Abstract 18117: Cardiopoietic Stem Cell Therapy In Heart Failure: The Multicenter Randomized C-cure Trial
Background Cardiopoietic stem cells improve left ventricular function and blunt pathological remodeling in preclinical models of heart failure. In this first-in-man trial we assessed the feasibility and safety of autologous bone marrow-derived cardiac-specified stem cell therapy, and probed for efficacy signals in patients with heart failure of ischemic origin.
Methods The prospective, multicenter, randomized Cardiopoietic stem Cell therapy in heart failURE (C-CURE) trial was conducted at nine sites, in forty-five chronic ischemic heart failure patients assigned to receive standard-of-care versus standard-of-care plus cardiac-specified (cardiopoietic) stem cells (2:1 randomization). In the cell therapy arm, bone marrow was harvested and isolated mesenchymal stem cells cardiogenically committed. Derived cardiopoietic stem cells, meeting quality control, were delivered by endomyocardial injections using electromechanical guidance. If quality criteria were not met, patients were crossed-over to the control arm. Cross-over analysis was validated by intent-to-treat and per-protocol analysis. Data acquisition and analysis were carried out in blinded fashion.
Results. Cardiopoietic specification was achieved for each patient with dose attained in 75%, and successful delivery without complications in 100% of cases. There was no evidence of increased cardiac or systemic toxicity with cell therapy. Left ventricular ejection fraction was improved in cell therapy (n=21) (27.5±1.0 to 34.5±1.1%) versus standard-of-care (n=24) alone (28.2±1.4 to 28.0±1.4%; p<0.0001), associated with reduced left ventricular end-systolic volume (-25±3 versus -8±3 mL, p<0.001). Cell therapy yielded improved 6-min walk (+53±18 versus -20±15 m, p<0.004), and a superior composite clinical score encompassing cardiac structure/function in tandem with NYHA functional class, quality of life, physical performance, hospitalization and event-free survival.
Conclusion. This trial implements the new paradigm of organ-specified cell-based therapy. Cardiopoietic stem cell therapy was found feasible and safe with signs of benefit in ischemic heart failure, meriting definitive clinical evaluation.
- © 2012 by American Heart Association, Inc.