Despite advances in therapy for acute myocardial infarction, mortality and morbidity related to postmyocardial infarction left ventricular dysfunction remain high. To date, the clinical tools for preventing post- myocardial infarction heart failure have been limited to rapid reperfusion and postinfarction drug therapy.
Several preclinical studies and small clinical trials have demonstrated the potential benefit of bone marrowderived cell-based therapies in the treatment of post-myocardial infarction left ventricular dysfunction.
These studies have focused on the whole mononuclear cell fraction of bone marrow, because it is unclear which cell type or combination of cell types may be responsible for the promising early results
The REPAIR-AMI ( Reinfusion of Enriched Progenitor Cells And Infarct Remodeling in Acute Myocardial Infarction ) trial has evaluated the effects of intracoronary delivery of progenitor cells after primary percutaneous coronary intervention ( PCI ) for ST-segment elevation myocardial infarction.
The study involved 204 patients at 17 medical centers in Germany and Switzerland.
After bone marrow aspiration, patients were randomized to receive an intracoronary infusion of the infarct-related artery with autologous mononuclear progenitor cells ( BMC group ) or placebo medium, 3 to 6 days after acute myocardial infarction.
The primary end point of the study was absolute increase in left ventricular ejection fraction as measured by repeat left ventricular angiography at 4 months.
Ejection fraction was higher in both groups at 4 months compared with baseline, but the increase in EF was statistically significantly higher in the BMC group compared with the placebo group ( 5.5% vs 3.0%, P = .014 ).
In subgroup analyses, the improvement in EF with bone marrow cell infusion was evident among patients with a baseline EF of < 49% ( 7.5% for the BMC group vs 2.5%, P < .01 ), but was not significant in patients with an EF of > 49% ( 4.0% vs 3.7%, P = NS ).
In addition, patients treated within 5 days of their acute MI showed no benefit with bone marrow cell infusion compared with placebo, whereas patients treated after 5 days showed a significant increase in EF ( 7.0% vs 1.9%, P =.004 ).
Although the study was not powered to detect a difference in clinical end points, a trend toward a reduction of the composite of death, MI, or repeat revascularization was seen in the BMC group ( 21% vs 30%, P = .17 ).
The REPAIR-AMI trial demonstrated that intracoronary infusion of bone marrow mononuclear cells in patients after acute myocardial infarction improved left ventricular function at 4 months.
In addition, although care should be taken in interpreting subgroup analyses, it is interesting to note that the improvement in left ventricular function was most striking in patients with worse baseline left ventricular EF and in those treated ≥ 5 days after myocardial infarction.
Furthermore, treatment with bone marrow cells was found to be safe and associated with a trend toward a reduction in major cardiovascular events. In light of these results, the REPAIR-AMI investigators suggest that larger clinical trials designed to detect differences in clinical outcomes are now warranted. Still, the exact mechanism of benefit of the cells remains unclear.
Volker Schachinger, Goethe University, Frankfurt am Main, Germany
Source: American Heart Journal, 2006