1. Biochemical Investigations In Heart Disaeses

2. Overview Myocardial infarction Creatine kinase (CK)/ CK-MB
Lactate dehydrogenase (LDH)
Aspartate aminotransferase (AST)
Myoglobin
Cardiac troponins I and T
Time-course of plasma enzyme changes
Natriuretic peptide

4. What is Myocardial Infarction?
Myocardial ischemia results from the reduction of coronary blood flow to an extent that leads to insufficiency of oxygen supply to myocardial tissue
When this ischemia is prolonged & irreversible, myocardial cell death & necrosis occurs ---this is defined as:
myocardial infarction is the death & necrosis of myocardial cells as a result of coronary prolonged & irreversible ischemia

5. Previously:
WHO criteria for the diagnosis of myocardial infarction ( at least 2/3):
Typical history of chest pain
Presence of ECG changes
Rise of biochemical markers
With the advent of troponins, which is more sensitive biochemical marker, new definition:

6. Acute Coronary Syndromes
Unstable Angina
Non-ST-Segment Elevation MI (NSTEMI)
ST-Segment Elevation MI (STEMI)
Similar pathophysiology Similar presentation and early management rules STEMI requires evaluation for acute reperfusion intervention
Unstable angina with or without increase of troponins
ECG : include ST elevation, and T wave inversion
The increased levels of troponins although not associated by ECG changes indicates increased risk of subsequent cardiac events

8. Types of Biochemical Markers
1- Cardiac Enzymes (isoenzymes):
Total CK
CK-MB activity
CK-MB mass
Aspartate aminotransferase (AST)
Lactate dehydrogenase (LDH)
2- Cardiac proteins:
Myoglobin
Troponins

9. Cardiac Enzymes Total CK (sum of CK-MM, CK-MB & CK-BB)
non specific to cardiac tissue (available in skeletal ms.)
CK-MB (CK-2) activity
more specific than total CK
BUT: less specific than troponin I (available in sk. Ms)
appears in blood: within 4-6 hours of onset of attack
peak: hours
returns to normal: within days (no long stay in blood)
Advantages: - useful for early diagnosis of MI
- useful for diagnosis reinfarction
Disadvantages: not used for delayed admission (more than 2 days)
not 100% specific (elevated in sk.ms damage)

10. - appears one hour earlier than CK-MB activity (more sensitive)
CK-MB mass
- appears one hour earlier than CK-MB activity (more sensitive)
- So, useful for diagnosis of early cases & reinfarction
- BUT: not for diagnosis of delayed admission cases
& less specific than troponin I
Relative index = CK-MB mass / Total CK X 100
more than 5 % is indicative for MI

11. Lactate dehydrogenase (LDH)
LDH is a tetramer, each chain may be one of two types (H,M) where LDH1 is (H4) while LD5 is (M4)
LD1 & LD2 predominates in heart and red cells
LDH increases later than CK-Mb and Ck
Reaches a max. level in 48 h
Remains elevated for 5-6 days after the MI
A non-specific marker of tissue injury:
* High levels are found in liver, lung,
kidney and other diseases

12. Aspartate aminotransferase (AST)
AST is somewhat heart-specific than ALT
A non-specific marker of MI
It appears in liver and other diseases

13. Cardiac Proteins Myoglobin cytosolic protein
- not specific for cardiac tissue (also in sk.ms. & renal tissue)
- appears in blood EARLIER than other markers (within 1-4 hours)
So, with high sensitivity
- BUT: Returns to normal in 24 hours
So, not for delayed admission cases (after one day of onset of attack)

14. Troponins Troponins are structural proteins in cardiac myocytes
Involved in the interaction between actin and myosin for contraction
Troponins are also present in cytosol of cardiac myocytes
consists of 3 subunits: cTn T, cTnI & cTn C
with different structures & functions

15. cTn( I & T) are structurally different than muscle troponins .
The existence of the cardiac –specific isoform makes them the most specific of all biochemical markers for cardiac damage. Highly specific markers of detecting MI
In human heart the cTn are largely insoluble, but 3-5% exits as a soluble cytoplasmic pool.

16. This gives the biphasic response of troponins with a rapid rise and prolonged elevation. Appears in plasma in 3-4 h after the MI
Remains elevated for up to 10 days After a MI, cytosolic troponins are released rapidly into the blood (first few hours)
Structurally bound troponins are released later for several days MI can be diagnosed several days after the onset of chest pain

17. cTnI: 100 % cardiac specific
With greater sensitivity for diagnosing minor damage of MI
Appears in blood within 6 hours after onset of infarction
peak: around 24 hours
Disappears from blood after about one week (stays longer)
So, useful for diagnosis of delayed admission cases
Prognostic marker (relation between level in blood & extent of cardiac damage)

18. Time-course of enzyme changes
Plasma enzymes follow a pattern of activities after a MI
The initial lag phase lasts for about 3 hours
Enzymes rise rapidly to peak levels in hours
The levels return to normal based on enzyme half-life
Rapid rise and fall indicates diagnostic value.

19. Time-Course of Biochemical Marker Changes
Enzyme
Detectable
(hours)
Peak value
Duration
(days)
CK-MB
3-10
12-24
1.5-3
Total CK
5-12
18-30
2-5
AST
6-12
20-30
2-6
LDH
(heart specific)
8-16
30-48
5-14
Cardiac troponins
4-6
Up to 10

20. Blood samples collected at:. Baseline (upon admission)
Blood samples collected at: * Baseline (upon admission) * Between 6 to 12 hours after the onset of symptoms

22. Diagnosis of Heart Failure
Heart failure is a complex clinical condition in which the heart ‘s ability to pump is compromised.
The prognosis is poor if untreated, with a two-year survival rate of under 50%
The diagnosis can be difficult, especially the presenting symptoms can be due to many diseases.
The definitive diagnosis is best by echocardiography ( which can be limited or delayed

23. So: B-natriuretic peptide (BNP)
It is a neurohormone secreted by cardiac myocytes in response to volume expansion and pressure overload ,
It plays a role in circulatory homeostasis ( natriuresis, diuresis and vasodilatation).
In heart failure it increases , so we can differentiate between breathlessness due to cardiac disease or pulmonary cause.
The accuracy of its measurement is greatest in patients with more severe disease and poorest in those already receiving treatment

24. Reference Book
Lecture Notes on Clinical Biochemistry by Geoffry Beckett , Simon Walker ( 7th ed.)