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www.NATFonline.org/ethrombosis.php (September, 2008)
The Universal Definition for Myocardial Infarction for the 21st
Century (Part 1)
JOSEPH S. ALPERT, MD Professor and Head, Department of Medicine; University of
Arizona Medical Center, Tucson, Arizona USA
The clinical definition of myocardial infarction (MI) is based on the clinical presentation
of the patient combined with various laboratory tests. In the recent past, clinicians
frequently defined myocardial infarction in different ways. Seeking a consistent
universal definition for MI, the four major international cardiac societies (European
Society of Cardiology, American College of Cardiology, American Heart Association,
and the World Heart Federation) recently completed a second consensus process to
define MI in a universally acceptable and standardized manner.
Myocardial infarction is defined pathologically as myocardial cell, myocyte, necrosis as
a result of prolonged ischemia. These conditions are met in the clinical setting when
the following is observed: A rise and/or fall of cardiac biomarkers, preferably
troponins, with at least one value above the 99th percentile of the upper reference limit
together with evidence of myocardial ischemia as recognized by one of the following:
symptoms of ischemia, ECG changes of new ischemia, new pathological Q waves,
new regional wall motion abnormality or imaging evidence of new loss of viable
myocardium. Myocardial infarctions are divided into 5 subtypes: 1) spontaneous, 2)
secondary, 3) related to sudden cardiac death, 4) percutaneous coronary intervention
(with a subtype of stent thrombosis) or 5) coronary artery bypass grafting. [1,2]
Introduction:
In 2000, the European Society of Cardiology (ESC) and the American College of Cardiology
(ACC) redefined criteria for the diagnosis of myocardial infarction (MI), standardizing the
criteria for older MI definitions that were based on epidemiology. The new definition of MI
was a more clinically oriented definition involving elevation of blood troponin levels in the
clinical setting of myocardial ischemia [1]. Since 2000, a number of advances occurred in the
diagnosis and management of MI. Therefore, the leadership of the ESC, the ACC and the
American Heart Association (AHA) convened, together with the World Heart Federation
(WHF), a Global Task Force whose goal was to update the 2000 consensus document. The
Global Task Force involved expert working groups in the following areas: biomarkers, ECG,
imaging, interventional cardiology, clinical investigation, and global perspectives. The
recommendations of the various working groups were co-coordinated, and an updated
consensus document was created.[2].
Definition of myocardial infarction
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Myocardial infarction is defined pathologically as myocardial cell death resulting from
ischemia. This usually occurs in the setting of coronary arterial thrombosis. In the clinical
setting these conditions can be identified when the following criteria are met: detection of a
rise and/or fall of cardiac biomarkers, preferably troponin, with at least one value above the
99th percentile of the upper reference limit (URL) together with evidence of myocardial
ischemia as recognized by at least one of the following: symptoms of ischemia, ECG
changes of new ischemia or development of pathological Q waves, or imaging evidence of
new loss of viable myocardium or new regional wall motion abnormality (Table 1) [2]
Cardiac biomarkers
Cardiac troponins (cTn) I and T are the preferred biomarkers for the diagnosis of myocardial
injury because troponins have nearly absolute myocardial tissue specificity, as well as high
sensitivity, thereby reflecting very small zones of myocardial necrosis [3]. Optimal precision at
the 99th percentile URL for each assay should be a coefficient of variation ≤10% [4, 5]. When
troponin assays are not available, the best alternative is the MB fraction of CK measured by
mass assay. As with troponin, an increased CKMB mass value is defined as a measurement
above the 99th percentile URL using gender appropriate normal ranges [6]. However, given
its greater sensitivity and specificity, troponin is definitely the preferred biomarker for the
diagnosis of MI.
Both cTn I and cTnT perform comparably in terms of diagnostic accuracy. The one difference
between these two troponin assays (I and T) is seen in patients with renal failure in whom
there are greater numbers of elevations of cTnT unrelated to myocardial ischemic necrosis as
compared with cTnI. These elevations are usually stable over time [7] and do not rise and fall
as in acute myocardial infarction. Pathologic and longitudinal clinical studies suggest that
these persistently elevated troponin values denote real cardiac abnormalities in these patients
with renal insufficiency [8]. Moreover, these troponin elevations are highly prognostic [7].
Therefore, patients with renal insufficiency who have elevated levels of cTnT require further
cardiac clinical evaluation. When patients with renal failure demonstrate the characteristic rise
and/or fall of cTnT values, even from an abnormal baseline, these individuals should be
considered to be having an acute cardiac event, and they should be assessed and treated
accordingly [9,10].
It is important for the clinician and clinical scientist to remember that many disease entities can
injure myocardium (for example, trauma, myocarditis, chemotherapeutic agents, etc.) thereby
leading to elevated blood levels of troponin. These other entities are not the result of acute
ischemic heart disease. Careful clinical evaluation should be used to prevent these patients
from being diagnosed with an acute MI (Table 2).
Classification of myocardial infarction
Myocardial infarction can be a spontaneous event related to plaque rupture, fissuring, or
dissection of an atherosclerotic plaque or, as recently described, nodular plaque rupture with
ensuing coronary arterial thrombosis; this form of infarction is classified as a type 1 MI.
Alternatively, MI can result from increased myocardial oxygen demand and/or inadequate
2
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myocardial supply of oxygen and nutrients in the setting of atherosclerotic coronary artery
disease without luminal thrombosis. This may be the result of anemia, arrhythmia, and hyperor hypotension. Vasoconstriction or arterial spasm in patients with coronary artery disease
can cause a marked reduction in myocardial blood flow and also lead to severe myocardial
ischemia and MI. This second group of entities is termed type 2 MI (Table 3) [2].
One circumstance in which biomarkers are not of value in the diagnosis of MI is when the
patient presents with a typical clinical scenario for myocardial ischemia/infarction. The patient
then dies before the physician can detect blood biomarker elevation either because blood
samples for troponin determination were not obtained, or because the patient succumbed too
soon after the onset of symptoms for troponin values to become elevated. Such patients are
designated as having a type 3 MI (Table 3) [2].
Patients with an initially normal baseline blood troponin value who develop elevated troponin
values (greater than 3 X 99th percentile URL) following a percutaneous coronary intervention
(PCI) are designated as having had an acute MI (type 4a MI ). A second category of type 4 MI
is caused by stent thrombosis (termed type 4b MI; troponin values must be above the 99th
percentile URL). Elevated troponin values (greater than 5 X 99th percentile URL) following
coronary artery bypass grafting (CABG) are defined as a type 5 MI (Table 3). [2].
Electrocardiography (Tables 4 and 5)
The ECG criteria for the diagnosis of acute myocardial infarction from the 2007 consensus
document are listed in Table 4 [2]. ST elevation is measured from the J-point. J-point
elevation in men decreases with increasing age; however, this is not the case with women in
whom J point elevation is less than in men [11, 12]. The term “posterior MI” reflecting an
infarct at base of the left ventricle is no longer recommended. It is preferable to refer to this
MI as inferobasal [13].
As shown in Table 5, Q waves or QS complexes are usually diagnostic of a prior MI[13]. ST
or T wave abnormalities by themselves are non-specific findings that may reflect myocardial
ischemia or infarction, but also may be caused by other processes, e.g., electrolyte
abnormalities, drugs, etc. However, when ST-T abnormalities occur in the same leads as Qwaves, the likelihood of MI is increased [2].
Imaging techniques
Imaging techniques can be useful in the diagnosis of MI because of their ability to
demonstrate wall motion abnormalities or myocardial perfusion deficits in the presence of
elevated cardiac biomarkers. If for some reason, biomarkers have not been measured or may
have normalized, demonstration of new loss of myocardial viability alone, in the absence of
non ischemic causes, satisfies the diagnostic criteria for MI. However, if biomarkers have
been measured at appropriate times and are normal, the results from the biomarker
determinations take precedence over the imaging criteria.
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Echocardiography is the imaging technique of choice for detecting complications of acute
myocardial infarction including myocardial free wall rupture, acute ventricular septal defect,
and mitral regurgitation secondary to papillary muscle rupture or ischemia. Unfortunately,
echocardiography cannot distinguish regional wall motion abnormalities due to myocardial
ischemia from those that result from infarction. An important role for acute echocardiographic
study or radionuclide imaging is in patients with suspected MI and a non-diagnostic ECG. A
normal echocardiogram or resting ECG-gated scintigram has a 95-98% negative predictive
value for excluding acute MI [14, 15]. In this manner, imaging techniques can be quite useful
for early triage and discharge of patients with suspected MI [16].
References:
1. The Joint European Society of Cardiology/American College of Cardiology 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. Eur Heart J 2000; 21:1502-1513; J Am Coll Cardiol 2000;36: 959969.
2. Thygesen K, Alpert JS, White HD: joint ESC/ACCF/AHA/WHF Task Force for the
Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Eur
Heart J 2007;28: 2525-2538; Circulation 2007;116: 2634-2653; J Am Coll Cardiol
2007.50:2173-2195.
3. Katus HA, Rempris A, Neumann FJ, et al. Diagnostic efficiency of troponin T
measurement in acute myocardial infarction. Circulation 1991; 83: 902-912.
4. Apple FS, Jesse RL, Newby LK, et al. National Academy of Clinical Biochemistry and
IFCC Committee for Standardization of Markers Cardiac Damage Laboratory Medicine
Practice Guidelines: Analytical issues for biochemical markers of acute coronary
syndromes. Circulation 2007; 115:e352-e355.
5. Jaffe AS, Ravkilde J, Roberts R, et al. Its time for a change to a troponin standard.
Circulation 2000; 102: 1216-1220.
6. Panteghini M, Pagani F, Yeo KT, et al. Evaluation of imprecision for cardiac troponin
assays at low-range concentrations. Clin Chem. 2004; 50:327-332.
7. Apple F, Murakami M, Pearce L, Herzog C. Predictive value of cardiac troponin I and T
for subsequent death in end-stage renal disease. Circulation 2002; 106: 2941-2945.
8. Ooi DS, Isotalo PA, Veinot JP. Correlation of antemortem serum creatine kinase,
creatine kinase-MB, troponin I, and troponin T with cardiac pathology. Clin Chem 2000;
46: 338-44.
9. Hayashi T, Obi Y, Kimura T, Iio K-I, Sumitsuji S, Takeda Y, Nagai Y, and Imai E.
Cardiac troponin T predicts occult coronary artery stenosis in patients with chronic
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The online version of this article, along with access to discussion threads on NATF’s eForum, is available at:
www.NATFonline.org/ethrombosis.php (September, 2008)
kidney disease at the start of renal replacement therapy. Nephrol Dial Transplant 2008
Apr 10. [Epub ahead of print]
10. Le Ehy, Klootwijk PJ, Weimar W, Zietse R. Significance of acute versus chronic
troponin T elevation in dialysis patients. Nephron Clin Pract 2004; 98:c87-c92.
11. Mcfarlane PW. Age, sex, and the ST amplitude in health and disease. J
Electrocardiology 2001; 34: S35-S41.
12. Bayés de Luna A, Wagner G, Birnbaum Y, et al. A new terminology for the left
ventricular walls and for the location of myocardial infarcts that present Q wave based
on the standard of cardiac magnetic resonance imaging. A statement for healthcare
professionals from a Committee appointed by the International Society for Holter and
Noninvasive Electrocardiography. Circulation 2006; 114: 1755-1760.
13. Pahlm US, Chaitman BR, Rautaharju PM, et al. Comparison of the various
electrocardiographic scoring codes for estimating anatomically documented sizes of
single and multiple infarcts of the left ventricle. Am J Cardiol 1998; 81: 809-815.
14. Saeian K, Rhyne TL, Sagar KB. Ultrasonic tissue characterization for diagnosis of
acute myocardial infarction in the coronary care unit. Am J Cardiol 1994; 74:12111215.
15. Tatum JL, Jesse RL, Kontos MC, et al. Comprehensive strategy for the evaluation and
triage of the chest pain patients. Ann Emerg Med 1997; 29: 116-125.
16. Udelson JE, Beshansky JR, Ballin DS, et al. Myocardial perfusion imaging for
evaluation and triage of patients with suspected acute cardiac ischemia: a randomized
controlled trial. JAMA 2002; 288: 2693-2700.
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The online version of this article, along with access to discussion threads on NATF’s eForum, is available at:
www.NATFonline.org/ethrombosis.php (September, 2008)
Table 1: The Universal Definition from 2007
Acute myocardial infarction-- Any one of the following criteria meets the diagnosis for
myocardial infarction:
1. Detection of elevated values of cardiac biomarkers (preferably troponin) above the 99th
percentile of the upper reference limit (URL) together with evidence of myocardial ischemia with at
least one of the following:
a) Ischemic symptoms;
b) ECG changes indicative of new ischemia (new ST-T changes or new left bundle branch
block (LBBB));
c) Development of pathological Q waves in the ECG;
d) Imaging evidence of new loss of viable myocardium or new regional wall motion
abnormality.
2. Sudden unexpected cardiac death, including cardiac arrest, with symptoms suggestive of
myocardial ischemia, accompanied by new ST elevation, or new LBBB, or definite new thrombus
by coronary angiography but dying before blood samples could be obtained, or in the lag phase of
cardiac biomarkers in the blood.
3. For percutaneous coronary interventions (PCI) in patients with normal baseline values,
elevations of cardiac biomarkers above the 99th percentile URL are indicative of peri-procedural
myocardial necrosis. By convention, increases of biomarkers greater than 3 X 99th percentile URL
have been designated as defining PCI-related myocardial infarction.
4. For coronary artery bypass grafting (CABG) in patients with normal baseline values, elevations
of cardiac biomarkers above the 99th percentile URL are indicative of peri-procedural myocardial
necrosis. By convention, increases of biomarkers greater than 5 X 99th percentile URL plus either
new pathological Q waves or new LBBB, or angiographically documented new graft or native
coronary artery occlusion, or imaging evidence of new loss of viable myocardium have been
designated as defining CABG-related myocardial infarction.
5. Pathological findings post-mortem of an acute myocardial infarction.
Prior myocardial infarction:
1. Development of new pathological Q waves with or without symptoms.
2. Imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract,
in the absence of a non-ischemic cause.
3. Pathological findings post-mortem of a healed or healing MI.
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Table 2: Elevations of troponin in the absence of overt ischemic heart
disease [2]
Cardiac contusion, including ablation, pacing, cardioversion, or endomyocardial
biopsy
Congestive heart failure - acute and chronic
Aortic dissection, aortic valve disease or hypertrophic cardiomyopathy
Tachy- or bradyarrhythmias, or heart block
Apical ballooning syndrome (Takatsubo syndrome)
Rhabdomyolysis with cardiac injury
Pulmonary embolism, severe pulmonary hypertension
Renal failure
Acute neurological disease, including stroke, or subarachnoid hemorrhage
Infiltrative diseases, e.g., amyloidosis, hemochromatosis, sarcoidosis, and scleroderma
Inflammatory diseases, e.g., myocarditis, , or myocardial extension of endo/pericarditis
Drug toxicity, e.g., adriamycin, 5-fluorouracil, herceptin, snake venoms
Critically ill patients, especially with respiratory failure, or sepsis
Burns, especially if affecting >30% of body surface area
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Table 3: Clinical classification of different types of myocardial infarction [2]
Type 1: Spontaneous myocardial infarction related to ischemia due to a primary coronary
event such as plaque erosion and/or rupture, fissuring, or dissection.
Type 2: Myocardial infarction secondary to ischemia due to either increased oxygen demand
or decreased supply, e.g. coronary artery spasm, coronary embolism, anaemia,
arrhythmias, hypertension, or hypotension.
Type 3: Sudden unexpected cardiac death, including cardiac arrest, often with symptoms
suggestive of myocardial ischemia, accompanied by presumably new STelevation,
or new LBBB, or evidence of fresh thrombus in a coronary artery by angiography
and/or at autopsy, but death occurring before blood samples could be obtained, or at
a time before the appearance of cardiac biomarkers in the blood.
Type 4a: Myocardial infarction associated with PCI;
Type 4b: Myocardial infarction associated with stent thrombosis as documented by
angiography or at autopsy.
Type 5: Myocardial infarction associated with CABG.
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Table 4: ECG manifestation of acute myocardial ischemia (in absence of LVH and
LBBB) [2]
ST elevation
New ST elevation at the J point in two contiguous leads with the cut-off points:
≥ 0.2mV in men or ≥ 0.15mV in women in leads V2-V3 and/or ≥0.1 mV in other
leads
ST depression and T wave changes
New horizontal or down-sloping ST depression ≥0.05 mV in two contiguous
leads; and/or
T inversion ≥0.1 mV in two contiguous leads with prominent R wave or R/S
ratio >1
Table 5: ECG changes associated with prior myocardial infarction [2]
Any Q wave in leads V2-V3 ≥0.02 sec or QS complex in leads V2 and V3.
Q-wave > 0.03 sec and > 0.1 mV deep or QS complex in leads I, II, aVL, aVF or V4 -V6 in any
two leads of a contiguous lead grouping (I, aVL,V6; V4-V6; II, III, aVF).
R-wave ≥ 0.04 sec in V1-V2 and R/S ≥1 with a concordant positive T-wave in the absence of a
conduction defect.
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