Intracoronary Autologous Cardiac Progenitor Cell Transfer in Patients with Hypoplastic Left Heart Syndrome (TICAP): A Prospective Phase 1 Controlled Trial
Rationale: Hypoplastic left heart syndrome (HLHS) remains a lethal congenital cardiac defect. Recent studies have suggested that intracoronary administration of autologous cardiosphere-derived cells (CDCs) may improve ventricular function.
Objective: The aim of this study was to test whether intracoronary delivery of CDCs is feasible and safe in patients with HLHS.
Methods and Results: Between January 5, 2011, and January 16, 2012, 14 patients (1.8 ± 1.5 years) were prospectively assigned to receive intracoronary infusion of autologous CDCs 33.4 ± 8.1 days after staged procedures (n=7), followed by 7 controls with standard palliation alone. The primary endpoint was to assess the safety and the secondary endpoint included the preliminary efficacy to verify the right ventricular ejection fraction (RVEF) improvements between baseline and 3 months. Manufacturing and intracoronary delivery of CDCs were feasible and no serious adverse events were reported within the 18-month follow-up. Patients treated with CDCs showed RVEF improvement from baseline to 3-month follow-up (46.9 ± 4.6% to 52.1 ± 2.4%, P=0.008). Compared with controls at 18 months, cMRI analysis of CDC-treated patients showed a higher RVEF (31.5 ± 6.8% vs. 40.4 ± 7.6%, P=0.049), improved somatic growth (P=0.0005), reduced heart failure status (P=0.003), and lower incidence of coil occlusion for collaterals (P=0.007).
Conclusions: Intracoronary infusion of autologous CDCs appears to be feasible and safe in children with HLHS after staged surgery. Large phase 2 trials are warranted to examine the potential effects of cardiac function improvements and the long-term benefits of clinical outcomes.
- cell therapy
- hypoplastic left heart syndrome
- congenital heart disease
- cardiac progenitor cells
- cellular transplantation
- single ventricle
- Received June 23, 2014.
- Revision received October 31, 2014.
- Accepted November 14, 2014.