First name
Timothy
Middle name
J
Last name
Nelson

Title

Clinical Impact of Autologous Cell Therapy on Hypoplastic Left Heart Syndrome after Bidirectional Cavopulmonary Anastomosis.

Year of Publication

2020

Date Published

2020 Nov 07

ISSN Number

1532-9488

Abstract

<p>Preservation of right ventricle function (RV) is a key to favorable outcome in Hypoplastic Left Heart Syndrome (HLHS), but methods to preserve or improve RV function are limited. Our goal was to assess the clinical and functional impact of autologous umbilical cord blood-derived mononuclear cells (UCB-MNC) therapy when given to patients with HLHS at Stage II surgery. UCB-MNC patients were enrolled prospectively in a phase I, FDA monitored trial as previously described (Burkhart et. al., 2019). Matched retrospective controls were identified by review of clinical databases. Growth and RV echocardiographic variables were assessed in both groups pre-stage II through the first 6 months postoperatively. Statistical comparisons between the groups at similar post-operative time points were made to define potential impact of the cell therapy. There were 7 UCB-MNC patients and 17 controls. Pre-stage II, most parameters showed no differences between groups, although median fractional area change (FAC) was slightly greater in the controls (FAC: controls = 45% vs. UCB-MNC = 41% p=0.02). At dismissal, FAC and estimated Ejection Fraction (EF) decreased in controls, while both were unchanged from baseline in UCB-MNC patients (ΔFAC: -5% vs. -1%, p&lt;0.01; ΔEF: -8% vs. 0%, p=0.03 respectively). Subsequently, median FAC increased slightly in UCB-MNC patients over the 6 month follow-up period, while it decreased in controls (ΔFAC: UCB-MNC +3% vs. control -5%, p=0.03). Preoperative weight percentiles were similar in both groups (UCB-MNC 34%ile vs controls 22%ile, p=0.93). However, by 6 months post-operative, median weight percentile improved to 63% in the UCB-MNC treated group, but declined to 8% in controls (p=0.02). UCB-MNC therapy appears to limit the initial negative impact on RV FAC and EF seen after stage II surgery. During early follow up, FAC and weight percentile improved in UCB-MNC patients relative to controls, suggesting a beneficial effect of UCB-MNC therapy.</p>

DOI

10.1053/j.semtcvs.2020.11.002

Alternate Title

Semin Thorac Cardiovasc Surg

PMID

33171247

Title

Autologous stem cell therapy for hypoplastic left heart syndrome: Safety and feasibility of intraoperative intramyocardial injections.

Year of Publication

2019

Date Published

2019 Jun 07

ISSN Number

1097-685X

Abstract

<p><strong>OBJECTIVES: </strong>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.</p>

<p><strong>METHODS: </strong>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.</p>

<p><strong>RESULTS: </strong>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&nbsp;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.</p>

<p><strong>CONCLUSIONS: </strong>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.</p>

DOI

10.1016/j.jtcvs.2019.06.001

Alternate Title

J. Thorac. Cardiovasc. Surg.

PMID

31345560

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