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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
Author(s) -
Bolli Roberto,
Mitrani Raul D.,
Hare Joshua M.,
Pepine Carl J.,
Perin Emerson C.,
Willerson James T.,
Traverse Jay H.,
Henry Timothy D.,
Yang Phillip C.,
Murphy Michael P.,
March Keith L.,
Schulman Ivonne H.,
Ikram Sohail,
Lee David P.,
O'Brien Connor,
Lima Joao A.,
Ostovaneh Mohammad R.,
AmbaleVenkatesh Bharath,
Lewis Gregory,
Khan Aisha,
Bacallao Ketty,
Valasaki Krystalenia,
Longsomboon Bangon,
Gee Adrian P.,
Richman Sara,
Taylor Doris A.,
Lai Dejian,
Sayre Shelly L.,
Bettencourt Judy,
Vojvodic Rachel W.,
Cohen Michelle L.,
Simpson Lara,
Aguilar David,
Loghin Catalin,
Moyé Lem,
Ebert Ray F.,
Davis Barry R.,
Simari Robert D.
Publication year - 2021
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1002/ejhf.2178
Subject(s) - medicine , ejection fraction , heart failure , mesenchymal stem cell , placebo , cardiology , mace , cell therapy , cardiac function curve , adverse effect , cell , myocardial infarction , pathology , percutaneous coronary intervention , genetics , alternative medicine , biology
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.