Shuta Ishigami1, Shinichi Ohtsuki1, Suguru Tarui1, Daiki Ousaka1, Takahiro Eitoku1, Maiko Kondo1, Michihiro Okuyama1, Junko Kobayashi1, Kenji Baba1, Sadahiko Arai1, Takuya Kawabata1, Ko Yoshizumi1, Atsushi Tateishi1, Yosuke Kuroko1, Tatsuo Iwasaki1, Shuhei Sato1, Shingo Kasahara1, Shunji Sano1, Hidemasa Oh2. 1. From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan. 2. From the Departments of Cardiovascular Surgery (S.I., S.T., D.O., M.O., J.K., S.A., T.K., K.Y., A.T., Y.K., S.K., S.S.), Pediatrics (S.O., T.E., M.K., K.B.), Anesthesiology and Resuscitology (T.I.), and Radiology (S.S.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; and Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital (H.O.), Okayama, Japan. hidemasa@md.okayama-u.ac.jp.
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. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01273857.
RCT Entities:
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. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01273857.
Authors: Anna Klinke; Torben Schubert; Marion Müller; Ekaterina Legchenko; Jason G E Zelt; Tsukasa Shimauchi; L Christian Napp; Alexander M K Rothman; Sébastien Bonnet; Duncan J Stewart; Georg Hansmann; Volker Rudolph Journal: Cardiovasc Diagn Ther Date: 2020-10
Authors: Udit Agarwal; Alex George; Srishti Bhutani; Shohini Ghosh-Choudhary; Joshua T Maxwell; Milton E Brown; Yash Mehta; Manu O Platt; Yaxuan Liang; Susmita Sahoo; Michael E Davis Journal: Circ Res Date: 2016-11-21 Impact factor: 17.367