Mr Michał Tendera
Presenter report:Michal Tendera (Poland)
REGENT is a multicenter, randomized trial for comparison of intracoronary infusion of bone marrow-derived unselected mononuclear cells (MNC) and selected CD34+CXCR4+ cells in 200 patients with acute myocardial infarction and reduced LVEF ≤ 40%.The primary end-point was change in LV ejection fraction (LVEF) and volumes measured by MRI before and 6 months after the procedure. In patients receiving both selected and unselected bone marrow cells, LVEF increased significantly in comparison to baseline values by 3%.This increase, however, was not significantly higher in comparison to the control group. The changes in left ventricular volumes were also comparable in all groups. A significant increase in LVEF was observed in patients treated with either type of bone marrow cells who had baseline LVEF < median.Baseline LVEF was an independent predictor of significant increase in LVEF.At 6 months clinical follow-up, the major cardiovascular event rate was low, and there was no difference between the groups. In conclusion, treatment with intracoronary infusion of BMC did not lead to significant improvement of LVEF and LV volumes in comparison to the control group, however there was a trend towards significant improvement of LVEF in patients with severely depressed baseline LVEF receiving either MNC or CD34+CXCR4+ bone marrow cells. Intracoronary infusion of unselected and selected BMC proved to be safe and feasible.REGENT is the second-largest trial using bone marrow-derived cells in patients with acute MI and the first large trial for head-to-head comparison of selected and unselected cells. Population of CD34+CXCR4+ cells is enriched in cardiac committed progenitor cells, but so far, it has not been used in a clinical trial. These results suggest that in patients with severely depressed LVEF, administration of a relatively small number of CD34+CXCR4+ cells can have the same effect as an infusion of a larger number of MNC.Therefore, this cell population deserves further studies.
Discussant report:Drexler, Helmut (Germany) Cell therapy post myocardial infarction has received widespread attention as an approach to improve cardiac function and, possibly, to support regeneration of cardiac muscle in the face of loss of muscle by cell death due to sustained ischemia.Four randomized trials have been published so far and numerous are ongoing. Based on the current data, bone marrow cell (BMC) transfer within days post MI appears to be safe and has the potential to improve cardiac function. Post hoc analysis has suggested that improvement of cardiac function may be confined to patients with marked depressed LV ejection fraction (EF).Moreover, details such as isolation procedures, cell type, timing of cell transfer may be crucial for the success of BMC transfer. The REGENT trial, the second trial to enrol 200 patients, was designed to address some of these important issues prospectively; in particular: (1) is BMC transfer beneficial in patients with depressed LVEF and (2) do selected CD34+CXCR4+ BMCs, which are assumed to possess improved homing properties in the myocardium, have a superior beneficial effect.The results are a mixed bag, reassuring the optimists to go ahead with refined cell therapy strategies but may be supportive for the pessimists' view that BMCs post MI are hype rather than hope. While unselected BMCs and selected BMCs improved EF 6 months post MI, the difference between these groups and placebo was not significant.Yet, the percent increase in EF by BMCs was in a similar range as compared the REPAIR-AMI trial, with a similar number of patients enrolled. However, the variation in BMC treatment effect between patients was small in REPAIR-AMI and the group difference therefore significant. Again, a post hoc analysis of the selected BMC group supports the notion that more depressed LV EF at baseline may benefit. However, if such an analysis is negative for the group that received unselected BMC only, despite similar improvement of LVEF at 6 months, this observation for one subgroup may not be meaningful. What are the aspects that may support the optimists view, i.e. that these data are not completely negative and not to abandon BMC therapy post MI?Cell handling is crucial and information on cell number infused and data on the functional activity of infused cells are important. We don’t know the time delay between reperfusion by PCI and BMC transfer. 20 to 25% of patients had diabetes and many others had additional risk factors, which have a negative impact on the biological activity of cells, calling for preconditioning cells before application. Conclusion:Taken altogether, REGENT is a great effort and an excellently excecuted large cell therapy trial indicating once again that BMC therapy post MI is safe. Considering the results, the glass is half full and half empty!
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This congress report accompanies a presentation given at the ESC Congress 2008. Written by the author himself/herself, this report does not necessarily reflect the opinion of the European Society of Cardiology.
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