Tuesday, November 13, 2012

CLINICAL UTILITY OF CARDIAC BIOMARKER MEASUREMENT


Measurement of cardiac specific proteins and providing their characteristics during myocardial injury can add in the diagnosis of disease. E.g as shown in figure;

(Source: Tietz Clinical Chemistry, 4th Edition)
According to European society of cardiology/American college of cardiology (ESC/ACS) the differential diagnosis of AMI from non-AMI can be done by biochemical cardiac biomarkers specially cTnI and cTnT. The following are biochemical indicators for detecting myocardial necrosis:

1.      Concentration of cTnI and cTnT exceeding 99th percentile of the reference control group, on at least one occasion during the first 24 hour after the clinical event.

2.     CK-MB exceeding 99th percentile the reference value on two successive samples or maximal value exceeding twice the upper reference limit during first hours after the clinical event (although CK-MB should rise or fall, a rising or falling pattern of CK-MB should be considered diagnostic; values that remain elevated without change are rarely caused by MI).

3.      In the absence of troponin or CK-MB assay, total CK greater than two times the URL may be used.

To date monitoring ACS patient to assist in clinical classification, cardiac troponin is the preferred biomarker. 

(Source: Bishop's Clinical chemistry, 6th edition)
Early diagnosis of MI (≤ 6 hr) – possible with two markers CK-MB isoforms and Mb

Characteristics of Biochemical indicators during myocardial necrosis:

(Source: Tietz Clinical Chemistry, 4th Edition)
Early release, long persistence and undetectable in patient without cardiac disease has made troponin a choice of test in MI diagnosis

(Source: Tietz Clinical Chemistry, 4th Edition)

This indicates high clinical sensitivity of cardiac biomarkers after 2-8 hours of clinical event

Several markers should no longer be used to evaluate cardiac disease like AST, total CK activity, LDH, LD isoenzymes with exception of hydroxyl butyrate dehydrogenase (HBD), which is used to estimate infarct size. HBD has sequence homology to H subunit of LDH, so can be considered as LD1.

In majority of patients’ blood should be obtained for testing at hospital admission (0 hours), at 6 to 9 hours, and again at 12 to 24 hours if the earlier specimens are normal and clinical event of suspicion is high. For patient in need of early diagnosis a rapidly appearing biomarker like myoglobin has been suggested to be added to serial cardiac troponin monitoring.

Cardiac biomarkers, measures of myocardial necrosis, were prioritized for use as follows:
 
Cardiac troponin > CK-MB mass > CK-MB activity > CK. An adequate biomarker should show a rising or falling pattern (at least one sample) when tested 6 hours apart (E.g. one at 0 hour and another at 6 hour) in the setting of clinical ischemia and absence of non cardiac cause of biomarker elevation. 

A positive biomarker was defined as exceeding the 99th percentile or the lowest concentration at which a 10% CV can be demonstrated.


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