ABSTRACT
BACKGROUND: Bone marrow mononuclear cell fraction has been used as therapy for dilated cardiomyopathy in adults. Although case series are reported, there are no randomized controlled studies in children. METHODS: We designed a randomized, crossover, controlled pilot study to determine safety and feasibility of intracoronary stem cell therapy in children. The primary safety end-point was freedom from death and transplantation or any complication that could be considered related to bone marrow injection or anesthesia (e.g., infection, malignancy, anaphylaxis, renal deterioration). Other end-points were magnetic resonance imaging measurements and N-terminal prohormone brain natriuretic peptide. Participants included 10 children (mean age 7.2 years; range, 2.2-14.1 years; 6 boys) with cardiomyopathy (New York Heart Association/Ross Classification II-IV). Patients were crossed over at 6 months. RESULTS: The original protocol was completed by 9 patients. The safety end-point was achieved in all. Ratio of the geometric means for treatment effect adjusting for baseline was assessed for end-diastolic and end-systolic volumes (EDV, ESV): 0.93 for EDV (95% confidence interval 0.88-0.99, p = 0.01), indicating EDV was on average 7% lower in patients after stem cell treatment, and 0.90 for ESV (95% confidence interval 0.82-1.00, p = 0.05), indicating ESV was on average 10% lower after stem cell treatment compared with placebo. The primary efficacy end-point ejection fraction was not met. CONCLUSIONS: Bone marrow mononuclear cell therapy for cardiomyopathy is feasible and safe in children. Left ventricular volumes were significantly reduced 6 months after stem cell injection compared with placebo, which may reflect reverse remodeling.
Subject(s)
Bone Marrow Cells/cytology , Bone Marrow Transplantation/methods , Cardiomyopathy, Dilated/surgery , Heart Ventricles/physiopathology , Stem Cell Transplantation/methods , Ventricular Function, Left/physiology , Ventricular Remodeling , Adolescent , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/physiopathology , Child , Child, Preschool , Cross-Over Studies , Feasibility Studies , Female , Heart Ventricles/diagnostic imaging , Humans , Infant , Magnetic Resonance Imaging, Cine , Male , Pilot Projects , Stroke Volume/physiology , Transplantation, Autologous , Treatment OutcomeABSTRACT
This article discusses the main methods currently used in clinical practice to support patients with end-stage heart failure and the research into new devices under development, particularly for young children. With an increasing demand on the supply of organs available for heart transplant, alternative strategies are being sought to maintain patients with end-stage cardiac failure for longer periods of time. Devices that support a failing heart, allowing cardiac recovery in some cases, or more commonly accommodate the time to source a suitable donor heart for transplantation, provide crucial therapeutic options. Extra-corporeal membrane oxygenation and ventricular assist devices are the mainstay of such bridging therapy. Although providing essential support to critically ill patients, they are not without their own significant associated risks. Therapeutic advances aim to reduce the risks associated with these bridging systems, and new artificial devices are being developed to improve this supportive care.
