OVERVIEW

• Introduction
• Significance
• Discussion
• Conclusion
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 pumping about 7,600 liters of
100,000 times, blood.
• 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 fro myocardium, which is a special kind of mus
tissue.
• This muscle is so constructed that it is able perform the 60 to 70 contractions which the
healt adult human heart undergoes every minute.
• The myocardium of the heart wall is a worki muscle that needs a continuous supply of oxyg
and nutrients to function with efficiency.
• 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 coronary artery causing
necrosis.
• The MI is characterized by breathlessness, vomiting, collapse or
syncope, more severe and longer chest pain. Generally, the pain is
tightness, heaviness or constriction.
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.
• 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.
• 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.
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
• 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
2. Cardiac Markers
• Proteins used to monitor damage to cardiac tissue, typically cTnl,
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.
• 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]
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.
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
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.
• 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)
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
• 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)
• 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.
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
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
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.
• 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.
• 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.
• Table of Sensitivity and Specificity of Various Markers of Cardiac Injury
(from Wu, A.H., Diagnostic Enzymology in Clinical Laboratory
Medicine, 1994) specificity%
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.
• 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
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.
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
• 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.
• 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.
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.
• 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.