Infants with congenital heart disease, specifically left heart syndrome, who had cardiac stem-cell therapy after surgery showed improved cardiac and brain function after 3 years when compared with infants who had standard therapy, according to latest results from a clinical trial of progenitor cell infusion in infants.
The prospective, controlled study, published in the November issue of the Journal of Thoracic and Cardiovascular Surgery (2015;150:1198-1208), involved 14 infants with hypoplastic left heart syndrome (HLHS). Dr. Suguru Tarui and colleagues at Okayama University Hospital in Japan infused seven infants with intracoronary cardiosphere-derived cells (CDCs) 1 month after they had two- or three-stage palliative surgery. Seven controls had standard care alone. The trial is known TICAP (Three-year follow-up of the Transcoronary Infusion of Cardiac Progenitor Cells in Patients With Single-Ventricle Physiology) (ClinicalTrials.gov ID: NCT01273857).
Infants born with HLHS are known to have poor prognoses. HLHS has been associated with the highest mortality of all congenital heart lesions (Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2015;18:2-6).
The Okayama investigators conducted TICAP in 2011 and demonstrated the feasibility and safety of the intracoronary delivery of CDCs in infants with HLHS after staged procedures. The latest report looks at the secondary outcome of cardiac function through 36 months of follow-up, and is the first clinical trial to report on the mid-term results of cardiac progenitor therapy in congenital heart disease.
“CDC infusion could improve right ventricular function from 3 through 36 months of observation,” Dr. Tarui and colleagues said. “Patients treated by CDCs showed an increase in somatic growth and reduced heart failure status in mid-term follow-up.”
Upon entry into the study, all subjects were of similar age, body weight, and risk profiles. After 36 months, the CDC group showed no complications and significantly improved right ventricular injection fraction compared with controls. As a result, the CDC group had reduced brain natriuretic peptide levels, lower rates of unplanned catheterizations, and higher weight for age. No adverse events occurred in the CDC group, while two patients in the control group had complications (one developed heart failure, another developed enteropathy).
The investigators looked at predictors of cardiac functional efficacy in the CDC group and determined that younger age was associated with greater improvement of right ventricular ejection fraction, as measured on echocardiography. The lower weight-for-age Z score and reduced ejection fraction at the time of infusion may be predictors of cardiac function improvements at 3 years.
“This therapeutic strategy may merit somatic growth enhancement and reduce the incidence of heart failure,” Dr. Tarui and coauthors said.
They noted a number of limitations of their small clinical trial. The study was nonrandomized, and the cardiac interventions were not blinded, among others. “Larger phase II studies focusing on changes in cardiac function, myocardial fibrosis, and quality of life and clinical event rates are warranted to confirm these effects of CDC administration in patients with single ventricular physiology,” they said.
The government of Japan through its ministries of Health, Labor and Welfare, and Education, Culture Sports, Science and Technology provided funding for the study, as did the Research Foundation of Okayama University Hospital. The authors had no disclosures.