TY - JOUR
T1 - Allogeneic cardiosphere-derived cells for the treatment of heart failure with reduced ejection fraction
T2 - The Dilated cardiomYopathy iNtervention with Allogeneic MyocardIally-regenerative Cells (DYNAMIC) trial
AU - Chakravarty, Tarun
AU - Henry, Timothy D.
AU - Kittleson, Michelle
AU - Lima, Joao
AU - Siegel, Robert J.
AU - Slipczuk, Leandro
AU - Pogoda, Janice M.
AU - Smith, Rachel R.
AU - Malliaras, Konstantinos
AU - Marbán, Linda
AU - Ascheim, Deborah D.
AU - Marbán, Eduardo
AU - Makkar, Raj R.
N1 - Funding Information:
National Institutes of Health (HL095203).
Publisher Copyright:
© Europa Digital & Publishing 2020. All rights reserved.
PY - 2021
Y1 - 2021
N2 - 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). Here we report the results of the DYNAMIC trial. Methods and results: We enrolled 14 patients with EF ≤35% and NYHA Class III-IV despite maximal medical and device-based therapy in this single-centre, open-label trial. Intracoronary catheterisation delivered four escalating doses (totalling 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 nine 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 cm3, p=0.03) at six months. Quality of life (QoL) scores and NYHA class (p=0.006) improved at six 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 randomised trials.
AB - 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). Here we report the results of the DYNAMIC trial. Methods and results: We enrolled 14 patients with EF ≤35% and NYHA Class III-IV despite maximal medical and device-based therapy in this single-centre, open-label trial. Intracoronary catheterisation delivered four escalating doses (totalling 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 nine 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 cm3, p=0.03) at six months. Quality of life (QoL) scores and NYHA class (p=0.006) improved at six 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 randomised trials.
KW - Cell-based regenerative therapy
KW - Depressed left ventricular function
KW - Dilated non-ischaemic cardiomyopathy
KW - Ischaemic cardiomyopathy
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U2 - 10.4244/eij-d-19-00035
DO - 10.4244/eij-d-19-00035
M3 - Article
C2 - 31763984
AN - SCOPUS:85087132709
SN - 1774-024X
VL - 16
SP - E293-E300
JO - EuroIntervention
JF - EuroIntervention
IS - 4
ER -