Ischaemic Heart Disease CASE A

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Ischaemic Heart DiseaseCASE A
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CASE A

• Mr HA, aged 60 years, was brought in to AE
  complaining of chest pain, nausea and a suspected
  AMI.

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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

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CK the first to rise!
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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

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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.

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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.

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CASE A

• Mr HA, aged 60 years, was brought in to AE
  complaining of chest pain, nausea and a suspected
  AMI.

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CK-MB Index

• CK-MB in ng/mL / Total CK in U/L
• 100

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Clinical Chemistry
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Consistent with AMI?

• The level of CK-MB in Mr HAs 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

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Clinical Chemistry
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Consistent with AMI?

• Mr HAs 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

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CURRENT CRITERIA

• Mr HA, aged 60 years, was brought in to AE
  complaining of chest pain, nausea and a suspected
  AMI.
• Outline the current criteria for diagnosing
  acute myocardial infarction

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WHO CRITERIA

• A clinical history of ischaemic-type chest
  discomfort
• Changes on serially obtained ECG
• A rise and fall in serum cardiac markers

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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

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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

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Cardiac Markers

• Cardiac troponin I and CK-MB12 and their ratio
  are lab tests that have improved the diagnostic
  accuracy of MI
• Other markers compared to CK-MB

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Identifying Risk Factors In ACS

• Troponin IT are both important establishing
  risk stratification of patients with acute
  coronary syndrome
• Also CK-MB isoforms have a superior role

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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

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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

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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

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CK-MB mass Vs CK-MB activity

• CK-MB activity increases in MI in a greater
  extent (6) than in skeletal muscle trauma (
• 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

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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

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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

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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

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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.

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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.

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Reperfusion Monitoring The Use of Cardiac
Troponins

• 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