Abstract 14781: Intracoronary Cardiosphere-Derived Cells for Heart Regeneration after Myocardial Infarction: Determinants of Regenerative Efficacy in the Final 1-Year Results of the CADUCEUS Trial
Background: Cardiosphere-derived cells (CDCs) exert regenerative effects in post-myocardial infarction (MI) patients with left ventricular (LV) dysfunction, but durability of the effect is unclear. Here we report full one year results of the randomized controlled CADUCEUS trial.
Methods: Autologous CDCs (12.5-25M) grown from endomyocardial biopsy specimens were infused into the infarct-related artery in 17 patients with LV dysfunction 1.5-3 months post-MI. Eight patients were followed as routine-care controls.
Results: At baseline, mean LVEF (39%) and scar size (24% of LV) did not differ between study groups. In >15 months of follow-up, safety endpoints, including arrhythmia, were equivalent. At 12 months, magnetic resonance imaging revealed that CDC-treated patients had smaller scar size compared to controls (12.9±6.1% vs 20.3±7.5% of LV; p: 0.036) (Fig A). Scar mass decreased in CDC-treated subjects (-11.9±6.8g) but not controls (-1.7±7.8g, p: 0.014). Viable heart mass increased in CDC-treated subjects (+22.6±9.4g) but not controls (+1.8±8.7 g, p<0.001; Fig B), consistent with genuine tissue regeneration. Scar shrinkage correlated strongly with increased viability (p<0.001). Covariate analysis revealed two factors associated with greater scar size reduction in CDC-treated patients: higher baseline scar size (r=-0.89, p<0.001) (Fig C), and lower % of infused CD90+ cells (r=0.88, p<0.001) (Fig D). Scar size treatment effect did not correlate with time from MI to CDC infusion or with % of infused c-kit cells. The changes in LVEF in CDC-treated subjects (ΔLVEF=5.4±0.6% at 12 mos, p=0.079 compared to baseline) were consistent with the known relationship between scar size and EF post-MI.
Conclusions: Intracoronary infusion of autologous CDCs is safe and effective in regenerating infarcted myocardium at 12 months. Baseline scar size, and %CD90+ cells in the CDCs, merit prospective analysis as possible contributors to regenerative efficacy.
- Clinical trials
- Cardiac regeneration
- Myocardial infarction
- Regenerative medicine stem cells
- Stem cell therapy
- © 2012 by American Heart Association, Inc.