Abstract 12085: Arrhythmogenic Effects of Cardiac Mesenchymal Stem Cell Implantation: Results From the POSEIDON and TAC-HFT Trials
Introduction: Transendocardial injection of mesenchymal stem cells (MSC) in patients (pts) with ischemic cardiomyopathy (ICM) improves left ventricular function and structure, but it is unknown whether MSCs have pro- or anti-arrhythmic effects. We hypothesized that MSC implantation does not cause acute or long-term ventricular proarrhythmia.
Methods: Two blinded reviews of 24-48 hour ambulatory ECG monitors (AM) recorded among 88 pts with ICM from the POSEIDON and TAC-HFT MSC trials were performed at baseline, after injection (day 1-3), and long term (up to 12 months) post-injection. Premature ventricular complexes (PVCs) were quantified and converted to a percentage of total complexes. A ventricular ectopy (VE) run was defined as ≥ 3 consecutive PVCs. The subjects included 3 groups based on randomized allocation in the parent trials: MSC (N=48), Placebo (N=21), and Bone Marrow derived cells (BMC) (N=19). Wilcoxon Signed-Rank tests were used to test for statistical significance within groups, and the Kruskal-Wallis test was used to compare changes from baseline across groups.
Results: The mean age (±SD) was 60.9 ± 9.9 yrs (92% male), with mean ejection fraction of 32.2 ± 9.8%. Baseline PVC% ranged from median of 1.3% [IQR 0.3-2.0%] for placebo group, 0.14% [IQR 0.0-0.3%] for BMC group, and 0.87% [IQR 0.2-2.4%] for MSC group. By day 3 post-injection, the median PVC% in the placebo injection group decreased to 0.37% [IQR 0.1-2.2%] (p=0.02) while there was no change among the BMC group (p=0.46) or the MSC group (p=0.73). By 1 year, there were no differences from baseline in VE among the placebo (0.71% [IQR 0.2-1.6%]; p=0.54), BMC (0.16% [IQR 0.0-0.8%]; p=0.73), or MSC groups (0.41% [IQR 0.1-1.2%]; p=0.36). In the MSC group, there was a decrease in VE runs in pts with ≥ 1 VE run/24 hrs at baseline from a median of 1.53 [IQR 1.0-10.8] to 0.50 [IQR 0.0-3.5] (p=0.01) but not in the placebo group (1.81 [IQR 1.5-2.1] to 1.0 [IQR 0.8-1.0], p=0.07; intergroup comparison p=0.18). The BMC group had insufficient VE runs for comparison.
Conclusion: Transendocardial MSC implantation in pts with ICM was not associated with increased acute or long-term ventricular proarrhythmia. A significant decrease in VE runs observed in the MSC group suggests an antiarrhythmic effect of MSC injection.
Author Disclosures: A. Ramireddy: None. C.R. Brodt: None. D.L. DiFede: Research Grant; Modest; NHBLI. Consultant/Advisory Board; Modest; Biocardia Inc. A.M. Mendizabal: Employment; Significant; EMMES Corporation. J.O. Coffey: None. J.F. Viles-Gonzalez: None. A.W. Heldman: Ownership Interest; Modest; Vestion Inc.. R.J. Myerburg: None. J.M. Hare: Employment; Modest; Vestion. Ownership Interest; Modest; Biscayne. Ownership Interest; Significant; Vestion Inc. R.D. Mitrani: Consultant/Advisory Board; Modest; Medtronic, St. Jude, J&J.
- © 2014 by American Heart Association, Inc.