Transcript Ischaemic Heart Disease CASE A

Ischaemic Heart Disease
CASE A
CASE A:
 Mr
HA, aged 60 years, was brought in
to A&E complaining of chest pain,
nausea and a suspected AMI.
The Biochemical Markers

Creatinine Kinase: Biochemical marker of
myocardial damage.
 CK is a ubiquitous enzyme found in nearly all
tissues including striated muscle and the brain and
this reduces its specificity as a biochemical marker
for myocardial injury.
 CK values are the first to rise after an AMI, and
the first to return to normal if no further coronary
damage occurs
CK the first to rise!
CK-MB

CK-MB: An isoenzyme of CK which is more
specific to myocardial tissue
 Remains the most widely used enzyme marker,
and is still the preferred marker for the diagnosis
of AMI
 More specific than CK for MI
 The MB fraction is found predominantly in
cardiac muscle. It is important to show both a rise
in the serum concentration of CK-MB, and a rise
in the ratio of CK-MB to total CK to diagnose MI
LDH

Lactate Dehydrogenase (LDH): Isozymes
composed of combinations of two different
subunits "H" and "M".
 Subunit "H" predominates in heart muscle LDH
which is geared for aerobic oxidation of pyruvate.
 Rises acutely on initiation of an AMI. However,
they take 2-3 days to reach maximum and thus do
not play a major role in the diagnosis of AMI.
CK INDEX

CK-Index: The ratio of CK-MB to total CK
 In AMI the value rises 5-15 folds and takes 24hrs
to reach maximum. A low percentage can suggest
the CK to be from a purely skeletal source and
therefore rule out the possibility of MI.
CASE A:
 Mr
HA, aged 60 years, was brought in
to A&E complaining of chest pain,
nausea and a suspected AMI.
CK-MB Index

[CK-MB in ng/mL] / Total CK in U/L
100
Clinical Chemistry
Hrs after
admission
CK
Normal
Range
CK-MB
LDH
(immunoassay)
CK-MB
index
60-220U/L
0-6.0ug/L
0-1.9
100-210U/L
On
admission
91
5.6
6.15
297
2 hrs
382
29
7.6
260
10 hrs
668
66.1
9.9
18 hrs
470
43.3
9.2
26 hrs
331
28.1
8.5
34 hrs
219
11.6
5.3
44 hrs
142
4.2
2.95
Consistent with AMI?
The level of CK-MB in Mr HA’s clinical
chemistry results follows the classic pattern of rise
and fall related to a cardiac event.
 The usual pattern of CK-MB levels after an AMI:
 Increase 3-10hrs after the onset of infarction
 Peak at 12-24hrs
 Return to baseline after 36-72hrs

Clinical Chemistry
CK-MB Levels over time
70
60
50
CK-MB (ug/L)
0
2
40
10
18
26
30
34
44
20
10
0
0
5
10
15
20
25
Hours after administration
30
35
40
45
50
Consistent with AMI?
Mr HA’s clinical chemistry shows the CK-MB
levels from the time of admission to A and E
 Therefore, we can reasonably conclude that the
results have shown that an AMI has occurred.
 Based on this assumption, these results are
consistent with an AMI

CK-MB Levels over time
70
60
CK-MB (ug/L)
50
40
Series
30
20
10
0
0
5
10
15
20
25
Hours after administration
30
35
40
45
50
CURRENT CRITERIA

Mr HA, aged 60 years, was brought in to
A&E complaining of chest pain, nausea and
a suspected AMI.
 Outline the current criteria for diagnosing
acute myocardial infarction
WHO CRITERIA

A clinical history of ischaemic-type chest
discomfort
 Changes on serially obtained ECG
 A rise and fall in serum cardiac markers
CASE A

Outline the current criteria for diagnosing
acute myocardial infarction and the role
played by the measurement of serum
levels of the enzymes CK-MB1 and 2 in
diagnosis of myocardial infarction. Define
the difference in measuring CK-MB activity
compared to CK-MB mass
An Ideal Marker

Present early and in high concentration in the
myocardium
 Absent from non-myocardial tissue and serum
 Rapidly released into the blood at the time of the
myocardial injury
 Creatinine kinase (CK) isoforms, CK-MB1 and
CK-MB2 has long been upheld as biochemical
standards for diagnosing AMI
Cardiac Markers

Cardiac troponin I and CK-MB1&2 and
their ratio are lab tests that have improved
the diagnostic accuracy of MI
 Other markers compared to CK-MB
Identifying Risk Factors In
ACS

Troponin I&T: are both important
establishing risk stratification of patients
with acute coronary syndrome
 Also CK-MB isoforms have a superior role
CASE A

Outline the current criteria for diagnosing
acute myocardial infarction and the role
played by the measurement of serum levels
of the enzymes CK-MB1 and 2 in diagnosis
of myocardial infarction. Define the
difference in measuring CK-MB activity
compared to CK-MB mass
CK-MB mass Vs CK-MB activity

CK-MB activity measurements only
measure enzyme catalytic activity
 CK-MB mass measurements only measure
the amount of CK-MB released regardless
of its activity
 Compare and contrast both these terms
CK-MB mass Vs CK-MB activity
CK-MB activity
 Activity is detected
using electrophoresis
and immunoinhibition,
it has limited
reliability due to
interferences
CK-MB mass
 Not subject to
interferences mentioned in
immunoinhibition
 Measure of CK-MB mass
by immunoassay
involving monoclonal
antibodies is much
reliable, sensitive and
specific under 1µg/L
CK-MB mass Vs CK-MB activity


CK-MB activity increases
in MI in a greater extent
(>6%) than in skeletal
muscle trauma (<3%)
Specific for late diagnosis
but not sensitive enough
for early use ie relatively
non-specific and requires
longer time

CK-MB mass is
increased in both
skeletal muscle trauma
and myocardial
infarction
 Specific diagnosis
marker at 6 hours of
onset
Cardiac Troponins





Troponins are complex regulatory proteins that are
tightly complexed to the contractile apparatus of
muscle cells. Different Troponins isoforms appear
in different muscle cells.
Troponin T (cardiac selective)
Troponin I (cardiac selective)
Troponin C (non-cardiac selective)
Circulating levels are normally low, but they rise
rapidly after an AMI
Advantages of Cardiac
Troponins as Biomarkers of
MI
Cardiac troponins cTnT and cTnI:
High Sensitivity
High Specificity
Remain elevated in serum for a number of
days giving it a long diagnostic window
Reference interval effectively zero giving
very little background noise
Disadvantages of Cardiac
Troponins as Biomarkers of
MI
cTnT and cTnI measured in different
laboratories show different results
Non diagnostic marker due to cardiac trauma
other than an MI.
Ischaemic heart disease can exist even in the
absence of a raised cardiac troponin level.
Cannot be used as an early marker (appear 3-6
hrs after MI)
Prolonged troponin levels do allow detection of
re-infarction

Monitoring Following
Thrombolytic Therapy With
Streptokinase.
Trials clearly show that hospital and 30-40 day
mortality are statistically related to the level of
reperfusion at 90 minutes following thrombolytic
therapy.
 Kinetics of myocardial protein appearance in
circulation, namely CK-MB, myoglobin, cTnI and
cTnT, following their release from the injured
myocardium, depend on infarct perfusion and can
be used to assess coronary reperfusion early after
administration of thrombolytic therapy.
Reperfusion Monitoring: The Use
of Myoglobin

Compared to total CK activity, cTnI and cTnT
release, myoglobin can be used very early (within
90 minutes of thrombolytic therapy) to detect
reperfusion.
 A myoglobin to total CK activity ratio of >5.0
obtained from a single sample taken at the time of
admission predicts spontaneous reperfusion 90
minutes following thrombolytic therapy.
 A single myoglobin measurement at 90 min after
the start of therapy combined with clinical
variables improve prediction of reperfusion.
Reperfusion Monitoring: The Use
of Cardiac Troponins

1.
2.
3.
Guidelines to assess reperfusion:
An increase of cTnT levels to >0.5 µg/mL
at 60 minutes following therapy.
A relative increase in cTnT levels at 90
minutes following therapy of >6.8.
A 90 minute concentration/baseline
concentration following therapy of <6.0