@article{629564235df34b76b26dcce257717969,
title = "Cardiopoietic stem cell therapy in ischaemic heart failure: long-term clinical outcomes",
abstract = "Aims: This study aims to explore long-term clinical outcomes of cardiopoiesis-guided stem cell therapy for ischaemic heart failure assessed in the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial. Methods and results: CHART-1 is a multinational, randomized, and double-blind trial conducted in 39 centres in heart failure patients (n = 315) on standard-of-care therapy. The {\textquoteleft}active{\textquoteright} group received cardiopoietic stem cells delivered intramyocardially using a retention-enhanced catheter. The {\textquoteleft}control{\textquoteright} group underwent patient-level sham procedure. Patients were followed up to 104 weeks. In the entire study population, results of the primary hierarchical composite outcome were maintained neutral at Week 52 [Mann–Whitney estimator 0.52, 95% confidence interval (CI) 0.45–0.59, P = 0.51]. Landmark analyses suggested late clinical benefit in patients with significant left ventricular enlargement receiving adequate dosing. Specifically, beyond 100 days of follow-up, patients with left ventricular end-diastolic volume of 200–370 mL treated with ≤19 injections of cardiopoietic stem cells showed reduced risk of death or cardiovascular hospitalization (hazard ratio 0.38, 95% CI 0.16–0.91, P = 0.031) and cardiovascular death or heart failure hospitalization (hazard ratio 0.28, 95% CI 0.09–0.94, P = 0.040). Cardiopoietic stem cell therapy was well tolerated long term with no difference in safety readouts compared with sham at 2 years. Conclusions: Longitudinal follow-up documents that cardiopoietic stem cell therapy is overall safe, and post hoc analyses suggest benefit in an ischaemic heart failure subpopulation defined by advanced left ventricular enlargement on tolerable stem cell dosing. The long-term clinical follow-up thus offers guidance for future targeted trials.",
keywords = "Cardiopoiesis, Clinical trial, Heart failure, Longitudinal, Regenerative medicine, Stem cell",
author = "{for the CHART Program} and Jozef Bartunek and Andre Terzic and Davison, {Beth A.} and Atta Behfar and Ricardo Sanz-Ruiz and Wojciech Wojakowski and Warren Sherman and Heyndrickx, {Guy R.} and Marco Metra and Filippatos, {Gerasimos S.} and Waldman, {Scott A.} and Teerlink, {John R.} and Henry, {Timothy D.} and Gersh, {Bernard J.} and Roger Hajjar and Michal Tendera and Stefanie Senger and Gad Cotter and Povsic, {Thomas J.} and William Wijns",
note = "Funding Information: The CHART‐1 study was supported by Celyad, SA (Mont‐Saint‐Guibert, Belgium). Celyad has received research grants from the Walloon Region (Belgium, DG06 funding). Funding Information: J.B. and W.W. have been members of an institution that co‐founded Cardio3 BioSciences (now Celyad). J.B. reports that all consultancy/speakers fees and research contracts are directed to Cardiac Research Institute, Aalst, Belgium. A.T. and A.B. report that they are listed as co‐inventors on patents US 20080019944 and US 20120100533. They are supported by National Institutes of Health (HL134664), Marriott Family Foundation, Michael S and Mary Sue Shannon Family, Russ and Kathy VanCleve Foundation, and Mayo Clinic Center for Regenerative Medicine. W.W. reports institutional research grants from several device companies (including Biotronik, MiCell, MicroPort, and Terumo); speakers fees from Abbott Vascular, Biotronik, and MicroPort; and co‐founder of Argonauts Partners, an innovation facilitator. B.D. reports grants from Celyad, Amgen Inc., Cirius Therapeutics Inc., Laguna Pharmaceuticals, Novartis Pharmaceutical Corp, Sanofi, Roche Diagnostics Inc., Trevena Inc., NIH, and Ventrix; and personal fees from Novartis Pharma AG. G.C. reports grants from Celyad, Amgen Inc., Cirius Therapeutics Inc., Laguna Pharmaceuticals, Novartis Pharmaceutical Corp, Sanofi, Roche Diagnostics Inc., Trevena Inc., NIH, and Ventrix; and personal fees from Novartis Pharma AG. S.S. reports grants from Celyad, Amgen Inc., Cirius Therapeutics Inc., Laguna Pharmaceuticals, Novartis Pharmaceutical Corp, Sanofi, Roche Diagnostics Inc., Trevena Inc., NIH, and Ventrix. W.S. is a Biotechnology Consultant, previously CMO at Celyad. All other authors have no disclosures. Publisher Copyright: {\textcopyright} 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology",
year = "2020",
month = dec,
doi = "10.1002/ehf2.13031",
language = "English (US)",
volume = "7",
pages = "3345--3354",
journal = "ESC heart failure",
issn = "2055-5822",
publisher = "The Heart Failure Association of the European Society of Cardiology",
number = "6",
}