The document discusses myocardial infarction (MI) and methods for diagnosing it in a laboratory setting. It covers the anatomy and function of the heart, signs and symptoms of MI, and several cardiac biomarkers used to detect heart muscle damage, including myoglobin, troponin I and T, CK-MB, LDH, and BNP. It explains the tissue distribution, time course of elevation, and diagnostic sensitivity and specificity of each biomarker. Together with electrocardiogram findings, cardiac biomarkers are useful for confirming MI when symptoms are unclear.

1. Dipesh Tamrakar

2. OVERVIEW
Introduction
Significance
Discussions
Conclusion

3. INTRODUCTION
Heart is a vital organ of the body.
It is a muscular pump that circulates the blood. An
adult human heart weighs between 200 and 425 grams
and is slightly larger than a fist.
In an average lifetime, a person's heart may beat more
than 3.5 billion times.
Each day, the average heart beats 100,000 times,
pumping about 7,600 liters of blood.

5.  There are 3 layers of tissue that form the heart wall.
1. Epicardium - the outer layer
2. Myocardium - the middle layer
3. Endocardium - the inner layer
 The walls of the heart are largely made from
myocardium, which is a special kind of muscle
tissue.
 This muscle is so constructed that it is able to
perform the 60 to 70 contractions which the healthy
adult human heart undergoes every minute.
 The myocardium of the heart wall is a working
muscle that needs a continuous supply of oxygen
and nutrients to function with efficiency.

7. • Infarct is an area of tissue that has died because of
lack of oxygenated blood.
• MI is due to formation of occlusive thrombus at the
site of rupture or erosion of an athernomatous plaque
in coronory artery causing necrosis.
• The MI is characterized by breathlessness, vomitting,
collapse or syncope, more severe and longer chest
pain. Generally, the pain is tightness, heaviness or
constriction.

9. SIGNIFICANCE
Painless or silent myocardial infarction is mostly
common in older or diabetic patients.
The most important factor in diagnosing and treating a
heart attack is prompt medical attention.
Signs and symptoms among patients with "possible' or
"probable' acute MI are not enough; further
investigations are necessary to rule in or rule out the
diagnosis.

10. About 20 years ago, enzyme panels were introduced to
confirm or exclude acute MI among patients.
The diagnosis for many of these can be established
with an electrocardiogram or a series of ECGs obtained
as the infarct evolves.
Enzymatic confirmations consisting of CK, SGOT,
and LDH were employed initially.
Characteristic time-dependent elevations of these
enzymes would confirm the diagnosis, and
approximate date, of a presumed acute MI.

11. They are at high risk for sudden death in the
immediate post-infarction period; if they survive, they
are at high risk for re-infarction in the future.
Failure to establish the diagnosis also precludes
medical therapy and life-style modification that
increases positive risk factors in future.
All lab determinations are subject to false-positive
and false-negative results, and iso-enzyme tests used
to diagnose acute MI.

12. DISCUSSIONS
Laboratory diagnosis based discussions:
1. Electrocardiogram:
An electrocardiogram (ECG) is a recording of the
electrical activity of the heart and its visible record.
Abnormalities in the electrical activity usually occur
with heart attacks.
It appears in 3 major parts:
P wave
Q, R, S wave
T wave

13. Characteristic changes in case of MI on the ECG,
increase or decrease of ST segment is a secure
diagnosis of heart attack can be made quickly in the
emergency room and treatment can be started
immediately.
ECG is
55 – 75 % sensitive
99 % specific

14. 2. Cardiac Markers
Proteins used to monitor damage to cardiac tissue,
typically cTnI, cTnT, CKMB, and myoglobin
These are analyze to assess the severity, trend and post-
operative risks of heart disease
Approx. 20 % MI cases are silent and about 10 % of MI
are not clearly diagnosed by ECG, are diagnosed by
these markers.

15. Cardiac markers are
1.Enzymes: CK-MB, SGOT, LDH
2.Proteins: Troponin T , Troponin I, Myoglobin
3.Inflammatory markers: CRP, Amyloid A, WBC
[>50 % cases of MI are diagnosed only by cardiac
markers]

16. 2. Cardiac Profile Test:
Group 1 test:
Blood sugar F & PP
Blood Urea Nitrogen
Serum Creatinine
Serum Electrolytes : Na and K
Tests useful to find out the possibility of disturbed
carbohydrate metabolism and existance of pre-renal
conditions.

17. Group 2 test: (cardiac risk evaluation tests)
Total Cholesterol
HDL Cholesterol
TG Cholesterol
VLDL & LDL Cholesterol
Group 3 test: (cardiac injury panal tests)
CPK-MB
SGOT
LDH
SHBD
Troponin
Myoglobin

18. A
A
A
B
C
D
A = myoglobin or CKMB isoforms
B = cardiac troponin
C = CKMB
D = cardiac troponin after
unstable angina

19. a. Myoglobin
Myoglobin is a low-molecular weight protein (about
18 KD) found in all skeletal and cardiac muscle and is
involved in oxygen binding.
 Due to its small size and cytoplasmic location, it
appears in serum rapidly after release from injured
muscle of either skeletal or cardiac muscle.
Since myoglobin is found in most tissues, it has the
least specificity of any of the cardiac markers.

20. False positive results for diagnosis of myocardial
infarction may be encountered with skeletal muscle
injury and renal failure and thus should never be used
by itself.
In MI, myoglobin is found to be:
Initial rise in: 1 – 3 hrs
Peak level in: 6 – 9 hrs
Back to normal in: 24 hrs.

21. Carbonic anhydrase 3 can be done to differentiate
skeletal injury and MI. To MI , carbonic anhydrase 3
is negative.
Rapid immunoassay can be done by using
monoclonal antibodies for its estimation.
Myoglobin normal range: <170 ng/mL (>25%
increase over 90 min. suggests AMI)

22. b. Troponin
The contractile protein of the myofibril.
Of the markers currently available, cTnI and cTnT
offer the highest degree of cardiac specificity.
In MI, the troponin is found to be:
Initial rise in: 2-4 hours
Peak level in: 10 - 24 hrs
Back to normal in : 5 – 10 days

24. Troponin is a regulatory protein complex that
regulate muscle contraction.
It is located on the thin filament of the contractile
apparatus.
It consists of 3 protein subunits:
 troponin T (binds to tropomyosin)
 troponin I (inhibits myosin ATPase) and
Troponin C (binds to calcium)

25. Unlike other cardiac markers that are used to detect
cardiac damage, cTnI and cTnT have different
isoenzymes from those found in skeletal muscle and
thus they are specific for cardiac injury.
In addition to detecting an MI, elevations of either
cTnT or cTnI have prognostic value and are
associated with future adverse cardiac events.
Quantitative and qualitative monoclonal antibody
based immunoassay can be done for cTnI in serum or
plasma or whole blood.

26. Troponin I:
Human cTnI has additional post-translational 31 a.a
residue on the amino terminal end compared with
skeletal muscle cTnI giving it unique cardiac
specificity.
cTnI values between 0.07 - 0.20 ng/mL suggest
myocardial ischemia or early infarction serial testing is
indicated. Values greater than >0.2 ng/mL are
consistent with MI.
Reference range: < 0.07 ng/mL.
For MI, after 8 hours of onset of symptoms:
90% sensitivity
85% specificity

27. Troponin T:
cTnT is encoded by different gene than encoded skeletal
muscle isoforms.
Uniqueness of this marker is provided by 11 a.a at amino
terminal residue.
Serum cardiac troponin T > 0.1 ng/mL suggests
myocardial damage, an MI.
Reference range: <0.1 ng/mL
For MI, after 8 hours after onset of symptoms:
84% sensitivity
81% specificity

28. c. Creatine Kinase (CK) or Creatinine Phosphokinase
(CPK)
CK (molecular weight 86 kilodaltons) is an enzyme
responsible for the conversion of creatine into
phosphocreatine, the energy source for muscle
contraction.
Since CK is found in all muscle tissue, elevations of the
total activity of this enzyme are not specific for cardiac
damage.
 However, CK is a dimer and there are 3 different forms
of the enzyme (isoenzymes) with varied tissue
distribution.

29. CKMM – predominent in skeletal muscle
CKMB in heart muscle makes up about 20% of the
CK activity, whereas in skeletal muscle CKMB is
generally only about 1%.
CKBB – predominent in brain tissues
In MI, CKMB is found to be:
Initial rise in: 3 - 8 hrs
Peak level in: 10 - 24 hrs
Returns to normal within 2 – 3 days.

30. Reference range: 10–13 units/L
CK/GOT ratio also helpful in diagnosis of MI. the
ration below 10 indicates MI whereas the ratio above
10 indicates muscular damage.
It is estimated by Modified Huges methods and UV-
kinetic method.

31. Table of Sensitivity and Specificity of Various
Markers of Cardiac Injury (from Wu, A.H.,
Diagnostic Enzymology in Clinical Laboratory
Medicine, 1994) specificity %
Marker 2-8
hrs
8-24 hrs 24-72 hrs 72 hrs
Myoglobin 95 75 0 0
CK-MB 60 95 98 50
Troponin 75 95 98 98

32. d. Natriuretic peptides
B-type natriuretic peptide (BNP) is secreted primarily
by the ventricular myocardium in response to wall
stress, including volume expansion and pressure
overload.
Increased BNP levels may correlate with greater
severity of myocardial ischemia.

33. BNP level is also predictive of adverse cardiac events
in patients with MI.
The 2 main biomarkers:
B-type natriuretic peptide (BNP)
amino terminal-related fragment NT-proBNP
myocardial stretch causes elevations of these peptides
which are diagnostic and prognostic in the setting of
heart failure

34. e. SGOT (Serum Glutamate Oxaloacetate
Tranasminase):
The mitochondria of heart muscles are rich in SGOT
and releases on cell distruction.
In MI, the SGOT is found to be:
 initial rise in: 3 - 8 hrs after onset of the attack
return normal in: 3 – 6 days.
It is estimated in lab by Reitman and Frankel’s
method or UV-Kinetics method.

35. f. LDH (Lactate Dehydrogenase)
It is found in cytoplasm of all cells weighing 135 KD.
The highest activity of LD are found in skeletal
muscle, liver, heart, kidney and RBC.
There are 5 isoforms of LD , composed of 4 subunits
peptides of 2 distinct types designated M (for
Muscle) and H (for Heart):
1. LD1 – HHHH : heart, kidney and RBC
2. LD2 – HHHM : RBC
3. LD3 – HHMM :Brain
4. LD4 – HMMM : Liver
5. LD5 – MMMM : Muscle

36. Cardiac muscles are rich in LD1
In MI, LD1 is found to be raised as:
Initial rise: 6 – 12 hrs
Peak level: 72 - 144 hrs
Back to normal within 8 - 14 days.
LD1 is clinically 90 % sensitive at 24 hrs of
symptoms onset.

37. The ratio of LD1/LD2 is normally <1 but in case of
MI LD1 increases over LD2 which is also called
“Flipped LD pattern”(90 % sensitive and 85 %
specific).
The estimation of LDH is done by Kings method or
UV-Kinetic method.

38. CONCLUSION
Cardiac markers are biomarkers measured to
evaluate heart function.
There should be appropriate choose of cardiac marker
depending on the initial onset of pain and its time
period.
We have to choose wisely the accurate marker on
appropriate time of diagnosis.
The MI should be diagnosed with minimum false
positive or false negative.

39. We can use different biomarkers like cardiac markers
along with other diagnostic tool ECG to diagnose MI.
We should never rely on only single test pattern.
We can use different guidelines for cardiac profile
test which are 100% specific and sensitive.
Choose of appropriate cardiac marker can be helpful
in accurate diagnosis of MI.