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CARDIAC MARKEROF

CORONARY HEART DISEASE

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ISCHEMIC HEART DISEASE

is caused by an imbalance between the myocardial blood flow , and The metabolic demand of the myocardium.

Reduction in coronary blood flow

is related to progressive atherosclerosis with increasing occlusion of coronary arteries.

Blood flow can be further decreased by superimposed events such as :

vasospasm, thrombosis, or circulatory changes

leading to hypoperfusion.

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Factors reducing coronary blood flow include:

Decreased aortic diastolic pressure

Increased intraventricular pressure and myocardial contraction

Coronary artery stenosis, which can be further subdivided into the following etiologies:

Fixed coronary stenosisAcute plaque change (rupture, hemorrhage)Coronary artery thrombosisVasoconstriction

Aortic valve stenosis and regurgitation

Increased right atrial pressure

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KRITERIA Dx. IMA (WHO)

2 diantara :

1. chest pain khas2. perubahan ECG3. perubahan enzim jantung

The American College of Cardiology (ACC) and the European Society of Cardiology (ESC)Meredefinikan Kriteria Dx IMA :

Cardiac marker adalah yg terpenting dalam menegakkan Dx IMA

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According to these bodies, AMI is now defined :as a typical rise and fall of biochemical markers (eg, troponin, creatine kinase–MB, [CK-MB]), with at least one of the following:

Ischemic symptoms

New pathologic Q waves on ECG

Ischemic ECG changes (ST-segment elevation or depression)

Coronary artery intervention

Pathologic findings of AMI

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Creatine Kinase-MB Isoenzymes

Dx AMI :

2 serial elevations above the diagnostic cutoff level or a single result more than twice the upper limit of normal.

Although CK-MB is more concentrated in the myocardium (approximately 15% of the total CK), it also exists in skeletal muscle. The cardiospecificity of CK-MB is not 100%.

False-positive elevations occur in a number of clinical settings, including trauma, heavy exertion, and myopathy.

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CK-MB

first appears 4-6 hours after symptom onset,

peaks at 24 hours,

returns to normal in 48-72 hours.

Its value in the early and late (>72 h) diagnosis of AMI is limited. However, its release kinetics can assist in diagnosing reinfarction if levels rise after initially declining in the time period after AMI.

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Relative index, CKMB, and total CK

the ratio of CK-MB (mass)/total CK X 100 can assist the clinician in differentiating false-positive elevations of CK-MB arising from skeletal muscle.

Ratio <3 is consistent with a skeletal muscle source. Ratios >5 are indicative of a cardiac source. Ratios 3 - 5 represent a gray zone.

No definitive diagnosis can be established without serial determinations to detect a rise.The diagnosis of AMI must not be based on an elevated relative index alone. The relative index is only useful when both the total CK and the CK-MB levels are increased.

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Creatine kinase-MB isoformsCK-MB1 and CK-MB2.

CK-MB2 is the tissue form and initially is released from the myocardium after MI. It is converted peripherally in serum to the CK-MB1 isoform. This occurs rapidly after symptom onset.

analyzed using high-voltage electrophoresis. Automated analyzers with rapid turnaround times are available. The ratio of CK-MB2/CK-MB1 is calculated. Normally, the tissue CK-MB1 isoform predominates; thus, the ratio characteristically is less than 1. A result is positive if CK-MB2 is elevated and the ratio is more than 1.7

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CK-MB2

is detected in serum within 2-4 hours after onset and peaks at 6-9 hours.

It is an early marker for AMI.

sensitivity of 92% at 6 hours after symptom onset compared with 66% for CK-MB and 79% for myoglobin.

The major disadvantage of this assay is that it is relatively labor intensive for the laboratory.

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Myoglobin

an early marker of MI. It is a heme protein found in skeletal and cardiac muscle. Its low molecular weight accounts for its early-release profile. typically rises 2-4 hours after onset of infarction, peaks at 6-12 hours, and returns to normal within 24-36 hours.

Rapid myoglobin assays are available, but overall they suffer from lack of cardiospecificity. Serial sampling every 1-2 hours can increase the sensitivity and specificity. A rise or delta of 25-40% over 1-2 hours is strongly suggestive of AMI. In most studies, myoglobin only achieved a 90% sensitivity for AMI. The negative predictive value of myoglobin is not high enough to exclude the diagnosis of ACS

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Cardiac troponins

The troponins are regulatory proteins found in :skeletal and cardiac muscle.

The 3 subunits that have been identified include troponin I (TnI), troponin T (TnT), and troponin C (TnC).

the skeletal and cardiac subforms for TnI and TnT are distinct, and immunoassays have been designed to differentiate between them.

This explains the unique cardiospecificity of the cardiac troponins. Skeletal TnI and TnT are structurally different. No cross-reactivity occurs between skeletal and cardiac TnI and TnT with the current assays.

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Studies on the release kinetics of the cardiac troponins :they are not early markers of myocardial necrosis.

They appear in serum within 4-8 hours after symptom onset, (similar in timing to the release of CK-MB)however, they remain elevated for as long as 7-10 days post-MI.

An elevated troponin level enabled risk stratification of patients with ACS and identified patients at high risk of adverse cardiac events (ie, death, MI) up to 6 months after the index event.

Sensitive/cardiospecific, and provide prognostic information for patients with ACS. They have become the cardiac markers of choice for patients with ACS.

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Lactate dehydrogenase (LDH) :

The LDH has been supplanted by other tests. It begins to rise in 12 to 24 hours following MI,peaks in 2 to 3 days, gradually dissipating in 5 to 14 days.

Measurement of LDH isoenzymes is necessary for greater specificity for cardiac injury.

There are 5 isoenzymes (1 through 5). Ordinarily, isoenzyme 2 is greater than 1, but with myocardial injury, this pattern is "flipped" and

1 is higher than 2.

LDH-5 from liver may be increased with centrilobular necrosis from passive congestion with congestive heart failure following ischemic myocardial injury.

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Aspartate aminotransferas (AST)/Serum glutamic oxalo acetic acid (SGOT)

SGOT is an enzyme that is also released with myocardialInfarction

SGOT rises to a maximum at 24 hours &Declines to normal levels at about 48 hours postinfarction

However, it is not specific to cardiac disease in that it mayReflect disease of

the lungliver, orskeletal muscle

Therefore, it is not a reliable marker & is now rarely usedIn diagnosis

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What Is the Best Marker ?

The best marker depends on the time from onset of symptoms. The earliest markers are myoglobin and the CK-MB isoforms.

CK-MB and troponins are ideal in the intermediate period of 6-24 hours. (the troponins are not early markers)

Only 35% of patients with NSTEMI have (+) troponins at baseline evaluation. One of the medicolegal pitfalls for the clinician is to mistakenly rule out NSTEMI on the basis of a single negative determination of troponin in the early 3- to 6-hour time frame after symptom onset.

The troponins are recommended for evaluation of patients who present more than 24 hours after symptom onset.

Lactic dehydrogenase (LDH) isoenzymes no longer are recommended and should be abandoned.

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Base line 2-4 h 6-12 h 12-24 h > 24 h

Early(CKMB isoforms, myoglobin)

X X X

Intermediate(CK-MB, TnI, TnT) X X X X

Late(TnI, TnT)

X

[ CLOSE WINDOW ]Table

Table . Time of measurement cardiac marker

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0 24 48 72 96 120 144hours from onset of symptoms

RelativeEnzymeactivity

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5

0

TroponinCKLDHSGOT

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