Harold M Burkhart1, Muhammad Yasir Qureshi2, Joseph W Rossano3, Susana Cantero Peral4, Patrick W O'Leary2, Matthew Hathcock5, Walter Kremers5, Timothy J Nelson6. 1. Division of Cardiovascular and Thoracic Surgery, University of Oklahoma, Oklahoma City, Okla. Electronic address: harold-burkhart@ouhsc.edu. 2. Division of Pediatric Cardiology, Mayo Clinic, Rochester, Minn. 3. Cardiac Center, Children's Hospital of Philadelphia, Philadelphia, Pa. 4. Division of General Internal Medicine, Mayo Clinic, Rochester, Minn. 5. Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minn. 6. Division of Pediatric Cardiology, Mayo Clinic, Rochester, Minn; Division of General Internal Medicine, Mayo Clinic, Rochester, Minn; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minn; Center for Regenerative Medicine, Mayo Clinic, Rochester, Minn.
Abstract
OBJECTIVES: Staged surgical palliation for hypoplastic left heart syndrome results in an increased workload on the right ventricle serving as the systemic ventricle. Concerns for cardiac dysfunction and long-term heart failure have generated interest in first-in-infant, cell-based therapies as an additional surgical treatment modality. METHODS: A phase 1 clinical trial was conducted to evaluate the safety and feasibility of direct intramyocardial injection of autologous umbilical cord blood-derived mononuclear cells in 10 infants with hypoplastic left heart syndrome at the time of stage II palliation. RESULTS: All 10 patients underwent successful stage II palliation and intramyocardial injection of umbilical cord blood-derived mononuclear cells. Operative mortality was 0%. There was a single adverse event related to cell delivery: An injection site epicardial bleed that required simple oversew. The cohort did not demonstrate any significant safety concerns over 6 months. Additionally, the treatment group did not demonstrate any reduction in cardiac function in the context of the study related intramyocardial injections of autologous cells. CONCLUSIONS: This phase 1 clinical trial showed that delivering autologous umbilical cord blood-derived mononuclear cells directly into the right ventricular myocardium during planned stage II surgical palliation for hypoplastic left heart syndrome was safe and feasible. Secondary findings of preservation of baseline right ventricular function throughout follow-up and normalized growth rates support the design of a phase 2b follow-up trial.
OBJECTIVES: Staged surgical palliation for hypoplastic left heart syndrome results in an increased workload on the right ventricle serving as the systemic ventricle. Concerns for cardiac dysfunction and long-term heart failure have generated interest in first-in-infant, cell-based therapies as an additional surgical treatment modality. METHODS: A phase 1 clinical trial was conducted to evaluate the safety and feasibility of direct intramyocardial injection of autologous umbilical cord blood-derived mononuclear cells in 10 infants with hypoplastic left heart syndrome at the time of stage II palliation. RESULTS: All 10 patients underwent successful stage II palliation and intramyocardial injection of umbilical cord blood-derived mononuclear cells. Operative mortality was 0%. There was a single adverse event related to cell delivery: An injection site epicardial bleed that required simple oversew. The cohort did not demonstrate any significant safety concerns over 6 months. Additionally, the treatment group did not demonstrate any reduction in cardiac function in the context of the study related intramyocardial injections of autologous cells. CONCLUSIONS: This phase 1 clinical trial showed that delivering autologous umbilical cord blood-derived mononuclear cells directly into the right ventricular myocardium during planned stage II surgical palliation for hypoplastic left heart syndrome was safe and feasible. Secondary findings of preservation of baseline right ventricular function throughout follow-up and normalized growth rates support the design of a phase 2b follow-up trial.
Authors: Sunjay Kaushal; Joshua M Hare; Aakash M Shah; Nicholas P Pietris; Judith L Bettencourt; Linda B Piller; Aisha Khan; Abigail Snyder; Riley M Boyd; Mohamed Abdullah; Rachana Mishra; Sudhish Sharma; Timothy C Slesnick; Ming-Sing Si; Paul J Chai; Barry R Davis; Dejian Lai; Michael E Davis; William T Mahle Journal: Pediatr Cardiol Date: 2022-04-08 Impact factor: 1.838
Authors: Saji Oommen; Susana Cantero Peral; Muhammad Y Qureshi; Kimberly A Holst; Harold M Burkhart; Matthew A Hathcock; Walter K Kremers; Emma B Brandt; Brandon T Larsen; Joseph A Dearani; Brooks S Edwards; Joseph J Maleszewski; Timothy J Nelson Journal: Cell Transplant Date: 2022 Jan-Dec Impact factor: 4.139
Authors: Filippo Rapetto; Demetris Taliotis; Qiang Chen; Iakovos Ttofi; Dominga Iacobazzi; Paolo Madeddu; Serban C Stoica; Ben Weil; Mark W Lowdell; Massimo Caputo Journal: JACC Case Rep Date: 2021-05