ArticlePDF AvailableLiterature Review

Troponin assays for the diagnosis of myocardial infarction and acute coronary syndrome: Where do we stand?

Authors:
  • Galilee Medical Center, Nahariya, Israel

Abstract

Under normal circumstances, most intracellular troponin is part of the muscle contractile apparatus, and only a small percentage (< 2-8%) is free in the cytoplasm. The presence of a cardiac-specific troponin in the circulation at levels above normal is good evidence of damage to cardiac muscle cells, such as myocardial infarction, myocarditis, trauma, unstable angina, cardiac surgery or other cardiac procedures. Troponins are released as complexes leading to various cut-off values depending on the assay used. This makes them very sensitive and specific indicators of cardiac injury. As with other cardiac markers, observation of a rise and fall in troponin levels in the appropriate time-frame increases the diagnostic specificity for acute myocardial infarction. They start to rise approximately 4-6 h after the onset of acute myocardial infarction and peak at approximately 24 h, as is the case with creatine kinase-MB. They remain elevated for 7-10 days giving a longer diagnostic window than creatine kinase. Although the diagnosis of various types of acute coronary syndrome remains a clinical-based diagnosis, the use of troponin levels contributes to their classification. This Editorial elaborates on the nature of troponin, its classification, clinical use and importance, as well as comparing it with other currently available cardiac markers.
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Troponin assays for the diagnosis
of myocardial infarction and acute
coronary syndrome: where do
we stand?
Arie Eisenman
Institution, Address
Tel.: Phone
Fax: Fax
arie.eisenman@naharia.health.
gov.il
K
EYWORDS:
Acute coronary syndrome,
myocardial infraction, troponin I,
troponin T
Under normal circumstances, most intracellular troponin is part of the muscle contractile
apparatus and only a small percentage (< 2–8%) is free in the cytoplasm. The presence of
a cardiac-specific troponin in the circulation at levels above normal is good evidence of
damage to cardiac muscle cells, such as myocardial infarction, myocarditis, trauma,
unstable angina, cardiac surgery or other cardiac procedures. Troponins are released as
complexes leading to various cut-off values depending on the assay used. This makes
them very sensitive and specific indicators of cardiac injury. As with other cardiac
markers, observation of a rise and fall in troponin levels in the appropriate time-frame
increases the diagnostic specificity for acute myocardial infarction. They start to rise
approximately 4–6 h after the onset of the acute myocardial infarction and peak at
approximately 24 h, as is the case with creatine kinase-MB. They remain elevated for
7–10 days giving a longer diagnostic window than creatine kinase. Although the diagnosis
of the various types of acute coronary syndrome remains a clinical-based diagnosis, the
use of troponin levels contributes to their classification. This article elaborates on the nature
of troponin, its classification, clinical use and importance, as well as comparing troponin
with other currently avaiable cardiac markers.
Expert Rev. Cardiovasc. Ther. 4(4), xxx–xxx (2006)
Ischemic heart disease remains the leading cause
of death in the USA and the western world
despite considerable advances in diagnosis and
management. Survival depends upon early diag-
nosis and prompt intervention. The three fun-
damental criteria for establishing the diagnosis
of myocardial infarction (MI) are serum cardiac
enzymes, clinical evaluation and electrocardio-
gram (ECG) patterns. Unfortunately, enzymes
are not specific for cardiac muscle and have a
narrow time-window. The long search for near
ideal markers, that are both specific and sensi-
tive, have brought about the development of
monoclonal antibodies to cardiac troponin (Tn)
I and T resulting in cardiac-specific assays
[1].
Tns are components of muscle contractile
structure along with actin and tropomyosin
[101]. There are three types: Tn I, T and C, and
are found in all muscle types. However, only
cardiac-specific forms of Tns I and T: cardiac-
specific Tn (cTn)T and cTnI can serve as
markers of myocardial damage
[8,17]. Due to
their high specificity and sensitivity, cardiac
Tns have replaced classical markers, such as cre-
atine kinase (CK)-MB
[2]. The increase in both
specificity and analytical sensitivity of these
markers led to a new definition and classifica-
tion of the original WHO criteria for acute cor-
onary insufficiency (ACI) and MI
[2,3]. Accord-
ing to the new definition, high Tn levels always
have pathological meaning. A value above the
normal limit (first decision point) defined by
the levels found in healthy individuals means
myocardial injury, but does not indicate the
origin. A higher value above the second deci-
sion point, with an appropriate history and
timing, can be taken as good evidence of a
myocardial infarction
[4].
C
ONTENTS
Troponin T
Troponin I
Risk stratification
Differential diagnosis
Role in the emergency
department & comparison
with other cardiac markers
Cost
Expert commentary
Five-year view
Key issues
References
Affiliation
Author Proof
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Expert Rev. Cardiovasc. Ther. 4(4), (2006)
Tn T and I are different molecules with different amino
acids, structures and functions that are both expressed in cardi-
omyocytes, but differ with respect to biochemical and analyti-
cal characteristics
[5]. This difference affects the method of
comparison, diagnostic sensitivity and diagnostic specificity of
the assays of cardiac Tn T and cardiac Tn I
[6].
Troponin T
Tn T is a cardiac-specific protein that binds to tropomyosin
and is one of the three polypeptide chains that make up the
Tn complex. It has a molecular weight of 36,000 and approx-
imately 7% is free in the cytosol of the cardiac myocyte. At
present there is only one manufacturer of cTnT assays (Roche
Diagnostics
®
, Indianapolis, IN, USA) and this has proved to
be a major advantage, as the supplied kits are of the same
generation, therefore, no standardization is required. Over
three generations of the assay have been introduced, each
with better sensitivity and specificity. The current Recom-
binant Human Cardiac Tn-T is produced in Escherichia coli
and is a single, nonglycosylated, polypeptide chain having a
molecular mass of 40 kDa. It is characterized by a very nar-
row margin of normal values represented by a maximum
third quartile of 0.50 µg/l. A singular value of Tn after 6 or
24 h is sufficient to confirm the diagnosis of a MI
[7].The
manufacturer claims that, on average TnT rises up to 1 h
sooner than TnI after an AMI and that the higher cytosolic
fraction compared with I (3%) makes TnT a superior marker
of reversible ischaemia.
cTnT can be measured on both laboratory and bedside basis.
Lewandrowski and colleagues compared the Roche Tn T Car-
diac Reader™ in an emergency department (ED) bedside labo-
ratory (point of care test [POCT]) with the general laboratory
Elecsys Tn T Method™
[22], and found that overall, the Car-
diac Reader demonstrated excellent agreement with the Elecsys
Tn T assay (Roche Diagnostics) (Y = 1.09X + 0.05, r = 0.96)
over the range of values from 0.1–2 ng/ml
[8].
The current third-generation assay allows approximately
35% more patients to be classified, according to recent defini-
tions, as having acute MI (AMI) on admission and is capable
of superior identification of low-risk patients with signs of
very minor myocardial necrosis (cTnT > 0.01–0.02 µg/l), and
thereby an increased risk of future events
[9].
Troponin I
TnI is released into the circulation as a ternary complex with
Tns C and T, or as a binary with Tn C, but TnT, TnI has never
been detected in skeletal muscle. TnI has a molecular weight of
28,000 Da and only approximately 3% is free in the cytosol.
High levels of cTnI are detected within 4–6 h from the onset of
chest pain, reaching a peak within approximately 12 h and
remain high for 3–10 days after infarction.
Although many manufacturers produce cTnI assays, cTnT
is manufactured by only one company. This is a problem
owing to the resultant lack of standardization and variety of
sensitivities among assays
[10]. Therefore, despite the existence
of a correlation between different systems and points of care,
Tn I numeric values are not exchangeable from one method
to another. Cut-off values may be different, and this requires
careful consideration of the format for reporting the POC test
during implementation
[8]. That is why in 2001, the Interna-
tional Federation of Clinical Chemistry and Laboratory Med-
icine (IFCC) Committee on Standardization of Markers of
Cardiac Damage, published special guidelines addressing the
quality specifications for Tn assays in order to guarantee an
analytical performance satisfying medical requirements and to
standardize the quality of commercial methods
[10]. Tn stand-
ardization is a challenge for the near future that may lead to
an improved follow-up of patients and comparison between
cohorts
[3].
The cTnT and the various cTnI assays differ with respect to
method comparison, diagnostic sensitivity and diagnostic spe-
cificity
[6]. The superiority claim of one study over the other has
led to a lasting controversy. Although in one study analysis no
significant difference between the general accuracy of Tn T and
Tn I was found in distinguishing patients with and without
AMI, according to the receiver operator characteristic
[11], in
another study the cTnT concentrations of all subjects were
below the detection limit
[6]. However, AccuTnI was able to dif-
ferentiate the two subgroups from each other in healthy sub-
jects. These results express more the differences in the release of
cTnI and cTnT from the cytoplasm, and the thin filaments of
the cardiomyocytes than the modifications of the Tns circulat-
ing in the blood
[6].
As with cTnT, many assays, first, second and third genera-
tion, are at present available to determine the concentration
of cTnI
[12]. Bionda and colleagues compared the clinical and
analytical performance of two Tns assays; cTnI, second gener-
ation, (AccuTnI™) on Access 2 of Beckman Coulter and Tn
Tc, third generation, (Tn T STAT) on Elecsys 2010 of Roche
Diagnostics
[12]. They found that the study on Beckman
Coulter for cTnI (at the cut-off of 0.04 microg/L and at the
99 degrees percentil, 0.06 µg/L for a CV
10%), demon-
strated a superior specificity (76%) and predictive positive
value (89%) with a sensitivity of 100% at 0.1 µg/L, fixed and
used in the laboratory for its better agreement between sensi-
bility/specificity and its imprecision below 10%
[12]. For the
cTnT values published by Roche Diagnostics (0.01 µg/L), at
the 99 degrees percentil and 0.03 µg/L for a CV
10%, the
specificity is lower, so the decisional value 0.1 µg/L seems to
be more suitable
[12].
In another study, Karciauskaite investigated the clinical specifi-
city and sensitivity of cTnT and cTnI tests in patients admitted
to hospital with suspected acute coronary syndrome (ACS)
[11]. It
was found that when performed in separate patients, the sensitiv-
ity of the Tn T test in diagnosing AMI was 85%, and the specifi-
city was 87.2%, while Tn I test sensitivity was 76% and the spe-
cificity was 76.2%
[11]. However, in cases when both Tn T and I
tests were performed, the sensitivity of Tn T was 100% and the
specificity was 78% while the sensitivity and the specificity of Tn
I were 86% and 78%, respectively
[11].
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Risk stratification
The main importance of Tn assays is risk stratification for coro-
nary heart disease (CHD). It is now firmly established that the
Tns are superior markers, for both diagnostic and risk stratifica-
tion of subsequent cardiac risk in ACS
[2]. Tn is more useful than
CK-MB in predicting 1-year mortality among ACS patients
[13].
Patients with AMI according to thr American College of Cardi-
ology/European Society of Cardiology (ACC/ESC) definition and
are Tn positive have been demonstrated to be at a higher risk of
further coronary event in both the short and long term
[101,14,15].
By contrast, patients who are Tn negative have a lower risk of cor-
onary event and do not need hospitalization
[101]. However, in
order to assure a good prognosis for the long term it is still recom-
mended that early exercise testing and clinical data should be
included
[16]. A high recurrence rate of angina pectoris and
increased number of combined end points of cardiac events have
been registered in patients with positive TnI during follow-up
[17].
Elevated TnI serves as an important risk factor in patients
with non-ST elevations MI. Such patients with a positive Tn
result are at increased risk
[16]. An active, early-invasive, inter-
vention therapy is of benefit for Tn I-positive patients, but it
makes no more benefits for TnI negative patients
[17].
A moderate increase of cTnI values does not have the same
implication as higher cTnI values
[15]. The correlation appears
to be both qualitative and quantitative. Although increased
cTnI values are associated with worse outcomes it is unclear
whether outcomes change among a lower risk, heterogeneous
patient group with cTnI elevation
[15]. Few studies have
reported outcomes other than MI or death, based on the peak
Tn value
[15].
cTnI is also useful for identifying patients who have under-
gone vascular surgery and who have an increased risk for short-
term mortality and perioperative MI
[18]. Recent studies suggest
that any elevation of Tn in the postoperative period is indica-
tive of increased risk of long-term cardiac complications. This
prognostic value has been previously demonstrated in other
clinical settings, such as invasive coronary intervention (surgical
myocardial revascularization and percutaneous coronary inter-
vention) and after heart valve surgery
[2].
Differential diagnosis
The early generation of Tn T assay released was not entirely
cardiac-specific and some false-positive results were obersved
in patients with myopathies and renal failure. Indeed, the
mRNA for cardiac-specific Tn T has been identified in skele-
tal muscle in some circumstances, however the antibodies
used in the current assay do not recognize this form. There-
fore, at the present time, cTnT can be considered as cardiac-
specific as Tn I. Nevertheless, some studies demonstrated that
the possibility of few false-positive or -negative cTnT values
still exists and must be taken in consideration when clinical
findings are not in good accordance with laboratory results
[12]. To increase this accordance four independent clinical pre-
dictors were identified: typical chest pain; diabetes mellitus;
previous coronary surgery and ST segment depression
[16].
For the diagnosis of AMI a positive test in serial Tn measure-
ments have a positive likelihood ratio of 17 and a negative likeli-
hood ratio of 0.04. In a population, in which the overall rate of
MI is 6%, the post-test probability of MI infarction with a posi-
tive Tn test alone is approximately 45%, while the post-test
probability with a negative test is approximately 0.2%
[19].
Generally speaking, a rise in Tn levels indicates cardiac dam-
age, regardless of the mechanism (ischemic or not). However, not
all cardiac injuries are primary: secondary causes of cardiac injury
include pulmonary embolism (PE), myocarditis, pericarditis,
congestive heart failure, septic shock and myocardial contusion.
In those cases too, elevation of Tns has been demonstrated to be
associated with a bad outcome
[101]. The mechanism involved in
extra cardiac injury with Tn level elevation is usually a strain or
enlargement of the right ventricle. Those patients are at signifi-
cantly greater risk of death after PE than patients with only one
or no adverse prognostic marker
[20]. One study evaluated Tn I
values and echocardiographic data in 141 patients with acute-PE,
and found a correlation between the two parameters and with
30-day mortality
[20].
The specificity of cTnI for patients with chronic renal failure,
skeletal muscle trauma and disease was better than all other
markers including cTnT
[21]. Therefore, in contrary to other
non-specific markers, in multiple trauma cases, Tn measure-
ment, especially cTnI, may help in diagnosing or ruling out
cardiac injury.
cTnI is an effective marker for the retrospective diagnosis of
AMI, and consideration should be given to its use in place of
CK-MB
[21]. The clinical efficiency of cTnI is better than either
CK-MB or myoglobin, owing mainly to the wider diagnostic
window. Creatine kinase-MB subforms, myoglobin, as well as
Tn T or I are less accurate before 6 h and, all markers except
Tn I, are less accurate after 10 h
[22].
Elevated levels of Tn, especially cTnI, are frequently found in
patients with chronic renal failure including those on dialysis
treatment and have been demonstrated to be a poor prognostic
factor for survival. The exact source of this elevation is poorly
understood
[23], and it is not yet clear if cTnT and cTnI in
patients with end-stage renal disease under hemodialysis are com-
parable
[5]. It may represent uremic myocarditis or coronary artery
disease. cTnT and a known CHD have been also demonstrated to
be relevant, independent risk factors which may account for up to
50% of mortality in patients with chronic renal failure undergo-
ing long-term hemodialysis
[23]. In these patients a rise and fall in
Tn levels may be required to make a definitive diagnosis of MI.
Following cardiac surgery, electrocardiography and creatine
kinase isoenzyme MB (CK-MB) activities are of limited value
in diagnosing a nontransmural infarction
[7].
Cardiac bypass surgery causes a marked rise in serum Tn
levels. For this reason care must be taken when using this tool
to assess for perioperative infarction in this setting. Collection
of a timed sequence of samples may be of benefit.
Tn T is characterized by a very narrow margin of normal values
represented by a maximum third quartile of 0.50 µg/l. A singular
value of Tn after 6 or 24 h may be sufficient evidence to confirm
Author Proof
Eisenman
4
Expert Rev. Cardiovasc. Ther. 4(4), (2006)
the diagnosis of a Perioperative MI (PMI) [7]. The appearance of
Q-waves after coronary surgery has long been considered sugges-
tive for PMI. However, it now seems that most Q-waves appear-
ing on ECG after coronary surgery are not associated with major
myocardial tissue damage, and according to Tn-T a quarter of the
Q-waves are not associated with myocardial necrosis. Further-
more, the appearance of Q-waves had little influence on short-
term clinical outcome. Therefore, the use of Q-wave criteria as the
gold standard for diagnosis of PMI is doubtful
[23], and a positive
Tn test in this case is especially important.
Role in the emergency department and comparison with other
cardiac markers
About 20% of the patients encountered in the ED, in the
western world, complain of chest pain. Evaluation of patients
with acute chest pain in the ED is hazardous, time-consum-
ing and expensive, and often results in an uncertain diagnosis
[22]. The implication of a wrong diagnosis may be serious,
there is a risk that on one hand, patients suffering from an
acute life threatening coronary event may be wrongly sent
home presumed to have chest pain of an innocent nature,
while on the other hand, patients with benign chest pain may
be unjustly admitted to hospital and undergo futile and
expensive investigation to rule out a coronary event. Current
diagnosis still relies on clinical judgment, ECG interpreta-
tion and a rise of cardiac markers in the serum. Myoglobin
and CK-MB have been the cardiac markers routinely used to
diagnose an acute coronary event. Although not specific,
myoglobin is the earliest marker to exclude AMI due to its
abundance in muscle tissue and its low molecular weight. It
is detected within 2 h after the onset of the event and
decreases to a normal value within 24–36 h. The CK-MB
concentration is a sensitive and an early indicator for myo-
cardial damage in patients with chest pain. It rises 2–8 h after
MI, and reaches a peak after 24 h and remains elevated even
after 72 h. Both activity and mass assays exist. There is evi-
dence that CK-MB mass assays are significantly more sensi-
tive than CK-MB activity measurement. cTnI and cTnT,
however, have replaced CK-MB for the diagnosis of cardio-
myocyte necrosis
[3]. Tn T and I are superior to CK-MB
(mass or activity) and CK in the identification of patients
with AMI
[24] and cTnI is more sensitive than CK-MB mass
for detection of myocardial injury in patients with small
increases oin total CK
[25]. The clinical sensitivity for detec-
tion of myocardial injury for cTnI was 100% compared with
81.8% for CK-MB. Nevertheless, Tn I and T are by no mean
early markers’ of cardiac events and a negative result shortly
after the onset of chest pain is of no more value than a nega-
tive CK-MB
[101]. That is why their role in the ED is contro-
versial. In this respect, another recently introduced marker,
the ischemia modified albumin (IMA) is intended for use in
conjunction with ECG and cardiac Tn as an aid to short-
term risk stratification of patients presenting with chest pain
suggestive of cardiac origin
[26]. A negative IMA may help to
rule out ACS in low risk patients
[26].
Wu and colleagues claimed that the superior clinical efficiency
of cTnI compared with either CK-MB or myoglobin, was mainly
due to the wider diagnostic window
[21]. In fact, the main advan-
tage of a Tn assay is retrospective; it is the only effective marker
for the retrospective diagnosis of AMI, as after 10 h cTnI remains
the most accurate of all markers and should, therefore, replace
both CK-MB and myoglobin
[22]. However, combining multiple
sampling of CK-MB with a single confirmatory Tn testing may
provide a superior cost–effective testing protocol for suspected
AMI patients
[24].
As mentioned above, Tn assays often carry two decision
points. One is the top of the reference interval, defined by the
levels found in healthy individuals, and a second is a higher
value indicating a high probability of MI (WHO definition). A
value above the second decision point together with an appro-
priate history and timing, can be taken as good evidence of a
MI (WHO definition). A value below this level, but above the
upper limit of normal still indicates cardiac myocyte injury due
to some cause. In the clinical setting of ischemic heart disease
this has been classified as an AMI
[4].
In an attempt to save time and duration of stay, many EDs
currently use commercially available bedside assays (POCT).
Hamm and colleagues investigated the usefulness of such bed-
side tests for the detection of cTnT and cTnI in the evalua-
tion of patients with acute chest pain in the ED
[22]. It
appeared that bedside tests for cardiac-specific Tns are highly
sensitive for the early detection of myocardial-cell injury in
ACSs. Saying that, a useful scheme of workup in the ED may
be as follows:
If the POCT-Tn I result is elevated, it is followed up with a
laboratory Tn I assay.
If the Tn I result is not elevated, no follow-up assay is con-
ducted and the POCT result is used as part of the clinicians
rationale to rule out MI
[27,28].
Negative test results are associated with low risk and allow
rapid and safe discharge of patients with an episode of acute
chest pain from the ED
[22]. However, Eisenman and colleagues
warn that although bedside assays of Tn are invaluable tools for
the clinician, and their use is costeffective in the setting of ED
and in the present recommended cut-off levels, only Tn I, but
not Tn T, allow the safe discharge of patients not requiring
acute hospital care
[29].
Cost
The drawback of Tn assays as their relatively high cost com-
pared to other cardiac enzyme tests. However, the utilization
of Tn T and I in a broad spectrum of ED patients with sus-
pected myocardial ischemia improves hospital resource utili-
zation and reduces costs
[19]. A randomized study from Con-
necticut concluded that for patients with ACS the use of a Tn
test, rather than other tests, can reduce significantly both the
duration of stay and overall costs
[19]. On average, Tn meas-
urements in Bridgeport hospital saved approximately
US$ 900 per patient total costs representing a potential
annual saving of about US$ 4 million
[19].
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The ESC/ACC current guidelines recommend that an early
diagnosis of ACS should rely on a combination of an early myo-
cardial damage marker (e.g., myoglobin or CK-MB) and a more
specific marker (e.g., Tn)
[4]. When various approaches were
examined, measurement of CK-MB mass followed by exercise
testing in appropriate patients seemed the most competitive strat-
egy (US$ 43,000 per year of life saved) for patients 55–64 years of
age. For patients 65–74 years of age, measurement of CK-MB
mass followed by cTnI measurement had an incremental
cost–effectiveness ratio of US$ 47,400 per year of life saved and
was also the most cost–effective strategy when early exercise test-
ing could not be performed, CK-MB values were normal, and
ischemic changes were seen on electrocardiography. Significant
reductions in duration of hospital stay were also seen in Tn T
patients both with (3.6 vs 4.7 days; p = 0.01) and without (1.2 vs
1.6 days; p = 0.03) ACSs compared with controls
[19].
For younger patients and those with a low to moderate proba-
bility of MI, measurement of CK-MB mass plus early exercise
testing is a cost-effective initial strategy. cTnI measurement can be
a cost-effective second test in higher-risk subsets of patients if the
CK-MB level is normal and early exercise testing is not an option.
Expert commentary
The introduction of Tn essays has, no doubt, revolutionized the
approach to patients presenting to the ED with chest pain. New
generations of the essay now offer high sensitivity and specificity
which make Tn a near ideal cardiac marker. A positive test always
means myocardial damage, most likely due to a coronary event,
although differential diagnosis exists especially when the rise is
modest. Ever since the introduction of Tn a new situation has
developed in an ED that some would callTn syndrome. The
syndrome consists of patients who have a positive Tn test despite
having neither typical chest pain nor an abnormal ECG pattern.
Many ED physicians who have learned to rely on positive Tn tests
as an unequivocal evidence to myocardial injury will admit them
immediately to the cardiology ward where soon it appears that
they are in fact suffering from something else. So, a good recom-
mendation would be to refer to a positive Tn test as good evi-
dence of a coronary event but not the only evidence. Other crite-
ria, such as clinical impression and ECG pattern are still
important. Another area of interest is multiple trauma. Before the
advent of Tn it was impossible to use other nonspecific markers to
rule out or indicate cardiac injury and other invasive imaging
methods had to be undertaken. Now, a single Tn test is sufficient
to imply whether the heart is involved in a multiple trauma event
or not, saving effort, time and money.
Five-year view
The overall mortality from MI, at the present decade, is declining
due to novel reperfusion interventions. Yet it is estimated that a
third of patients having an acute coronary event die suddenly, out
of hospital, owing to late recognition and treatment, and tremen-
dous efforts are being invested by organizations, such as the Amer-
ican Heart Organisation and the European Resuscitation Council
to find ways to reduce the time between the appearance of chest
pain and therapeutic intervention. Future efforts will focus on the
early diagnosis of MI in the ED in order to intervene as soon as
possible. The search for an ideal early marker for the early detec-
tion of AMI in the ED will continue. Unfortunately, although
highly sensitive and specific, current Tn assays cannot be consid-
ered as ideal cardiac marker for tracing acute coronary patients in
the ED because of their relatively late time frame. Yet, their overall
diagnostic and prognostic role for the long term is crucial and will
become established in many years to come.
References
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(2005) (Epub).
3 Lavoinne A, Cauliez B. Cardiac troponin I
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cardiomyocyte. Rev. Med. Intern. 25,
115–123 (2004).
Key issues
Cardiac troponin (Tn) testing is a key diagnostic element for the diagnosis and management of patients with acute coronary
syndromes (ACSs) together with other diagnostic criteria such as clinical judgement and electrocardiogram pattern.
The role of Tn is especially defined for patients without ST segment elevation and is increasingly used in noncoronary diseases to
indicate prognostically important cardiac damage.
Patients without ST-elevations but with positive Tn results have an increased risk of death or myocardial infarction
The use of Tns has the capacity to reduce hospital resources, unjustified admissions and duration of stay.
A positive Tn test at any time indicates the need for detailed investigation of the cardiac status of the patient.
If the measurement has been made longer than 6 h after the onset of chest pain, a negative Tn test can only be used to indicate a
low risk of a subsequent cardiac event. Negative values longer than 12 h after the onset of pain are more reliable.
Bedside tests for cardiac-specific Tns are highly sensitive for the early detection of myocardial-cell injury in ACS.
Negative test results are associated with low risk and allow for rapid and safe discharge of patients with an episode of acute chest
pain from the emergency department.
Author Proof
Eisenman
6
Expert Rev. Cardiovasc. Ther. 4(4), (2006)
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Website
101 AJones G. Troponins.
www.sydpath.stvincents.com.au/tests/
Troponin.htm
Affiliation
•Arie Eisenman
Institution, Address
Tel.: Phone
Fax: Fax
Arie.Eisenman@naharia.health.gov.il
... Furthermore, various diseases, other than MI, may cause an increase in the circulating level of TNNT, including direct myocardial injury and various primary noncardiac diseases (5). Additionally, the increase in TNNT2 blood plasma levels may be maintained for ≤2 weeks following MI (6), thus, this parameter is not sufficient to monitor the disease status and the potential therapeutic effects of a treatment. Imaging techniques, including coronary computed tomography angiography, are alternative diagnostic methods; however, the iodinated contrast media used in coronary computed tomography angiography may lead to contrast-induced nephropathy (7). ...
... TNNT2 is one of the most used biomarkers for MI, and high levels of TNNT2 are detectable for ≤2 weeks following MI (6). In the present study, the expression levels of all five candidate biomarkers (ANT3, CO3, A1AG1, TRFE and CATZ) were identified to be notably decreased following treatment in iTRAQ and MRM quantification analysis. ...
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Myocardial infarction (MI) is a disease characterized by high morbidity and mortality rates. MI biomarkers are frequently used in clinical diagnosis; however, their specificity and sensitivity remain unsatisfactory. Urinary proteome is an easy, efficient and noninvasive source to examine biomarkers associated with various diseases. The present study, to the best of the authors' knowledge, is the first to examine the urinary proteome using the isobaric tags for relative and absolute quantitation (iTRAQ) technology to identify potential diagnostic biomarkers of MI. The urinary proteome was analyzed within 12 h following the first symptoms of early‑onset MI and at day 7 following percutaneous coronary intervention via iTRAQ labeling and two‑dimensional liquid chromatography‑tandem mass spectrometry. Candidate biomarkers were validated by multiple reaction monitoring (MRM) analysis. A total of 233 urinary proteins were differentially expressed. Gene enrichment analysis identified that the urinary proteome in patients with MI was associated with atherosclerosis, abnormal coagulation and abnormal cell metabolism. In total, 12 differentially expressed urinary proteins were validated by MRM analysis, five of which were associated with MI for the first time in the present study. Binary logistic regression analysis suggested that the combination of five urinary proteins (antithrombin‑III, complement C3, α‑1‑acid glycoprotein 1, serotransferrin and cathepsin Z) may be used to diagnose MI with 94% sensitivity and 93% specificity. In addition, the protein expression levels of three proteins were significantly restored to normal levels following surgical treatment. The verified candidate biomarkers may be used for the diagnosis of MI, and for monitoring the disease status and the effects of treatments for MI. The present results may facilitate future clinical applications of the urinary proteome to diagnose MI.
... Cardiac troponin-I level above 0.16 ng/ml may be a risk factor for congestive heart failure (CHF) (Williams et al., 2002). Cardiac troponins (I and T) leakage out of themyocardial cells occur within 4-6 hours following onset of acute myocardial infarction with peak leakages at about 24hours after the attack (Eisenman, 2006) due to a gradual degeneration of myofibrils with release of the troponin complex (Bertinchant et al., 1996). Serum cardiac troponin levels remain elevated for up to about 2 weeks unlike creatinine kinase which is metabolized more rapidly. ...
... Persistent presence of troponins makes it a better diagnostic marker of myocardial injury compared to creatinine kinase. Troponins also have almost complete tissue specificity, hence the preferred markers for evaluating myocardial injury (Eisenman, 2006) and cardiac troponin I (cTnI) has not been identified in other tissues outside the myocardium (Bodor et al., 1995). Clinically significant (p<0.05) ...
... Although the chronic effects of radiation on the heart are well known, there are a limited number of studies analyzing acute heart damage in patients undergoing EBRT, and the findings of these are ambiguous [28,[30][31][32][33][34][35]. To our knowledge, there has only been a single study assessing IORT in this context [28]. ...
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PurposeTo assess acute cardiac toxicity caused by intraoperative radiotherapy (IORT) with low-energy x‑rays for early breast cancer.Methods We prospectively analyzed pre- and postoperative troponin I and NT-proBNP in 94 women who underwent breast-conserving surgery between 2013 and 2017 at the Department of Gynecology and Obstetrics of the University Medical Center Mannheim, Germany. Thirty-nine women received IORT using low-energy x‑rays during breast-conserving surgery while 55 patients without IORT formed the control group. Demographic and surgical parameters as well as cardiac markers were evaluated.ResultsThere were no significant differences concerning age and side of breast cancer between the groups. Furthermore, no significant difference between the troponin I assays of the IORT and control groups could be found (preoperatively: 0.017 ± 0.006 ng/ml vs. 0.018 ± 0.008 ng/ml; p = 0.5105; postoperatively: 0.019 ± 0.012 ng/ml vs. 0.018 ± 0.010 ng/ml; p = 0.6225). N‑terminal fragment of B‑type natriuretic peptide (NT-proBNP) was significantly higher in the control group 24 h after surgery (preoperatively: 158.154 ± 169.427 pg/ml vs. 162.109 ± 147.343 pg/ml; p = 0.56; postoperatively: 168.846 ± 160.227 pg/ml vs. 232.527 ± 188.957 pg/ml; p = 0.0279).Conclusion Troponin I levels as a marker of acute cardiac toxicity did not show any significant differences in patients who received IORT during breast-conserving surgery compared to those who did not.
... In the present study, an X-ray coronary angiography demonstrated that the chronic myocardial ischemia model was stably established. CK-MB, LDH, Myo and cTnI levels are considered to be important indicators of myocardial damage, and are signifi-cantly increased by blockage of the LAD (28)(29)(30)(31)(32). In addition, AST and ALT have previously been used to diagnose coronary heart disease (33,34). ...
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Traditional Chinese medicines, including Radix Salvia miltiorrhiza (SM) and Lignum Dalbergia odorifera (DO) extracts, have historically been used to treat myocardial ischemia and other cardiovascular diseases. The volatile oil of DO (DOO) is one of the main components of DO. The aim of the present study was to assess the cardioprotective effects and possible underlying mechanisms of SM‑DOO in pigs with ameroid constriction‑induced chronic myocardial ischemia. An ameroid constrictor was placed around the left anterior descending coronary artery of pigs to induce chronic myocardial ischemia. At weeks 2, 6 and 8, myocardial injury markers and blood gas levels were detected. At week 8, coronary angiography, echocardiography and hemodynamics analysis were performed to evaluate myocardial function. Following sacrifice, myocardial tissue was collected and subjected to morphological, histopathological and apoptosis assays. Western blotting was used to detect the protein expression of Bcl‑2 associated X (Bax), Bcl‑2, Akt, phosphorylated (p)‑Akt, glycogen synthase kinase (GSK)‑3β and p‑GSK‑3β. It was revealed that SM‑DOO treatment following chronic myocardial ischemia significantly downregulated the expression of myocardial injury markers, ameliorated myocardial oxygen consumption, increased collateralization, reduced regional cardiac dysfunction and limited the extent of myocardial damage. Furthermore, the results of an apoptosis assay revealed that the apoptosis rate was decreased, the expression of Bax decreased and Bcl‑2 increased, and the ratio of Bcl‑2/Bax was increased. Further experiments indicated that treatment with SM‑DOO increased the phosphorylation of Akt and GSK‑3β. These findings suggest that SM‑DOO treatment ameliorates myocardial injury in a chronic myocardial ischemia model, and that the underlying mechanisms responsible may be associated with the activation of the Akt/GSK‑3β signal pathway. Thus, experimental evidence that SM‑DOO may be an effective drug for the prevention and treatment of chronic myocardial ischemia in clinical applications has been provided.
... Troponin I was found to be significantly increased in MI compared to CSA and NC. This finding concurs with the well-known phenomenon where an increased level of cardiac-specific troponin in the circulation is good evidence of damage to cardiac muscle cells, such as MI, myocarditis, trauma, unstable angina, cardiac surgery, or other cardiac procedures (35). ...
Article
Background Biochemical detection of chronic stable angina (CSA) and myocardial infarction (MI) are challenging. To address the shortcomings of the conventional biochemical approach for detection of MI, we applied serum lacking proteins and lipoprotein-based metabolomics in an approach using proton nuclear magnetic resonance (¹H NMR) spectroscopy for screening of coronary artery disease (CAD) and especially MI. Our aim was to discover differential biomarkers among subjects with normal coronary (NC), CSA, and MI. Methods The study comprised serum samples from nondiabetic angiographically proven CAD [CSA (n = 88), MI (n = 90)] and NC (n = 55). ¹H NMR spectroscopy was used to acquire metabolomics data. Clinical variables such as troponin I (TI), lactate dehydrogenase (LD), creatine kinase (CK, CK-MB, CK-MM), serum creatinine, and lipid profiles were also measured in all subjects. Metabolomic data and clinical measures were appraised separately using a chemometric approach and ROC analysis. Results The screening outcomes revealed that the pattern of methylguanidine, lactate, creatinine, threonine, aspartate, and trimethylamine (TMA), and TI, LD, CK, and serum creatinine were changed in CAD compared to NC. Statistical analysis demonstrated high precision (93.6% by NMR and 67.4% by clinical measures) to distinguish CAD from NC. Further analysis indicated that methylguanidine, arginine, and threonine, and TI, LD, and serum creatinine were significantly changed in CSA compared to MI. Statistical analysis demonstrated high accuracy (88.2% by NMR and 92.1% by clinical measures) to discriminate CSA from MI. Conclusions In contrast to other laboratory methods, ¹H NMR–based metabolomics of filtered sera appears to be a robust, rapid, and minimally invasive approach to probe CSA and MI.
... These results are in agreement with Calvert et al. [33], who reported that myocardial ischemia-reperfusion resulted in significant elevation in serum CPK-MB and troponin levels, and also with the results of Chinda et al. [34], who found significant elevation in HR and infarct size with myocardial ischemia-reperfusion. These data are consistent with Eisenman [35], who observed increased HR and increased CPK-MB levels during MI. In addition, Surawicz [36] reported that the 'T' wave was elevated in rats immediately after coronary ischemia and remained elevated for 5 h after ischemia. ...
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... 38 Myocyte injury may be caused by myocardial infarction, myocarditis, trauma, unstable agina, cardiac surgery, or other cardiac procedures. 39 Walker 40 stated that troponin I is the most sensitive and specific marker of myocardial injury, which can provide information on the relative severity, extent, or duration of myocardial injury, while Wells and Sleeper 41 considered it the "gold standard" biomarker of myocardial injury. Table 3. Comparisons between degree of inflammation, degeneration, edema, and fibrosis in the different studied group by w 2 analysis. ...
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Clozapine (CLZ) is considered the most effective drug in treatment of resistant schizophrenia. However, its cardiotoxic effect has raised concerns about its safety. Captopril is a well-known angiotensin-converting enzyme inhibitor with unique antioxidant properties. The aim of this study was to investigate the protective effect of captopril against CLZ-induced myocarditis, and since both drugs have hematotoxic effects, this study aimed to clarify the effect of their combined use on the bone marrow. The study was conducted for 4 weeks on 50 adult male albino rats divided into five groups: group I (negative control), group II (positive control), group III treated with captopril 5 mg/kg/day, group IV treated with CLZ 25 mg/kg/day, and group V treated with captopril (5 mg/kg) 1 hour before CLZ (25 mg/kg/day). CLZ group showed a significant increase in serum troponin I, marked histopathological changes, and immunohistochemical staining of DNA degradation product 8-hydroxy-2-deoxy guanosine (8-OHdG). It significantly increased malondialdehyde level and decreased glutathione peroxidase. Captopril coadministration decreased the histopathological hallmarks and biochemical marker of myocarditis and attenuated CLZ effects on the oxidative stress parameters and 8-OHdG, suggesting its protective action against CLZ-induced myocarditis. Complete blood count and bone marrow evaluation was normal indicating that captopril, in the protective dose given, didn’t increase the risk of CLZ-induced hematotoxicity
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Abstract HIV breaks down the body’s immune system and progressively leads to Acquired Immune Deficiency Syndrome, a fatal illness, prevalent more in Africa, Nigeria inclusive. Patients infected with HIV have an increased risk of developing heart disease. Information on cardiac status in HIV infected subjects in Nigeria is scanting. The study assessed the impact of HIV infection on serum Apolipoprotein and lipid profiles.A total of 390 (M = 220, F = 170) subjects were studied.The subjects were grouped based on WHO criteria for staging HIV infection Symptomatic HIV on Antiretroviral therapy (ART), Symptomatic HIV not on ART, Asymptomatic HIV subjects andHIV seronegative controls.Enzyme linked Immuno Assay (ELISA) was used for Apolipoproteins, Myoglobin and Troponin I. Spectrophotometric method was used for lipid profile and enzyme cardiac markers. The results showed significantly elevated serum levels of Apo A1, CK-T, CK-MB, but significantly lower level of total cholesterol (T-Chol), LDL, LDH and AST in male than in femalesymptomatic HIV infected subjects on ART at P<0.05.There were significantly higher serum enzyme activities of CK-T, CK-MB, levels of Apo C2, Apo E,TChol, LDL but lower serum activities of LDH, AST and HDL in male than in femalesymptomatic HIV infected subjectsnot on ART at P<0.05. The activities of CK-T, CK-MB;T-Chol, LDL, Apo C2 level were significantly higher but Apo A2, LDH and AST were significantly lower in male than in female asymptomatic HIV positive subjects studied at P<0.05.Conclusively, therewere increased levels of CK-T, CK-MB, total cholesterol, LDL, Apo C2 but lower levels of LDH and AST in male than in female HIV positive subjects studied. Key Words: Apoliporotein, lipid, HIV, CK-T, CK-MB
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The research included studying of myeloperoxidase in human serum, The normal value of myeloperoxidase activity was found (27.71±0.74 U/ml) in control group for both sexes at(19-70 year), with no sex difference, while it was affected by age and smoking. The study also showed a significant increase in myeloperoxidase activity (38.95±1.01 U/ml) in serum of atherosclerosis patients group for both sexes at (31-80 year) in comparison with control, on the other hand, myeloperoxidase activity in serum of patients group was affected by sex, age, smoking and the intake of statins. The results also indicated a significant increase in the concenteration of total cholesterol, low density lipoprotein -cholesterol, C-reactive protein and troponin. While a significant decrease in high density lipoprotein -cholesterol, total protein, albumin, globulin, chloride and arylesterease in serum of patients group in comparison with control. Correlation study was performed between the measured biochemical parameters and myeloperoxidase activity in serum by linear correlation coefficient, The results also showed that there was a significant positive correlation between myeloperoxidase activity and troponin in atherosclerosis patients. Also, the research included the isolation of myeloperoxidase from normal human serum using different biochemical techniques, including: precipitation by ammonium sulfate, dialysis, gel filtration chromatography on sephadex G-100. The results predicted that spicefic activity and the number of fold of purification were (8.865 U/ml) and (25) respectively for partially purified enzyme. Furthermore, the comparative molecular weight of the partially isolated myeloperoxidase was (151±1.8 kDa) using gel filtration chromatography. The results were predicted also that myeloperoxidase containing heam group, zinc and calcium elements, which indicated that the enzyme is glycoproteins type. The study showed that the optimum conditions of myeloperoxidase were obtained at the first minute using sodium citrate (0.1 M) as buffer at pH (5.0), at a temperature (45 ºC) and (12 mM) of ο-dianisidin as substrate. It was found that Vmax and Km have the values of (24.27 U/ml) and (2.443 mM) respectively. Ethylene diamine tetraacetic acid, sodium azide, 2-mercaptoethanol and sodium chloride showed inhibition on the activity of myeloperoxidase, where sodium azide had more inhibition in the activity and in an irreversible non competitive inhibition type.
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Despite advances in diagnosis and management, ischemic heart disease remains the leading cause of death in the USA. Serum cardiac enzymes, one of the three fundamental criteria for establishing the diagnosis of myocardial infarction, are not specific for cardiac muscle and have a narrow time-window. The recent development of monoclonal antibodies to cardiac troponin I and troponin T has resulted in cardiac-specific assays. Several published studies have documented the utility of troponin proteins in the evaluation of myocardial necrosis. A brief overview of the characteristics and clinical utility of troponin T and I is presented here.
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Context.—Emergency department (ED) overcrowding has reached crisis proportions in the United States. Many hospitals are seeking to identify process reengineering efforts to reduce crowding and ED patient length of stay (LOS). Objectives.—To investigate the impact of a point-of-care testing (POCT) satellite laboratory in the ED of a large academic medical center. Setting.—The ED of the Massachusetts General Hospital, Boston, Mass. Design and Outcome Measures.—Evaluation of physician satisfaction, turnaround time (TAT), and ED LOS before and after implementation of a POCT laboratory. ED LOS was measured by patient chart audits. TAT was assessed by manual and computer audits. Clinician satisfaction surveys measured satisfaction with test TAT and test accuracy. Results.—Blood glucose, urine human chorionic gonadotropin, urine dipstick, creatine kinase–MB, and troponin tests were performed in the ED POCT laboratory. Test TAT declined an average of 87% after the institution of POCT. The ED LOS decreased for patients who received pregnancy testing, urine dipstick, and cardiac markers. Although these differences were not significant for individual tests, when the tests were combined, the decreased LOS was, on average, 41.3 minutes (P = .006). Clinician satisfaction surveys documented equivalent satisfaction with test accuracy between the central laboratory and the POCT laboratory. These surveys also documented dissatisfaction with central laboratory TAT and increased satisfaction with TAT of the POCT program (P < .001). Conclusions.—The POCT satellite laboratory decreased test TAT and decreased ED LOS. There was excellent satisfaction with test accuracy and TAT.
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Context.—The rapid and accurate diagnosis of the etiology of chest pain is of central importance in the triage of patients presenting to emergency departments. The “first-draw” sensitivity of serum cardiac markers is known to be low on initial presentation; however, less is understood regarding the predictive value of a positive test in this situation. Objective.—To determine the ability of a critical pathway combining medical history and physical examination, electrocardiographic findings, point-of-care testing, and central laboratory data to accurately predict the presence of acute coronary ischemia. Methods.—We investigated the positive predictive value of a testing algorithm for first-draw specimens in clinical practice, combining a qualitative, point-of-care, triple-screen testing panel for cardiac markers, including myoglobin, creatine kinase–MB, and cardiac troponin I, with confirmation of the rapid assay in the central hospital laboratory by quantitative assays for creatine kinase–MB and cardiac troponin T. Results.—While a positive result on any of the individual cardiac markers of the point-of-care test had a positive predictive value for the acute coronary syndrome of only 36% (creatine kinase–MB, 41%; myoglobin, 36%; and troponin I, 65%), the positive predictive value for the diagnosis of acute coronary syndrome increased to 76% if all 3 point-of-care markers were simultaneously positive. The positive predictive value for acute coronary syndrome for a positive confirmatory result in the hospital laboratory for either creatine kinase–MB or cardiac troponin T was 61%. Among those patients with a positive marker on both the point-of-care test and the laboratory test, a careful retrospective review of the clinical history (with exclusion of patients with nonischemic cardiac pathologies and renal insufficiency) increased the positive predictive value of this algorithm to 98%. Conclusions.—Our data suggest that qualitative, point-of-care, triple-screen cardiac marker testing of patients with chest pain at initial presentation may exhibit relatively low positive predictive values. Positive predictive value can be significantly improved by rapid confirmation in the hospital laboratory and careful review of clinical findings.
Article
Background— Cardiac troponin I (cTnI) is a highly sensitive and specific marker for myocardial injury that predicts outcomes in patients with acute coronary syndromes. Cardiovascular complications are the leading cause of morbidity and mortality in patients who have undergone vascular surgery. However, postoperative surveillance with cardiac enzymes is not routinely performed in these patients. We evaluated the association between postoperative cTnI levels and 6-month mortality and perioperative myocardial infarction (MI) after vascular surgery. Methods and Results— Two hundred twenty-nine patients having aortic or infrainguinal vascular surgery or lower extremity amputation were included in this study. Blood samples were analyzed for cTnI immediately after surgery and the mornings of postoperative days 1, 2, and 3. An elevated cTnI was defined as serum concentrations >1.5 ng/mL in any of the 4 samples. Twenty-eight patients (12%) had postoperative cTnI >1.5ng/mL, which was associated with a 6-fold increased risk of 6-month mortality (adjusted OR, 5.9; 95% CI, 1.6 to 22.4) and a 27-fold increased risk of MI (OR, 27.1; 95% CI, 5.2 to 142.7). Furthermore, we observed a dose-response relation between cTnI concentration and mortality. Patients with cTnI >3.0 ng/mL had a significantly greater risk of death compared with patients with levels ≤0.35 ng/mL (OR, 4.9; 95% CI, 1.3 to 19.0). Conclusions— Routine postoperative surveillance for cTnI is useful for identifying patients who have undergone vascular surgery who have an increased risk for short-term mortality and perioperative MI. Further research is needed to determine whether intervention in these patients can improve outcome. Received June 26, 2002; revision received August 14, 2002; accepted August 16, 2002.
Article
Purpose. – Cardiac troponin I and troponin T have replaced creatine kinase MB (CK-MB) for the diagnosis of cardiomyocyte necrosis. Cardiac specificity of these new markers leads to a change in our practice.Current knowledge and key points. – Following necrosis, intracellular proteins are released into blood. This easy concept overlaps a biological complexity since troponins are released as complexes leading to various cut-off values depending on the assay used, as least for cardiac troponin I. The increase in both specificity and analytical sensitivity of these markers reached to propose a new definition of myocardial infarction. The diagnosis of acute coronary syndrome is a clinical based diagnosis, the use of troponin contributing to their classification. Finally, pathological processes leading to cardiac injury may induce an increase in the cardiac troponin level.Future prospects and projects. – Troponin standardization is a challenge for the near future leading to better follow-up of patients and comparison between cohorts.
Article
The authors report an evaluation of the Roche Cardiac Reader point-of-care troponin T assay (Roche Diagnostics, Indianapolis, IN) in an emergency department STAT laboratory. Overall, the Cardiac Reader showed excellent agreement with the Elecsys troponin T assay (Roche Diagnostics, Indianapolis, IN) (Y = 1.09X + 0.05, r = 0.96) over the range of values from 0.1 ng/ml to 2 ng/ml. The Cardiac Reader agreed with the laboratory-based assay in terms of the diagnostic classification of the patient in 96.2% of cases. Only one of the discordant results (< 1%) could be considered clinically relevant, albeit the discordance would most likely not have occurred on serial testing, as is commonly performed. These data demonstrate that the Roche Cardiac Reader troponin T assay can be performed successfully outside the laboratory in a point-of-care emergency department setting. In contrast to other point-of-care devices for testing of troponin, the Roche Cardiac Reader gives equivalent numeric values to the manufacturers clinical laboratory method. Systems available for troponin I testing at the point of care, and in the central laboratory, typically yield results that correlate, but produce different numeric and cutoff values. This may create issues when comparing emergency department point-of-care test results with serial follow-up laboratory values after patients are admitted to hospital units. Likewise, cutoff values may be different, and this requires careful consideration of the format for reporting the point-of-care test during implementation. In contrast, the Cardiac Reader troponin T system eliminates this problem and, therefore, may be easier to standardize with the clinical laboratory.
Article
The authors report an evaluation of the Roche Cardiac Reader point-of-care troponin T assay (Roche Diagnostics, Indianapolis, IN) in an emergency department STAT laboratory. Overall, the Cardiac Reader showed excellent agreement with the Elecsys troponin T assay (Roche Diagnostics, Indianapolis, IN) (Y = 1.09X + 0.05, r = 0.96) over the range of values from 0.1 ng/ml to 2 ng/ml. The Cardiac Reader agreed with the laboratory-based assay in terms of the diagnostic classification of the patient in 96.2% of cases. Only one of the discordant results (< 1%) could be considered clinically relevant, albeit the discordance would most likely not have occurred on serial testing, as is commonly performed. These data demonstrate that the Roche Cardiac Reader troponin T assay can be performed successfully outside the laboratory in a point-of-care emergency department setting. In contrast to other point-of-care devices for testing of troponin, the Roche Cardiac Reader gives equivalent numeric values to the manufacturers clinical laboratory method. Systems available for troponin I testing at the point of care, and in the central laboratory, typically yield results that correlate, but produce different numeric and cutoff values. This may create issues when comparing emergency department point-of-care test results with serial follow-up laboratory values after patients are admitted to hospital units. Likewise, cutoff values may be different, and this requires careful consideration of the format for reporting the point-of-care test during implementation. In contrast, the Cardiac Reader troponin T system eliminates this problem and, therefore, may be easier to standardize with the clinical laboratory.
Article
Following cardiac surgery, electrocardiography and creatine kinase isoenzyme MB (CK-MB) activities are of limited value in diagnosing a non-transmural infarction. With the recent availability of an assay to detect serial levels of the specific cardiocyte contractile protein troponin T the possibility has been increased of closing a diagnostic gap among cardiosurgical patients. Ninety patients with severe diffuse three-vessel disease undergoing myocardial revascularization were grouped by their postoperative electrocardiographic (ECG) findings (group I--unchanged ECG; group II--new Q-waves representing perioperative myocardial infarction (PMI)). Serial levels of troponin T and the activity of CK-MB were measured 6, 12, 24 and 48 h after aortic unclamping. The course of CK-MB activity was compared to a profile and values derived from patients with unchanged (n = 1312) or new Q-wave ECGS (n = 89). In 72 patients (80.0%) with unchanged postoperative ECG (group I) serial troponin T levels remained constantly low and reached a median peak value of 0.37 microgram/l (quartile 0.13-0.50 microgram/l) after 24 h. Serial CK-MB activities demonstrated the typical non-ischemic course with a monoexponential decline from an initial median peak value of 15.5 U/l (quartile 12.0-21.0 U/l) to 7.0 U/l (quartile 6.0-9.0 U/l). In seven patients (7.8%) with new Q-waves and a pathologic CK-MB profile (group II) troponin T reached median levels of 10.47 micrograms/l (quartile 6.34-12.50 micrograms/l) (P < 0.001 I vs II). Four of five patients with a new right bundle branch block demonstrated low troponin T levels below 1 microgram/l and a normal CK-MB profile. Among six patients with unchanged QRS-configuration and elevated troponin T levels between 0.84 and 4.99 micrograms/l CK-MB activity showed a characteristic PMI pattern in two patients. Troponin T is characterized by a very narrow margin of normal values represented by a maximum third quartile of 0.50 microgram/l. A singular value of troponin after 6 h or 24 h may be sufficient evidence to confirm the diagnosis of a PMI.
Article
Serial plasma concentrations of myoglobin, creatine kinase MB (CK-MB) isoenzyme, and cardiac troponin I (cTnI) were measured in 25 patients with a confirmed diagnosis of acute myocardial infarction (AMI), and 74 patients who were suspected of AMI but were subsequently ruled out for this diagnosis. The cutoff concentration for the cTnI assay was optimally determined to be 2.5 ng/mL. Of the three markers, myoglobin had the highest clinical sensitivity (50 percent) when blood was collected between 0 to 6 h after the onset of chest pain. Assays for all serum markers used had high clinical sensitivity (> 93 percent) 6 to 24 h after onset. The CK-MB remained highly sensitive for 48 h, while cTnI was sensitive for up to 72 h. Between 72 and 150 h, cTnI had a clinical sensitivity of 70 percent as compared to 21 percent and 18 percent for myoglobin and CK-MB, respectively. The clinical specificity of cTnI for non-AMI patients was equivalent to CK-MB and significantly higher than for myoglobin. The clinical efficiency of cTnI for all samples was better than either CK-MB or myoglobin, owing mainly to the wider diagnostic window. The specificity of cTnI for 59 patients with chronic renal failure, skeletal muscle trauma and disease was better than all of these markers including cardiac troponin T (cTnT). Results of this study show that cTnI is an effective marker for the retrospective diagnosis of AMI, and consideration should be given to its use in place of CK-MB.
Article
This study compared the diagnostic accuracy of the measurement of serum cardiac troponin I (cTnI) with creatine kinase (CK) MB mass in patients with minor myocardial injury whose measured total CK activity did not exceed twice the upper reference limit (300 U/L for men; 200 U/L for women). Forty-eight consecutive patients presenting with chest pain and with in-hospital documentation of myocardial injury were enrolled. Electrocardiogram, echocardiogram, and serial serum CK-MB mass, cTnI, and total CK were measured over 36 h after admission. Peak total CK activity was within normal limits in 28 patients (58%). The mean (+/- SD) peak CK-MB mass and cTnI concentrations were: 16.4 (11.8) micrograms/L and 132 (13.0) micrograms/L; respectively. The peak biochemical marker index (defined as CK-MB or cTnI divided by its respective upper reference limit) was significantly (P < 0.05) higher for cTnI than for CK-MB from 7 to 36 h. The clinical sensitivity for detection of myocardial injury for cTnI was 100% [95% confidence interval (CI): 87.2% to 100%], compared with 81.8% (CI: 67.3% to 91.8%) for CK-MB. Thus, cTnI was more sensitive than CK-MB mass for detection of myocardial injury in patients with small increases of total CK.