Biochemical Markers
for Diagnosis of
Myocardial Infarction
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
Biochemical Changes in Acute Myocardial Infarction
(mechanism of release of myocardial markers)
ischemia to myocardial muscles (with low O2 supply)
anaerobic glycolysis
increased accumulation of Lactate
decrease in pH
activate lysosomal enzymes
disintegration of myocardial proteins
cell death & necrosis
clinical manifestations
(chest pain)
release of intracellular
contents to blood
BIOCHEMICAL
MARKERS
ECG
changes
Diagnosis of Myocardial Infarction
1- Clinical Manifestations
2- ECG
3- Biochemical Markers
Criteria of ideal markers
for myocardial infarction
1- Specific: to myocardial muscle cells (no false positive)
2- Sensitive:
- rapid release on onset of attack (diagnose early cases)
- so, can detect minor damage
- no miss of positive cases (no false negative)
3- Prognostic: relation between plasma level & extent of damage
4- Persists longer: so, can diagnose delayed admission
6- Reliable: procedure depends on evidenced principle
5- Simple, inexpensive:
- can be performed anywhere by low costs
- no need for highly qualified personnel
7- Quick: low turnaround time
Types of Biochemical Markers
for Diagnosis of Myocardial Infarction
1- Cardiac enzymes (isoenzymes):
Total CK
CK-MB activity
CK-MB mass
LDH
AST
2- Cardiac proteins:
Myoglobin
Troponins
Cardiac Enzymes
• Total CK
(sum of CK-MM, CK-MB & CK-BB)
non specific to cardiac tissue (available also in skeletal muscles)
• CK-MB (CK-2) activity
More specific than total CK
BUT: less specific than cardiac troponin I (as CK-MB is also available in skeletal muscles)
Appears in blood: within 4 - 6 hours of onset of attack (used for early cases)
Reaches maximum peak within: 12 - 24 hours
Returns to normal: after 2 - 3 days of onset (no long stay in blood. So, not for delayed admissions)
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 skeletal muscle damage)
Cardiac Enzymes cont.
• 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 cardiac troponin I
• Relative index = CK-MB mass / Total CK X 100
more than 5 % is indicative for MI
Cardiac Enzymes cont.
• 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)
5 isomers are available, but, each predominates in a certain organ.
LD1 & LD2 predominates in heart
Detected in blood: 18-16 hours after onset of MI attacks (not for early cases)
Reaches a maximum peak level: in 48 h
Remains elevated for: 5-6 days after MI (may remain elevated up to 14 days)
Disadvantages:
A non-specific marker of as it is also elevated in diseases of liver, lung, kidney, RBCs etc
Cardiac Enzymes cont.
• Aspartate aminotransferase (AST)
A non-specific marker of MI as it appears also in liver & other organs diseases
(N.B. AST is somewhat more heart-specific than ALT)
Detected in blood: 6-12 hours after onset of MI attacks (not for early cases)
Reaches a maximum peak level: in 30 hours
Returns to normal : after 2 - 6 days after MI
Cardiac Proteins
• Myoglobin
- Non specific for cardiac tissue (as it is elevated also in skeletal muscle &
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)
Cardiac Proteins cont.
• Cardiac Troponins
Protein complex located on the thin filament of striated muscles
consists of 3 subunits: cTn T, cTn I & cTn C with different structures &
functions
cTnI & cTnT are used are biomarkers for MI diagnosis
Cardiac troponins (cTn) are different from skeletal muscle troponins
So, more specific for MI diagnosis
Cardiac Proteins cont.
• Cardiac Troponin I (cTn I)
100 % cardiac specific
With greater sensitivity for diagnosing minor damage of MI
Appears in blood: within 6 hours after onset of infarction
Reaches maximum peak: around 24 hours
Disappears from blood: after about 10 days (stays longer)
So, useful for diagnosis of delayed admission
Prognostic marker :
Matching relation between level in blood & extent of cardiac damage
Recommendations for use of biochemical markers for
diagnosis of myocardial infarction
1- Recommended for all patients complaining of chest pain (with clinical examination & ECG)
2- Sample
Type:
plasma
Timing: i. on admission
ii. serial ( at least every one hour in a period 6-9 hours)
should be referenced to admission & onset of pain
3- Test should be with low turnaround time
Less than one hour (accepted)
Less than half an hour is preferred
4- Types of Markers used:
Early markers: as Myoglobin: Appears in blood early (within less 4 fours)
BUT not specific & not persists for long period (less than 2 days)
Definitive markers: Troponin:
Appears in blood later than myoglobin (within 6 hours)
BUT 100% specific, prognostic & stays longer (one week)
5- Troponin is currently the marker of choice
should be available in all cardiac & emergency centers
(if not, CK-MB mass is the second choice)
Time Course for Biomarkers of Myocardial Infarction
Marker
Detectable
(hours)
Peak value
(hours)
Duration
(days)
cTn I
4-6
12 - 24
Up to 10
CK-MB
3 - 10
12 - 24
1.5 - 3
Myoglobin
1-4
12
1
Total CK
5 - 12
18 - 30
2-5
AST
6 - 12
20 - 30
2-6
LDH
8 - 16
30 - 48
5 - 14
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
Diagnosis of Heart Failure
b-natriuretic peptide (BNP)
• BNP is a neurohormone secreted by cardiac myocytes in response to
volume expansion & pressure overload ,
• It plays a role in circulatory homeostasis (natriuresis, diuresis &
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