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SELECTED QUOTES
CRITERIA FOR ACUTE MYOCARDIAL INFARCTION
The term myocardial infarction should be used when
there is evidence of myocardial necrosis in a clinical setting
consistent with myocardial ischemia. Under these conditions any one
of the following criteria meets the diagnosis for myocardial
infarction:
- Detection of 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 with at least one of the
following:
-
- Symptoms of ischemia;
- ECG changes indicative of new ischemia [new ST-T
changes or new left bundle branch block (LBBB)];
- Development of pathological Q waves in the
ECG;
- Imaging evidence of new loss of viable myocardium
or new regional wall motion abnormality.
- Sudden, unexpected cardiac death, involving cardiac arrest,
often with symptoms suggestive of myocardial ischemia, and
accompanied by presumably new ST elevation, or new LBBB, and/or
evidence of fresh thrombus by coronary 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.
- For percutaneous coronary interventions (PCI) in patients
with normal baseline troponin 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. A
subtype related to a documented stent thrombosis is
recognized.
- For coronary artery bypass grafting (CABG) in patients with
normal baseline troponin 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.
- Pathological findings of an acute myocardial
infarction.
BIOMARKER EVALUATION
Myocardial infarction is diagnosed when blood levels of sensitive
and specific biomarkers such as cardiac troponin or CKMB are
increased in the clinical setting of acute myocardial ischemia.
Although elevations in these biomarkers reflect myocardial
necrosis, they do not indicate its mechanism. Thus, an elevated
value of cardiac troponin in the absence of clinical evidence of
ischemia should prompt a search for other aetiologies of myocardial
necrosis.
The preferred biomarker for myocardial necrosis is cardiac
troponin (I or T), which has nearly absolute myocardial tissue
specificity as well as high clinical sensitivity, thereby
reflecting even microscopic zones of myocardial necrosis. An
increased value for cardiac troponin is defined as a measurement
exceeding the 99th percentile of a normal reference population (URL
= upper reference limit). Detection of a rise and/or fall of the
measurements is essential to the diagnosis of acute myocardial
infarction. The above-mentioned discriminatory percentile is
designated as the decision level for the diagnosis of myocardial
infarction, and must be determined for each specific assay with
appropriate quality control. Optimal precision [coefficient of
variation (CV)] at the 99th percentile URL for each assay should be
defined as £ 10 %. Better precision (CV £ 10 %) allows for more
sensitive assays. The use of assays that do not have independent
validation of optimal precision (CV £ 10 %) is not recommended.
Blood samples for the measurement of troponin should be drawn on
first assessment (often some hours after the onset of symptoms) and
6–9 h later. An occasional patient may require an additional sample
between 12 and 24 h if the earlier measurements were not elevated
and the clinical suspicion of myocardial infarction is high. To
establish the diagnosis of myocardial infarction, one elevated
value above the decision level is required. The demonstration of a
rising and/or falling pattern is needed to distinguish background
elevated troponin levels, e.g. patients with chronic renal failure,
from elevations in the same patients which are indicative of
myocardial infarction. However, this pattern is not absolutely
required to make the diagnosis of myocardial infarction if the
patient presents > 24 h after the onset of symptoms. Troponin
values may remain elevated for 7–14 days following the onset of
infarction.
If troponin assays are not available, the best alternative is
CKMB (measured by mass assay). As with troponin, an increased CKMB
value is defined as a measurement above the 99th percentile URL,
which is designated as the decision level for the diagnosis of
myocardial infarction. Gender-specific values should be employed.
The CKMB measurements should be recorded at the time of the first
assessment of the patient and 6–9 h later in order to demonstrate
the rise and/or fall exceeding the 99th percentile URL for the
diagnosis of myocardial infarction.
REINFARCTION
Traditionally, CKMB has been used to detect reinfarction. However,
recent data suggest that troponin values provide similar
information. In patients where recurrent myocardial infarction is
suspected from clinical signs or symptoms following the initial
infarction, an immediate measurement of the employed cardiac marker
is recommended. A second sample should be obtained 3–6 h later.
Recurrent infarction is diagnosed if there is a ³ 20 % increase of
the value in the second sample. Analytical values are considered to
be different if they are different by >3 SDs of the variance of
the measures. For troponin, this value is 5–7 % for most assays at
the levels involved with reinfarction. Thus, a 20 % change should
be considered significant, i.e. over that expected from analytical
variability itself. This value should also exceed the 99th
percentile URL.
DIAGNOSTIC CRITERIA FOR MYOCARDIAL INFARCTION WITH
PCI
In the setting of PCI, the balloon inflation during a procedure
almost always results in ischemia whether or not accompanied by
ST-T changes. The occurrence of procedure-related cell necrosis can
be detected by measurement of cardiac biomarkers before or
immediately after the procedure, and again at 6–12 and 18–24 h.
Elevations of biomarkers above the 99th percentile URL after PCI,
assuming a normal baseline troponin value, are indicative of
post-procedural myocardial necrosis. There is currently no solid
scientific basis for defining a biomarker threshold for the
diagnosis of peri-procedural myocardial infarction. Pending further
data, and by arbitrary convention, it is suggested to designate
increases more than three times the 99th percentile URL as
PCI-related myocardial infarction (type 4a).
If cardiac troponin is elevated before the procedure and not
stable for at least two samples 6 h apart, there are insufficient
data to recommend biomarker criteria for the diagnosis of
peri-procedural myocardial infarction. If the values are stable or
falling, criteria for reinfarction by further measurement of
biomarkers together with the features of the ECG or imaging can be
applied.
A separate subcategory of myocardial infarction (type 4b) is
related to stent thrombosis as documented by angiography and/or
autopsy. Although iatrogenic, myocardial infarction type 4b with
verified stent thrombosis must meet the criteria for spontaneous
myocardial infarction as well.
DIAGNOSTIC CRITERIA FOR MYOCARDIAL INFARCTION WITH CABG
Any increase of cardiac biomarkers after CABG
indicates myocyte necrosis, implying that an increasing magnitude
of biomarker is likely to be related to an impaired outcome. This
has been demonstrated in clinical studies employing CKMB where
elevations five, 10 and 20 times the upper limit of normal after
CABG were associated with worsened prognosis. Likewise, the
increase of troponin levels after CABG indicates necrosis of
myocardial cells, which predicts a poor outcome, in particular when
elevated to the highest quartile or quintile of the troponin
measurements.
Unlike the prognosis, scant literature exists concerning the use
of biomarkers for defining myocardial infarction in the setting of
CABG. Therefore, biomarkers cannot stand alone in diagnosing
myocardial infarction (type 5). In view of the adverse impact on
survival observed in patients with significant biomarker
elevations, this Task Force suggests, by arbitrary convention, that
biomarker values more than five times the 99th percentile of the
normal reference range during the first 72 h following CABG, when
associated with the appearance of 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, should be considered as diagnostic of a CABG-related
myocardial infarction (type 5 myocardial infarction).
DEFINITION OF MYOCARDIAL INFARCTION IN CLINICAL
INVESTIGATIONS
The Task Force strongly endorses the concept of the
same decision limit for each biomarker employed for myocardial
infarction types 1 and 2, and, likewise, the same higher three- and
five-fold decision limits in the setting of myocardial infarction
types 4a and 5, respectively. In clinical trials, as in clinical
practice, measurement of cardiac troponin T or I is preferred over
measurement of CKMB or other biomarkers for the diagnosis of
myocardial infarction. Assessment of the quantity of myocardial
damage (infarct size) is also an important trial end-point.
Although the specific measurements vary depending on the assay and
whether cardiac troponin T or I is used, in most studies troponin
values correlate better with radionuclide-and MRI-determined
infarct size than do CK and CKMB.
REFERENCES
Thygesen K, Alpert JS, White HD, on behalf of the
Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of
Myocardial Infarction. Universal Definition of Myocardial
Infarction. Circulation 2007; 116: 2634-2653
AUTHOR
Suzanne Ekelund, MSc
Senior Clinical Biochemist
Radiometer Medical ApS
Åkandevej 21
2700 Brønshøj
Denmark
Phone: +45 3827 3116
E-mail: suzanne.ekelund@radiometer.dk |
