Abstract 7: Intracoronary Autologous Cardiac Progenitor Cell Transfer In Children With Hypoplastic Left Heart Syndrome: 2-year Results Of The Ticap Trial

Abstract

Backgrounds: Hypoplastic left heart syndrome (HLHS) is a severe congenital heart malformation. Objective: The aim of this study is to determine whether intracoronary delivery of autologous cardiosphere-derived cells (CDCs) was feasible and safe to treat the children with HLHS. Methods: Four-teen patients with HLHS undergoing staged palliations were prospectively enrolled in this trial between January, 2011, and January, 2012. Seven patients constitutively assigned to receive intracoronary CDCs injection followed by 7 patients allocated to a control group with standard care alone. The primary endpoint was to assess the safety and the secondary endpoint was the preliminary efficacy by assessing the improvements of the right ventricular function during the follow-up. Results: No major complications were reported within 24 months of CDC infusion. Echocardiography showed that improvement of right ventricular ejection fraction (RVEF) was greater in the CDC-treated group (+5.3±3.2%) than in controls (+0.1±3.4%, P=0.01) at 3-month follow up. This cardiac function enhancement was manifested even in long-term observation (+7.8±4.9% vs. +2.2±3.1% at 1 year, P=0.03; +8.8±3.7% vs. +3.4±6.4% at 2 years, P=0.04). The absolute improvements in RVEF between 2 groups was confirmed by using right ventriculogram (RVG: +8.9±7.6% vs. +2.0±2.8% at 1 year, P=0.02; +8.1±6.0% vs. +2.9±3.9% at 2 years, P=0.04). In addition, RVEF on cMRI was also markedly improved in CDC-treated patients from 36.1±7.5% at baseline to 42.7±8.7% at 1 year (P=0.04) and to 42.4±7.6% at 2 years (P=0.047). Heart failure status was reduced in CDC-treated group as shown by significant decrease in Ross Heart Failure Class (2.6±0.8 at baseline vs. 1.4±0.5 at 2 years, P=0.01). Moreover, Z scores for weight-for-age was significantly increased from −4.0±2.7 at baseline to −2.2±1.4 at 2 year (P=0.02), whereas all of these parameters did not change in control subjects. Conclusion: These results of 2-year follow-up of TICAP trial suggest that intracoronary infusion of autologous CDCs is feasible and safe to treat the children with HLHS. This novel therapeutic strategy may impact on cardiac function as well as clinical symptom of heart failure status and somatic growth in long-term outcome.