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Editorial
A Call for Universal Definitions in Cardiovascular Disease
Joseph S. Alpert, MD; Kristian Thygesen, MD, DSc
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that could be used to correct the gap between therapeutic achievements and diagnostic advances. The task force was successful in
creating such a document, which was published simultaneously in
the European Heart Journal and the Journal of the American
College of Cardiology.1 Since the publication of this report, which
emphasized the use of newer, highly sensitive and specific biomarkers of myocardial cell necrosis in the diagnosis of MI, many
investigators have explored the implications of the revised definition
of MI compared with older, more traditional (and less specific)
diagnostic criteria.2–10 Most of these studies have demonstrated that
the new biomarker-based definition of MI resulted in an increased
number of patients identified as having had an MI. This is, of
course, not surprising, because the new biomarker used, troponin, is
considerably more sensitive and more specific than biomarkers such
as total creatine kinase (CK) and its isoform, CK-MB, that had been
used routinely before the advent of troponin assays. Because the
new troponin assay identified smaller infarcts than did CK-MB, it
was predicted early on that the short-term prognosis for patients
with such troponin-positive, CK-MB–negative infarcts would be
better than that for patients with both positive troponin and positive
CK-MB measurements.5
This increase in the number of patients labeled with the
disease entity “myocardial infarction” presents clinical and
investigative cardiologists with a number of conundrums. For
example, a patient who formerly would have been discharged
from the hospital with a diagnosis of angina or even unstable
angina now falls under the diagnostic rubric of MI. The latter
diagnosis has important psychological and social implications
for the patient. Depending on the patient’s employment, certain
careers may be interdicted by a diagnosis of MI. Thus, commercial or military jet pilots may be precluded from returning to
work. Driving or flying licenses may be temporarily suspended.
The specter of disability may be raised by the patient, his or her
family members, or an employer. All of these factors can also
bring about major psychological distress for the patient. Indeed,
post-MI depression and sexual dysfunction have been reported
commonly in patients after a recent MI. Further controversy has
been generated by the observation that a sizable number of
patients develop elevated blood troponin values after successful
percutaneous coronary intervention (PCI). Given the widespread
use of PCI, evidence of postprocedural myocardial cell necrosis
is of great concern to cardiologists, patients, and, of course, in
our society, civil liability attorneys. The first task force assembled to draft a universal definition of MI was cognizant of this
potentially controversial outcome, ie, a sizeable number of
patients undergoing PCI would be labeled as having had a
postprocedural MI. The challenge of this aspect of the new
definition for MI remains a conundrum to this day.
To seek a resolution to the post-PCI difficulty just elucidated,
as well as to strengthen and clarify a number of the points made
in the original redefinition-of-MI document, a second task force
was convened in 2004 to rework, clarify, and expand on the
efining concept or object enables humans to communicate effectively with each other concerning that defined
entity. Medicine has struggled through its long history
to define accurately the various diseases that are a daily component of the human condition. Accurate, clear, and easily
interpreted definitions of a disease entity allow physicians to
communicate among themselves and ultimately to explain to
patients the implications of the specific conditions from which
they suffer. The clinical scientist also requires an accurate
definition of a specific disease. Often, a checklist is used to assist
the investigator in identifying patients with the specific illness
that is being studied. If the clinical scientist’s diagnostic criteria
are accurate and reproducible, then similar patients with that
disease entity can be entered into the clinical trial, the results of
which may be generalized for the management of other patients
who satisfy the same disease criteria. Furthermore, under favorable circumstances, results from one clinical trial can be compared and even combined with the results of other trials, as long
as the same disease definition and criteria were used in the
comparative investigations.
Article p 790
Unfortunately, the ideal world of a universally understood and
applied definition does not exist in the domain of acute myocardial
infarction (MI). Over the many years that clinical research has been
performed on patients with acute MI, different definitions using
contemporary diagnostic tools have been used, and consequently it
is often a challenge to compare the “apples” in 1 study to the
“oranges” in another. Similar problems arise in the arena of public
health statistics because physicians use different algorithms to
define MI in the clinical setting, leading to inaccuracies when public
health data are collated from discharge summaries. Thus, studies
involving large databases that use hospital discharge diagnoses can
contain significant inaccuracies because different physicians have
used different definitions of MI.
In an attempt to improve the accuracy of the diagnosis of MI by
physicians and to make it simpler to compare results in future MI
clinical trials, a multinational task force met in 1999 under the
auspices of the European Society of Cardiology and the American
College of Cardiology. The goal of this task force was to develop a
simple, clinically oriented, universal definition for MI that could be
used both in daily clinical practice and in clinical investigation and
The opinions expressed in this article are not necessarily those of the
editors or of the American Heart Association.
From the University of Arizona College of Medicine, Tucson, Ariz
(J.S.A.), and Aarhus University Hospital, Aarhus, Denmark (K.T.).
Correspondence to Joseph S. Alpert, MD, Department of Medicine,
University of Arizona Health Science Center, 1501 N Campbell Ave,
#6334, Tucson, AZ 85724. E-mail [email protected]
(Circulation. 2006;114:757-758.)
© 2006 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
DOI: 10.1161/CIRCULATIONAHA.106.648030
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758
Circulation
August 22, 2006
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original redefinition. The final report of this second task force for
an expanded redefinition of MI is anticipated during 2007. The
new report will expand the criteria for defining an MI by adding
new material on ECG criteria, imaging modalities, the patient
who presents with sudden death as the initial manifestation of his
or her infarct, and finally, implications of the redefinition for
developing countries. The question of how to label small
elevations in blood troponin values that occur after PCI remains
controversial. Most of the delegates on the second task force
favored calling these tiny, procedure-related episodes of myocardial injury true infarcts because they occurred in the setting of
recognizable coronary arterial ischemic interventions. However,
it was believed that these PCI-related events should be classified
as infarcts distinct from the spontaneous or “wild-type” MI that
usually presents with the traditional clinical scenario of substernal chest discomfort accompanied by ischemic ECG alterations.
Given the continuing interest, discussion, and debate surrounding
the redefinition of MI, the prospective investigation by Roger and
colleagues11 from the Minnesota Mayo Clinic, published in this
issue of Circulation, is of considerable scientific and clinical import.
These investigators used several meticulously standardized definitions of MI, including that suggested by the first task force for the
revision of the definition. Their carefully done comparison involved
1851 patients with the after-discharge diagnoses of acute and old
MI, unstable angina, coronary heart disease, angina pectoris, and
other forms of ischemic heart disease. After informed consent was
obtained, each patient had at least 1 and often serial determinations
of blood troponin, CK, and CK-MB. The biochemical data were
correlated with clinical information and with short-term (30-day)
follow-up.
As expected, the new (troponin) definition of MI identified
substantially more patients with ischemic myocardial necrosis than
did CK alone or CK combined with CK-MB. Depending on the
level of troponin selected as the cutoff point beyond which MI was
diagnosed, as well as on the number of samples taken and the
comparator used, the percentage increase in the number of infarcts
diagnosed by troponin alone ranged from 35% to 112%. In all
subsets, the number of infarcts identified by the troponin definition
was substantially larger than the number of infarcts that would have
been identified by CK or CK-MB determinations. Equally interesting was a much smaller but noticeable group of patients who were
diagnosed as having had an MI by elevated CK-MB measurements
in the face of normal troponin values. Clearly, this small but
clinically important group of patients was falsely diagnosed as
having had an infarct by the CK-MB criterion. This observation
underscores the fact that troponin analysis increases both sensitivity
and specificity of infarct diagnosis.
Patients with troponin-positive infarcts were older, more
likely to be women, and less likely to have clinically evident left
ventricular failure than the CK-positive or CK-MB–positive
patients. In addition, troponin-positive patients were less likely
to experience chest discomfort suggestive of ischemia. The
overwhelming majority (94%) of troponin-positive infarct patients had non–ST-elevation MI. Many of the patients with
troponin-positive but CK-negative or CK-MB–negative infarcts
were discharged with the diagnosis of unstable angina. Indeed,
fewer than half of the patients with infarcts diagnosed solely on
the basis of an abnormal troponin measurement received a
discharge diagnosis of MI. Finally, the prognosis of patients with
infarcts diagnosed solely by abnormal troponin values was better
at 30 days (5% mortality) than patients with positive CKdetermined or CK-MB– determined MI (11% mortality).
There are a number of important implications of this carefully
done prospective, observational trial. First, the new troponinbased definition of MI has yet to be accepted and applied by
many clinicians. Second, there are a substantial number of
patients with quite small infarcts who can only be identified by
highly sensitive and specific troponin measurements. These
latter patients tend to be older women with less reported chest
discomfort and with a better short-term prognosis than individuals who are found to have elevated CK-MB values. Presumably, the better short-term prognosis is the result of the smaller
size of the troponin-diagnosed infarcts. It is the fervent hope of
the authors of this editorial that, after the publication during 2007
of the new and more thoroughly revised definition of MI that
will result from the current deliberations of the second task force,
the suggested redefinition of MI will be universally used.
Disclosures
Dr Alpert serves as a consultant for Sanofi-Aventis, Novartis, and
Exeter Communications. Dr Thygesen serves as a consultant for
Sanofi Aventis, Servier, Pfizer, and Medtronic. Neither author
consults or receives any remuneration from companies involved in
the manufacture or sale of equipment, chemicals, etc, used in
diagnostic testing for patients with possible myocardial infarction,
the topic of the editorial.
References
1. Alpert JS, Thygesen K; on behalf of the Joint ESC/ACC Committee. Myocardial
infarction redefined: a consensus document of The Joint European Society of
Cardiology/American College of Cardiology Committee for the Redefinition of
Myocardial Infarction. J Am Coll Cardiol. 2000;36:959–969.
2. Pell JP, Simpson E, Rodger JC, Finlayson A, Clark D, Anderson J, Pell
AC. Impact of changing diagnostic criteria on incidence, management,
and outcome of acute myocardial infarction: retrospective cohort study.
BMJ. 2003;326:134 –135.
3. Ferguson JL, Beckett GJ, Stoddart M, Walker SW, Fox KA. Myocardial
infarction redefined: the new ACC/ESC definition, based on cardiac troponin,
increases the apparent incidence of infarction. Heart. 2002;88:343–347.
4. Trevelyan J, Needham EW, Smith SC, Mattu RK. Impact of the recommendations for the redefinition of myocardial infarction on diagnosis and
prognosis in an unselected United Kingdom cohort with suspected cardiac
chest pain. Am J Cardiol. 2004;93L:817– 821.
5. Birkhead JS, Norris RM. Redefinition of myocardial infarction. Lancet.
2001;358:764.
6. Meier MA, Al-Badr WH, Cooper JV, Kline-Rogers EM, Smith DE, Eagle
KA, Mehta RH. The new definition of myocardial infarction: diagnostic
and prognostic implications in patients with acute coronary syndromes.
Arch Intern Med. 2002;162:1585–1589.
7. Koukkunen H, Penttila K, Kemppainen A, Pentilla IL, Halinen MO,
Rantanen T, Pyorala K. Differences in the diagnosis of myocardial
infarction by troponin T compared with clinical and epidemiological
criteria. Am J Cardiol. 2001;88:727–731.
8. Kontos MC, Fritz LM, Anderson FP, Tatum JL, Ornato JP, Jesse RL.
Impact of the troponin standard on the prevalence of acute myocardial
infarction. Am Heart J. 2003;146:446 – 452.
9. White HD. Things ain’t what they used to be: impact of a new definition
of myocardial infarction. Am Heart J. 2002;144:933–937.
10. Amit G, Gilutz H, Cafri C, Wolak A. What have the new definition of
acute myocardial infarction and the introduction of troponin measurements done to the coronary care unit? Impacts on admission rate,
length of stay, case mix, and mortality. Cardiology. 2004;102:171–176.
11. Roger VL, Killian JM, Weston SA, Jaffe AS, Kors J, Santrach PJ,
Tunstall-Pedoe H, Jacobsen SJ. Redefinition of myocardial infarction: prospective evaluation in the community. Circulation. 2006;114:790–797.
KEY WORDS: Editorials
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myocardial infarction
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coronary disease
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diagnosis
A Call for Universal Definitions in Cardiovascular Disease
Joseph S. Alpert and Kristian Thygesen
Circulation. 2006;114:757-758
doi: 10.1161/CIRCULATIONAHA.106.648030
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
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