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

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.

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Congenital Brain Anomalies Associated With the Hypoplastic Left Heart Syndrome

PEDIATRICS ◽

10.1542/peds.85.6.984 ◽

1990 ◽

Vol 85 (6) ◽

pp. 984-990 ◽

Cited By ~ 1

Author(s):

Tracy A. Glauser ◽

Lucy B. Rorke ◽

Paul M. Weinberg ◽

Robert R. Clancy

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Hypoplastic Left Heart Syndrome ◽

Left Heart ◽

Hypoplastic Left Heart ◽

Brain Anomalies ◽

Physical Features ◽

Left Heart Syndrome

This study details the type, frequency, and clinical presentation of developmental brain anomalies in 41 infants with the hypoplastic left heart syndrome encountered during a 52-month interval. Overall, 29% of the infants had either a major or minor central nervous system abnormality. Overt central nervous system malformations, including 3 cases of agenesis of the corpus callosum and 1 case of holoprosencephaly, were seen in 4 infants (10%). Micrencephaly (brain weight at autopsy more than 2 SDs below the mean for age) was found in 27% of the infants. An immature cortical mantle was seen in 21% of the study group. Seven infants (17%) had specific recognizable patterns of malformation. The absence of dysmorphic physical features did not preclude overt or subtle central nervous system malformations. Conversely, the presence of dysmorphic features did not reliably indicate an underlying brain anomaly. Infants who had hypoplastic left heart syndrome as one of multiple nonneurologic malformations were more likely to have micrencephaly than those infants with hypoplastic left heart syndrome as an isolated abnormality. Occurrence of developmental neuropathology was elevated in those infants with hypoplastic left heart syndrome who did not have a recognizable pattern of malformation but who were small for gestational age, microcephalic, or had ocular abnormalities. Infants with hypoplastic left heart syndrome deserve careful genetic, ophthalmologic, and neurologic evaluations, imaging of their intracranial anatomy, and long-term neurologic follow-up.

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ALTERED LOADING CONDITIONS IN FETAL HYPOPLASTIC LEFT HEART SYNDROME INITIATE LONG-TERM CHANGES IN RIGHT VENTRICULAR FUNCTION

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(11)62039-1 ◽

2011 ◽

Vol 57 (14) ◽

pp. E2039 ◽

Cited By ~ 2

Author(s):

Paul A. Brooks ◽

Nee S. Khoo ◽

Lisa K. Hornberger

Keyword(s):

Right Ventricular ◽

Ventricular Function ◽

Hypoplastic Left Heart Syndrome ◽

Right Ventricular Function ◽

Loading Conditions ◽

Left Heart ◽

Hypoplastic Left Heart ◽

Long Term Changes ◽

Left Heart Syndrome

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Decreased right ventricular longitudinal strain in children with hypoplastic left heart syndrome during staged repair and follow-up: does it have implications in clinically stable patients?

The International Journal of Cardiovascular Imaging ◽

10.1007/s10554-020-01870-0 ◽

2020 ◽

Vol 36 (9) ◽

pp. 1667-1677

Author(s):

Roshan D’Souza ◽

Yan Wang ◽

Renzo J. C. Calderon-Anyosa ◽

Andrea E. Montero ◽

Maalika M. Banerjee ◽

...

Keyword(s):

Right Ventricular ◽

Hypoplastic Left Heart Syndrome ◽

Longitudinal Strain ◽

Left Heart ◽

Hypoplastic Left Heart ◽

Left Heart Syndrome

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Abstract 11909: Transcoronary Infusion of Cardiac Progenitor Cells in Hypoplastic Left Heart Syndrome: 3-year Results of the TICAP Trial

Circulation ◽

10.1161/circ.132.suppl_3.11909 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Shuta Ishigami ◽

Suguru Tarui ◽

Takuya Goto ◽

Daiki Ousaka ◽

Kenji Baba ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Function ◽

Hypoplastic Left Heart Syndrome ◽

Controlled Study ◽

Growth Enhancement ◽

Left Heart ◽

Hypoplastic Left Heart ◽

Ventricular Ejection Fraction ◽

Safety And Efficacy ◽

Left Heart Syndrome

Backgrounds: Hypoplastic left heart syndrome (HLHS) is still one of the severe congenital heart defects. The first results of the TICAP trial (NCT01273857) conducted in our hospital have shown that intracoronary infusion of cardiosphere-derived cells (CDCs) in children with HLHS was feasible and safe; however, the mid-term safety and efficacy of CDCs infusion in these patients remain unsolved. The aim of this study is to evaluate the safety and efficacy of CDCs injection during mid-term period and to determine the factors that may be related to the beneficial effects of cardiac function after cell injection. Methods and Design: This phase 1 trial is a prospective controlled study. Fourteen patients with HLHS undergoing staged-2 or -3 palliations were enrolled between January 2011, and January 2012. Seven patients assigned to receive intracoronary CDCs infusion 1 month after the cardiac surgery followed by 7 patients allocated to a control with standard care alone. The primary endpoint was to assess the safety and the secondary endpoint was to evaluate the cardiac function and heart failure status. Results: No complications including tumor formation were reported within 3 years after CDC infusion. Echocardiogram showed a significantly greater improvement in right ventricular ejection fraction (RVEF) in children receiving CDCs than in controls at 3 years (+8.0 ± 4.7% vs. +2.2 ± 4.3%, P=0.03). In cardiac MRI study, improvement of RVEF at 3 years was significantly greater in the CDC-treated group than in controls (+5.7 ± 4.9 vs. -1.0 ± 4.6%, P=0.04). These cardiac function improvements resulted in reduced brain natriuretic peptide levels (P=0.04), lower incidence of unplanned catheter interventions (P=0.04), and higher weight-for-age Z score (WAZ) (P=0.02) at 3 years compared with those of controls. As independent predictors of treatment responsiveness, absolute changes in RVEF at 3 years were negatively correlated with age, WAZ, and RVEF at CDC infusion (age: r=-0.91, P=0.005; WAZ: r=-0.88, P=0.009; EF: r=-0.90, P=0.006). Conclusions: Intracoronary CDC infusion in patients with HLHS was safe and improved RVEF during 3 years of follow-up. This therapeutic strategy may merit somatic growth enhancement and reduce the incidence of heart failure.

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