Ischaemic Heart Disease CASE A

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					Ischaemic Heart Disease
        CASE A
            CASE A:

 MrHA, 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:

 MrHA, 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   CK          CK-MB           CK-MB   LDH
admission               (immunoassay)   index
Normal      60-220U/L   0-6.0ug/L       0-1.9   100-210U/L
Range
On          91          5.6             6.15    297
admission
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

                                                                                                   0
                                                                                                   2
CK-MB (ug/L)




               40
                                                                                                   10
                                                                                                   18
                                                                                                   26
               30
                                                                                                   34
                                                                                                   44

               20



               10



               0
                    0   5   10     15   20              25                30   35   40   45   50
                                             Hours after administration
      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



               50
CK-MB (ug/L)




               40

                                                                                                 Series

               30



               20



               10



               0
                    0   5   10   15   20               25               30   35   40   45   50
                                           Hours after administration
      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            CK-MB mass
                           Not subject to
 Activity is detected
                            interferences mentioned in
  using electrophoresis
                            immunoinhibition
  and immunoinhibition,
                           Measure of CK-MB mass
  it has limited            by immunoassay
  reliability due to        involving monoclonal
  interferences             antibodies is much
                            reliable, sensitive and
                            specific under 1µg/L
     CK-MB mass Vs CK-MB activity

   CK-MB activity increases       CK-MB mass is
    in MI in a greater extent       increased in both
    (>6%) than in skeletal
                                    skeletal muscle trauma
    muscle trauma (<3%)
                                    and myocardial
   Specific for late diagnosis
    but not sensitive enough        infarction
    for early use ie relatively    Specific diagnosis
    non-specific and requires       marker at 6 hours of
    longer time                     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 in different
 cTnT and cTnI measured
 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
    Guidelines to assess reperfusion:
1.   An increase of cTnT levels to >0.5 µg/mL
     at 60 minutes following therapy.
2.   A relative increase in cTnT levels at 90
     minutes following therapy of >6.8.
3.   A 90 minute concentration/baseline
     concentration following therapy of <6.0

				
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posted:9/6/2012
language:English
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