Intracoronary autologous cardiac progenitor cell transfer in patients with hypoplastic left heart syndrome: The TICAP Prospective Phase 1 Controlled Trial

Shuta Ishigami, Shinichi Ohtsuki, Suguru Tarui, Daiki Ousaka, Takahiro Eitoku, Maiko Kondo, Michihiro Okuyama, Junko Kobayashi, Kenji Baba, Sadahiko Arai, Takuya Kawabata, Ko Yoshizumi, Atsushi Tateishi, Yosuke Kuroko, Tatsuo Iwasaki, Shuhei Sato, Shingo Kasahara, Shunji Sano, Hidemasa Oh

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Rationale: Hypoplastic left heart syndrome (HLHS) remains a lethal congenital cardiac defect. Recent studies have suggested that intracoronary administration of autologous cardiosphere-derived cells (CDCs) may improve ventricular function. Objective: The aim of this study was to test whether intracoronary delivery of CDCs is feasible and safe in patients with hypoplastic left heart syndrome. Methods and Results: Between January 5, 2011, and January 16, 2012, 14 patients (1.8±1.5 years) were prospectively assigned to receive intracoronary infusion of autologous CDCs 33.4±8.1 days after staged procedures (n=7), followed by 7 controls with standard palliation alone. The primary end point was to assess the safety, and the secondary end point included the preliminary efficacy to verify the right ventricular ejection fraction improvements between baseline and 3 months. Manufacturing and intracoronary delivery of CDCs were feasible, and no serious adverse events were reported within the 18-month follow-up. Patients treated with CDCs showed right ventricular ejection fraction improvement from baseline to 3-month follow-up (46.9%±4.6% to 52.1%±2.4%; P=0.008). Compared with controls at 18 months, cardiac MRI analysis of CDC-treated patients showed a higher right ventricular ejection fraction (31.5%±6.8% versus 40.4%±7.6%; P=0.049), improved somatic growth (P=0.0005), reduced heart failure status (P=0.003), and lower incidence of coil occlusion for collaterals (P=0.007). Conclusions: Intracoronary infusion of autologous CDCs seems to be feasible and safe in children with hypoplastic left heart syndrome after staged surgery. Large phase 2 trials are warranted to examine the potential effects of cardiac function improvements and the long-term benefits of clinical outcomes.

Original languageEnglish
Pages (from-to)653-664
Number of pages12
JournalCirculation Research
Volume116
Issue number4
DOIs
Publication statusPublished - Feb 13 2015

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Hypoplastic Left Heart Syndrome
Patient Transfer
Stem Cells
Stroke Volume
Ventricular Function
Heart Failure
Safety
Incidence
Growth

Keywords

  • Cell therapy
  • Congenital heart disease
  • Hypoplastic left heart syndrome
  • Stem cells

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Medicine(all)

Cite this

Intracoronary autologous cardiac progenitor cell transfer in patients with hypoplastic left heart syndrome : The TICAP Prospective Phase 1 Controlled Trial. / Ishigami, Shuta; Ohtsuki, Shinichi; Tarui, Suguru; Ousaka, Daiki; Eitoku, Takahiro; Kondo, Maiko; Okuyama, Michihiro; Kobayashi, Junko; Baba, Kenji; Arai, Sadahiko; Kawabata, Takuya; Yoshizumi, Ko; Tateishi, Atsushi; Kuroko, Yosuke; Iwasaki, Tatsuo; Sato, Shuhei; Kasahara, Shingo; Sano, Shunji; Oh, Hidemasa.

In: Circulation Research, Vol. 116, No. 4, 13.02.2015, p. 653-664.

Research output: Contribution to journalArticle

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abstract = "Rationale: Hypoplastic left heart syndrome (HLHS) remains a lethal congenital cardiac defect. Recent studies have suggested that intracoronary administration of autologous cardiosphere-derived cells (CDCs) may improve ventricular function. Objective: The aim of this study was to test whether intracoronary delivery of CDCs is feasible and safe in patients with hypoplastic left heart syndrome. Methods and Results: Between January 5, 2011, and January 16, 2012, 14 patients (1.8±1.5 years) were prospectively assigned to receive intracoronary infusion of autologous CDCs 33.4±8.1 days after staged procedures (n=7), followed by 7 controls with standard palliation alone. The primary end point was to assess the safety, and the secondary end point included the preliminary efficacy to verify the right ventricular ejection fraction improvements between baseline and 3 months. Manufacturing and intracoronary delivery of CDCs were feasible, and no serious adverse events were reported within the 18-month follow-up. Patients treated with CDCs showed right ventricular ejection fraction improvement from baseline to 3-month follow-up (46.9{\%}±4.6{\%} to 52.1{\%}±2.4{\%}; P=0.008). Compared with controls at 18 months, cardiac MRI analysis of CDC-treated patients showed a higher right ventricular ejection fraction (31.5{\%}±6.8{\%} versus 40.4{\%}±7.6{\%}; P=0.049), improved somatic growth (P=0.0005), reduced heart failure status (P=0.003), and lower incidence of coil occlusion for collaterals (P=0.007). Conclusions: Intracoronary infusion of autologous CDCs seems to be feasible and safe in children with hypoplastic left heart syndrome after staged surgery. Large phase 2 trials are warranted to examine the potential effects of cardiac function improvements and the long-term benefits of clinical outcomes.",
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T2 - The TICAP Prospective Phase 1 Controlled Trial

AU - Ishigami, Shuta

AU - Ohtsuki, Shinichi

AU - Tarui, Suguru

AU - Ousaka, Daiki

AU - Eitoku, Takahiro

AU - Kondo, Maiko

AU - Okuyama, Michihiro

AU - Kobayashi, Junko

AU - Baba, Kenji

AU - Arai, Sadahiko

AU - Kawabata, Takuya

AU - Yoshizumi, Ko

AU - Tateishi, Atsushi

AU - Kuroko, Yosuke

AU - Iwasaki, Tatsuo

AU - Sato, Shuhei

AU - Kasahara, Shingo

AU - Sano, Shunji

AU - Oh, Hidemasa

PY - 2015/2/13

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N2 - Rationale: Hypoplastic left heart syndrome (HLHS) remains a lethal congenital cardiac defect. Recent studies have suggested that intracoronary administration of autologous cardiosphere-derived cells (CDCs) may improve ventricular function. Objective: The aim of this study was to test whether intracoronary delivery of CDCs is feasible and safe in patients with hypoplastic left heart syndrome. Methods and Results: Between January 5, 2011, and January 16, 2012, 14 patients (1.8±1.5 years) were prospectively assigned to receive intracoronary infusion of autologous CDCs 33.4±8.1 days after staged procedures (n=7), followed by 7 controls with standard palliation alone. The primary end point was to assess the safety, and the secondary end point included the preliminary efficacy to verify the right ventricular ejection fraction improvements between baseline and 3 months. Manufacturing and intracoronary delivery of CDCs were feasible, and no serious adverse events were reported within the 18-month follow-up. Patients treated with CDCs showed right ventricular ejection fraction improvement from baseline to 3-month follow-up (46.9%±4.6% to 52.1%±2.4%; P=0.008). Compared with controls at 18 months, cardiac MRI analysis of CDC-treated patients showed a higher right ventricular ejection fraction (31.5%±6.8% versus 40.4%±7.6%; P=0.049), improved somatic growth (P=0.0005), reduced heart failure status (P=0.003), and lower incidence of coil occlusion for collaterals (P=0.007). Conclusions: Intracoronary infusion of autologous CDCs seems to be feasible and safe in children with hypoplastic left heart syndrome after staged surgery. Large phase 2 trials are warranted to examine the potential effects of cardiac function improvements and the long-term benefits of clinical outcomes.

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KW - Cell therapy

KW - Congenital heart disease

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KW - Stem cells

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