Kenta Hirai: Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama Japan. ORCID
Ryusuke Sawada: Department of Pharmacology Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama Japan. ORCID
Tomohiro Hayashi: Department of Pediatrics Kurashiki Central Hospital Okayama Japan.
Toru Araki: Department of Pediatrics National Hospital Organization Fukuyama Medical Center Hiroshima Japan.
Naomi Nakagawa: Department of Pediatric Cardiology Hiroshima City Hiroshima Citizens Hospital Hiroshima Japan. ORCID
Maiko Kondo: Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama Japan.
Kenji Yasuda: Department of Pediatrics Shimane University Faculty of Medicine Izumo Shimane Japan. ORCID
Takuya Hirata: Department of Pediatrics Kyoto University Graduate School of Medicine Kyoto Japan. ORCID
Tomoyuki Sato: Department of Pediatrics Jichi Medical University Tochigi Japan.
Yuki Nakatsuka: Department of Data Science, Center for Innovative Clinical Medicine Okayama University Hospital Okayama Japan. ORCID
Michihiro Yoshida: Department of Data Science, Center for Innovative Clinical Medicine Okayama University Hospital Okayama Japan. ORCID
Shingo Kasahara: Department of Cardiovascular Surgery Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama Japan. ORCID
Kenji Baba: Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Okayama Japan. ORCID
Hidemasa Oh: Department of Regenerative Medicine, Center for Innovative Clinical Medicine Okayama University Hospital Okayama Japan. ORCID
BACKGROUND: Cardiosphere-derived cell (CDC) infusion was associated with better clinical outcomes at 2 years in patients with single ventricle heart disease. The current study investigates time-to-event outcomes at 8 years. METHODS AND RESULTS: This cohort enrolled patients with single ventricles who underwent stage 2 or stage 3 palliation from January 2011 to January 2015 at 8 centers in Japan. The primary outcomes were time-dependent CDC treatment effects on death and late complications during 8 years of follow-up, assessed by restricted mean survival time. Among 93 patients enrolled (mean age, 2.3±1.3 years; 56% men), 40 received CDC infusion. Overall survival for CDC-treated versus control patients did not differ at 8 years (hazard ratio [HR], 0.60 [95% CI, 0.21-1.77]; =0.35). Treatment effect had nonproportional hazards for death favoring CDCs at 4 years (restricted mean survival time difference +0.33 years [95% CI, 0.01-0.66]; =0.043). In patients with heart failure with reduced ejection fraction, CDC treatment effect on survival was greater over 8 years (restricted mean survival time difference +1.58 years [95% CI, 0.05-3.12]; =0.043). Compared with control participants, CDC-treated patients showed lower incidences of late failure (HR, 0.45 [95% CI, 0.21-0.93]; =0.027) and adverse events (subdistribution HR, 0.50 [95% CI, 0.27-0.94]; =0.036) at 8 years. CONCLUSIONS: By 8 years, CDC infusion was associated with lower hazards of late failure and adverse events in single ventricle heart disease. CDC treatment effect on survival was notable by 4 years and showed a durable clinical benefit in patients with heart failure with reduced ejection fraction over 8 years. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01273857 and NCT01829750.
