• Shuta Ishigami, Shinichi Ohtsuki, Takahiro Eitoku, Daiki Ousaka, Maiko Kondo, Yoshihiko Kurita, Kenta Hirai, Yosuke Fukushima, Kenji Baba, Takuya Goto, Naohiro Horio, Junko Kobayashi, Yosuke Kuroko, Yasuhiro Kotani, Sadahiko Arai, Tatsuo Iwasaki, Shuhei Sato, Shingo Kasahara, Shunji Sano, and Hidemasa Oh.
• From 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.).
• Circ. Res. 2017 Mar 31; 120 (7): 1162-1173.

RationalePatients 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.ObjectiveTo determine whether intracoronary delivery of autologous CDCs improves cardiac function in patients with single ventricle physiology.Methods And ResultsWe 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.ConclusionsIntracoronary 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 RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01829750.© 2017 American Heart Association, Inc.

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