Is There a Role for Intravenous Stem Cell Delivery in Nonischemic Cardiomyopathy?
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The delivery of stem cells to the heart in the setting of ischemic or nonischemic cardiomyopathy has almost exclusively relied on intramyocardial (IM) or intracoronary (IC) routes of administration. This strategy is based on several preclinical1 and human studies2 demonstrating minimal engraftment of cells in the heart when delivered by an intravenous (IV) infusion and the demonstration that higher engraftment in the heart is associated with greater improvement in left ventricular (LV) function.3,4 In patients with nonischemic cardiomyopathy, Vrtovec et al2 randomized 110 patients to IC autologous CD34+ stem cells (n=55) or control. During a 5-year period, those patients randomized to IC delivery of CD34+ cells had a higher event-free survival and sustained improvements in left ventricular ejection fraction (LVEF) and exercise capacity by 6-minute walk test. In a subgroup of patients (n=43) that received labeled cells to measure engraftment (5.7% at 18 hours), only those patients with homing above the median sustained an improvement in LVEF at 1 year, supporting the importance of cell engraftment in mediating efficacy. In a second study,4 the same group compared IC versus IM delivery of the same dose of CD34+ stem cells to a similar group (n=40) of patients with nonischemic cardiomyopathy. They observed that retention of cells measured by SPECT (single photon emission computed tomography) at 18 hours after delivery was 4-fold greater by IM delivery versus IC (19.2 versus 4.4%) and that IM delivery was associated with a significantly greater increase in LVEF (8.1 versus 4.2%) and 6-minute walk test distance at 6 months. These findings strongly support the concept that the initial engraftment of cells strongly correlates with improved LV function and exercise capacity.
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Fate of IV Delivered Stem Cells
Imaging of IV delivered radiolabeled stem cells in humans and animals reveals …