REperfusion Facilitated by LOcal Adjunctive Therapy in ST-elevation Myocardial Infarction
REperfusion Facilitated by LOcal Adjunctive Therapy in ST-elevation Myocardial Infarction
The purpose of this study is to determine whether intra-coronary adenosine or sodium
 nitroprusside (SNP) delivered selectively via a thrombus aspiration catheter (or if
 unsuccessful via a coronary microcatheter) following thrombus aspiration in Primary
 Percutaneous Coronary Intervention (P-PCI) reduces microvascular obstruction (MVO) parameters
 and infarct size as measured with cardiac MRI, compared with standard treatment following
 thrombus aspiration in patients presenting with ST-elevation myocardial infarction (STEMI).
>100,000 patients suffering STEMI present in the UK each year. P-PCI in the UK is increasing
 exponentially. In 2004 there were <1500 P-PCI and in 2007 and 2008 these figures had
 increased to 5902 and 9224 respectively (BCIS database).

 Although P-PCI delivered quickly is more effective than thrombolysis, the efficacy of this,
 essentially mechanical, technique is limited by the unpredictable phenomenon of no-reflow and
 the under-stated lesser degrees of MVO. As more UK centres adopt P-PCI the dilemma of how to
 attenuate MVO will remain. Currently there is no consensus on the optimal management to
 prevent or attenuate MVO particularly when thrombus laden lesions are treated with P-PCI.

 There is divergent clinical practice, even within institutions, in the UK and worldwide. This
 is because there is no solid evidence base to inform clinicians. The current options for
 interventional cardiologists are:

 1. Routinely aspirate thrombus and give IC vasodilator during the intervention but only in
 high burden thrombus formation lesions.

 2. Perform a standard P-PCI only and then give IV vasodilator if angiographic no-reflow
 develops.

 3. Routinely consider that angiographically silent MVO (i.e a grade below true "no-reflow")
 may have important impact on infarct size and clinical outcome and treat
 prophylactically.

 Few if any clinicians follow this thinking. Indeed, it appears impossible to predict the
 incidence of (no-reflow/MVO) from the presenting angiogram (pre- or post- wire or balloon)
 and it can be argued that irrespective of thrombus burden it would be better to undertake
 prophylactic treatment in all patients, following the use of aspiration catheter, with
 delivery of agents able, in theory at least, to reduce (angiographically undetectable) MVO.
 Several studies of IC adenosine or SNP have shown favourable effects in attenuating MVO.
 However, the size of effect with either drug and whether indeed there is a difference between
 them in reducing MVO and infarct size is undetermined.

 The objectives of our proposed study are to determine:

 1. Whether adjunctive pharmaco-therapy at time of P-PCI and following thrombus aspiration,
 reduces CMR-determined MVO and infarct size.

 2. Whether there is a difference between adenosine and SNP in reducing CMR-detected MVO and
 infarct size, both given selectively and distally via a thrombus aspiration catheter or
 a coronary microcatheter.

 3. The correlation of angiographic, including the recently designed computer-assisted
 myocardial blush quantification 'Quantitative Blush Evaluator'(QuBE), and other
 myocardial perfusion markers, with CMR detected MVO and infarct size, as well as with
 clinical outcome (MACE) at 30 days.
Inclusion Criteria:

 -  ≥ 18 years age.

 -  Informed ASSENT (verbal consent) prior to angiography.

 -  STEMI ≤ 6 hrs of symptom onset, requiring primary reperfusion by PCI.

 -  Single-vessel coronary artery disease (non culprit disease ≤70% stenosis at
 angiography)

 -  TIMI flow 0/I at angiography.

 Exclusion Criteria:

 -  Contraindications to: P-PCI *, CMR**, contrast agents, or study medications:
 Adenosine***, SNP****, Aspirin, Thienopyridine and Bivalirudin.

 -  SBP ≤ 90mmHg

 -  Cardiogenic Shock

 -  Previous Q wave myocardial infarction

 -  Culprit lesion not identified or located in a by-pass graft

 -  Stent thrombosis.

 -  Left main disease.

 -  Known severe asthma.

 -  Known stage 4 or 5 chronic kidney disease (eGFR<30ml/min).

 -  Pregnancy.

 Notes:

 -  * Exclusion criteria for P-PCI (presentation timing, inadequate arterial access etc);
 patient unable to tolerate "prolonged" PCI procedure (in operators' opinion).

 -  ** Absolute contra-indication to CMR (Pacemaker, ICD, intra-cranial metal clips).

 -  *** Contraindications to Adenosine (known hypersensitivity to Adenosine, sick sinus
 syndrome, second or third degree atrio-ventricular block - except in patients with
 functioning artificial pacemaker, long QT syndrome has been defined as QTc > 450 ms at
 baseline). ECG will be undertaken just after the first dose of the study drug and
 QT/QTc will be recorded and compared to the baseline. If the QTc recorded after the
 first dose of the study drug exceeds 450ms or there is an increase in the QT/QTc of >
 60 ms from baseline, the second dose will be abandoned and this will be recorded.

 -  **** Contraindications to SNP (known hypersensitivity to SNP, compensatory
 hypertension - as may be seen in arteriovenous shunts or coarctation of the aorta,
 high output failure, congenital optic atrophy or tobacco amblyopia).