European Journal of Heart Failure | 2021
The CONCERT‐HF trial: a sweet and sour symphony
Abstract
The current issue of the Journal reports the final conclusions of the CONCERT-HF (Combination Of meseNchymal and c-kit+ Cardiac stEm cells as Regenerative Therapy for Heart Failure) trial.1 This is a phase II, randomized, placebo-controlled clinical trial designed to assess the feasibility, safety, and effect of autologous bone marrow-derived mesenchymal stem cells (MSCs) and c-kit+ cells (CPCs), alone and in combination, compared to placebo (cell-free PlasmaLyte-A medium) when administered by transendocardial injection in patients with ischaemic cardiomyopathy. Participants had tissue samples collected from their heart and bone marrow to prepare the cell-based products. The main conclusions of this trial indicate that CPCs are safe, with promising, yet not incontrovertible, efficacy effects in terms of a reduction in the primary endpoint. The CONCERT-HF trial has had a long and bumpy journey. Its scientific foundation is rooted in the work of Anversa, the Director of the Harvard Medical School laboratory for regenerative medicine from 2007 to 2015. In 2007, Anversa and colleagues reported that adult hearts contain cells that express the haematological stem cell marker c-kit, and that c-kit+ cardiac cells are clonogenic, multipotent, and capable of self-renewal (i.e. genuine heart stem cells).2 This generated such a burst of enthusiasm that a phase I clinical trial using such c-kit+ cardiac stem cells was designed and launched by the same team. The SCIPIO (Cardiac Stem Cell Infusion in Patients with Ischemic CardiOmyopathy) trial, published in The Lancet in 2011, recruited 16 patients with myocardial infarction; in 14 of them, the ejection fraction