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Published on: October 8, 2016
Intracoronary Cardiac Progenitor Cells in Single Ventricle Physiology: The PERSEUS (Cardiac Progenitor Cell Infusion
Shuta Ishigami1, Shinichi Ohtsuki1, Takahiro Eitoku1
1From the Departments of Cardiovascular Surgery (S.I., D.O., T.G., N.H., J.K., Y. Kuroko, Y. Kotani, S.A., S.K., S. Sano), Pediatrics (S.O., T.E., M.K., Y. Kurita, K.H., Y.F., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S. Sato), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Japan; and Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital, Japan (H.O.).
Insights
Cardiosphere-derived cells (CDCs) significantly improved cardiac function in patients with single ventricle physiology. This regenerative therapy enhanced heart function, growth, and quality of life, offering a promising treatment for congenital heart failure.
Area of Science:
- Regenerative Medicine
- Cardiology
- Pediatric Cardiac Surgery
Background:
- Single ventricle physiology poses high mortality risks due to ventricular dysfunction.
- Congenital heart failure in these patients is a significant clinical challenge.
- Preliminary studies suggested cardiosphere-derived cells (CDCs) efficacy in heart failure.
Purpose of the Study:
- To evaluate the efficacy of intracoronary autologous CDCs in improving cardiac function.
- To assess the impact of CDCs on ventricular function in single ventricle patients.
- To determine if CDC therapy can enhance outcomes post-cardiac surgery.
Main Methods:
- A phase 2 randomized controlled study involving 41 patients with single ventricle physiology.
- Patients received intracoronary infusion of CDCs 4-9 weeks after staged palliation or underwent reconstruction alone.
- Cardiac function, ventricular volumes, heart failure status, somatic growth, and quality of life were assessed over 12 months.
Main Results:
- CDC treatment led to significantly greater improvements in ventricular function at 3 months compared to controls (+6.4% vs +1.3%, P=0.003).
- Late CDC infusion in controls also improved ventricular function (P<0.0001).
- At 1 year, CDC infusion improved ventricular function, volumes, somatic growth, quality of life, and reduced heart failure status and cardiac fibrosis.
Conclusions:
- Intracoronary CDC infusion after staged palliation promotes reverse remodeling and improves cardiac function in single ventricle patients.
- This therapy holds potential to enhance heart failure status, somatic growth, and quality of life.
- CDC treatment may also reduce parental stress associated with caring for these children.
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 that cardiosphere-derived cells (CDCs) may be effective against congenital heart failure.
Objective:
To determine whether 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 in a 1:1 ratio 41 patients who had single ventricle physiology undergoing stage 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 improvement in cardiac function at 3-month follow-up. Four months after palliation, controls had an alternative option to receive late CDC infusion on request (study B). Secondary outcomes included ventricular function, heart failure status, somatic growth, and health-related quality of life after a 12-month observation. At 3 months, the absolute changes in ventricular function were significantly greater in the CDC-treated group than in the controls (+6.4% [SD, 5.5] versus +1.3% [SD, 3.7]; P=0.003). In study B, a late CDC infusion in 17 controls increased the ventricular function at 3 months compared with that at baseline (38.8% [SD, 7.7] versus 34.8% [SD, 7.4]; P<0.0001). At 1 year, overall CDC infusion was associated with improved ventricular function (41.4% [SD, 6.6] versus 35.0% [SD, 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 quality of life, 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 quality of life in patients and reduce parenting stress for their families.
Clinical Trial Registration:
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01829750.
