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

Published on Nov 7, 2020in Seminars in Thoracic and Cardiovascular Surgery2.133
· DOI :10.1053/J.SEMTCVS.2020.11.002
Marie Vincenti1
Estimated H-index: 1
(Mayo Clinic),
Patrick W. O'Leary40
Estimated H-index: 40
(Mayo Clinic)
+ 4 AuthorsJoan Wobig1
Estimated H-index: 1
(Mayo Clinic)
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 prestage II through the first 6 months postoperatively. Statistical comparisons between the groups at similar postoperative time points were made to define potential impact of the cell therapy. There were 7 UCB-MNC patients and 17 controls. Prestage 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
27 CitationsSource
#1Harold M. Burkhart (OU: University of Oklahoma)H-Index: 53
#2Muhammad Yasir Qureshi (Mayo Clinic)H-Index: 10
Last. Joan WobigH-Index: 1
view all 35 authors...
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...
20 CitationsSource
#1Christopher E. Mascio (Children's Hospital of Philadelphia)H-Index: 14
#2Mallory L. Irons (UPenn: University of Pennsylvania)H-Index: 4
Last. Thomas L. Spray (Children's Hospital of Philadelphia)H-Index: 87
view all 10 authors...
Abstract Objective Hypoplastic left heart syndrome is one of the most common and challenging lesions requiring surgical intervention in the neonatal period. The Norwood procedure for hypoplastic left heart syndrome was first reported in 1983. The objective of this study was to describe early outcomes after the Norwood procedure at a single institution over 30 years. Methods This retrospective cohort study included all patients with hypoplastic left heart syndrome (and variants) who underwent the...
27 CitationsSource
Abstract Patients with systemic morphological right ventricles (RVs), including congenitally corrected transposition of the great arteries and dextro-transposition of the great arteries with a Mustard or Senning atrial baffle repair, have a high likelihood of developing systemic ventricular dysfunction. Unfortunately, there are a limited number of clinical studies on the efficacy of medical therapy for systemic RV dysfunction. We performed a systematic review and meta-analysis to assess the effe...
26 CitationsSource
#1Wojciech Mądry (Medical University of Warsaw)H-Index: 2
Last. Marcin MyszkowskiH-Index: 1
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: Introduction: In this study, we assessed the adequacy of the two echocardiographic parameters representing the longitudinal systolic function of the ventricles, MAPSE & TAPSE, in perioperative monitoring. Aims: 1. The assessment of MAPSE and TAPSE during the early (4 weeks) postoperative period after surgical correction of congenital heart defects in infants, performed with CPB. 2. The verification of the hypothesis, that the significant decline of TAPSE observed in this period is not related ...
3 CitationsSource
#1Gregory J. BittleH-Index: 12
#2David L.S. MoralesH-Index: 54
Last. Sunjay KaushalH-Index: 20
view all 14 authors...
Hypoplastic left heart syndrome is a type of congenital heart disease characterized by underdevelopment of the left ventricle, outflow tract, and aorta. The condition is fatal if aggressive palliative operations are not undertaken, but even after the complete 3-staged surgical palliation, there is significant morbidity because of progressive and ultimately intractable right ventricular failure. For this reason, there is interest in developing novel therapies for the management of right ventricul...
20 CitationsSource
#1Chetan Ambastha (UMB: University of Maryland, Baltimore)H-Index: 3
#2Gregory J. Bittle (UMB: University of Maryland, Baltimore)H-Index: 12
Last. Sunjay Kaushal (UMB: University of Maryland, Baltimore)H-Index: 20
view all 13 authors...
One of the most complex forms of congenital heart disease (CHD) involving single ventricle physiology is hypoplastic left heart syndrome (HLHS), characterized by underdevelopment of the left ventricle (LV), mitral and aortic valves, and narrowing of the ascending aorta. The underdeveloped LV is incapable of providing long-term systemic flow, and if left untreated, the condition is fatal. Current treatment for this condition consists of three consecutive staged palliative operations: the first is...
5 CitationsSource
#1Sridhar Venkatachalam (UTMB: University of Texas Medical Branch)H-Index: 2
#2Geru Wu (UTMB: University of Texas Medical Branch)H-Index: 12
Last. Masood Ahmad (UTMB: University of Texas Medical Branch)H-Index: 23
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The right ventricle has unique structural and functional characteristics. It is now well recognized that the so-called forgotten ventricle is a key player in cardiovascular physiology. Furthermore, there is accumulating evidence that demonstrates right ventricular dysfunction as an important marker of morbidity and mortality in several commonly encountered clinical situations such as heart failure, pulmonary hypertension, pulmonary embolism, right ventricular myocardial infarction, and adult con...
17 CitationsSource
#1Somjate Suntratonpipat (U of A: University of Alberta)H-Index: 2
#2Nee S. Khoo (U of A: University of Alberta)H-Index: 10
Last. Edythe B. Tham (U of A: University of Alberta)H-Index: 9
view all 9 authors...
Background Single right ventricles (SRV) are postulated to be disadvantaged compared with single left ventricles (SLV). We compared the evolution of SRV versus SLV function during infancy using conventional measures and speckle-tracking echocardiography (STE). We hypothesized that the SRV is mechanically disadvantaged during early infancy. Methods SRVs ( n = 32) were compared with SLVs ( n = 16) at the neonatal (presurgery) and pre-bidirectional cavopulmonary anastomosis (pre-BCPA) stages. Funct...
6 CitationsSource
#1Shuta Ishigami (Okayama University)H-Index: 4
#2Shinichi OhtsukiH-Index: 10
Last. Hidemasa OhH-Index: 21
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RATIONALE: Patients with single ventricle physiology are at high risk of mortality resulting from ventricular dysfunction. The preliminary results of the phase 1 trial showed that cardiosphere-derived cells (CDCs) may be effective against congenital heart failure. OBJECTIVE: To determine whether intracoronary delivery of autologous CDCs improves cardiac function in patients with single ventricle physiology. METHODS AND RESULTS: We conducted a phase 2 randomized controlled study to assign in a 1:...
76 CitationsSource
Cited By2
#1James K. Kirklin (UAB: University of Alabama at Birmingham)H-Index: 83
#1M. R. Abdullah (Children's Memorial Hospital)H-Index: 9
#1Mohamed Abdullah (Children's Memorial Hospital)
Last. Sunjay Kaushal (Children's Memorial Hospital)H-Index: 20
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