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Abstract & Commentary
Synopsis: Autologous bone marrow stem cells injected into the infarct-related artery, after successful PCI, improves LVEF at 6 months, compared to controls.
Source: Wollert KC, et al. Intracoronary Autologous Bone-Marrow Cell Transfer After Myocardial Infarction: The BOOST Randomised Controlled Clinical Trial. Lancet. 2004;364:141-148.
The inherent time delays in achieving reperfusion in acute myocardial infarction (MI) often result in myocardial damage. Autologous bone marrow stem cells have shown promise for repairing this damage. Thus, Wollert and colleagues designed a randomized trial of intracoronary injections of autologous bone marrow stem cells in patients with acute ST elevation MI who had successful percutaneous intervention (PCI) with stenting. Eligible patients had to have single vessel disease and evidence of left ventricular (LV) wall motion abnormalities, but also had to be stable. After the 60 patients were enrolled and randomized to either autologous bone marrow infusion into the infarct-related artery or control groups (30 each), each patient underwent cardiac MRI, with contrast. The primary end point was global LV ejection fraction (EF) change from baseline to 6 months. The enrolled subjects were mainly male, hypertensive smokers, with left anterior descending lesions. Appropriate medical therapy was 93-100% in both groups.
Results: Baseline LVEF (mean, 3.5 days post PCI) increased from 50% to 56.7% (P < .003) in the stem cell group, as compared to 51% to 52% in the control group (P = NS). Measures of LV volumes, mass, and infarct size (late contrast enhancement) did not change significantly in either group. The beneficial change in EF was seen across all subgroups and was unrelated to characteristics of the cells infused. Regional wall motion analysis showed that the beneficial effect was confined to the peri-infarct zone. Formal electrophysiologic (EP) testing was done in 90% of the patients, and no difference was seen in inducible arrhythmias. Also, there was no difference in clinical outcomes or in-stent restenosis between the 2 groups. Wollert et al concluded that autologous bone marrow stem cells injected into the infarct-related artery, after successful PCI, improves LVEF at 6 months, compared to controls.
Comment by Michael H. Crawford, MD
Stem cells are the hot new thing in cardiac research, and the use of autologous bone marrow cells avoids ethical and legal issues. After several preliminary feasibility studies, Wollert et al from Germany have completed a randomized, controlled trial in humans. The results are encouraging for several reasons. The procedure appeared safe, as no untoward effects were observed. Of special concern are arrhythmias, since prior studies have shown that other types of cells, when incorporated into the myocardium, become disordered regions, which increase the propensity to arrhythmias. There was no increase in clinical arrhythmias, and EP testing was no different in the 2 groups. Part of the reason for this lack of arrhythmias may have been the observation that the cells were not transformed into myocytes. If they were not adding to the myocyte pool, how were they increasing LVEF? Although this was not a mechanistic study, other data suggest that these cells may have a paracrine effect that promotes angiogenesis. This may also explain why there was no effect on remodeling (no change in LV volumes). That the procedure changed EF without changing LV volumes, suggests that it improved the inotropic state of the myocardium, perhaps through these paracrine pathways. Whether such a change will be sustained in the absence of structural changes in the myocardium, will require further long-term follow-up.
The study population was somewhat unique in that 40% were referred from other hospitals for rescue angioplasty. Thus, the average duration of symptoms to PCI was 8.5 hours. This is certainly beyond the optimal time for recovery of myocardium. Yet, this procedure, done 3-5 days later, was able to show some positive benefit. Presumably, stunning was over by then, otherwise, the improvement would be expected. Finally, the controls did not have a sham procedure, which raises the question of whether just doing a bone marrow harvest and another cardiac catheterization has some positive effect on LV performance that persists. Although encouraging, this stem cell procedure is not ready for prime time.
Dr. Crawford, Professor of Medicine, Chief of Clinical Cardiology University of California San Francisco, is Editor of Clinical Cardiology Alert.