Intracoronary Cardiac Progenitor Cells in Single Ventricle Physiology: The PERSEUS Randomized Phase 2 Trial
Rationale: Patients with single ventricle physiology are at high risk of mortality resulting from ventricular dysfunction. The preliminary results of the phase 1 trial showed cardiosphere-derived cells (CDCs) may be effective against congenital heart failure.
Objective: To determine if intracoronary delivery of autologous CDCs improves cardiac function in patients with single ventricle physiology.
Methods and Results: We conducted a phase 2 randomized controlled study to assign 41 patients in a 1:1 ratio who had single ventricle physiology undergoing staged-2 or -3 palliation to receive intracoronary infusion of CDCs 4 to 9 weeks after surgery or staged reconstruction alone (study A). The primary outcome measure was to assess cardiac function improvement at 3-month follow-up. Four months after palliation, controls had an alternative option to receive late CDC-infusion upon request (study B). Secondary outcomes included ventricular function, heart failure status, somatic growth, and health-related quality of life (QOL) after a 12-month observation. At 3 months, the absolute changes in ventricular function were significantly greater in the CDC-treated group than in controls (+6.4% [SD 5.5] vs. +1.3% [3.7]; P=0.003). In study B, a late CDC-infusion in 17 controls increased the ventricular function at 3 months compared with baseline (38.8% [SD 7.7] vs. 34.8% [7.4]; P<0.0001). At 1 year, overall CDC infusion was associated with improved ventricular function (41.4% [SD 6.6] vs. 35.0% [8.2]; P<0.0001) and volumes (P<0.001), somatic growth (P<0.0001) with increased trophic factors production, such as insulin-like growth factor-1 and hepatocyte growth factor, and QOL, along with a reduced heart failure status (P<0.0001) and cardiac fibrosis (P=0.014) relative to baseline.
Conclusions: Intracoronary infusion of CDCs after staged palliation favorably affected cardiac function by reverse remodeling in patients with single ventricle physiology. This impact may improve heart failure status, somatic growth, and QOL in patients, and reduce parenting stress for their families. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT01829750.
- single ventricle physiology
- hypoplastic left heart syndrome
- cardiovascular surgery
- cardiac progenitors
- cell therapy
- stem cell
- congenital heart disease
- heart regeneration
- heart failure
- coronary intervention
- Received November 1, 2016.
- Revision received December 29, 2016.
- Accepted January 3, 2017.