Editorial
Things ain’t what they used to be: Impact of a new
definition of myocardial infarction
Harvey D. White, DSc Auckland, New Zealand
See related articles on pages 957 and 981.
In September 2000 a new definition of myocardial
infarction (MI) was promulgated by the Joint European
Society of Cardiology/American College of Cardiology
(ESC/ACC) Committee.1 The definition is based largely
on rising and falling levels of the cardio-specific bi-
omarkers, troponin T and troponin I, in the appropri-
ate clinical context.
The ESC/ACC Committee has been criticized for
changing the definition of MI, and some commentators
have said there is little justification for adopting their
recommendations at face value.2-6 The criticisms have
largely focused on 2 issues. The first is the impact on
epidemiology caused by difficulties in making compari-
sons with previous populations classified according to
a different definition. With the change in definition,
the number of patients receiving a diagnosis of MI will
rise and the case fatality rates will fall, thus it will be
difficult to compare prevalence trends over time. This
means that audits of the prevalence of MI and patient
outcomes will need to continue using previous defini-
tions for a transition period in order to obtain compar-
ative data. Notwithstanding the value of epidemiologi-
cal studies such as the Monitoring Trends and
Determinants in Cardiovascular Disease (MONICA)
Project,7 new epidemiological studies using the new
definition of MI are needed to provide comparative
data for research in future years.
The second major criticism is the lack of attention
given in the recommendations to the diagnosis of MI
in situations where troponin levels cannot be deter-
mined. The release of troponins from the myocardial
contractile apparatus in response to prolonged isch-
emia occurs slowly, and thus troponin levels in the
blood do not rise for at least 3 to 4 hours after the
onset of ischemia. The new definition of MI does not
cater for patients who present very early, before their
troponin levels have had time to rise, or who die be-
fore signs of myocardial necrosis have developed suffi-
From the Cardiology Department, Green Lane Hospital, Auckland, New Zealand.
Reprint requests: Harvey White, DSc, Cardiology Department, Green Lane Hospital,
Private Bag 92-189, Auckland 1030, New Zealand.
E-mail: harveyw@adhb.govt.nz
Am Heart J 2002;144:933-7.
Copyright 2002, Mosby, Inc. All rights reserved.
0002-8703/2002/$35.00 ⫹ 0 4/4/129780
doi:10.1067/mhj.2002.129780
ciently to be detected at autopsy. Thus there is still a
place for definitions of MI not based entirely on tro-
ponins. The diagnosis of MI should always take into
account information obtained clinically and from imag-
ing modalities such as angiography, echocardiography,
radionuclide scanning or magnetic resonance imaging,
which may show regional wall motion abnormalities
with thinning of the myocardium.1
In this issue of the Journal, Newby et al8 describe
the discussions and recommendations from a meeting
held in January 2001 to consider the implications of
the new definition. Three recommendations were
made.
1. Any elevation of creatine kinase-MB (CK-MB) or tropo-
nin is associated with a worse prognosis and should be
considered an event whether it occurs in the context of
an acute coronary syndrome, percutaneous coronary
intervention (PCI), or coronary artery bypass grafting
(CABG).
2. Continuous measures of myocardial necrosis, rather
than dichotomous measures, should be used.
3. The troponin assays currently available do not meet the
recommendations defined by the ESC/ACC Committee,
and need to be improved.
To these important and cogent recommendations I
would add 4 further comments. First, although Europe
and the United States are prominent on the interna-
tional stage, they are not the whole world. The ESC/
ACC recommendations have worldwide ramifications
(including cost implications), which should have been
considered, and the change in definition to a largely
troponin-based one may not be possible to implement
in Africa, Asia, South America, and many parts of East-
ern Europe.
Second, the emphasis on troponins at a time when
none of the available troponin assays had been shown
to fulfil the Committee’s recommendations of 10% pre-
cision and a 99th percentile coefficient of variation (ie,
the detection limit) has been problematic. Many labo-
ratories worldwide have not yet performed formal lo-
cal reference range studies to determine whether they
fulfil the recommended criteria for precision at the
detection limit. They should do so as a matter of ur-
gency, and should provide clinicians with supporting
data for the particular assay they use. It is almost 2
years since the new definition was promulgated. Tests
that are used for diagnosis and management of serious
medical conditions must be accurate, and it would
seem reasonable to set a time limit of 3 years after

934 White
publication of the ESC/ACC recommendations for as-
says to achieve the recommended level of precision.
Any assays that don’t measure up should be with-
drawn in the interests of patient care.
In an article accompanying the paper by Newby et
al,8 Apple et al9 make further comments about imple-
mentation of the ESC/ACC recommendations. They
make a number of recommendations, including using a
cut-off value of ⱕ10% imprecision (which was above
the 99th percentile of the reference range for all as-
says) until assays improve. This idea has considerable
merit. They also make recommendations regarding the
definition of MI associated with PCI, namely that an
increase above the cut-off value determined at 10%
imprecision should be considered an MI, and that an
increase of ⱖ25% in cases where the troponin level
was already increased should be defined as recurrent
injury associated with PCI.
There are now several troponin assays available (eg,
the Roche Diagnostics troponin T assay) that fulfil the
ESC/ACC recommendations (personal communication).
Several troponin I assays come close to fulfilling the
recommendations. Apart from the precision of the as-
says themselves, it will be important for individual lab-
oratories to show that they can achieve the required
standards routinely.10
Another issue is that some laboratories may assay
troponins only once a day or just several times a week.
The ACC/American Heart Association (AHA) guidelines
recommend that laboratories should provide cardiac
biomarker results within 30 to 60 minutes,11 and the
US National Academy of Clinical Biochemistry recom-
mends bedside or point-of-care testing if laboratories
cannot provide cardiac biomarker results consistently
within 1 hour.12
Third, the ESC/ACC Committee did not give any rec-
ommendations for an implementation strategy. Many
hospitals worldwide still do not perform troponin test-
ing. For example, in a recent survey, only 70% of hos-
pitals in Scotland had troponin testing available.13 Hap-
hazard introduction of the new definition has already
led to hospitals in the same community using different
criteria for the diagnosis of MI. The transition might
have been smoother if the introduction of the new
definitions had been coordinated by national cardiac
societies, the World Heart Federation and the World
Health Organization. Major educational efforts are re-
quired to educate doctors and the public that there is
now a new definition of what constitutes a heart at-
tack, and national heart foundations should take a lead-
ing role in such initiatives. Many patients will now be
told that they have had a heart attack who would not
have been diagnosed as such previously. It is impor-
tant that they are told that for most patients the future
after a heart attack is excellent.
American Heart Journal
December 2002
As the ESC/ACC Committee indicated, the new defi-
nition has had wide implications for patients and clini-
cal practice. The Committee’s recommendations affect
driving and rehabilitation guidelines; sick leave and
disability entitlements; employers’ perceptions about
employability; advice as to when patients can return to
work or fly; pilot licensing; life, health and travel insur-
ance; coding of diagnostic groups; epidemiology; clini-
cal trials; and health funding and public policy.
In New Zealand the new definitions have already
been accepted by the Land Transport Safety Authority,
which governs driver licencing. Thus patients who
have a positive troponin test (without elevation of
other myocardial proteins) after PCI or in connection
with a non-ST-elevation acute coronary syndrome are
classified in the same way and must not drive a private
vehicle for 2 weeks, and must not drive a commercial
vehicle for 4 weeks.
The psychological impact of the diagnosis of MI on
individuals and their families should not be underesti-
mated, and the response—whether conscious or sub-
conscious—will vary enormously. Of course, telling
patients that they have had a heart attack should not
be the only information given. Not all MIs are the
same,14 and the implications for social activities, em-
ployment, and patients’ prognoses will vary widely
according to the extent of myocardial necrosis, evi-
dence of inducible ischemia, predisposition to ventric-
ular arrhythmias, the severity of coronary artery dis-
ease, whether revascularization has been performed,
and the degree of impairment of left ventricular func-
tion. This information should be conveyed and dis-
cussed with patients and their families.
Fourth, the ESC/ACC Committee gave no recommen-
dations as to the definition of MI in patients undergo-
ing CABG, although a consensus conference in 1998
recommended that the CK-MB threshold should be 5
times the upper limit of normal.15 (The same confer-
ence recommended that the CK-MB threshold for PCI
should be 3 times the upper limit of normal). Defining
the troponin levels that correlate with increased risk
after CABG is a different concept than defining the
level at which to label an event “MI” based on an isch-
emic cause. In the setting of CABG, a positive tropo-
nin test signifies that myocyte necrosis has occurred,
and patients should be risk-stratified according to their
troponin level and other risk factors. There is clear
evidence that patients with increased cardiac protein
levels after CABG have worse outcomes. In the Arterial
Revascularization Therapy (ARTS) Study,16 which com-
pared multivessel stenting with CABG, elevated CK-MB
levels were detected in 30.5% of patients treated with
PCI and 62% of those treated with CABG. The 12-
month mortality rate in the latter group increased sig-
nificantly when CK-MB levels rose above 5 times nor-
mal (7% vs 0% in the 38% of patients without elevated
American Heart Journal
White 935
Volume 144, Number 6

Figure 1

Microvascular obstruction after plaque rupture. Despite recurrent micro emboli, the levels of CK-MB do not reach the diagnostic threshold,
whereas because of the long half life and higher sensitivity of the assays, the diagnostic threshold for troponin is reached. CK-MB, Creatine
kinase-MB. Adapted with permission from: Goldman BU, Christenson RH, Hamm CW, et al. Implications of troponin testing in clinical medi-
cine. Curr Control Trials Cardiovasc Med 2001;2:75-84.

CK-MB levels), and there was a trend towards a higher

Figure 2
mortality rate in those with CK-MB levels above 3
times normal (5.4%). I believe that, as with periproce-
dural events associated with PCI, events associated
with CABG should be reported separately in clinical
trials.
A rise in troponin levels in patients with non-ST-ele-
vation acute coronary syndromes clearly signifies an
increased risk of death or MI. Meta-analysis has shown
that elevated troponin levels are associated with a
9-fold increased risk of death or MI within the subse-
quent 30 days.17 Elevated troponin levels in patients
with acute coronary syndromes have a prognostic
value that is out of proportion to the extent of myo-
cyte necrosis and left ventricular impairment, and
probably indicate the occurrence of microinfarctions
due to platelet microemboli from ulcerated, complex
and unstable atheromatous coronary artery plaques
(Figure 1). Increasing risk in different clinical scenarios with the same tropo-
Various different populations of patients develop nin level. ACS, Acute coronary syndrome; CABG, coronary artery
bypass grafting; LAD, left anterior descending coronary artery; LV,
elevated troponin levels (eg, after an acute coronary
left ventricular; PCI, percutaneous coronary intervention.
syndrome, PCI, or CABG). It is possible that similar
degrees of troponin elevation are associated with simi-
lar outcomes irrespective of the etiology of myocardial
necrosis. Another possibility is that these populations
will have differing prognoses even though they have branch, may have an excellent prognosis based on fac-
the same magnitude of troponin elevation (Figure 2). tors other than those associated with myocyte necro-
For example, a patient with an occluded branch artery sis, whereas a patient presenting with a non-ST-eleva-
after PCI, such as a small diagonal or obtuse marginal tion acute coronary syndrome with a thrombus-rich,

936 White
fissured and unstable plaque in the left anterior de-
scending coronary artery is likely to have an unstable
clinical course and a poor prognosis even though the
rise in troponin levels may be no greater.
The prognostic importance of troponin elevations
after PCI was shown in the Sibrafiban versus aspirin to
Yield Maximum Protection from ischemic Heart events
post-acute corONary sYndromes (SYMPHONY) trial, in
which 82% of patients underwent PCI with stenting.
Forty-eight percent had elevated troponin I levels,
whereas only 29% had elevated CK-MB levels.18 Twen-
ty-six percent of patients who tested negative for tro-
ponins before the procedure tested positive after the
procedure, and these patients had a combined hazard
ratio (HR) for death or MI within 90 days of 4.3 (95%
CI 1.4-13.5) versus those without elevated troponin
levels. Multivariate analysis including baseline charac-
teristics and procedural variables showed that troponin
I (entered as a continuous variable) was an indepen-
dent predictor of the time to death or MI (P ⫽ .0001).
In a recent meta-analysis of 2605 patients who were
followed up for 1.5 to 77 months after PCI, those with
elevated troponin levels (measured using a variety of
troponin assays and a variety of cutpoints) after the
procedure were found to have double the rates of
mortality (HR 2.09, CI 1.42-3.08) and MI (HR 2.27, CI
1.62-3.16).19 Troponin elevations occur more fre-
quently after stenting and are higher than after PCI
without stenting, but because stenting produces better
outcomes, the risk gradient may not be so pronounced
and may be concentrated in patients with the greatest
troponin elevations.20
The mechanism for the increase in adverse events
associated with troponin elevations after PCI is un-
clear. Small myocardial scars resulting from plaque or
platelet emboli may act as a focus for arrhythmogen-
esis and sudden death. The impaired prognosis could
also be due to an underlying unifying factor, such as
inflammation.15 Alternatively, it is possible that the
troponin elevation is not the cause of a poor progno-
sis, but rather the result of diffuse coronary disease
with an increased plaque burden.
Elevated troponin levels are found in most patients
after CABG, but some patients may have only small
increases (eg, those undergoing off-pump CABG).21
Troponin levels have been shown to be superior to
CK-MB levels as a predictor of inhospital death or MI
after CABG.21 As with PCI, it is likely that outcomes
will vary according to the etiology of the troponin
rise— but whatever the cause, such a rise signifies that
myocyte necrosis has occurred, and the prognosis will
be worse than if it had not occurred. There are a num-
ber of reasons why cardiac protein levels may rise af-
ter CABG, such as ischemic causes, anesthetic factors,
atrial cannulation, aortic cross-clamping, handling of
the heart,22 suturing of heart muscle, inadequate myo-
American Heart Journal
December 2002
cardial protection, and factors related to graft patency,
including plaque and platelet embolism, spasm and
thrombosis.
Where the resources are available, troponin testing
should be considered mandatory for prognostic evalua-
tion of patients with non-ST-elevation acute coronary
syndromes, diagnosis of MI, and treatment selection
(also taking into account other clinical information and
tests).23-26 Use of the new definitions of MI may actu-
ally reduce costs because the greater precision of tro-
ponin testing for risk assessment should mean that un-
necessary hospitalization and drug usage can be
reduced in low-risk patients, while those with elevated
troponin levels should be more likely to receive appro-
priate antithrombotic therapy, revascularization,27,28
and secondary preventative measures such as aspirin
and statins.
A heart attack in 2002 is not the same as a heart at-
tack in previous years. I believe that the new defini-
tion will lead to improved patient care and conse-
quently better patient outcomes. There is much work
to be done to ensure that assays are of an appropriate
standard and to educate the public that, as the old Ted
Parsons song says, “Things ain’t what they used to be.”
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