Authors:
Jozef Bartunek, MD, PhD, Atta Behfar, MD, PhD, Dariouch Dolatabadi, MD, Marc Vanderheyden, MD, Miodrag Ostojic, MD, PhD, Jo Dens, MD, PhD, Badih El Nakadi, MD, Marko Banovic, MD, Branko Beleslin, MD, PhD, Mathias Vrolix, MD, PhD, Victor Legrand, MD, PhD, Christian Vrints, MD, PhD, Jean Louis Vanoverschelde, MD, PhD, Ruben Crespo-Diaz, PhD, Christian Homsy, MD, Michal Tendera, MD, PhD, Scott Waldman, MD, PhD, William Wijns, MD, PhD, & Andre Terzic, MD, PhD
Summary:
Objectives - To evaluate the feasibility and safety of autologous bone marrow-derived and cardiogenically-oriented mesenchymal stem cell therapy, and probe for efficacy signals in patients with chronic heart failure.
Background - In preclinical heart failure models, cardiopoietic stem cell therapy improves left ventricular function and blunts pathological remodelling.
Methods - The prospective, multicenter, randomized Cardiopoietic stem Cell therapy in heart failURE (C-CURE) trial was conducted in patients with heart failure of ischemic origin who received standard-of-care or standard-of-care plus lineage-specified stem cells. In the cell therapy arm, bone marrow was harvested and isolated mesenchymal stem cells exposed to a cardiogenic cocktail. Derived cardiopoietic stem cells, meeting release criteria under Good Manufacturing Practice, were delivered by endomyocardial injections guided by left ventricular electromechanical mapping. Data acquisition and analysis were carried out in blinded fashion. The primary endpoint was feasibility/safety at 2-year follow-up. Secondary endpoints included cardiac structure/function and measures of global clinical performance 6 months post-therapy.
Results - Mesenchymal stem cell cocktail-based priming was achieved for each patient with dose attained in 75%, and delivery without complications in 100% of cases. There was no evidence of increased cardiac or systemic toxicity induced by cardiopoietic cell therapy. Left ventricular ejection fraction was improved by cell therapy (27.5±1.0 to 34.5±1.1%) versus standard-of-care alone (27.8±2.0 to 28.0±1.8%, p<0.0001), and was associated with a reduction in left ventricular end-systolic volume (–24.8±3.0 versus –8.8±3.9 mL, p<0.001). Cell therapy also improved the 6-min walk distance (+62±18 versus –15±20 m, p<0.01), and provided a superior composite clinical score encompassing cardiac parameters in tandem with NYHA functional class, quality of life, physical performance, hospitalization and event-free survival.
Conclusions - The C-CURE trial implements the paradigm of lineage guidance in cell therapy. Cardiopoietic stem cell therapy was found feasible and safe with signals of benefit in chronic heart failure, meriting definitive clinical evaluation.
Source:
Journal of the American College of Cardiology; (04/10/13)