Cardiosphere-Derived Injections Improve Heart Function in Children with Hypoplastic Left Heart Syndrome

Hypoplastic Left Heart Syndrome or HLHS accounts for 2 to 3 percent of all congenital heart disease. It shows a prevalence rate of two to three cases per 10,000 live births in the United States. HLHS is the most common form of functional single ventricle heart disease. The National Inpatient Sample database has estimated that there were an estimated 16,781 cases of HLHS among neonates born between 1988 and 2005 in the United States. More males have HLHS than females with the male to female ratio being about 1.5:1. Despite its low incidence relative to other congenital cardiac disorders, HLHS, if left untreated, is responsible for 25 to 40 percent of all neonatal cardiac deaths.

In HLHS patients, the left ventricle (the main pumping chamber of the heart), aorta, and related components are underdeveloped.

Children born with HLHS typically require surgery within a few days of birth and additional long-term treatment is required to address issues associated with right ventricular-dependent circulation.

Results from a clinical trial conducted by researchers at Okayama University and Okayama University Hospital show that children who suffer from HLHS seem to benefit from injections of cardiosphere-derived cells (CDCs).

Apparently in children, cardiac progenitor cells that can differentiate into several different heart-specific cell types are more abundant and self-renewing in children than adults.

The research group, led by Hidemasa Oh, monitored the heart function of seven patients who had received injections of cells and a control group of seven patient who had not received any such injections. They concluded that, “Our prospective controlled study, the first pediatric phase I clinical trial of stem cell therapy for heart disease to our knowledge, suggests that intracoronary infusion of autologous cardiac progenitor cells is a feasible and safe approach to treat children with HLHS.”

The cardiac progenitor cells used in this study came directly from the hearts of the patients. When these heart-specific progenitor cells are isolated and grown in cell culture, they form tiny balls of cells called “cardiospheres.” These patient-derived cardiosphere-derived cells (CDCs) were administered to the experimental subjects in this study after they were confirmed to contain a normal number of chromosomes and express a host of heart-specific genes. The transcoronary administration of the CDCs did not produce any adverse effects.

The heart functions monitored by the research group included the right ventricular ejection fraction or RVEF, end-systolic volume (ESV), which is the volume of blood within the ventricle at the maximum point of contraction, and the end-diastolic volume or EDV, which is the volume of blood at the maximum filling point, stroke volume, and cardiac output. Additionally, the levels of brain natriuretic peptide or BNP (a direct measure of heart failure) were also monitored. BNP is made by the ventricles of the heart in response to excessive stretching of the heart muscle.

Because of the rarity of this disease, this study was necessarily small. This study was also a non-randomized study. Therefore, this study is more of an evaluation of the safety of this procedure rather than its efficacy. However, the improvement in the RVEP in the stem cell-treated patients compared to the non-treated group 18 months after CDC administration provides possible evidence of the efficacy of this treatment.

Clearly more work is needed, but we will know more as the data rolls in.