Safety and Efficacy of Autologous, Intracoronary Stem Cell Injections in Total Coronary Artery Occlusions

This study is composed of one phase. The objective of Phase I is to assess the safety and feasibility of performing escalating doses of autologous AC133+ selected bone marrow-derived stem cell with intracoronary infusion via epicardial vessels supplying collateral flow to areas of viable ischemic myocardium in the distribution of a chronic totally occluded vessel. Additionally, focus on the assessment of the benefit achieved from the infusion of stem cells and subsequent angiogenesis at 6 months will be observed.

Potential candidates are patients with a known total occlusion of an epicardial vessel, with a documented chronically ischemic territory supplied by collateral conduits.

Secondary Objectives include:

• Improvement in ETT as determined by: total exercise duration on the 6 month ETT in seconds time to: onset of angina, one mm ST depression, onset of angina or one mm ST depression (whichever occurs first)
• Reduction in the area of ischemia will be evaluated by nuclear (sestamibi) stress imaging with exercise or pharmacologic stress.
• Improvement in viability within the chronically ischemic zone as measured by nuclear (sestamibi) stress imaging.
• Improvement in angina as per Angina Questionnaire (The Seattle Angina Questionnaire) at 7, 14, 30, 90, 180, and 365 days.
• Major adverse cardiac events (MACE) assessment (composite endpoint including cardiac death, myocardial infarction, ischemia-driven target vessel revascularization, CABG, CVA, and rehospitalization for angina), MACE definitions:

Myocardial Infarction (All ST segment elevation MIs as diagnosed on electrocardiogram by a staff cardiologist and all non-ST segment elevation MIs as defined by elevation in cardiac enzyme markers per the hospital laboratory guidelines) Cerebral Vascular Accidents (e.g., acute neurological event).

• Concomitant Medication usage (e.g., changes in utilization of PRN or sublingual nitroglycerin for angina)
• ECG changes at day of discharge, 7, 14, 30, 90, 180, and 365 days.
• Functional capacity (e.g., exercise duration (time) and changes in METS achieved on treadmill study at 6 month follow-up).
• Echocardiogram assessment of left ventricular ejection fraction and regional wall motion abnormalities at 180 days (e.g., changes in regional wall motion score and/or changes in left ventricular ejection fraction).

Inclusion criteria

• The patient must have at least one region of chronically ischemic myocardium formerly perfused by a coronary artery which is now 100% occluded and not revascularizable by conventional percutaneous or surgical methods.
• Well-established collateral vessels at least 1.5-mm luminal diameter by coronary angiography to the chronically ischemic myocardium must be identified at the time of diagnostic coronary angiography.
• Evidence of viable myocardium in the area supplied by collateral conduits intended for stem cell infusion must be demonstrated by nuclear (sestamibi) stress imaging.
• Left ventricular ejection fraction of >45% as per 2D echocardiogram.
• Patient must experience class II - IV angina as defined by the Canadian Cardiovascular Society (CCS).
• Patient will be followed by the investigating team over the 12 month follow-up period.
• The patient must be at least 18 years of age and have signed an informed consent.
• If the patient is a female of child-bearing potential, a pregnancy test is negative.

Exclusion criteria

Patients meeting any of the following exclusion criteria will be excluded from the study:

• Patient with coronary lesions amenable to percutaneous coronary intervention including brachytherapy, or where CABG is indicated.
• Any contraindication for cardiac catheterization and percutaneous coronary intervention as per institutional guidelines.
• Any contraindication for bone marrow aspiration as per institutional guidelines.
• Myocardial infarction within the previous 3 months.
• Documented bleeding diathesis.
• Known malignancy involving the hematopoietic/lymphoid system.
• Patients with baseline ECG abnormalities that would hinder interpretation of baseline ECG uninterpretable for ischemia (e.g., left bundle branch block, left ventricular hypertrophy with strain pattern, Wolff-Parkinson-White syndrome).
• Patients with severe co-morbidities including renal failure (serum creatinine > 2.0).
• Anticipated unavailability for follow-up visits secondary to psychological or social reasons.
• NYHA class III or IV congestive heart failure
• Anemia with hemoglobin concentration < 8 mg/dl
• Thrombocytopenia with platelet count < 100 x 103