Impact of Cardiac Progenitor Cells on Heart Failure and Survival in Single Ventricle Congenital Heart Disease
Rationale: Intracoronary administration of cardiosphere-derived cells (CDCs) in patients with single ventricles resulted in a short-term improvement in cardiac function.
Objective: To test the hypothesis that CDC infusion is associated with improved cardiac function and reduced mortality in patients with heart failure.
Methods and Results: We evaluated the effectiveness of CDCs using an integrated cohort study in 101 patients with single ventricles, including 41 patients that received CDC infusion and 60 controls treated with staged palliation alone. Heart failure with preserved (HFpEF) or reduced ejection fraction (HFrEF) was stratified by the cardiac function after surgical reconstruction. The main outcome measure was to evaluate the magnitude of improvement in cardiac function and all-cause mortality at 2 years. Animal studies were conducted to clarify the underlying mechanisms of HFpEF and HFrEF phenotypes. At 2 years, CDC infusion increased ventricular function (stage 2: +8.4% ± 10.0% vs +1.6% ± 6.4%, P=0.03; stage 3: +7.9% ± 7.5% vs -1.1% ± 5.5%, P<0.001) compared with controls. In all available follow-up data, survival did not differ between the 2 groups (Log-rank P=0.225), whereas overall patients treated by CDCs had lower incidences of late failure (P=0.022), adverse events (P=0.013), and catheter intervention (P=0.005) compared with controls. CDC infusion was associated with a lower risk of adverse events (hazard ratio: 0.411 [95% confidence interval, 0.179 to 0.942], P=0.036). Notably, CDC infusion reduced mortality (P=0.038) and late complications (P<0.05) in patients with HFrEF but not with HFpEF. CDC-treated rats significantly reversed myocardial fibrosis with differential collagen deposition and inflammatory responses between the heart failure phenotypes.
Conclusions: CDC administration in patients with single ventricles showed favorable effects on ventricular function and was associated with reduced late complications except for all-cause mortality after staged procedures. Patients with HFrEF but not HFpEF treated by CDCs resulted in significant improvement in clinical outcome.
- Received October 29, 2017.
- Revision received January 9, 2018.
- Accepted January 23, 2018.