Abstract 3983: Normalization of Coronary Microvascular Function in the Infarct Artery by Bone Marrow-derived Progenitor Cells after Acute Myocardial Infarction: Results from the Double-blind, Placebo-controlled Repair-AMI Trial
Recently, intracoronary (i.c.) infusion of bone marrow-derived progenitor cells (BMC) in patients (pts) with reperfused acute myocardial infarction (AMI) has been shown to augment cardiac function and prevent endsystolic volume expansion. This was partially attributed to an improved progenitor cell-mediated neovascularization, but clear evidence from studies in humans is missing so far. Therefore, the “i.c. Doppler substudy” of the randomized, double-blind, and placebo-controlled REPAIR-AMI trial (Reinfusion of Enriched Progenitor cells And Infarct Remodeling in Acute Myocardial Infarction) aimed to investigate the effects of an i.c. BMC therapy on coronary microcirculation in pts with reperfused AMI. In this substudy, a total of 54 pts were enrolled (BMC: n=28; placebo: n=26). Coronary flow reserve (CFR) in the infarct artery as well as in a reference (ref.) vessel was assessed by i.c. Doppler at the time of study therapy and at 4 months follow-up.
Results: At the time of study therapy (3–7 days after AMI), CFR was reduced in the infarct artery as compared to the ref. vessel in both groups (BMC: 2.0±0.1 in the infarct artery vs. 2.9±0.2 in the ref. vessel, p<0.05; placebo: 1.9±0.1 in the infarct artery vs. 2.8±0.2 in the ref. vessel, p<0.05). At 4 months, CFR in the infarct artery had slightly improved in the placebo group (+0.88±0.18; p<0.001 vs. initial), but was markedly enhanced by 90% (+1.80±0.25; p=0.005 vs. placebo) in BMC-treated pts resulting in a complete normalization of CFR (3.8±0.2, p<0.001 vs. initial & placebo). In the infarct artery, adenosine-induced minimal vascular resistance declined slightly in placebo pts (from 1.77±0.12 to 1.52±0.15 mmHg*s/cm, p<0.05), but considerably decreased by -29±6% in the BMC group (from 1.86±0.19 to 1.20±0.12 mmHg*s/cm, p<0.05 vs. initial & placebo).
Conclusion: Intracoronary infusion of BMCs normalizes coronary flow reserve in the infarct artery in pts with reperfused AMI. The restoration of microvascular function was associated with a significant improvement of maximal vascular conductance capacity. These data provide clinical proof-of-concept that progenitor cell transplantation promotes vascular repair, either through paracrine mechanisms or directly due to an improved neovascularization.