Huddinge Hospital, Huddinge,
Sweden
3 Department of Clinical Biochemistry, Ålborg Hospital,
Ålborg, Denmark
4 Point-of-care testing; Myocardial infarction; Unstable
Department of Pathology, Mayday University Hospital,
London, United Kingdom
5
Notfallaufnahme, Allgemeines Krankenhaus – Universitäts-
kliniken, Wien, Austria
6 Department of Clinical Chemistry, Helsingborg Hospital,
Helsingborg, Sweden
7 Institut für Klinische Chemie, Johannes-Gutenberg-Univer-
sität, Mainz, Germany
8
Evaluation Department Patient Care, Roche Diagnostics
GmbH, Mannheim, Germany
We present the results of a multicenter evaluation of a
new point-of-care system (Cardiac Reader) for the
quantitative determination of cardiac troponin T (CAR-
DIAC T Quantitative test) and myoglobin (CARDIAC M
test) in whole blood samples.
The Cardiac Reader is a CCD camera that optically
reads the immunochemical test strips. The measuring
range is 0.1 to 3 µg/l for CARDIAC T Quantitative and
30 to 700 µg/l for CARDIAC M. Both tests are calibrated
by the manufacturer. The reaction times of the tests
are 12 or 8 minutes, respectively.
Method comparisons were performed with 281 he-
parinized blood samples from patients with suspected
acute coronary syndromes. The results obtained with
CARDIAC T Quantitative showed a good agreement
compared with cardiac troponin T ELISA (r = 0.89; y =
0.93x + 0.02). The method comparison between CAR-
DIAC M and Tina-quant Myoglobin also showed a good
agreement between both assays (r = 0.98; y = 0.92x +
1.6). Test lot-to-lot comparisons yielded differences of
2% and 6% for CARDIACT Quantitative and of 0 to 11%
for CARDIACM.
The within-run imprecision with blood samples and
control materials was acceptable for CARDIAC T Quan-
titative (CV 10 to 15%) and good for CARDIAC M (CV 5
to 10%). The between-instrument CV was below 7%
for CARDIACT Quantitative and below 5% for CAR-
DIACM.
The cross-reactivity of CARDIAC T Quantitative with
skeletal troponin T was approximately 0.003%. No sig-
nificant analytical interference was detected for any of
the assays in investigations with biotin (up to 100
µg/l), hemoglobin (up to 0.125 mmol/l), hematocrit (26
to 52%), bilirubin (up to 340 µmol/l), triglycerides (up
to 5.0 mmol/l), and 18 standard drugs.
With the Cardiac Reader reliable quantitative results
can be easily obtained for both cardiac markers. The
system is, therefore, particularly suitable for use in
emergency rooms, coronary care units and small hos-
pitals.
Key words: Troponin T; Myoglobin; Cardiac enzymes;
angina pectoris.
Abbreviations: cTnT cardiac troponin T; sTnT skeletal
troponin T.
Introduction
The value of the determination of cardiac troponin T
(cTnT) for diagnosis, risk stratification and therapeutic
and clinical decision-making in patients with acute
coronary syndromes has been demonstrated in many
retrospective and prospective studies (1–3). Due to its
high early sensitivity, myoglobin complements mea-
surement of troponinT with the ability for exclusion di-
agnosis of acute myocardial infarction (4–10), the diag-
nosis of reinfarction (11) and assessment of
reperfusion in thrombolysis (12–18).
Since its introduction in 1994, a rapid bedside test al-
lows quick and simple qualitative determination of
cTnT. Over three generations of the test, the detection
limit has improved from the original 0.3µg/l (19–21) to
0.2µg/l in the second generation (22, 23) and finally to
0.1µg/l in the third (24, 25). At the same time, cross-re-
activity with skeletal troponinT (sTnT) has been elimi-
nated by replacement of one of the antibodies (25).
Comparative studies have shown this test to be suffi-
ciently robust to be used by clinic staff outside a labo-
ratory environment, delivering results of comparable
analytical quality (25, 26).
Similarly, there is a rapid qualitative test for early de-
terminations of myoglobin (27).
However, purely qualitative determinations of tro-
poninT and myoglobin limit their range of appli-
cations. In the case of troponin T, although triage is
possible on the basis of qualitative results alone, a
quantitative prognostic assessment of cardiac risk
(28–30) or a decision for a certain therapy can only be
made if the exact troponinT concentration is known
(31, 32, Ohman, personal communication). For myo-
globin, a quantitative value is almost indispensable,
568 Müller-Bardorff et al.: Point-of-care-system for troponin T and myoglobin
since it is only through an evaluation of its release ki-
netics that a reliable infarct diagnosis can be made (5,
8–10, 33, 34). Release kinetics are also required for as-
sessment of reperfusion.
We have therefore developed a system, based on the
existing troponinT rapid test, that permits a quantita-
tive determination of troponin T. A completely new
quantitative myoglobin test was also developed for
this system. We describe the operating principle of this
new system for rapid determination of troponinT and
myoglobin in heparinized blood and present the results
of a multicenter evaluation.
Materials and Methods
Test principle of the Cardiac Reader
The Cardiac Reader (Roche Diagnostics, Mannheim, Ger-
many) is a system for quantitative bedside determinations of
myoglobin (CARDIACM) and troponinT (CARDIACT Quantita-
tive). The chemical reaction principle of the test strips has
been described previously (20, 21). The Cardiac Reader is a
camera with a charged coupled device that optically records
the reflectance signal from the detection zone of the immuno-
chemical test strips (Figure1). Signal and control lines are
identified by a pattern recognition algorithm. The intensity of
the signal line is proportional to the concentration of the ana-
lytes troponin T and myoglobin. The optical signal is con-
verted into concentration via a lot-specific calibration curve
(see below), which is stored in a code chip.
The tests require a 150µl sample of heparinized blood and
the reaction times are approximately 8min for myoglobin and
approximately 12min for troponinT determination.
For CARDIACT Quantitative the quantitative measurement
range is 0.1 to 3µg/l troponin T; the display shows values be-
low 0.05µg/l as “negative”, values between 0.05 and 0.1µg/l
as “low”, and values above 3.0µg/l as “high”. For CARDIAC
M, the quantitative measurement range is from 30 to 700µg/l
myoglobin; values below this range are displayed as “nega-
tive” and values above as “high”.
Fig. 1 Test principle of Cardiac Reader.
1 M comprised a daily single determination of both CARDIAC
Tina-quant and Enzymun-Test are trademarks of a member
of the Roche group.
Calibration of the Cardiac Reader
CARDIACM was calibrated identically as CARDIACT Quantita-
tive. Parallel samples of heparinized blood and serum were
collected from over a hundred patients with suspected acute
coronary syndromes. Heparinized blood samples were used
to determine the reflectance with CARDIACM, and serum
samples to measure the myoglobin concentration with Tina-
quant Myoglobin (Roche Diagnostics)1. The resulting pairs of
values were used to calibrate this lot of CARDIACM by regres-
sion analysis. This lot served as a master lot for calibrating fur-
ther lots. Using this master lot, and a new lot to be calibrated,
measurements were taken on 18blood samples spiked with
various concentrations of myoglobin. The concentrations ob-
tained with the master lot served as target concentrations for
the new lot; the corresponding reflectance values were ob-
tained directly from measurements. The resulting pairs of val-
ues (target concentration/reflectance) were then used to es-
tablish the calibration curve for the new lot of CARDIACM.
The lot-specific calibration curve is communicated to the
reader via a code chip. The agreement of code and test strip is
checked by the bar code (Figure 1) on the bottom of the test
strip.
Imprecision and between-instrument variability
Investigations of within-series imprecision and of inter-in-
strument variability were carried out on heparinized blood
samples collected from healthy volunteers and spiked with
troponin T-containing sera or purified myoglobin and with
control material (controls of the Cardiac Reader system and
calibrators of the reference methods). Hematocrit of all spiked
samples was readjusted to the initial value of the original
donor blood sample. Each sample was measured 10times at
20different instruments using one lot. For each series (n = 10)
at each instrument, mean value and coefficient of variation
(CV) were calculated. The CVs for the within-series impreci-
sion given in the result section were calculated as mean val-
ues of the 20 CVs with 20 instruments. The between-instru-
ment CVs were calculated as the CVs of the serial mean values
from 20 instruments. Serial measurements were done by one
laboratory technician.
Method comparisons
Method comparisons were done at seven centers using alto-
gether 281 sets of heparinized blood and serum samples col-
lected in parallel from unselected patients with suspected acute
coronary syndromes. Patients with recent cardiac surgery or
other type of interventional therapy, patients with renal and/or
skeletal disease or injury were not excluded. Multiple specimen
collection per patient was possible. We compared CARDIAC T
Quantitative (lot 226003) with cTnT ELISA (Enzymun-Test Tro-
ponin T, Roche Diagnostics)1 on multiple ES300 instruments
(Roche Diagnostics) in accordance with the manufacturer’s in-
structions, using a cut-off value of 0.1 µg/l (35).
We compared CARDIACM (lot226012-20) with Tina-quant
Myoglobin (Roche Diagnostics) on multiple Hitachi instru-
ments (Roche Diagnostics). The reference range is <69µg/l
(36) and a cut-off of 70µg/l was used in the evaluations.
Lot numbers in use for troponin T on the ES 300 analyzer
and myoglobin on the Hitachi were the same for all seven
centers contributing to the multicenter study.
Daily quality control
The quality control of CARDIAC T Quantitative and CARDIAC
control troponin T level 1 and 2 or both CARDIAC control myo-
 Müller-Bardorff et al.: Point-of-care-system for troponin T and myoglobin 569

Tab. 1 Results of lot-to-lot comparisons.

Test Lot vs. Lot Regression equation r N Range of values (µg/l)

CARDIAC TQuantitative 226003 226005 y = 1.05x 0.93 50 0.1–2.2

226003 226013 y = 1.03x–0.01 0.92 57 0.1–2.8
226003 226014 y = 0.97x–0.01 0.96 73 0.1–2.5
226003 226026 y = 0.94x–0.01 0.96 148 0.1–3.0
226003 226031 y = 1.02x 0.97 227 0.1–3.0
CARDIAC M 226007 226008 y = 1.00x+1.0 0.98 359 30–660
226012–20 226009 y = 1.11x–1.0 0.99 142 30–540
226012–20 226012–30 y = 1.00x–2.0 0.97 176 30–660

Tab. 2 Cardiac reader. Interference studies.

Cardiac troponin T [µg/l] Myoglobin [µg/l]

Interferent 0 0.1–0.2 1 40–50 80–150 300–500

Skeletal troponin T (µg/l)

0 (reference) negative 100 100 n.d. n.d. n.d.
500 negative 110 109 n.d. n.d. n.d.
1000 negative 125 128 n.d. n.d. n.d.
Biotin (µg/l)
0 (reference) negative 100 100 100 100 100
2 negative 96 94 93 75 99
100 negative 87 61 98 66 91
Hemoglobin (mmol/l)
0 (reference) negative 100 100 100 100 100
0.075 negative 94 99 105 99 94
0.125 negative 100 98 n.d. 100 97
Bilirubin (µmol/l)
0 (reference) negative 100 100 100 n.d. 100
170 negative 104 104 100 n.d. 96
340 negative 89 105 100 n.d. 89
Triglycerides (mmol/l)
<0.8–3.5 (reference) negative 100 100 100 100 100
3.5–5.0 negative 93–110 91–100 95–100 132–133 85–109
Sample volume (µl)
135 negative 94 90 95 91 91
150 (reference) negative 100 100 100 100 100
165 negative 107 113 103 105 108

n.d. = not determined. Concentration given as final sample concentration. The percentage
recovery compared to reference is shown.

globin level 1 and 2 (Roche Diagnostics), respectively, at each
center. The quality control of cTnT ELISA and Tina-quant myo-
globinwas performed at each center with the respective pack-
age controls.
Lot-to-lot comparison
To check the reproducibility of the calibration, five lots of CAR-
DIACM (226007, 226008, 226009, 2260012-20, 2260012-30)
and six lots of CARDIACT Quantitative (226003, 226005,
226013, 226014, 226026, 226031) were investigated using
fresh heparinized blood collected from patients with sus-
pected acute coronary syndromes. The numbers of samples
are listed in Table1.
Interference studies
To check for interfering factors, heparinized blood or plasma
was spiked with potential interfering substances (sTnT), bi-
otin, hemoglobin, bilirubin, 18standard drugs) from a stock
solution (for final concentrations see Table2; for concentra-
tions of the drugs see Table 3 and ref. 37) and with a human
serum sample containing troponinT in a high concentration.
The influence of triglycerides was investigated using human
lipemic serum samples spiked with troponinT sera. To deter -
mine the influence of hematocrit, samples collected from pa-
tients with coronary artery disease were used. Volume depen-
dence was investigated using heparinized blood samples
from healthy donors spiked with a human serum sample con-
taining troponinT in a high concentration.
Cross-reactivity of CARDIACT Quantitative with sTnT was
calculated according to the following formula:
recovered sTnT concentration
—————————————— x 100%
original sTnT concentration
Comparisons of recoveries in the hematocrit study were per-
formed by a h-test according to Kruskal-Wallis with a level of
significance of p < 0.05.
570 Müller-Bardorff et al.: Point-of-care-system for troponin T and myoglobin

Tab. 3 Cardiac reader. Influence of drugs. Results

Analyte Within-series imprecision

Cardiac troponin T Myoglobin
[µg/l] [µg/l] The within-series CV (Figure 2) was 5 to 10% for CAR-
DIACM and 10 to 15% for CARDIACT Quantitative. This
Drug 0 0.2–0.4 50–80 140–200 imprecision is observed both with blood and with con-
trol materials and is fairly constant regardless of the
No drug (reference) negative 100 100 100 concentration of the analyte.
Acetaminophen (mg/l)
20 n.d. n.d. n.d. n.d.
Between-instrument variability
200 negative 100 101 108
Acetylcysteine (mg/l) The between-instrument CV for CARDIACM was 5 to
30 n.d. n.d. 110 105 10% in the concentration range below 100 µg/l and 2
150 negative 104 123 118 to 3% in the range above 100 µg/l. For CARDIAC T
Acetylsalicylic acid (mg/l)
Quantitative the between-instrument CV was 4 to 9%
300 n.d. n.d. n.d. n.d.
(Figure 3).
1000 negative 100 106 101
Ampicillin (mg/l)
200 n.d. 88 n.d. n.d. Accuracy in the method comparison
1000 negative 126 103 101
Both Cardiac Reader methods were in good agreement
Ascorbic acid (mg/l)
with the laboratory methods.
30 n.d. n.d. n.d. n.d.
300 negative 111 96 91
Figure 4 shows the combined method comparison of
Calcium dobesilate (mg/l) all centers between CARDIACM and Tina-quant Myo-
20 n.d. 95 n.d. n.d. globin. This shows that CARDIACM was calibrated cor-
200 negative 119 102 101 rectly, as the results obtained are 8% lower relative to
Cefoxitin (mg/l) the reference and calibration method when the whole
250 n.d. n.d. n.d. n.d. test range is regarded.
2500 negative 109 97 89
Cyclosporine (mg/l)
1 n.d. n.d. n.d. n.d.
5 negative 100 100 98
Heparin (U/l)
10 n.d. n.d. 92 98
5000 negative 93 86 101
Ibuprofen (mg/l)
50 n.d. 93 n.d. n.d.
500 negative 126 106 97
Intralipid (mg/l)
2000 n.d. n.d. n.d. n.d.
10000 negative 100 99 99
Levodopa (mg/l)
4 n.d. n.d. n.d. n.d.
20 negative 99 106 94
Methyldopa (mg/l)
2 n.d. n.d. n.d. n.d.
20 negative 103 100 91
Metronidazole (mg/l)
10 n.d. n.d. n.d. n.d.
200 negative 102 99 95
Phenylbutazone (mg/l)
100 n.d. n.d. n.d. n.d.
400 negative 101 99 92
Rifampicin (mg/l)
20 n.d. 107 n.d. n.d.
60 negative 77 107 104
Tetracycline (mg/l)
10 n.d. 92 n.d. n.d.
50 negative 125 98 97
Theophylline (mg/l)
10 n.d. n.d. n.d. n.d.
100 negative 103 100 94

n.d. = not determined. Concentrations given as final sample Fig. 2 Within-series imprecision of CARDIAC M(a) and CAR-
concentration. The percentage recovery compared to refer- DIAC T Quantitative (b). j blood samples, m controls, n = 10
ence is shown. replicates.
 Müller-Bardorff et al.: Point-of-care-system for troponin T and myoglobin
Fig. 3 Between-instrument imprecision of CARDIAC M (a)
and CARDIAC TQuantitative (b). j blood samples, m controls,
n = 20 instruments.
Fig. 4 Multicenter method comparison of CARDIAC M vs.
Tina-quant Myoglobin. y= 0.92x + 1.6; r = 0.98. HVB = he-
parinized venous blood.
The same analysis for CARDIACT Quantitative with
the cTnTELISA reference method showed a bias of 7%
for the whole test range (Figure 5).
When the results obtained with CARDIACT Quantita-
tive were compared with the reference method cTnT
571
Fig. 5 Multicenter method comparison of CARDIAC T Quan-
titative vs. cTnT ELISA. y= 0.93x + 0.02; r = 0.89. HVB = he-
parinized venous blood.
ELISA using the clinical cut-off of 0.1 µg/l, there was a
99% concordance (278 of 281 values). The three dis-
crepant values were (CARDIACT Quantitative [µg/l] /
cTnT ELISA [µg/l]): negative/0.12; 0.14/0.08; 0.14/0.09.
The same analysis was performed for myoglobin; the
patients were subdivided into two groups by the cut-off
level of 70 µg/l for myoglobin. Again, there was a good
concordance of the values received with CARDIAC M
when compared with those of the Tina-quant Myoglo-
bin method (94%; 264 of 281 values). Ten of the 17 dis-
crepant paired values were between 60 and 80 µg/l, 4
between 50 and 90µg/l.
Daily quality control
The results of the daily quality control are listed in
Table 4. With CARDIAC M and CARDIAC T Quantitative,
slightly poorer recovery and imprecision were observed
from “day-to-day” than “within” series, which may be
attributable to daily variations in reconstitution of the
controls. The values obtained with the reference meth-
ods show the variation to be within the target ranges.
Lot-to-lot variability
In lot-to-lot comparisons, the lots of CARDIACT Quan-
titative investigated showed good agreement with one
another, as did the lots of CARDIACM (Table1). For
CARDIACT Quantitative, the correlation coefficients r
were between 0.92 and 0.97 and the accuracy differ-
ences were between –6% and +5%. CARDIAC M
showed correlation coefficients between 0.97 and 0.99
with accuracy differences ranging from 0% to +11%.
Interference
In investigations with biotin (up to 100 µg/l), hemoglo-
bin (up to 2000 mg/l), bilirubin (up to 200 mg/l), and
572 Müller-Bardorff et al.: Point-of-care-system for troponin T and myoglobin

Tab. 4 Summary of the results of the daily quality control in the multicenter evaluation.

Target value (µg/l) Mean day-to-day imprecision Median day-to-day recovery

(range) (CV in %) (range) (%)

CARDIAC T Quantitative Negative All negative Negative

0.37 16.5 (9.5–23.7) 88 (61–101)
CARDIAC M 94 7.7 (5.9–10.2) 98 (87–107)
431 8.7 (7.5–10.4) 91 (85–103)
Enzymun troponin T 0.00 – –
3.16 6.1 (3.1–11.1) 103 (97–109)
Tina-quant Myoglobin 53 3.4 (0.0–6.2) 100 (98–101)
260 2.2 (0.8–3.4) 99 (99–101)

Tab. 5 The effect of the hematocrit on the relative recovery
of the troponin T concentration (cTnT ELISA) by CARDIAC T
Quantitative and of the myoglobin concentration (Tina-quant
Myoglobin) by CARDIAC M.
Hematocrit (%) CARDIAC T CARDIAC M
Quantitative
Recovery (%) n Recovery (%) n
25–34 98 22 103 14
35–44 94 132 106 66
45–54 87 40 106 12
The medians for different hematocrit ranges are shown.
triglycerides (up to 5000 mg/l), no significant analytical
interference was detected, i.e. all deviations from ex-
pected values were ≤ 10%. Overdosing or underdosing
by 15µl affected the test result by no more than 10%
(Table2).
Appreciable cross-reactivity with sTnT was only ob-
served at concentrations from 1000µg/l. Cross-reactiv-
ity was, therefore, calculated to be approximately
0.003% (Table2).
Various standard drugs did not influence the recov-
ery with CARDIACT Quantitative and CARDIACM by
more than 26% when toxic concentrations of the drugs
were used, and by no more than 12% when therapeutic
concentrations were used (Table 3).
No significant correlation was found between hema-
tocrit and the recovery of the reference method con-
centrations by the Cardiac Reader tests (CARDIAC T
Quantitative: r = 0.12, CARDIACM: r = –0.05). The
slightly lower recovery with CARDIAC M at higher
hematocrits is not significant (p > 0.05) in the h-test ac-
cording to Kruskal-Wallis (Table 5).
Discussion
Newer cardiac markers like the troponins have con-
tributed substantially to the diagnostic workup of pa-
tients with suspected myocardial infarction. Risk strati-
fication of patients with unstable angina and suspected
minor myocardial damage is possible with a marker
such as troponin T rather than simple ruling in or out of
myocardial infarction based on classic WHO criteria.
A crucial point for the clinical utility of a marker is the
time from the first investigation of the patient and
blood sampling until the time a result is available
which is then used for clinical and therapeutic decision-
making by the physician. In this setting, point-of-care
systems will offer a more rapid result.
It is now possible to test highly specific troponin T
and the early marker myoglobin quantitatively with a
turnaround time of less than 15 minutes at the bedside.
No significant analytical interference was found
when various standard drugs, triglycerides, bilirubin
and biotin were tested. Underdosing or overdosing a
blood sample by 15 µl (standard volume 150 µl) influ-
enced the test result by no more than 10%. The cross-
reactivity with skeletal troponin T was calculated to be
approximately 0.003%. No significant correlation was
found between the hematocrit and the concentration-
dependent recovery with both quantitative bedside as-
says.
Addition of all the errors (imprecision, lot-to-lot vari-
ability, accuracy in the method comparison) yielded a
total error range of ±25% for CARDIACT Quantitative
and ±30% for CARDIACM. The variation of a test result
is of most importance in the range near the cut-off
level. At the cut-off for troponinT (0.1µg/l), CARDIAC T
Quantitative, therefore, has a maximum range of varia-
tion between 0.075 and 0.125µg/l, after taking into ac-
count the differences between lots and the comparison
with the reference method. At the cut-off for myoglobin
(70µg/l), CARDIACM has a calculated maximum range
of variation from 49 to 91µg/l. However, in serial mea-
surements with CARDIACM, which is the primary need
for a quantitative myoglobin value, only imprecision
remains as a source of variation, so that the total error
range diminished to ±15% (59 to 81µg/l at the cut-off).
When using the clinical cut-off of 0.1 µg/l, there were
only 1% discordant results between CARDIACT Quan-
titative and the reference method cTnT ELISA. Compar-
ing the two myoglobin tests with the cut-off level of 70
µg/l, we found 6% discordant results. These discrepan-
cies of 1% with troponin T and 6% with myoglobin are
probably caused by imprecision of both the tested
method and the reference method.
The Cardiac Reader was designed to allow a rapid
 Müller-Bardorff et al.: Point-of-care-system for troponin T and myoglobin
point-of-care determination of two essential cardiac
markers. The clinical performance of the quantitative
bedside assays for troponin T and myoglobin is being
further investigated in clinical studies ongoing at pre-
sent. Preliminary results from these studies show the
gain in time by using the Cardiac Reader compared to
conventional laboratory testing (72 minutes, p <
0.0001) (Collinson, unpublished data).
The design of the Cardiac Reader meets the require-
ments on the use of cardiac markers in point-of-care
testing as recommended by two scientific societies.
The International Federation of Clinical Chemistry and
Laboratory Medicine (IFCC) Guidelines on biochemical
markers in coronary artery disease (39), which are in
line with the National Academy of Clinical Biochem-
istry (NACB) Guidelines (40), recommend the routine
use of cardiac troponins in acute coronary syndromes.
The value of myoglobin as an early marker of cardiac
damage has been acknowledged in the IFCC Guide-
lines on cardiac markers as well as in the NACB Guide-
lines. The importance of point-of-care testing has been
emphasized both in the IFCC Guidelines and the NACB
Guidelines. Moreover the NACB Guidelines recom-
mend a turnaround time of one hour or less for bio-
chemical testing.
Conclusions
The Cardiac Reader represents an analytically reliable
and easy method that further extends the spectrum of
applications of the visual troponin T rapid assay test in
early infarct diagnostics, in reperfusion control, and in
cardiac risk assessment. With these attributes, it is,
therefore, suited for adoption by emergency depart-
ments, coronary care units and small hospitals with
few cardiac patients where investment in larger and
more expensive equipment is not justified.
Acknowledgements
This study was funded by Roche Diagnostics (Mannheim, Ger-
many). Dr. Katus is a consulstant for Roche Diagnostics and
holds a patent for troponin T jointly with Roche Diagnostics.
References
1. Dean KJ. Cardiac troponin T as a marker of myocardial in-
jury. In: Wu AHB, editor. Pathology and laboratory medicine
3: cardiac markers. Totowa: Humana Press, 1998: 205–27.
2. Gerhardt W, Ljungdahl L. Troponin T. A sensitive and spe-
cific diagnostic and prognostic marker of myocardial dam-
age. Clin Chim Acta 1998; 272:47–57.
3. Rottbauer W, Greten T, Müller-Bardorff M, Remppis A, Ze-
helein J, Grünig E, et al. Troponin T: a diagnostic marker for
myocardial infarction and minor cardiac cell damage. Eur
Heart J 1996; 17:Suppl F:3–8.
4. Bakker AJ, Koelemay MJ, Gorgels JP, van Vlies B, Smits R,
Tijssen JG, et al. Troponin T and myoglobin at admission:
value of early diagnosis of acute myocardial infarction. Eur
Heart J 1994; 15:45–53.
573
5. Brogan GX, Friedman S, McCuskey C, Cooling DS, Berruti
L, Thode HC, et al. Evaluation of a new rapid quantitative
immunoassay for serum myoglobin versus CK-MB for rul-
ing out acute myocardial infarction in the emergency de-
partment. Ann Emerg Med 1994; 24:665–71.
6. Castaldo AM, Ercolini P, Forino F, Basevi A, Vrenna L,
Castaldo P, et al. Plasma myoglobin in the early diagnosis
of acute myocardial infarction. Eur J Clin Chem Clin
Biochem 1994; 32:349–53.
7. De Winter RJ, Koster RW, Sturk A, Sanders GT. Value of
myoglobin, troponin T, and CK-MB mass in ruling out an
acute myocardial infarction in the emergency room. Circu-
lation 1995; 92:3401–7.
8. Montague C, Kircher T. Myoglobin in the early evaluation
of acute chest pain. Am J Clin Pathol 1995; 104:472–6.
9. Tucker JF, Collins RA, Anderson AJ, Hess M, Farley IM,
Hagemann DA, et al. Value of serial myoglobin levels in the
early diagnosis of patients admitted for acute myocardial
infarction. Ann Emerg Med 1994; 24:704–8.
10. Woo J, Lacbawan FL, Sunheimer R, LeFever D, McCabe JB.
Is myoglobin useful in the diagnosis of acute myocardial
infarction in the emergency department setting? Am J Clin
Pathol 1995; 103:725–9.
11. Klootwijk P, Cobbaert C, Fioretti P, Kint PP, Simoons ML.
Noninvasive assessment of reperfusion and reocclusion
after thrombolysis in acute myocardial infarction. Am J
Cardiol 1993; 72:75G–84G.
12. Abe J, Yamaguchi T, Isshiki T, Naka H, Taguchi J, Ishizaka
N, et al. Myocardial reperfusion can be predicted by myo-
globin/creatine kinase ratio of a single blood sample ob-
tained at the time of admission. Am Heart J 1993;
126:279–85.
13. Ellis AK, Little T, Masud ARZ, Liberman HA, Morris DC,
Klocke FJ. Early noninvasive detection of successful reper-
fusion in patients with acute myocardial infarction. Circu-
lation 1988; 78:1352–7.
14. Ishii J, Nomura M, Ando T, Hasegawa H, Kimura M,
Kurokawa H, et al. Early detection of successful coronary
reperfusion based on serum myoglobin concentration:
comparison with serum creatine kinase isoenzyme MB ac-
tivity. Am Heart J 1994; 128:641–8.
15. Jurlander B, Clemmensen P, Ohman EM, Christenson R,
Wagner GS, Grande P. Serum myoglobin for the early non-
invasive detection of coronary reperfusion in patients with
acute myocardial infarction. Eur Heart J 1996; 17:399–406.
16. Lavin F, Kane M, Forde A, Gannon F, Daly K. Comparison of
five cardiac markers in the detection of reperfusion after
thrombolysis in acute myocardial infarction. Br Heart J
1995; 73:422–7.
17. Miyata M, Abe S, Arima S, Nomoto K, Kawataki M, Ueno
M, et al. Rapid diagnosis of coronary reperfusion by mea-
surement of myoglobin level every 15 min in acute my-
ocardial infarction. J Am Coll Cardiol 1994; 23:1009–15.
18. Zabel M, Hohnloser SH, Köster W, Prinz M, Kasper W, Just
H. Analysis of creatine kinase, CK-MB, myoglobin, and tro-
ponin T time-activity curves for early assessment of coro-
nary artery reperfusion after intravenous thrombolysis.
Circulation 1993; 87:1542–50.
19. Antman EM, Grudzien C, Sacks DB. Evaluation of a rapid
bedside assay for detection of serum cardiac troponin T. J
Am Med Assoc 1995; 273:1279–82.
20. Collinson PO, Gerhardt W, Katus HA, Müller-Bardorff M,
Braun S, Schricke U, et al. Multicentre evaluation of an im-
munological rapid test for the detection of troponin T in
whole blood samples. Eur J Clin Chem Clin Biochem 1996;
34:591–8.
21. Müller-Bardorff M, Freitag H, Scheffold T, Remppis A,
 574 Müller-Bardorff et al.: Point-of-care-system for troponin T and myoglobin
Kübler W, Katus HA. Development and characterization of
a rapid assay for bedside determinations of cardiac tro-
ponin T. Circulation 1995; 92:2869–75.
22. Christenson RH, Fitzgerald RL, Ochs L, Rozenberg M,
Frankel WL, Herold DA, et al. Characteristics of a 20-minute
whole blood rapid assay for cardiac troponin T. Clin
Biochem 1997; 30:27–33.
23. Gerhardt W, Ljungdahl L, Collinson PO, Lovis C, Mach F,
Sylvén C, et al. An improved rapid troponin T test with a
decreased detection limit: a multicentre study of the ana-
lytical and clinical performance in suspected myocardial
damage. Scand J Clin Lab Invest 1997; 57:549–58.
24. Gambke B, Herkner H, Hirschl MM, Laggner AN, Sylvén C,
Rasmanis G, et al. Analytical and clinical evaluation of an
improved qualitative troponin T rapid test (T ROPT sensi-
tive) for whole blood samples [abstract]. The Official Pub-
lication of MEDLAB 97 Abstracts. 12th European Congress
of Clinical Chemistry, Basel Switzerland, 17–22 Aug
1997:118.
25. Hirschl MM, Herkner H, Laggner AN, Sylvén C, Rasmanis
G, Collinson PO, et al. Analytical and clinical performance
of an improved qualitative troponin T rapid test in labora-
tories and critical care units. Arch Pathol Lab Med 2000;
124(4):583–7.
26. Sylvén C, Lindahl S, Hellkvist K, Nyquist O, Rasmanis G.
Excellent reliability of nurse-based bedside diagnosis of
acute myocardial infarction by rapid dry-strip creatine ki-
nase MB, myoglobin, and troponin T. Am Heart J 1998;
135:677–83.
27. Schouten Y, de Winter RJ, Gorgels JPMC, Koster RW,
Adams R, Sanders GT. Clinical evaluation of the CARDIAC
STATus, a rapid immunochromatographic assay for simul-
taneous detection of elevated concentrations of CK-MB
and myoglobin in whole blood. Clin Chem Lab Med 1998;
36:469–73.
28. Brimhall BB, Johnson P, Goldman L, Lee T, Sacks D. Diag-
nostic and prognostic value of cardiac troponin T in pa-
tients with acute chest pain [abstract]. Clin Chem 1995;
41:S167.
29. Lindahl B, Venge P, Wallentin L, for the FRISC Study Group.
Relation between troponin T and the risk of subsequent
cardiac events in unstable coronary artery disease. Circu-
lation 1996; 93:1651–7.
30. Ohman EM, Armstrong PW, Christenson RH, Granger CB,
Katus HA, Hamm CW, et al. for the GUSTO-IIA Investiga-
tors. Cardiac troponin T levels for risk stratification in acute
myocardial ischemia. N Engl J Med 1996; 335:1333–41.
View publication stats
31. Hamm CW, Heeschen C, Goldmann BU, Barnathan E,
Simoons ML, for the CAPTURE investigators. Value of tro-
ponins in predicting therapeutic efficacy of abciximab in
patients with unstable angina [abstract]. J Am Coll Cardiol
1998; 31:185A.
32. Lindahl B, Venge P, Wallentin L, for the Fragmin in Unsta-
ble Coronary Artery Disease (FRISC) Study Group. Tro-
ponin T identifies patients with unstable coronary artery
disease who benefit from long-term antithrombotic pro-
tection. J Am Coll Cardiol 1997; 29:43–8.
33. Mastropaolo W. Use of delta one-hour myoglobins to rule
out myocardial infarction less than four hours after onset
of symptoms [abstract]. Clin Chem 1996; 42:S95.
34. Sunheimer R, Bushnell A, McCabe J, Woo J. Myoglobin as
an early marker for detecting acute myocardial infarction
in the emergency department. Clin Chem 1996; 42:S105.
35. Müller-Bardorff M, Hallermayer K, Schröder A, Ebert C,
Borgya A, Gerhardt W, et al. Improved troponin T ELISA
specific for cardiac troponin T isoform: assay development
and analytical and clinical validation. Clin Chem 1997;
43:458–66.
36. Panteghini M, Altinier S, Dolci A, Pagani F, Pergolini P, Ver-
nocchi A, et al. Multicenter evaluation of five methods for
myoglobin determination. Clin Chem 1998; 44:A121.
37. Breuer J. Report on the symposium “Drug effects in clini-
cal chemistry methods”. Eur J Clin Chem Clin Biochem
1996; 34:385–6.
38. Panteghini M, Apple FS, Christenson RH, Dati F, Mair J, Wu
AH. Use of biochemical markers in acute coronary syn-
dromes. IFCC Scientific Division, Committee on Standard-
ization of Markers of Cardiac Damage. International Feder-
ation of Clinical Chemistry. Clin Chem Lab Med 1999;
37:687–93.
39. Wu AH, Apple FS, Gibler WB, Jesse RL, Warshaw MM,
Valdes R. National Academy of Clinical Biochemistry Stan-
dards of Laboratory Practice: recommendations for the
use of cardiac markers in coronary artery diseases. Clin
Chem 1999; 45:1104–21.
Received 5 January 2000; revised 8 March 2000;
accepted 9 March 2000
Corresponding author: Prof. Dr. Hugo A. Katus, Medizinische
Universität zu Lübeck, Medizinische Klinik II, Ratzeburger
Allee 160, D-23562 Lübeck, Germany
Tel.: +49-451-500-2501, Fax: +49-451-500-6437
Email: katus@medinf.mu-luebeck.de