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 'active' group received cardiopoietic stem cells delivered intramyocardially using a retention-enhanced catheter. The 'control' 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.

Epicardial Transplantation of Autologous Cardiac Micrografts During Coronary Artery Bypass Surgery

“…Moreover, injection of bone marrow mesenchymal cells with or without c-kit positive cardiac cells improved the patients' quality of life compared to placebo ( 36 ). In the CHART-1 trial, intramyocardially injected cardiopoietic stem cells were associated with reduced risk of death or cardiovascular hospitalization in a subpopulation of patients with advanced LV enlargement as compared to a sham procedure ( 37 ). Despite the lack of evidence in reduction of infarct scar area or improvement in LVEF, these encouraging results indicate that cell-based therapies can have long term effects in preventing progression of HF.…”

Stem cell‐based therapies for cardiac diseases: The critical role of angiogenic exosomes

“…136 Up to date, stem cells with different origins (embryonic, fetal, and adult tissues) and differentiation potency (e.g., pluripotent and multipotent) were utilized for improving neo-vessel formation and consequently enhanced functional recovery of the ischemic heart. 137 Regarding the literature, initial reports indicated that adult stem cells (e.g., MSCs) could enhance neo-vessel formation through differentiation toward ECs lineages. Over time, some faulty published studies led to serious concerns about adult stem cell differentiation toward ECs and their putative roles in promoting angiogenesis.…”

Screening for Regenerative Therapy Responders in Heart Failure

“…Conventionally, selection of candidates for cardiac stem cell therapy relies on a cut-off value, such as LV ejection fraction <40%. Recent clinical study sub-analyses, however, document signs of cardiopoietic stem cell efficacy associated with a tight phenotypic profile, namely a range of LV dilatation, a marker of organ remodeling [ 46 , 47 ]. Candidate titration was validated in a model of staged infarction size.…”