Intracoronary autologous cardiosphere-derived cell (CDC) infusion in patients with functional single ventricle resulted in significant improvements at two years in ventricular function, somatic growth, heart failure status and event-free survival, according to the results of a study presented Tuesday by Toshikazu Sano, MD.
“Cardiosphere-derived cell infusion in patients with single-ventricle physiology was associated with improved cardiac function at two years regardless of the proceeding stage procedure,” said Sano, of the department of vascular surgery at Okayama University Hospital in Japan. “These better outcomes may be attributed to decreased incidence of rehospitalization or repeated cardiac surgery for recurrent heart failure, as well as reduced the parenting stress during child care for their families.”
Cardiosphere-derived cells are enriched with a cardiac progenitor cell population that can give rise to cardiomyocytes, smooth muscle and endothelial cells in vitro and in vivo. Along with these direct-differentiation capabilities toward cardiovascular-lineage specification for myocardial repair, recent studies have shown that cardiosphere-derived cells are able to transfer exosomes, which contain various molecular constituents of their cell of origin, including proteins and micro RNA, as biologically active cell-derived small vesicles.
In this study, Sano and colleagues assessed the long-term effects and clinical outcomes of intracoronary infusion of autologous CDCs in patients with single-ventricle physiology compared with patients treated by staged palliation alone. The study included 101 patients who underwent stage 2 or stage 3 surgical palliation with single-ventricular physiology between January 2011 and March 2015. Forty-one patients were assigned to receive CDC infusion into coronary arteries four weeks after staged palliation. Sixty patients were treated by staged palliation alone.
Compared with stage palliation alone, patients treated with the CDC infusion had significantly improved cardiac function (P<.05) and somatic growth (P<.01). In addition, CDC infusion was associated with improved event-free survivals such as late failure, adverse events and catheter intervention.
Multivariate analyses showed that both CDC infusion (P<.02) and heart failure status ( P<.03) were significant affecters for adverse events at two years.
The researchers also categorized study patients into two subgroups: heart failure with preserved or reduced ejection fraction (cardiac function <50 percent). CDC infusion improved cardiac function at two years in both groups. In patients with reduced ejection fraction receiving CDC, the incidence of all-cause mortality, late failure, adverse events and unplanned catheter intervention were significantly reduced compared with those treated by surgical reconstruction alone.
“In patients with preserved ejection fraction, the functional benefits brought by cell therapy was neither associated with improved mortality nor reduced late complication after staged palliation. It may require further studies to investigate the underlying mechanisms to innovate novel therapy to treat these patients,” Sano said.