CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 10, November 2012
AFRICA
531
Editorial
Measurement of cardiac troponins to detect myocardial
infarction using high-sensitivity assays:
South African guidelines
value above the decision limit (99th percentile value), using an
assay with an imprecision (coefficient of variation)
≤
10%
if
accompanied by a strong pre-test likelihood, the diagnosis being
based mainly on the latter.
1
Repeat measurements display the
dynamic pattern of troponin values and aid in differentiating
between acute and chronic causes of troponin elevation in the
circulation.
4
The guidelines defined for South Africa (SA)
7
differ from
those in the Consensus document.
1
They state: ‘The percentage
change (rise or fall) in hs-cT levels in two samples three hours
apart is used to establish a diagnosis of MI when the troponin
level is below the WHO cut-off. For troponin I a 50% change in
an initial value is diagnostic of MI. In the case of troponin T, a
50%
change in an initial value of
<
53,
or a 20% change in an
initial value between 53 and 100 ng/l, is diagnostic of MI.’ They
are similar to those set by the study group on biomarkers in
cardiology of the ESC Working Group on Acute Cardiac Care,
in that the 50% change rule is applied for the second sample,
9
but
they do not apply the WHO cut-off point and state as prerequisite
for rule-in that the values at three hours (and optionally at six
hours) be greater than the URI.
In the South African guidelines,
7
the WHO cut-off values are
also taken into consideration for decision making, in that values
between the URL and the WHO cut-off values are subject to
repeat measurement at three hours, the percentage change being
dependent on the first assessment value being smaller than the
WHO cut-off values. Of note is that use of change as a measure
for rule-in may increase the specificity for MI, but at the cost
of a decrease in sensitivity,
9-11
and that, as stated by Thygesen
et al
.,
1
‘
It should be clear that dynamic changes are not specific
for MI but rather are indicative of active myocardial injury with
necrosis’.
The validity of the use of the URL
12-15
as well as repeated
measurements at three hours for rule-in or rule-out of MI
3,16-18
have been substantiated in several studies. The selection strategy
for the reference population, however, markedly influences the
99
th percentile reference values for troponin assays if it does not
consider relevant demographic, biological and clinical variables
and this affects the diagnostic performance of highly sensitive
immunoassays,
4,19-21
as suggested in the SA guidelines.
7
Furthermore, inter-assay differences concerning reference
values for specific populations appear to impact on risk
stratification.
22-24
A higher cut-off point for the diagnosis on
NSTEMI may be appropriate in patients with mildly elevated
hs-TnI and without evidence for STEMI,
25
and use of absolute
change over serial measurements is suggested to perform better
and decrease time to rule-in and rule-out of NSTEMI compared
with relative change.
11,26-29
With the use of specific cardiac markers with higher sensitivity,
new perspectives have emerged on the nature of myocardial
necrosis and injury, which are associated with acute coronary
syndrome (ACS). The third universal definition of myocardial
infarction
1
now classifies myocardial infarction (MI), based
on the relevant pathology, clinical presentation, prognosis and
treatment strategy, as spontaneous MI (type 1), MI secondary
to an ischaemic imbalance (type 2), cardiac death due to sudden
fatal MI (type 3), and MI associated with revascularisation
procedures (types 4 and 5). What has also become evident is the
extent of necrosis and injury that is associated with pathologies
of other organs and conditions.
1-3
The clinical circumstances associated with elevated values
of cardiac troponin (c-Tn) due to myocardial injury have
been listed,
1
and comprise conditions related to primary
myocardial ischaemia, conditions related to supply/demand
imbalance of myocardial ischaemia, conditions not related to
myocardial ischaemia and conditions related to multi-factorial or
indeterminate myocardial injury. A shift in focus is apparent, not
only from valuing these highly sensitive cardiac biomarkers for
their exceptional diagnostic sensitivity and negative predictive
value for the diagnosis of MI, but also for their application in
ACS risk stratification.
1,4-6
Guidelines on the use of high-sensitivity cardiac troponin
(
hs-cT) markers have recently been set in the consensus statement
of the Ethics and Guidelines Standing Committee of the South
African Heart Association.
7
This editorial aims to appraise these
guidelines in the light of more recent research findings and
newer guidelines.
The committee recommends that high-sensitivity troponin
assays be widely adopted as the preferred biomarker for the
diagnosis of myocardial infarction, based on evidence of earlier
diagnosis of MI, more reliable ruling out of MI, and shortening
of the chest pain triage (to four hours compared to former
assays). All cardiac troponin measurements are to be reported
in ng/l. The first sample is to be collected on first assessment,
followed by a second sample after three hours, should the first
value be lower than the 99th percentile (URL) of a normal
reference population for the specific assay, or between the URL
and the WHO-defined URL for MI. Serial measurements are to
be reported as percentage change. A specific algorithm for both
hs-cTropT and hs-cTropI is proposed for the diagnosis of MI.
The Expert Consensus document on the third universal
definition of myocardial infarction
1
states that sample repeat
may be three to six hours later, followed by further sampling
depending on uncertainty concerning timing of the initial
symptoms and whether the injury was evolving or resolving.
4,8,9
Rule-in for MI constitutes a rise and/or fall in values, with one
