title: Intracoronary Cardiac Progenitor Cells in Single Ventricle Physiology: The PERSEUS (Cardiac Progenitor Cell Infusion to Treat Univentricular Heart Disease) Randomized Phase 2 Trial.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01829750.
authors.affiliation: 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.).
authors.forename: Shuta
authors.initials: S
authors.lastname: Ishigami
authors.affiliation: 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.).
authors.forename: Shinichi
authors.initials: S
authors.lastname: Ohtsuki
authors.affiliation: 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.).
authors.forename: Takahiro
authors.initials: T
authors.lastname: Eitoku
authors.affiliation: 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.).
authors.forename: Daiki
authors.initials: D
authors.lastname: Ousaka
authors.affiliation: 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.).
authors.forename: Maiko
authors.initials: M
authors.lastname: Kondo
authors.affiliation: 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.).
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kurita
authors.affiliation: 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.).
authors.forename: Kenta
authors.initials: K
authors.lastname: Hirai
authors.affiliation: 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.).
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Fukushima
authors.affiliation: 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.).
authors.forename: Kenji
authors.initials: K
authors.lastname: Baba
authors.affiliation: 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.).
authors.forename: Takuya
authors.initials: T
authors.lastname: Goto
authors.affiliation: 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.).
authors.forename: Naohiro
authors.initials: N
authors.lastname: Horio
authors.affiliation: 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.).
authors.forename: Junko
authors.initials: J
authors.lastname: Kobayashi
authors.affiliation: 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.).
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kuroko
authors.affiliation: 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.).
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kotani
authors.affiliation: 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.).
authors.forename: Sadahiko
authors.initials: S
authors.lastname: Arai
authors.affiliation: 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.).
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Iwasaki
authors.affiliation: 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.).
authors.forename: Shuhei
authors.initials: S
authors.lastname: Sato
authors.affiliation: 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.).
authors.forename: Shingo
authors.initials: S
authors.lastname: Kasahara
authors.affiliation: 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.).
authors.forename: Shunji
authors.initials: S
authors.lastname: Sano
authors.affiliation: 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.). hidemasa@okayama-u.ac.jp.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Oh
mesh_terms: D002675:Child, Preschool; D003331:Coronary Vessels; D005260:Female; D006801:Humans; D007223:Infant; D007261:Infusions, Intra-Arterial / Q000009:adverse effects / Q000379:methods; D008297:Male; D032446:Myoblasts / Q000166:cytology / Q000637:transplantation*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000637:transplantation*; D033581:Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D018754:Ventricular Dysfunction / Q000628:therapy*
keywords: cell therapy; heart disease; heart failure; hypoplastic left heart syndrome; stem cell