Safety Study of Transmyocardial Revascularization (TMR) With Bone Marrow Aspirate (BMAC) for Angina Reduction (PHOENIX)

Inclusion Criteria:

• Adult patient, 18 years of age or older, male or female.
• Left ventricular ejection fraction greater than or equal to 40% (documented within 6 months of the TMR procedure.
• Patient with medically refractory, stable, Class IV angina according to the Canadian Cardiovascular Society angina scale. Optimal medical therapy is defined as maximum tolerable and stable doses of beta-blockers, statins, anti-platelets and long acting nitrates without control of symptoms for at least 30 days.
• Patient with at least a 15 cm² (or 15% of the surface area in the distal 2/3 of the left ventricle free wall to allow for a minimum of 15 TMR channels) documented region of the myocardium in the distal two-thirds of the left ventricle with reversible ischemia. Patients will be enrolled based on images used to determine eligibility for TMR within the previous 6 months. However, all patients will have baseline and follow-up MRIs taken per a standardized protocol and adjudicated by a core lab.
• Has a documented left ventricular wall thickness of ≥8 mm.
• Patient is not a candidate for treatment by direct coronary revascularization methods (i.e., CABG or PCI) as documented by an independent interventional cardiologist and an independent cardiothoracic surgeon on the Angiographic Screening Form.
• Patient is able to perform the baseline exercise tolerance test (ETT).
• Patient, if female, has no childbearing potential or has had a negative urine or serum pregnancy test within 7 days of the procedure.
• Patient has a bone marrow aspirate total nucleated count of at least 15 x 106/mL at the time of harvest.
• Patient has provided informed consent.

Exclusion Criteria:

• Cannot undergo a surgical procedure, thoracotomy or general anesthesia.
• Has any mechanical or prosthetic heart valve.
• Has a history of bone marrow disease (especially Non-Hodgkin's Lymphoma and Myelodysplastic Syndrome) that prohibits autologous bone marrow derived cell transplantation.
• Has severe, new onset or increasing angina. In addition, patients who cannot be weaned from intravenous anti-anginal medications for at least 48 hours preoperatively are to be excluded. Severe, new onset and increasing angina is defined as: Severe angina - angina occurring at rest and usually prolonged >20 minutes occurring within a week of presentation; new onset angina - angina of at least Canadian Cardiovascular Society Classification (CCSC) III severity with onset within 2 months of initial presentation; and increasing angina - previously diagnosed angina that is distinctly more frequent, longer in duration, or lower in threshold, (i.e., increased by at least one CCSC class within 2 months of initial presentation to at least CCSC III severity.
• Has had a STEMI (ST Elevation Myocardial Infarction) or NSTEMI (Non-STEMI) within 4 weeks of the TMR procedure.
• Has decompensated heart failure, or a diagnosis of NYHA Functional Class III/IV heart failure.
• Has a hemorrhagic propensity that cannot be addressed with drug management.
• Has severe or life-threatening arrhythmia (e.g., ventricular tachycardia or fibrillation) within one week prior to the TMR procedure.
• Is unable to undergo a cardiac MRI procedure.
• Has uncontrolled diabetes with HbA1C > 10%.
• Has anemia defined as hematocrit < 33% in women and <39% in men.
• Has moderate to severe renal dysfunction defined as serum creatinine >1.8 mg/dL.
• Has moderate to severe liver dysfunction defined as> ALT/AST >5X the upper limit of normal.
• Is unable or unwilling to return for follow-up.
• Is participating in another clinical investigation within the prior 30 days.