doi: 10.1111/j.1742-6723.2009.01225.
x Emergency Medicine Australasia (2009) 21, 433–434
Troponin assays: More questions than answers?
Anne-Maree Kelly
Joseph Epstein Centre for Emergency Medicine Research at Western Health, Sunshine Hospital,
St Albans, Victoria, Australia emm_1225 433..434
See also pp. 465–71
The introduction of cardiac troponin assays has revolu-
tionized the diagnosis, definition and treatment of acute
coronary syndromes (ACS). They are both highly sensi-
tive for the detection of myocardial damage and, in the
setting of chest pain, powerful prognostic indicators of
future adverse cardiac events.1 Over the decade
since their introduction, understanding of troponin has
evolved. Troponin elevation was initially thought to be
highly specific for cardiac damage. It is now increasingly
recognized that levels can be elevated in conditions other
than ACS (Table 1).2,3 In some, but not all of these, an
association with increased mortality has been shown.
Tests have also become more accurate, resulting in low-
ering of definitions for the upper limit of normal, for
example, for troponin I, from the order of 2 to 0.04 mg/L:
a 50-fold change! This has resulted in increased sensitiv-
ity for ACS, but at the expense of specificity.4,5
Concerns about diagnostic specificity and test perfor-
mance have led some ACS experts to suggest that a
threshold level of two to five times the upper limit of
normal should be used to guide therapeutic intervention,
rather than simply a level about the so-called normal
range.6 This is supported by a small retrospective study
that found that 49% of patients with an initial troponin I
in this ‘grey zone’ had a troponin rise pattern consistent
with ACS on serial testing, whereas 36% had a pattern
consistent with chronic troponin elevation without acute
myocardial damage, and 15% had a rapid rise and fall
pattern not indicative of myocardial injury.7
The findings reported by Flindell and colleagues add
to both our understanding and potentially our confusion
about what an abnormal troponin assay in the ED
means.8 Interestingly, they have looked at the signifi-
cance of an abnormal troponin assay from a fresh angle
– that of outcome of any patient who had the test, rather
Anne-Maree Kelly, MD, MClinEd, FACEM, Director.
© 2009 The Author
Journal compilation © 2009 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine
EDITORIAL
than confining their study to a chest pain or cardiac
symptom cohort. This approach has both strengths and
weaknesses. Their results clearly demonstrate a strong
relationship between an abnormal troponin level and
increased short-term mortality and hospital
re-admission. This in itself is not surprising. More chal-
lenging is the finding that, for the small number of
patients discharged from the ED with an abnormal
troponin level, short-term mortality was so high (mor-
tality 11.3% at 2 days and 19.6% at 28 days; odds ratio
compared with patients discharged with normal tropo-
nin 60.4 at 2 days and 19.4 at 28 days). The reason for
this finding remains unexplained. The authors report
that 79% of the discharged troponin-positive group had
discharge diagnoses other than ischaemic heart disease,
but do not report what they were. They also do not
report what proportion had serial biomarker testing or
the proportions with acute and chronic troponin eleva-
tion patterns.
Importantly, the research design used in the study
does not allow for individual case review, so assessment
of clinical decision-making and its relationship with
cause of death cannot be made. What proportion of
these cases truly represents missed preventable mortal-
ity remains unanswered. We also need to put these
alarming numbers in perspective. The discharged
troponin-positive group represents 0.92% of patients
discharged from the ED and 0.22% of the total sample
of 73 965 presentations.
The authors make a case for hospital admission for
all patients with an abnormal troponin, irrespective of
cause, on the basis of potentially preventable mortality.
Hospital admission of itself does not ensure adequate
assessment or management of patients. Indeed, a
narrow focus on an abnormal troponin as potentially
 A-M Kelly

Table 1. Non-ACS causes of troponin elevations2,3
Acute rheumatic fever
Cardiac contusion
Cardiac infiltrative disorders
Cardiac transplantation
Chemotherapy
Chronic renal insufficiency
Congestive cardiac failure
Coronary vasospasm
Direct current cardioversion
Emphysema (COAD)
Envenomation (e.g. jellyfish, scorpion)
Heterophile antibody
Hypotension
Hypovolaemia
Idiopathic
Ingestion of sympathomimetic agents
Intracranial haemorrhage or stroke
Left ventricular hypertrophy
Myocarditis/pericarditis
Physical exertion
Polymyositis/dermatomyositis
Pulmonary embolism
Pulmonary hypertension
Sepsis/ systemic inflammatory response syndrome
Seropositive rheumatoid arthritis
Supraventricular tachycardia/atrial fibrillation
ACS, acute coronary syndrome; COAD, chronic obstructive
airways disease.
indicating ACS might result in inappropriate investiga-
tions or treatment, at risk to the patient and cost to
health services. Perhaps of more concern, it could also
result in a delay to appropriate treatment for the
patient’s condition.
What is required is appropriate clinical assessment,
serial biomarker assays (if indicated) and a manage-
ment plan tailored to the patient’s condition. The
study’s results cannot tell us one way or the other
whether appropriate assessments were made in the
cases in question, or had the patients been admitted
whether a different outcome might have occurred. A
significant proportion of troponin-positive patients, par-
ticularly those with chronic troponin elevations, might
be quite appropriately managed in the community. This
does not underplay their mortality risk. Rather, it
accepts that these patients have chronic illnesses requir-
ing long-term supervision. The study also does not tell
us what proportion of patients chose to leave hospital
against medical advice.
Studies such as this are powerful tools to alert clini-
cians to potential problems in systems of care. Their
weakness is the inability to provide data about the con-
tributing factors to the outcome found. They are a start-
ing point. The hypotheses they raise, in this case that
there is preventable mortality associated with a positive
troponin level in patients discharged from the ED,
require detailed analysis at the case level to confirm or
refute the hypothesis, and to identify improvements to
systems of care. We need to understand ‘why’ if we are
going to fix it.
The troponin story, particularly from the emergency
medicine perspective, is far from over. Debate continues
about the significance and management of troponin
levels in the one to five times upper limit of normal zone.
The use of troponin for risk stratification of conditions
other than ACS is also under active exploration. Timing
of serial troponin assays is in flux as more sensitive
tests become more widely available. And research con-
tinues to identify even better biomarkers for identifica-
tion of ACS. Watch this space!
References
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434 © 2009 The Author

Journal compilation © 2009 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine