Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1162-1173 |
| Number of pages | 12 |
| Journal | Circulation Research |
| Volume | 120 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Mar 31 2017 |
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Keywords
- cell therapy
- heart disease
- heart failure
- hypoplastic left heart syndrome
- stem cell
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
Intracoronary cardiac progenitor cells in single ventricle physiology : the perseus (cardiac progenitor cell infusion to treat univentricular heart disease) randomized phase 2 trial. / Ishigami, Shuta; Ohtsuki, Shin-ichi; Eitoku, Takahiro; Ousaka, Daiki; Kondo, Maiko; Kurita, Yoshihiko; Hirai, Kenta; Fukushima, Yosuke; Baba, Kenji; Goto, Takuya; Horio, Naohiro; Kobayashi, Junko; Kuroko, Yosuke; Kotani, Yasuhiro; Arai, Sadahiko; Iwasaki, Tatsuo; Sato, Shuhei; Kasahara, Shingo; Sano, Shunji; Oh, Hidemasa.
In: Circulation Research, Vol. 120, No. 7, 31.03.2017, p. 1162-1173.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Intracoronary cardiac progenitor cells in single ventricle physiology
T2 - the perseus (cardiac progenitor cell infusion to treat univentricular heart disease) randomized phase 2 trial
AU - Ishigami, Shuta
AU - Ohtsuki, Shin-ichi
AU - Eitoku, Takahiro
AU - Ousaka, Daiki
AU - Kondo, Maiko
AU - Kurita, Yoshihiko
AU - Hirai, Kenta
AU - Fukushima, Yosuke
AU - Baba, Kenji
AU - Goto, Takuya
AU - Horio, Naohiro
AU - Kobayashi, Junko
AU - Kuroko, Yosuke
AU - Kotani, Yasuhiro
AU - Arai, Sadahiko
AU - Iwasaki, Tatsuo
AU - Sato, Shuhei
AU - Kasahara, Shingo
AU - Sano, Shunji
AU - Oh, Hidemasa
PY - 2017/3/31
Y1 - 2017/3/31
N2 - 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.
AB - 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.
KW - cell therapy
KW - heart disease
KW - heart failure
KW - hypoplastic left heart syndrome
KW - stem cell
UR - http://www.scopus.com/inward/record.url?scp=85009178481&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85009178481&partnerID=8YFLogxK
U2 - 10.1161/CIRCRESAHA.116.310253
DO - 10.1161/CIRCRESAHA.116.310253
M3 - Article
C2 - 28052915
AN - SCOPUS:85009178481
VL - 120
SP - 1162
EP - 1173
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 7
ER -