IMPACT-CABG Trial: Implantation of Autologous CD133+ stem Cells in Patients Undergoing CABG

Inclusion Criteria:

• ·         Age:  18 years to 75 years.
• ·         Patients who have severe chronic ischemic cardiomyopathy manifested by Canadian Cardiovascular Society (CCS) class II or greater angina, and/or New York Heart Association (NYHA) class II or greater, AND who have undergone diagnostic coronary angiography demonstrating ≥70% diameter narrowing of at least 2 major coronary arteries or of branches or ≥50% diameter narrowing of the left main coronary artery.
• ·         A significant left ventricular systolic dysfunction evaluated by echocardiography or LV angiography (LV ejection fraction ≤45% but ≥25%) due to prior myocardial infarction. This area of left ventricular dysfunction should be akinetic or severely hypokinetic, but not dyskinetic or aneurismal, when assessed by echocardiography or LV angiogram. This territory should be irrigated by one or a branch of the three major vascular territories (i.e. left circumflex, right coronary artery, or left anterior descending artery distribution) that will be bypassed during the surgical procedure.
• ·         Willingness to participate and ability to provide informed consent.

Exclusion Criteria:

• ·         Contraindications to magnetic resonance imaging (MRI) including presence of an implantable cardiac defibrillator or permanent pacemaker, or cases in which it is anticipated that an ICD or PPM will be implanted prior to the 6 month follow-up (thus precluding performance of follow-up MR scans), or claustrophobia.
• ·         Lack of ischemic symptoms (angina) prior to referral for CABG (i.e., patients with only 'silent' ischemia will be excluded).
• ·         Need for urgent or emergent revascularization.
• ·         Need for concomitant surgical procedure at the time of CABG (e.g. valve repair or replacement, aneurysm resection, etc.).
• ·         Hemodynamically unstable patients, as defined by heart rate ≤40/min or ≥100/min, and/or systolic blood pressure <90 mmHg or ≥200 mmHg, and/or ongoing need for intravenous inotropic or vasopressor medications.
• ·         Patients with confirmed myocardial infarction within 2 weeks, and/or rising cardiac biomarker proteins (i.e. troponin), and/or worsening ECG changes.
• ·         Prior CABG surgery.
• ·         Stroke within 3 months before planned CABG.
• ·         Immunosuppressive medication (e.g. cyclophosphamide, prednisone, etanercept, etc.)
• ·         Severe chronic renal insufficiency (serum creatinine ≥ 200 mmol/dl or need for dialysis), liver disease, (i.e. diagnosis of cirrhosis, chronic hepatitis, or elevation of serum transaminases ≥3 times the upper limit of normal), peripheral arterial disease (claudication as the primary factor limiting activity), cerebrovascular disease requiring concomitant carotid endarterectomy,active non-dermatological malignancy requiring on-going treatment, or any other condition that would place the patient at increased risk for complications according to the judgment of the attending cardiologist or cardiac surgeon
• ·         Contra-indication for bone marrow aspiration (Thrombocytopenia <50.000 mm3, INR >2.0, use of antiplatelet agents other than aspirin).
• ·         Hemoglobin < 10g/dL, white blood cell count < 4,000/mm3, absolute neutrophil count < 1500/mm3
• ·         Active infection, with a temperature higher than 37.5°C within 48 hrs prior to surgery and an unexplained white blood cell count over 10,000/mm3
• ·         Significant cognitive impairment
• ·         Any condition associated with a life expectancy of less than 6 months
• ·         Participation in other studies
• ·         Patients known allergic reaction or contraindication to any of the component of the Myelodysplastic syndrome (MDS)
• ·         History of severe ventricular tachy-arrythmias
• ·         CD133+ enriched cells
• ·         Pregnancy
• ·         Positive laboratory test results for syphilis, HIV, HBC, HCV, HTLV1 and HTLV2
• ·         Inability or unwillingness to provide written informed consent
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