thrombolysis for AMI

see also thrombolytics, acute myocardial infarction (AMI/STEMI/NSTEMI)

• NB. if coronary re-perfusion is indicated, percutaneous coronary intervention (primary PCI or “hot angioplasty”) is usually the preferred option if available within 2 hours
• NB. acute AMI warranting emergency coronary re-perfusion Rx defined as:
  • chest pain consistent with ischaemia lasting > 20mins, not relieved by S/L nitrates, and,
  • ECG criteria:
    • ST elevation >= 2mm in >= 2 contiguous chest leads, or,
    • ST elevation >= 1mm in >= 2 contiguous limb leads, or,
    • new LBBB
    • see also: ECG Diagnosis of AMI
• NB. resolution of pain does NOT mean that coronary re-perfusion is no longer indicated!!!!
• coronary re-perfusion should still be considered as long as ECG criteria persist and time since onset of pain is still within criteria
• NB. coronary re-perfusion should still be considered in pts with evolving infarcts up to 24hrs from onset of chest pain if there is evidence of on-going ischaemia
  • ie. ongoing chest pain with ST elevation
  • coronary re-perfusion in this circumstance is based on risk vs benefit for individual patient
  • benefit greatest if anterior AMI & those with evidence of cardiac failure

• depends upon consideration of:
  • time from onset of symptoms
  • risk of complications from STEMI
  • risk of bleeding from thrombolysis - see thrombolytics
  • time to transfer to a cath lab
• consider thrombolysis (aim to give within 30min of arrival) if no C/I and:
  • onset of pain is within 12 hours AND delay to PCI > 2hrs, or,
  • onset of pain 12-24hrs with continued pain or ECG changes AND PCI unavailable

• cardiogenic shock or acute severe cardiac failure
• failed re-perfusion or re-occlusion
• as part of an invasive strategy in stable patients for PCI 3-24hrs after thrombolysis

• limited applicability - only 15-25% eligible
• failure to achieve infarct-related artery patency (15-40%)
• presence of high grade stenosis after successful thrombolysis (75-80%)
• immediate re-occlusion & recurrent ischaemia (15-20%)
• serious bleeding complications: 0.5-1.0% risk of haemorrhagic stroke
• poor results in certain subgroups:
  • those with increased risk of bleeding
  • elderly
  • cardiogenic shock
  • previous bypass graft surgery

• seminar article in Lancet April 18, 1998 vol 351(9110)
• the only indicators that are of some use in early detection of successful thrombolysis is:
  • abrupt cessation of chest pain predicts reperfusion
    • sens. 66-84%, spec. < 30%
    • only occurs in 30-50% of pts
  • resolution of ST elevation on 12 lead ECGs at 40min & 120min after commencement of thrombolysis
    • 25-50% fall either in:
      • sum of all leads with ST elevation, or,
      • single worst lead
    • sensitivity 52-97%, spec. 43-88%
    • 30day mortality rates: <30% fall in ST ⇒ 18%; 30-70% fall ⇒ 5%; > 70% fall ⇒ 2.5%
• other indicators of successful thrombolysis are:
  • CK-MB peak on 1st day - wash-out effect
  • reperfusion arrhythmias

• TIMI flow grades:
  • 0 & 1: angiographic occlusion
  • 2: impaired flow
  • 3: angiographically normal flow
• TIMI 3 flow is achieved in only 31% pts with SK and 54% pts with tPA, thus substantial proportion of pts have suboptimal result which may be due to:
  • failure of epicardial reperfusion:
    • inability to achieve lytic state
      • in pts given SK, this may be indicated by:
        • inadequate reduction of fibrinogen levels
        • raised levels of thrombin/antithrombin III complexes
      • this may be addressed with repeat thrombolysis but:
        • additional risk of intracranial h'age - presumably a summation of previous risk ie. now 0.94% rather than 0.49% as inferred from SK vs SK + tPA in GUSTO-1
        • cannot easily detect failed lytic state thus would Rx many who would not benefit
    • mechanical factors at fissured plaque
      • this may be addressed by:
        • rescue angioplasty but this is usually delayed and thus has not been shown to be of benefit
        • intra-aortic balloon pumping has been shown to improve both vessel patency & LV function
          • this has a role in the hypotensive pt with cardiogenic shock
  • failure of microcirculatory perfusion (“no reflow”):
    • early:
      • associated with capillary occlusion with platelet microthrombi which are resistant to thrombolytic agents, which may paradoxically increase platelet reactivity & thrombin activity
      • can this be addressed by intensified antiplatelet Rx:
        • abciximab
    • late:
      • due to loss of microvascular integrity due to endothelial & myocardial oedema which is partly mediated by oxygen radical injury at the time of reperfusion, esp. if there is delay in thrombolysis
• conclusions:
  • failure of ST segment resolution in a pt with:
    • limited infarction (ST elevation in 5 or less leads) & who is haemodynamically stable should be Mx conservatively since this is a low risk group.
    • hypotension & cardiogenic shock should be considered for immediate angioplasty even if this requires transfer to another centre.
    • ST elevation in 6 or more leads & continuing ischaemic chest pain then either repeat thrombolysis or rescue angioplasty (according to availability) seem justifiable.
      • early signs of haemodynamic instability (tachycardia or falling BP) should lower threshold for action
      • if angioplasty undertaken, adjunctive Rx may be required:
        • intra-aortic balloon pumping
        • abciximab