Allogeneic Cardiosphere-derived Cells for the Treatment of Heart Failure with Reduced Ejection Fraction: Results of the Dilated cardiomYopathy iNtervention with Allogeneic Myocardially-regeneratIve Cells (DYNAMIC) trial.

AIMS: The DYNAMIC trial assessed the safety and explored the efficacy of multivessel intracoronary infusion of allogeneic cardiosphere-derived cells (CDCs) in patients with heart failure and reduced ejection fraction (HFrEF). METHODS AND RESULTS: We enrolled 14 patients with EF≤35% and NYHA III-IV despite maximal medical- and device-based therapy in this single-center, open-label trial. Intracoronary catheterization delivered four escalating doses (totaling 37.5-75 million cells) by sequential non-occlusive technique to all three major coronary arteries. The primary safety endpoint was a composite of post-infusion TIMI flow, ventricular tachycardia/fibrillation, sudden death, major adverse cardiac events or acute myocarditis within 72 hours. Twelve patients were male and EF averaged 23.0% (±4.5%). No primary safety endpoints were observed. Two patients died of HFrEF progression 9- and 12-months following infusion. Compared to baseline, there was an improvement in EF (26.8% vs. 22.9%, p=0.023) and left ventricular end-systolic volume (139.5 vs. 177.8, p=0.03) at 6 months. Quality of life (QoL) scores and NYHA class (p=0.006) improved at 6 months. At 12 months, the improvement in EF and QoL remained significant. CONCLUSIONS: Global intracoronary infusion of allogeneic CDCs is safe and feasible. The efficacy of allogeneic CDCs in HFrEF needs to be tested in larger randomized trials.