A Phase II Study of Autologous Mesenchymal Stromal Cells and c-kit Positive Cardiac Cells, Alone or in Combination, in Patients with Ischemic Heart Failure: The CCTRN CONCERT-HF Trial.

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 ischemic 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 centers enrolled 125 participants with left ventricular ejection fraction (LVEF) of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in NYHA 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 (MLHFQ score) was significantly improved by MSCs alone (P = 0.050) and MSCs+CPCs (P = 0.023) vs. placebo. LVEF, LV volumes, scar size, 6-min walking distance, and peak VO2 did not differ significantly among groups. Conclusions This is the first multicenter 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 ischemic HF without affecting LV 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.