From Safety to Benefit in Cell Delivery During Surgical Repair of Ebstein Anomaly: Initial Results.

Published on Feb 1, 2021in The Annals of Thoracic Surgery3.639
· DOI :10.1016/J.ATHORACSUR.2020.11.065
Joseph A. Dearani95
Estimated H-index: 95
(UR: University of Rochester),
Bryan C. Cannon29
Estimated H-index: 29
(UR: University of Rochester)
+ 10 AuthorsKaren Cavanaugh2
Estimated H-index: 2
(Mayo Clinic)
Abstract Background The objective of this study is to assess the safety and early impact of intramyocardial delivery of autologous bone marrow-derived mononuclear cells (BM-MNC) at time of surgical Ebstein repair. Methods Patients with EA (ages 6 months to 30 years) scheduled to undergo repair of the TV were eligible to participate in this open label, non-randomized Phase I clinical trial. BM-MNC target dose was 1-3 million cells/kg. Ten patients have undergone surgical intervention and cell delivery to the right ventricle (RV) and completed 6 month follow-up. Results All patients underwent surgical tricuspid valve repair and uneventful BM-MNC delivery; there were no ventricular arrhythmias and no adverse events related to study product or delivery. Echocardiographic RV myocardial performance index improved and RV fractional area change showed an initial decline and then through study follow-up. There was no evidence of delayed myocardial enhancement or regional wall motion abnormalities at injection sites on 6-month follow-up MRI. Conclusions Intramyocardial delivery of BM-MNC following surgical repair in EA can be performed safely. Echocardiography variables suggest a positive impact of cell delivery on the RV myocardium with improvements in both RV size and wall motion over time. Additional follow-up and comparison to control groups are required to better characterize the impact of cell therapy on the myopathic RV in Ebstein anomaly.
#1Heather N. Anderson (Mayo Clinic)H-Index: 6
#2Joseph A. Dearani (Mayo Clinic)H-Index: 95
Last. Philip L. Wackel (Mayo Clinic)H-Index: 6
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Implantable loop recorders (ILR) are utilized for long-term rhythm monitoring. Typical placement of the Medtronic Reveal LINQ along the left parasternal border may compromise the quality and/or feasibility of future imaging studies. We sought to evaluate the utility of placing an ILR in the left anterior axillary position and the impact on the quality of cardiac imaging. We reviewed patients from May 2017 to June 2018 who had placement of a Reveal LINQ device in the left anterior axillary positi...
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#1Harold M. Burkhart (OU: University of Oklahoma)H-Index: 53
#2Muhammad Yasir Qureshi (Mayo Clinic)H-Index: 10
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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 blo...
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#2Imre J. PavoH-Index: 13
Last. Dietmar Schranz (University of Giessen)H-Index: 35
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Pediatric heart failure (HF) is rare. The prognosis is generally poor. HF is most frequently related to cardiomyopathy or congenital heart disease (CHD). Associated phenotypes are HF with preserved (HFpEF) or reduced ejection fraction (HFrEF); both in children with biventricular or univentricular circulation. Cardiac growth, differentiation, proliferation and consecutively regenerative and repair mechanisms are inversely related to the patient’s age; edaphic and circulating cardiac progenitor ce...
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Background Ebstein anomaly has heterogeneous anatomy and numerous operative techniques are described. Cone repair provides a near anatomic tricuspid valve repair. The purpose of this study was to examine our experience with cone repair. Methods Cone repair was performed in 235 consecutive patients with Ebstein anomaly, 134 children (57%) and 101 adults (43%), from June 2007 to October 2015. Median age was 15.6 years (range, 6 months to 73 years). Cone repair was the first operation in 192 patien...
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#2Allison K. Cabalka (Mayo Clinic)H-Index: 30
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Abstract Myocardial dysfunction after Fontan palliation for univentricular congenital heart disease is a challenging clinical problem. The medical treatment has a limited impact, with cardiac transplant being the ultimate management step. Cell-based therapies are evolving as a new treatment for heart failure. Phase 1 clinical trials using regenerative therapeutic strategies in congenital heart disease are ongoing. We report the first case of autologous bone marrow–derived mononuclear cell admini...
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#1Hidemasa Oh (Okayama University)H-Index: 21
Dramatic evolution in medical and catheter interventions and complex surgeries to treat children with congenital heart disease (CHD) has led to a growing number of patients with a multitude of long-term complications associated with morbidity and mortality. Heart failure in patients with hypoplastic left heart syndrome predicated by functional single ventricle lesions is associated with an increase in CHD prevalence and remains a significant challenge. Pathophysiological mechanisms contributing ...
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#1Zaniar Ghazizadeh (Tehran University of Medical Sciences)H-Index: 9
#2Sadaf Vahdat (Royan Institute)H-Index: 7
Last. Nasser Aghdami (Royan Institute)H-Index: 30
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Abstract Aims Regenerative therapies based on resident human cardiac progenitor cells (hCPCs) are a promising alternative to medical treatments for patients with myocardial infarction. However, hCPCs are rare in human heart and finding efficient source and proper surface marker for isolation of these cells would make them a good candidate for therapy. Main methods We have isolated 5.34 ∗ 106 ± 2.04 ∗ 105/g viable cells from 35 heart tissue samples of 23 patients with congenital heart disease obt...
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#1Joseph A. DearaniH-Index: 95
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Ebstein anomaly accounts for 1% of all congenital heart disease. It is a right ventricular myopathy with failure of tricuspid valve delamination and highly variable tricuspid valve morphology that usually results in severe regurgitation. It is the only congenital heart lesion that has a range of clinical presentations, from the severely symptomatic neonate to an asymptomatic adult. Neonatal operation has high operative mortality, whereas operation performed beyond infancy and into adulthood has ...
43 CitationsSource
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Introduction Stem cell therapy has emerged as potential therapeutic strategy for damaged heart muscles. Umbilical cord blood (UCB) cells are the most prevalent stem cell source available, yet have not been fully tested in cardiac regeneration. Herein, studies were performed to evaluate the cardiovascular safety and beneficial effect of mononuclear cells (MNCs) isolated from human umbilical cord blood upon intramyocardial delivery in a murine model of right ventricle (RV) heart failure due to pre...
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The current standard of care for neonates with hypoplastic left heart syndrome (HLHS) includes a series of cardiac operations culminating in a complete cavopulmonary connection. Given the increased workload placed on the right ventricle, development of ventricular dysfunction and heart failure are concerns. As this patient population ages, many may require cardiac transplantation. Cellbased strategies to treat heart failure in adults have been reported, but little is known about their feasibilit...
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Cited By2
#1Patrick W. O'Leary (Mayo Clinic)H-Index: 40
#2M. Yasir Qureshi (Mayo Clinic)H-Index: 5
Last. Angela R. MillerH-Index: 2
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Abstract null null Objective null To define the impact of tricuspid valve cone reconstruction (CR) on ventricular performance in Ebstein anomaly, both independently and after stem cell therapy. null null null Patients and Methods null The control group included 257 patients who had CR between June 2007 and December 2019. Ten subjects of a phase I stem cell therapy trial (May 2017 – March 2019) were compared with the controls to assess the echocardiographic impact on ventricular remodeling. null ...