@article{afb957e21c9f493dbad6f5bf5eb02dc3,
title = "A Phase II study of autologous mesenchymal stromal cells and c-kit positive cardiac cells, alone or in combination, in patients with ischaemic heart failure: the CCTRN CONCERT-HF trial",
abstract = "Aims: CONCERT-HF is an NHLBI-sponsored, double-blind, placebo-controlled, Phase II trial designed to determine whether treatment with autologous bone marrow-derived mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischaemic cardiomyopathy. Methods and results: Patients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12 months. Seven centres enrolled 125 participants with left ventricular ejection fraction of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in New York Heart Association class II or III. The proportion of major adverse cardiac events (MACE) was significantly decreased by CPCs alone (−22% vs. placebo, P = 0.043). Quality of life (Minnesota Living with Heart Failure Questionnaire score) was significantly improved by MSCs alone (P = 0.050) and MSCs + CPCs (P = 0.023) vs. placebo. Left ventricular ejection fraction, left ventricular volumes, scar size, 6-min walking distance, and peak oxygen consumption did not differ significantly among groups. Conclusions: This is the first multicentre trial assessing CPCs and a combination of two cell types from different tissues in HF patients. The results show that treatment is safe and feasible. Even with maximal guideline-directed therapy, both CPCs and MSCs were associated with improved clinical outcomes (MACE and quality of life, respectively) in ischaemic HF without affecting left ventricular function or structure, suggesting possible systemic or paracrine cellular mechanisms. Combining MSCs with CPCs was associated with improvement in both these outcomes. These results suggest potential important beneficial effects of CPCs and MSCs and support further investigation in HF patients.",
keywords = "Cell-based therapy, Clinical trial, Heart failure",
author = "{for the Cardiovascular Cell Therapy Research Network (CCTRN)} and Roberto Bolli and Mitrani, {Raul D.} and Hare, {Joshua M.} and Pepine, {Carl J.} and Perin, {Emerson C.} and Willerson, {James T.} and Traverse, {Jay H.} and Henry, {Timothy D.} and Yang, {Phillip C.} and Murphy, {Michael P.} and March, {Keith L.} and Schulman, {Ivonne H.} and Sohail Ikram and Lee, {David P.} and Connor O'Brien and Lima, {Joao A.} and Ostovaneh, {Mohammad R.} and Bharath Ambale-Venkatesh and Gregory Lewis and Aisha Khan and Ketty Bacallao and Krystalenia Valasaki and Bangon Longsomboon and Gee, {Adrian P.} and Sara Richman and Taylor, {Doris A.} and Dejian Lai and Sayre, {Shelly L.} and Judy Bettencourt and Vojvodic, {Rachel W.} and Cohen, {Michelle L.} and Lara Simpson and David Aguilar and Catalin Loghin and Lem Moy{\'e} and Ebert, {Ray F.} and Davis, {Barry R.} and Simari, {Robert D.}",
note = "Funding Information: : All investigators received funding from the NIH National Heart, Lung, and Blood Institute (NHLBI) for conduct of the CONCERT‐HF trial through the Cardiovascular Cell Therapy Research Network (CCTRN). R.F.E. is a staff member of the National Heart, Lung, and Blood Institute (NHLBI), the source of funding for the CONCERT‐HF trial. The views expressed in this article are those of the authors and do not necessarily represent the views of the NHLBI, National Institutes of Health, or the United States Department of Health and Human Services. I.H.S. is currently a staff member of the National Institute of Diabetes and Digestive, and Kidney Diseases (NIDDK). The views expressed in this article are those of the authors and do not necessarily represent the views of the NIDDK, National Institutes of Health, or the United States Department of Health and Human Services. J.M.H. is a scientific co‐founder and holds equity in Vestion, Inc. Vestion did not fund or participate in this study. Dr. Hare's role in Vestion has been disclosed to the University of Miami and to the steering committee of the CCTRN, and appropriate management plans have been instituted. T.D.H. has served as a consultant for Biosense Webster. C.J.P. has served as a consultant for XyloCor, Caladrius, Imbria, and Biocardia; and has grants with Adelphi Values, Brigham and Women's Hospital, Department of Defense, Gilead Sciences, Inc., McJunkin Foundation, Mesoblast, and Sanofi US. E.C.P. has served as a consultant for Mesoblast. D.A.T. is co‐founder of Stem Cell Security. P.C.Y. has served as a consultant for Terumo. All other authors have nothing to disclose. Conflict of interest Funding Information: This work was supported by National Institutes of Health [HL087318, HL113530, HL113460, HL087394, HL113457, HL087366, HL087365]. Publisher Copyright: {\textcopyright} 2021 European Society of Cardiology.",
year = "2021",
month = apr,
doi = "10.1002/ejhf.2178",
language = "English (US)",
volume = "23",
pages = "661--674",
journal = "European Journal of Heart Failure",
issn = "1388-9842",
publisher = "Oxford University Press",
number = "4",
}