Intracoronary Autologous Bone-Marrow Cell Transfer after Myocardial Infarction: A Double-Blind, Randomized, and Placebo-

1. Intracoronary Autologous Bone-Marrow Cell Transfer after Myocardial Infarction Intracoronary Autologous Bone-Marrow Cell Transfer after Myocardial Infarction: A Double-Blind, Randomized, and Placebo-Controlled Clinical Trial Presented at American College of Cardiology Scientific Sessions 2005 Presented by Dr. Stefan Janssens

2. Intracoronary Autologous Bone-Marrow Cell Transfer after Myocardial Infarction 66 acute MI† patients; time after symptom onset > 2 hours; successful reperfusion post-PCI; documented LV dysfunction Placebo controlled. Randomized. Blinded. Mean age 56 years. 14% female. 24 hours later Intracoronary autologous bone-marrow cell transfer** n=32 Placebo n=34 • Endpoints (mean follow-up 4 months): • Global LVEF, LV mass index and infarct size † defined as cumulative ST segment elevation ≥ 6 mm ** bone marrow aspiration was performed and transferred to an open infarct-related artery. The transfer was performed intracoronary using over-the-wire balloon catheter during 3 coronary occlusions. Patients were monitored in-hospital for 7 days and underwent follow-up through 4 months. PET and MRI were performed at the initial hospitalization and at 4 month follow-up. Presented at ACC Scientific Sessions 2005

3. Intracoronary Autologous Bone-Marrow Cell Transfer after Myocardial Infarction Improvement in Global LV Ejection Fraction Over 4 Months • Bone marrow cell harvest volume averaged 130 mL, with 304 million total nucleated cells and 172 mononuclear cells • The infarct artery was in the left coronary in 62% of patients and the right coronary in 37%. • Post-PCI TIMI flow grade 3 was present in 91% of patients. All but one patient received aspirin, and glycoprotein IIb/IIIa inhibitors were used in 78% of the bone marrow group and 64% of the placebo group • Global LVEF increased by 2.1% in the bone marrow group and 3.9% in the placebo group Presented at ACC Scientific Sessions 2005

4. Intracoronary Autologous Bone-Marrow Cell Transfer after Myocardial Infarction Systolic Wall Motion from baseline to 4 months End Diastolic Wall Thickness Reduction from baseline to 4 months Remote Area p=0.05 Infarct Region p=0.04 Placebo Placebo BMC BMC Placebo Placebo BMC BMC Infarct Region p=0.49 Border Zone p=0.94 • There was no difference in change in systolic wall motion in either region • End diastolic wall thickness reduction was larger in the bone marrow group compared with placebo in both the infarct region and the remote area • There were no differences in the PET perfusion indices or metabolic indices in the infarct region or in the border zone Presented at ACC Scientific Sessions 2005

5. Intracoronary Autologous Bone-Marrow Cell Transfer after Myocardial Infarction Other Principle Findings: • At 4 months, LV mass index (p=0.018) and infarct size (p=0.036) were lower in the bone marrow group compared with the placebo group • Similar results were observed in infarct size in the subgroup of patients who underwent PCI within 6 hours and in patients with infarct size > 20% of LV mass index • There was no difference in adverse events during admission or at 4 month-follow-up, with atrial tachycardia on Holter in 19% of the bone marrow group and 15% of the placebo group Presented at ACC Scientific Sessions 2005

6. Intracoronary Autologous Bone-Marrow Cell Transfer after Myocardial Infarction • Among patients with recent reperfusion therapy following myocardial infarction, treatment with intracoronary autologous bone-marrow cell transfer was associated with reductions in infarct size compared with placebo but was not associated with changes in left ventricular systolic functional recovery. • Bone marrow transfer was not associated with an increase in myocardial blood flow or oxidative metabolism on PET scan. • While earlier studies have evaluated autologous bone-marrow cell transfer post-MI, the present study is the first to do so in a double-blind placebo controlled manner. Given the safety profile and the potential benefit in infarct size, larger randomized trials of autologous bone-marrow cell transfer are warranted. Presented at ACC Scientific Sessions 2005