Lecture 4
Year MBBSth
(Pathology)
Cardiac Biomarkers
By
Brig (R) Prof Aamir Ijaz
MCPS, FCPS, FRCP (Edin), MCP-HPE
Professor Chemical Pathology
Modi Uddin Islamic Medical College, Mirpur AJK
Definition of Myocardial Infarction
(in 1980s)
WHO Criteria
Myocardial Infarction is diagnosed if 2 out of following 3 of
are present
1. Prolonged chest pain
2. ECG changes
3. Serum enzyme concentrations
Cardiac Markers of the 21Century
ØTroponin I Associated Markers
ØTroponin T
Ø B-type natriuretic peptide
ØMB (isoenzyme
of CK) Ø Ischemia modified albumin
ØCKMM isoforms Ø C-reactive protein
ØCKMB isoforms
ØMyoglobin
MI - diagnostics
yesterday
AST
CK
Serumconcentration
LDH
HBDH
0 1 2 3 4 5 6 7
Days after infarction
Infarction
MI-diagnostics
today
50
Multiples of upper reference value
• cTroponins
15 • Myoglobin
• CK-MB
10
5 Cut off
1 2 3 4 5 6 7 10
Infarction Days after infarction
4th Universal Definition of Myocardial Infarction
(Aug 2018)
“The term acute myocardial infarction should be used when there is
acute myocardial injury with clinical evidence of acute myocardial
ischaemia and with detection of a rise and/or fall of cardiac Troponin
values with at least one value above the 99th percentile URL and at
least one of the following:
• Symptoms of myocardial ischaemia;
• New ischaemic ECG changes or Q Waves
• • Imaging evidence of new loss of viable myocardium or new regional
wall motion abnormality in a pattern consistent with an ischaemic
aetiology”
Why demonstration of ‘rise and/or fall’ of
troponins is essential for the diagnosis of
myocardial infarction (MI)
• To distinguish MI from other cardiac conditions
• In other forms of cardiac disease, the rise in troponin
is usually constant
Acute Coronary Syndrome (ACS)
• A spectrum of conditions that occur due to acute myocardial
ischemia and/or infarction
• Result of an abrupt reduction in blood flow through the
coronary artery circulation.
Categories of ACS
• non–ST elevation (NSTE) ACS: It is further divided into
1. Unstable angina (UA) and
2. Non–ST-elevation myocardial infraction (NSTEMI).
UA is distinguished from NSTEMI by the absence of an elevation of
cardiac biomarker levels.
• ST-elevation MI (STEMI): The major discriminating feature of
STEMI is the presence of symptoms of myocardial
ischemia/injury along with persistent ECG ST-segment elevation
in addition to the presence of cardiac biomarkers.
MCQ.1 The Best Clinical Utility of Troponins is in:
a. Non-ST Elevation MI (NSTEMI)-ACS
b. STEMI-ACS
c. Type 1 MI
d. Type 2 MI
e. Unstable Angina
a. NSTEMI-ACS
Troponins
ØRegulatory proteins in
striated muscle
ØResponsible for
calcium-modulated
interaction
ØExist in a number of
isoforms
Ø Cardiac specific forms
immunologically
separable
Ø Troponin T (TpnT)
Ø Troponin I (TpnI)
What is High Sensitivity (hs)Troponin ?
The term “high-sensitivity” addresses an assay’s characteristics and not a
difference in the forms of cardiac troponin (I or T) being measured.
High Sensitivity in hsTrop means High Analytical Sensitivity and NOT high Clinical
Sensitivity
Analytical Sensitivity means the ability of test to measure the smallest quantity –
called Limit of Detection (LOD)
New generation of hs Tropinins has lower LOD i.e. these assays can measure low
concentration of troponins
Our Article Published an an Indexed Journal
MCQ 2: The biggest advantage of
Troponin over other biomarkers is:
a. Also detects LVF
b. Cardiac Specificity
c. Cost Effectiveness
d. Earlier rise
e. User Friendly analysis
b. Cardiac Specificity
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Cardiac Troponins
• Very specific for heart muscle as they are
genetically distinct
• Cardiac Troponin T (cTrop T)
• Cardiac Troponin I (cTrop I)
• Troponin C ?
Q.1 : What is the difference between
Troponin T and Troponin I
• Hardly any
• cTroponin I is claimed to be better than cTrop T in
patients with renal impairment
• cTroponin T is a propriety of Roche Diagnostics
• All other manufacturers make cTroponin I
Poor Specificity of Troponin for MI
• Very important point to be kept in mind :
• Troponin is organ specific but not disease
specific
• It is raised in any disease or manipulation in heart
Troponin Release Kinetics
ØPattern of release in MI is BIPHASIC.
ØDetectable in blood 4-12 h, similar to CKMB
ØPeaks 12-38 h
ØRemains elevated for 5-10 days
Bedside Testing or
Point of Care Testing (POCT)
Qualitative POCT Troponin-
One Line Two lines !!
• Qualitative POCT is very
commonly used in our set up
• Usually based on
“Immunochromatography
Technique” (ICT).
• One line : Negative and Two
lines Positive
• Easy, less expensive and rapid
Why “One Line Two Lines” is Bad
• Positive only when levels of
troponins are very high (Poor
Sensitivity)
• We cannot diagnose Acute MI
with qualitative tests
A Simple Question
• How can “One Line Two Lines” demonstrate
rise and / or fall ?
• It can`t !!
• So Qualitative POCT is mere wastage of resources
A Patient Safety Issue
In a Non ST Elevation MI (Non-STEMI) a negative
qualitative test can be dangerous
Say No to:
“One Line Two Line” (Qualitative POCT)
Final Words
Say No To “ONE LINE TWO LINES”
MCQ 3: A 52 years old male underwent abdominal
surgery. At 2nd post operative day, he developed some
chest discomfort, but his ECG was normal. His CK was
1755 U/L (Ref Value: < 195) and CK-MB was 56 U/L (Ref
Value: < 25).
What is the most probable cause of this enzyme
change?
a. Cardiac Failure
b. Muscular Injury due to surgery
c. Myocardial Infarction
d. Myopathy
b. Muscular Injury due to surgery
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Limitation of CKMB
ØFalse increase in surgical patients without cardiac
injury
ØFalse elevations in
Ø Skeletal muscle injury
Ø Marathon runners
Ø Chronic renal failure
Ø Hypothyroidism
ØMI detection not timely enough for thrombolytic
intervention. MB peaking takes >12h
MCQ 5: A 71 years old male was admitted in Coronary Care
Unit with suspected Congestive Cardiac Failure. The most
helpful biochemical marker for the diagnosis of heart
failure is:
a. BNP
b. Plasma Aldosterone
c. Plasma Electrolytes
d. Plasma Renin Activity
e. Troponin T
a. BNP
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Role of BNP
ØDetermination of biological standards for diagnosis,
prognosis & treatment of HF
ØB-Type Natriureteric Peptide (BNP)
ØAmino-terminal propeptide equivalent, N-terminal-
proBNP or NT–pro BNP
ØRole in diagnosis of HF
ØUseful in predicting outcomes
ØTo guide treatment out of reach for now
Carry Home Message
ØMyocardial Infarction has been redefined with inclusion of
Biomarkers (troponins) as essential component of
diagnosis
ØTroponins I & troponinT should be the cardiac markers of
choice for diagnosis, evaluation of severity and
monitoring.
ØQualitative bedside (POCT) devices (One Line Two Lines)
should NOT be used in any medical set up due to
erroneous results
ØBNP is a very useful test for the diagnosis of cardiac failure
Thank You Very Much
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Thank You
