Gradual Versus Abrupt Reperfusion in Primary PCI (GUARD)
Condition: ST-elevation Acute Myocardial Infarction
MeSH terms: Myocardial Infarction; Infarction
Study type: Interventional

Summary: 
      After reopening of the infarct related artery by primary percutaneous coronary interventions
      (PPCI), microvascular damage at the related myocardial territory is not terminated
      immediately. This ongoing nature of microvascular damage leading to myocardial malperfusion
      is related to final infarct size. However, time course of the microvascular impairment
      /obstruction after PPCI in patients presented with ST-elevating acute myocardial infarction
      (STEMI) is not known. Routine primary percutaneous coronary interventions (PPCI) for
      ST-elevation acute myocardial infarction (STEMI) includes balloon angioplasty (or
      thrombectomy) followed immediately by stent implantation. However, stent implantation
      performed in this thrombotic setting may lead to a further microvascular damage by causing
      more distal embolisation and by inducing distal microvascular spasm by stretching the
      coronary vessel wall. Furthermore, sudden exposure of distal microcirculation to a high
      distal intracoronary pressure achieved by immediate stent implantation may exaggerate
      myocardial oedema which contributes microvascular damage substantially by external
      compression. However, results of studies investigating the efficacy of delayed stenting
      (24-48 hours later) in patients in whom TIMI -3 flow was achieved after balloon angioplasty
      were inconsistent.

      In this study, STEMI patients undergoing PPCI, in whom epicardial reperfusion was achieved
      (TIMI-3 flow) by wire crossing or by balloon angioplasty or aspiration thrombectomy, will be
      randomised to immediate and delayed stenting groups. Delayed stenting will be performed at
      the time when coronary auto regulation was recovered which is going to be determined based on
      the continuous intracoronary hemodynamic monitoring after reperfusion.
    

Detailed description: 
      It was shown in ischemia/reperfusion models that after reopening of the occluded epicardial
      coronary artery, following initial hyperemic flow, myocardial blood flow in the area at risk
      rapidly and progressively declines and get stabilised approximately within 30 minutes.This
      finding implies that, in spite of the initial ischemic insult, coronary auto-regulation in
      the reperfused myocardial territory recovers. Nevertheless, this recovery requires some time
      after reperfusion was achieved. During total occlusion of an epicardial coronary artery,
      pre-arteriolar sphincters can be expected to be paralysed in widely open position in response
      to severely increased distal myocardial demand. Ischemic myocyte damage also contributes to
      malfunctioned pre-arteriolar sphincters. Therefore, full restoration of perfusion pressure
      distal to the infarct related artery by immediate stenting (direct or after angioplasty) may
      then fail to induce an immediate adaptive autoregulatory response (compensatory
      vasoconstriction) in the related microvascular territory, resulting in an inappropriately
      increased pressure in the damaged microcirculation. During total epicardial occlusion,
      ischemia/hypoxia induced damage and increased permeability at the capillary level lead to
      loss of structural integrity in the related microvascular territory. After immediate
      stenting, this severely damaged microcirculation is exposed to a suddenly increased
      uncontrolled intracoronary pressure which may consequently substantially contribute to
      intramyocardial haemorrhage and oedema.

      Therefore, it was hypothesised that gradual reperfusion with delayed stenting performed when
      coronary auto regulatory function was recovered may lessen the myocardial oedema and/or
      haemorrhage by preventing/limiting uncontrolled increase in pressure in the distal
      microcirculation.

      The recovery of coronary autoregulatory function in reperfused STEMI patients can be assessed
      by continuous monitoring of coronary (microvascular) blood flow and resistance values after
      restoration of epicardial blood flow by balloon angioplasty in individual basis.

      In this study, following establishment of TIMI-3 flow by balloon angioplasty, patients will
      be randomized to immediate or delayed stenting groups. Continuous intracoronary hemodynamic
      monitorization will be performed in re-opened infarct related artery using a coronary guide
      wire equipped with pressure and flow sensors for a total of 1hour in both groups.

      In delayed stent group, stent implantation will be performed in individual basis when
      coronary hemodynamic data indicates that coronary autoregulation was recovered (when initial
      hyperaemic flow response was subsided and baseline microvascular resistance was increased).
      Recovery of autoregulatory function will be determined by identification of stabilisation of
      baseline coronary flow velocity and baseline microvascular resistance in infarct related
      artery after balloon angioplasty. Stabilization will be decided by comparing basal coronary
      flow velocity and microvascular resistance values measured in non-infarct related coronary
      artery immediately before PPCI with the values that was being measured in re-opened infarct
      related artery. When baseline flow velocity and resistance values being recorded in IRA got
      close to the values measured in non-IRA, IRA will be stented. Intracoronary pressure and flow
      data will continuously be monitored until the end of 1 hour follow-up period.

      In immediate stenting group, stent implantation will be performed immediately following
      angioplasty. Intracoronary pressure and flow data will continuously be monitored using dual
      sensor coronary guide wire until the end of 1 hour follow up period.
    

Intervention name(s): deferred coronary stenting; immediate stenting
Intervention type(s): Device; Device
Intervention description(s): Final coronary stenting will be performed when coronary auto regulation was recovered (approximately 30 minutes after establishment of TIMI III flow şn the infarct related artery); Stent implantation will be performed immediately after balloon angioplasty (or thrombectomy or wire crossing) as it is performed in daily routine.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: primary percutaneous coronary intervention; microvascular obstruction; myocardial edema; microvascular resistance; acute myocardial infarction