scholarly journals A mouse model of hypoplastic left heart syndrome demonstrating left heart hypoplasia and retrograde aortic arch flow

2021 ◽  
Author(s):  
Anum Rahman ◽  
Taylor DeYoung ◽  
Lindsay S. Cahill ◽  
Yohan Yee ◽  
Sarah K. Debebe ◽  
...  
Keyword(s):  
Mouse Model ◽  
Aortic Arch ◽  
Hypoplastic Left Heart Syndrome ◽  
Left Heart ◽  
High Frequency Ultrasound ◽  
Hypoplastic Left Heart ◽  
Fetal Abnormalities ◽  
Cardiac Phenotype ◽  
Disease Penetrance ◽  
Left Heart Syndrome

In hypoplastic left heart syndrome (HLHS), the mechanisms leading to left heart hypoplasia and their associated fetal abnormalities are largely unknown. Current animal models have limited utility in resolving these questions as they either do not fully reproduce the cardiac phenotype, do not survive to term, and/or have very low disease penetrance. Here, we report the development of a surgically-induced mouse model of HLHS that overcomes these limitations. Briefly, we microinjected the fetal left atrium of embryonic day (E) 14.5 mice with an embolizing agent under high-frequency ultrasound guidance, which partially blocks blood flow into the left heart and induces hypoplasia. At term (E18.5), all positively embolized mice exhibit retrograde aortic arch flow, non-apex forming left ventricles and hypoplastic ascending aortas. We thus report the development of the first mouse model of isolated HLHS with a fully penetrant cardiac phenotype and survival to term. Our method allows for the interrogation of previously intractable questions, such as determining the mechanisms of cardiac hypoplasia and fetal abnormalities observed in HLHS, as well as testing of mechanism-based therapies which are urgently lacking.

Abstract 19315: Geometry, Reintervention, and Growth Patterns in the Reconstructed Aortic Arch With Interdigitating Technique in Patients With Hypoplastic Left Heart Syndrome and Variants

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Christoph Haller ◽  
Devin Chetan ◽  
Matthew Doyle ◽  
Arezou Saedi ◽  
Rachel Parker ◽  
...  
Keyword(s):  
Aortic Arch ◽  
Ventricular Function ◽  
Hypoplastic Left Heart Syndrome ◽  
Growth Characteristics ◽  
Stage Ii ◽  
Left Heart ◽  
Hypoplastic Left Heart ◽  
Z Scores ◽  
Arch Reconstruction ◽  
Left Heart Syndrome

Objectives: The interdigitating technique in aortic arch reconstruction in hypoplastic left heart syndrome and variants (HLHS) is very effective to minimize the recoarctation rate. Little is known on the aortic arch’s growth characteristics and the resulting clinical impact. Methods: 139 patients with HLHS underwent staged palliation between 2007 and 2014. 72 patients who underwent Norwood arch reconstruction with the interdigitating technique were included. Dimensions of the ascending aorta (AA), transverse arch (TA), isthmus (IA) and descending aorta (DA) in pre-stage II (P1, n=50) and pre-Fontan (P2, n=21) angiograms were measured and geometry and growth characteristics of the aortic arches were analyzed. Correlations between the aortic dimensions and clinical outcomes were assessed. Results: There were significant increases in diameters in all segments between P1 and P2 (p < .0005). The z-scores in AA, TA and IA were unchanged between P1 and P2 (p = .931/.425/.121), but increased significantly in DA at P2 (p = .039). The percent increase in diameters were comparable among 4 segments (mean, 146% in IA, 144 in DA, p=.648). There were correlations in dimensions and z-scores between P1 and P2 in AA (p = .029/.013) and TA (p = .001/ < .0005), but no correlations were found in IA (p = .140/.747) and DA (p = .075/.432). The most significant tapering in the arch dimension occurred between TA and IA in both time points (P1, 67.3% vs. P2, 61.1%, p=.303). The reverse coarctation index (TA/IA ratio) at P1 (r = .381, p = .042), but not coarctation index (CoAI, IA/DA ratio) at P1 (p = .774) had a significant correlation with post-stage II ventricular function. Balloon dilatation for recoarctation was needed in 2 (2.7%) patients prior to stage II palliation. CoAI at P1 was a predictor for ventricular dysfunction at latest follow-up (p=.017). Conclusions: Aortic arch growth after interdigitating reconstruction in HLHS is substantial and relatively constant. The isthmus growth is proportional to other segments. Overall reintervention rate for recoarctation is exceptionally low. CoAI prior to stage II palliation may be associated with long-term ventricular function.

A Non-Invasive Study Using MR-Derived Wave Intensity Analysis to Highlight the Effect of Surgical Arch Reconstruction on Ventriculo-Arterial Coupling in Patients With Hypoplastic Left Heart Syndrome

2012 ◽  
Author(s):  
Giovanni Biglino ◽  
Hopewell Ntsinjana ◽  
Jennifer A. Steeden ◽  
Catriona Baker ◽  
Silvia Schievano ◽  
...  
Keyword(s):  
Aortic Arch ◽  
Hypoplastic Left Heart Syndrome ◽  
Surgical Reconstruction ◽  
Intensity Analysis ◽  
Left Heart ◽  
Wave Intensity Analysis ◽  
Mr Images ◽  
Hypoplastic Left Heart ◽  
Non Invasive ◽  
Left Heart Syndrome

Hypoplastic left heart syndrome (HLHS) is a congenital heart disease whose staged surgical palliation aims to progressively separate the systemic and pulmonary circulations. The first stage or Norwood procedure [1] involves surgical reconstruction of the aortic arch, usually with pulmonary homograft patch [2]. Recent evidence suggested that, because of this extensive reconstruction, HLHS patients have abnormal elastic properties [3] and reduced distensibility [4,5] of the ascending aorta. However, the impact of the reconstructed aorta and its abnormal elastic properties on ventricular mechanics, i.e. ventriculo-arterial coupling mismatch, has not been assessed. In the light of this mismatch, a change in impedance on the arterial side will reflect on the ventricular side and quantification of this phenomenon may provide mechano-energetic information for further understanding a complex physiology such as palliated HLHS with aortic arch surgical reconstruction. In this study we suggest that wave intensity analysis (WIA) is a valid method for studying ventriculo-arterial coupling, as WIA is a hemodynamic index able to assess the performance of the heart and its interaction with arterial system. Previously, distensibility quantification necessitated either of invasive [5] or cuff [4] arterial pressure monitoring, or multiple magnetic resonance (MR) images acquisitions for transit time wave speed calculation [6]. Instead, here we propose a non-invasive and semi-automated method based only on MR images analysis, with single slice analysis for estimate of local distensibility. The method, including WIA, was developed as a plug-in for DICOM viewer OsiriX, and applied to two cohorts of single ventricle patients.

The Retrograde Aortic Arch in the Hybrid Approach to Hypoplastic Left Heart Syndrome

2009 ◽  
Vol 88 (6) ◽  
pp. 1939-1947 ◽  
Author(s):  
Serban C. Stoica ◽  
Alistair B. Philips ◽  
Matthew Egan ◽  
Roberta Rodeman ◽  
Joanne Chisolm ◽  
...  
Keyword(s):  
Aortic Arch ◽  
Hypoplastic Left Heart Syndrome ◽  
Hybrid Approach ◽  
Left Heart ◽  
Hypoplastic Left Heart ◽  
Left Heart Syndrome

scholarly journals Placental and fetal characteristics of the Ohia mouse line recapitulate outcomes in human hypoplastic left heart syndrome

2020 ◽  
Author(s):  
Rebecca L Wilson ◽  
Weston Troja ◽  
Jennifer Courtney ◽  
Helen N Jones
Keyword(s):  
Mouse Model ◽  
Mrna Expression ◽  
Hypoplastic Left Heart Syndrome ◽  
Fetal Growth ◽  
Fetal Weight ◽  
Left Heart ◽  
Heterozygous Genotype ◽  
Placental Development ◽  
Hypoplastic Left Heart ◽  
Left Heart Syndrome

AbstractCongenital heart defects (CHDs) are one of the most common birth defects worldwide. The morbidity and mortality associated with these defects is compounded by increased frequency of fetal growth abnormalities in the newborns. Inappropriate placental development and function has been implicated as a contributing factor to poor fetal growth in pregnancies complicated by CHDs however, the exact mechanisms are poorly understood. In the Ohia mouse model of hypoplastic left heart syndrome (HLHS), the double homozygous genotype had previously been shown to be embryonically lethal at mid-pregnancy; a time in which optimal establishment of the placenta is crucial to fetal survival. We aimed to characterize placental and fetal growth and development in the double heterozygous genotype to determine whether the genetic mutations associated with HLHS in the Ohia mouse also affect the placenta. The frequency of fetuses with reduced weight near term was shifted in the double heterozygous genotype compared to wildtype fetuses. This shift in fetal weight distribution was associated with reduced fetal capillary density in the placentas of the double heterozygotes as well as a reduction in placental mRNA expression of angiogenic factors placenta growth factor (Pgf) and fms-like tyrosine kinase-1 (Flt1) suggesting abhorrent placental angiogenesis. Positive correlations were observed between fetal weight and placenta mRNA expression of several nutrient transporters in the double heterozygous genotype but not observed in the wildtype. This data shows changes to placental angiogenesis and nutrient transport that are likely to contribute to inadequate fetal growth in the Ohia mouse model. Such differences are similar to findings in studies of human placentas from pregnancies with a fetus with HLHS and highlights the importance of this mouse model in continuing to understand the link between placental development and CHDs such as HLHS.New and NoteworthyWe used the Ohia mouse line, which is characterized with a hypoplastic left heart syndrome (HLHS)-like phenotype to investigate the contribution of placental development and function to fetal growth abnormalities associated with congenital heart defects (CHDs). We demonstrate an increase in the frequency of fetuses with lower fetal weight in the double heterozygous genotype which is associated with abnormalities to the placental microstructure, reduced placental fetal capillary density and placental mRNA expression of angiogenic factors Pgf and Flt1. These results are supported by similar studies of human placentas from HLHS pregnancies and highlights the usefulness of this model in furthering our understanding of abnormal fetal growth in CHDs.

Arch intervention following stage 1 palliation in hypoplastic left heart syndrome is associated with slower feed advancement: a report from the National Pediatric Quality Cardiology Improvement Collaborative

2020 ◽  
Vol 30 (3) ◽  
pp. 396-401
Author(s):  
Alicia H. Chaves ◽  
Carissa M. Baker-Smith ◽  
Geoffrey L. Rosenthal
Keyword(s):  
Aortic Arch ◽  
Hypoplastic Left Heart Syndrome ◽  
Left Heart ◽  
Feeding Problems ◽  
Hypoplastic Left Heart ◽  
Feeding Difficulties ◽  
Arch Obstruction ◽  
Z Scores ◽  
Stage 1 ◽  
Left Heart Syndrome

AbstractIntroduction:Infants undergoing stage 1 palliation for hypoplastic left heart syndrome may have post-operative feeding difficulties. Although the cause of feeding difficulties in these patients is multi-factorial, residual arch obstruction may affect gut perfusion, contributing to feeding intolerance. We hypothesised that undergoing arch reintervention following stage 1 palliation would be associated with post-operative feeding difficulties.Methods:This was a retrospective cohort study. We analysed data from the National Pediatric Cardiology Quality Improvement Collaborative, which maintains a multicentre registry for infants with hypoplastic left heart syndrome discharged home following stage 1 palliation. Patients who underwent arch reintervention (percutaneous or surgical) prior to discharge following stage 1 palliation were compared with those who underwent non-aortic arch interventions after stage 1 palliation and those who underwent no intervention. Median post-operative days to full enteral feeds and weight for age z-scores were compared. Predictors of post-operative days to full feeds were identified.Results:Among patients who underwent arch reintervention, post-operative days to full enteral feeds were greater than for those who underwent non-aortic arch interventions (25 versus 16, p = 0.003) or no intervention (median days 25 versus 12, p < 0.001). Arch intervention, multiple interventions, gestational age, and the presence of a gastrointestinal anomaly were predictors of days to full feeds.Conclusions:Repeat arch intervention is associated with a longer time to achieve full enteral feeding in patients with hypoplastic left heart syndrome after stage 1 palliation. Further investigation of this association is needed to understand the role of arch obstruction in feeding problems in these patients.

Neonatal hemodynamics in patients with hypoplastic left heart syndrome

2004 ◽  
Vol 14 (S1) ◽  
pp. 22-26
Author(s):  
James C. Huhta
Keyword(s):  
Aortic Arch ◽  
Hypoplastic Left Heart Syndrome ◽  
Venous Return ◽  
Left Heart ◽  
Genetic Abnormality ◽  
Hypoplastic Left Heart ◽  
Doppler Evaluation ◽  
Cardiac Diagnosis ◽  
Left Heart Syndrome ◽  
Rule Out

The neonate with hypoplastic left heart syndrome presents a challenge for clinical diagnosis and management. Three diagnostic goals must be met. First, it is necessary to make an etiologic cardiac diagnosis so as to rule out any genetic abnormality. Second, the anatomic cardiac diagnosis is made by segmental echocardiographic analysis, including details of the atrial arrangement, venous return, the patency of the arterial duct, atrial anatomy, and the arrangement of the aortic arch. Finally, the physiologic cardiac diagnosis is made by Doppler evaluation. In some patients, the diagnosis of hypoplastic left heart syndrome is not synonymous with functionally univentricular physiology, and a bi-ventricular repair can be achieved.1

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