Comparison of intracoronary selected CD 133+ bone marrow stem cells in cardiac recovery after acute myocardial infarct and left ventricular dysfunction: COMPARE-AMI a randomized controlled double blind clinical study

INTERVENTION: Early in the morning, bone marrow harvest under local analgesia, up to 100 ml, this takes approximately 60 minutes. Cell processing in the CEll therapy laboratory: CD133+ stem cells purification using the CliniMACS system from Miltenyi Biotech Inc. Later in the same day, and withing 24hrs from bone marrow harvest: intracoronary injection of autologous CD133+ selected stem cells, up to 10 millions cells. This procedure requires percutaneous intervention, requires approximately 60 to 90 minutes. CONDITION: Heart failure Myocardial infarct PRIMARY OUTCOME: Primary efficacy endpoint: ; ‐ The change in global left ventricular ejection fraction (LVEF) at 4 months relative to baseline measured by magnetic resonance imaging Primary safety endpoint: ; The change at 4 months in the coronary atherosclerotic burden progression in the proximal and distal to stented segment of the infarct‐related artery in treated patients as compared to controls. Intravascular ultrasound (IVUS) and fractional flow reserve (FFR, pressure catheter) are used to characterize the atherosclerotic plaque. SECONDARY OUTCOME: Device performance end point: ; Ability to produce a ; final cell product that contains a target CD133+ cells higher than 1x106 with a purity superior to 30% and a recovery superior to 10 %. this is evaluated by flow cytometry (FACs) analysis after processing the bone marrow. Efficacy: ; ‐Presence of clinically evident heart failure. ; ‐The change in global left ventricular ejection fraction (LVEF) at 4 months relative to baseline measured by quantitative left ventriculography (QLV). ; ‐The change in the infarct area viability at 4 months relative to baseline measured by positron emission tomography (PET) scan. ; ‐The changes in vital signs at follow up (Blood pressure: Systolic, diastolic, mean, Heart rate). ; ‐The number, doses of prescribed heart failure medication (inhibitors of angiotensin‐converting enzyme (ACE) or Angiotensin II Receptor Blockers (ARB), B‐blockers, Digoxin, Loop diuretics, Spironolactone) and anti‐arrhythmic drugs. ; ‐The change in global and regional wall motion score Index measured by quantitative left ventriculography (QLV, centerline method). ; ‐The change in global and regional wall motion score index as measured by resting echocardiography. ; ‐The change in global and regional wall motion score index as measured at maximal dobutamine infusion during low dose dobutamine echocardiography (LDDE). ; ‐The change in magnetic resonance imaging (MRI) assessments (left ventricular (LV) mass, LV end‐diastolic volume (LVEDV), LV end‐systolic volume (LVESV), LV ejection fraction (LVEF), infarct size = late enhancement volume). ; ‐The change in 99mTc‐methoxyisobutyl isonitrile (MIBI) scan (MIBI) assessments ( Resting perfusion defect, LVEF, LVEDV, LVESV). Safety and efficacy: ; ‐The occurrence of a Major Adverse Cardiac Event (MACE). ; ‐The change in global and regional wall motion score index as measured by resting echocardiography. ; ‐The change in LVEF relative to baseline measured by resting echo. ; ‐The change in MRI assessments (LV mass, LVEDV, LVESV, LVEF, infarct size measured by the late enhancement volume). Safety: ; ‐The occurrence of major arrhythmias defined as sustained ventricular tachycardia or survived sudden death. ; ‐The occurrence of a Major Adverse Cardiac Event (MACE) defined as cardiac death, myocardial infarction creatine‐kinase (CK) and creatine‐kinase‐muscle and brain (CK‐MB) over 2 times the upper limit of normal), coronary bypass grafting, or a repeat percutaneous intervention of the culprit lesion. INCLUSION CRITERIA: acute ST‐elevation myocardial infarct successfully reperfused by means of coronary stent implantation and demonstrated a substantial persistent LV dysfunction defined by a LVEF <50% but >25% on echocardiography obtained within 48 hours after the successful reperfusion therapy.