1. Biochemical Investigations In Heart Disaeses

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

3. 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

6. 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

7. 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:

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. Cardiac Proteins cytosolic protein Myoglobin
- 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)

11. Cardiac Troponins 100 % cardiac specific
Protein complex located on the thin filament of striated muscles
consists of 3 subunits: cTn T, cTnI & cTn C
with different structures & functions
cTnI & cTnT are used are biomarkers for MI diagnosis
Cardiac troponins (cTn) are different from skeletal muscle tropnins
So, more specific for MI diagnosis
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)

12. 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

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

14. 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.

15. Blood samples collected at:. Baseline (upon admission)
Blood samples collected at: * Baseline (upon admission) * Between 12 to 24 hours after the onset of symptoms

16. Time-Course of 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