Stem Cell Therapy as Adjunct to Revascularization
Stem Cell Therapy as Adjunct to Revascularization
The purpose of this study is to determine whether it is safe to receive an injection of your
 own bone marrow adult stem cells (autologous BM-MNC) to your heart wall during coronary
 artery bypass graft (CABG).
The experimental design will be a Phase I safety trial in which all subjects from the VA Salt
 Lake City Health Care System presenting with CAD and associated depressed LV function
 requiring myocardial surgical revascularization will be eligible for enrollment. Patients
 enrolled in the study will receive autologous BM-MNC as adjunct to CABG. The primary outcome
 measure will be safety as measured by the incidence of postoperative Serious Adverse Events
 (SAE) and Adverse Events (AE). The secondary outcome measures will be LV function, myocardial
 perfusion, and clinical improvement. The trial will have one experiment with one patient
 group. Group 1 (n=15) will follow standard Phase I dose escalation curve on a magnitude of
 0.5 log increase after every third patient. Dose escalation will continue until a dosage of 1
 x108 cells/pt is reached or maximum tolerated dose equivalent (MTDE) is identified. Cellular
 therapeutic products such as BM-MNCS do not possess the same pharmacologic profile as small
 molecule drugs, and thus, do not possess predictable metabolic activity and metabolite
 production, as do traditional pharmaceuticals. This can make the identity of a maximum
 tolerated dose somewhat difficult. We are therefore using the term MTDE instead of MTD to
 indicate a cell dosage that is consistent with clinical morbidity beyond obvious clinical
 benefit. The characteristics identifying a MTDE could be any adverse event felt to be related
 to the actual cell dosage or its escalation. Although unlikely, MTDE events could include
 microembolic phenomena, hematoma at the injection site, obvious myocardial congestion or
 ischemia at the injection site.
Inclusion Criteria:

 -  Veteran

 -  Age 18 or older

 -  Ability to give informed consent

 -  Have documented CAD and depressed LV function (EF <40%) that is felt to be
 appropriately treated with surgical revascularization by the VA Salt Lake City Health
 Care System Cardiothoracic Surgery team and in accordance with the published 2004
 ACC/AHA Guideline Update for Coronary Artery Bypass Graft Surgery; specifically, in
 accordance with the described indication for CABG in patients with Poor LV Function
 (see below).

 Class I

 1. CABG should be performed in patients with poor LV function who have significant left
 main coronary artery stenosis. (Level of Evidence: B)

 2. CABG should be performed in patients with poor LV function who have left main
 equivalent:

 significant (greater than or equal to 70%) stenosis of the proximal LAD and proximal
 left circumflex artery. (Level of Evidence: B)

 3. CABG should be performed in patients with poor LV function who have proximal LAD
 stenosis with 2- or 3-vessel disease. (Level of Evidence: B)

 Class IIa

 CABG may be performed in patients with poor LV function with significant viable
 noncontracting, revascularizable myocardium and without any of the above anatomic patterns.
 (Level of Evidence: B)

 -  NHYA/CCA Class I or higher

 -  Abnormal cardiac wall segment on preoperative data

 -  Acutely stable myocardium without evidence of cardiogenic shock or evolving myocardial
 infarction

 Exclusion Criteria:

 -  EF 40%

 -  CAD not amenable to CABG

 -  ACC/AHA Poor LV Function Class III - CABG should not be performed in patients with
 poor LV function without evidence of intermittent ischemia and without evidence of
 significant revascularizable viable myocardium. (Level of Evidence: B) Evidence of
 intermittent ischemia is defined clinically by Cardiovascular Disease Classification
 (see chart above). Objectively, this can be demonstrated by various modalities that
 can demonstrate ischemic myocardium. Such modalities include SCA, Echo, CMRI, and
 radionucleotide imaging.

 -  Patients undergoing cardiac re-operation

 -  Patients with operable valvular disease

 -  Patients with preexisting malignant arrhythmia

 -  Patients with preexisting systemic malignancy

 -  Patients with a contraindication to MRI

 -  Presence of ongoing local or systemic infection

 -  Participation in another clinical trial

 -  Emergency operation

 -  Preoperative cardiogenic shock or evolving myocardial infarction

 -  ASA Class V or contraindication to general anesthesia

 -  Pregnancy

 -  Prisoner

 -  Active history of alcohol or substance abuse

 -  Active psychiatric history leading to potential for poor study participation and
 follow-up