Induction of left ventricular hypoplasia by occluding the foramen ovale in the fetal lamb

Wong, Flora Yuen-Wait; Veldman, Alex; Sasi, Arun; Teoh, Mark; Edwards, Andrew; Chan, Yuen; Graupner, O; Enzensberger, C; Axt-Fliedner, R; Black, Mary Jane; Schranz, Dietmar

doi:10.1038/s41598-020-57694-4

Cited by 14 publications

(16 citation statements)

References 37 publications

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“…The above clinical evidence for feHLHS progression to HLHS, and for interventions to reduce risks of this progression, has led to the prevailing thought that the biomechanical stimuli of the heart exert influence on the growth and development of the heart, and can determine morphological outcomes. Large and small animal experiments have corroborated this notion, the occlusion of lamb fetal foramen ovale was shown to lead to the underdevelopment of LV chamber and aortic and mitral valves, 39 while left atrial ligation in chick embryo has led to hypoplastic LV 29 and evidence of fibroelastosis. 22 For this reason, an improved understanding of LV biomechanics during feHLHS may help develop future strategies for better prognosis or to improve intervention outcomes.…”

Section: Introductionmentioning

confidence: 91%

Fluid Mechanics of Fetal Left Ventricle During Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome

et al. 2022

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In cases of fetal aortic stenosis and evolving Hypoplastic Left Heart Syndrome (feHLHS), aortic stenosis is associated with specific abnormalities such as retrograde or bidirectional systolic transverse arch flow. Many cases progressed to hypoplastic left heart syndrome (HLHS) malformation at birth, but fetal aortic valvuloplasty can prevent the progression in many cases. Since both disease and intervention involve drastic changes to the biomechanical environment, in-vivo biomechanics likely play a role in inducing and preventing disease progression. However, the fluid mechanics of feHLHS is not well-characterized. Here, we conduct patient-specific echocardiography-based flow simulations of normal and feHLHS left ventricles (LV), to understand the essential fluid dynamics distinction between the two cohorts. We found high variability across feHLHS cases, but also the following unifying features. Firstly, feHLHS diastole mitral inflow was in the form of a narrowed and fast jet that impinged onto the apical region, rather than a wide and gentle inflow in normal LVs. This was likely due to a malformed mitral valve with impaired opening dynamics. This altered inflow caused elevated vorticity dynamics and wall shear stresses (WSS) and reduced oscillatory shear index at the apical zone rather than mid-ventricle. Secondly, feHLHS LV also featured elevated systolic and diastolic energy losses, intraventricular pressure gradients, and vortex formation numbers, suggesting energy inefficiency of flow and additional burden on the LV. Thirdly, feHLHS LV had poor blood turnover, suggesting a hypoxic environment, which could be associated with endocardial fibroelastosis that is often observed in these patients.

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Section: Introductionmentioning

confidence: 91%

Fluid Mechanics of Fetal Left Ventricle During Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome

et al. 2022

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“…Although this has not been previously investigated in a TOF cohort, perhaps the closest parallel theories that have been formally researched are in hypoplastic left heart syndrome, a lesion in which there are also two contrasting theories of underlying pathogenesis. Some animal studies have shown that the intentional reduction of flow across the mitral and aortic valve in fetal life can lead to the development of HLHS [18][19][20] . However, others have shown that there can be clinically significant left ventricular hypoplasia without associated valvar stenosis, more suggestive of a primary disturbance of cardiomyocytes mirroring a cardiomyopathy syndrome [21][22][23] .…”

Section: Discussionmentioning

confidence: 99%

“…Many have stressed the importance of understanding nuanced environmental and genetic contributors to congenital heart disease, as opposed to reliance on morphologic and hemodynamic models alone 16,17 . While there have been intentional investigations (with variable results) into the flow-mediated hypotheses of other lesions such as hypoplastic left heart syndrome, there has yet to be a formal study of such mechanisms in TOF [18][19][20][21][22][23] .…”

Section: Introductionmentioning

confidence: 99%

Thinking Outside the “Flow-Mediated” Box: An Analysis of Aortic Dilation in 100 Fetuses with Tetralogy of Fallot Compared to Matched Controls

Dasgupta¹,

Kaplinski²,

Reddy³

et al. 2023

Preprint

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Background: Aortic dilation in tetralogy of Fallot (TOF) is primarily attributed to increased aortic flow in utero. An alternative hypothesis is abnormal neural crest cell migration, with unequal septation of the truncus arteriosus resulting in a larger aorta and inherently hypoplastic pulmonary artery (PA). If so, we hypothesize the aorta to PA ratio (Ao:PA) in TOF is stable throughout gestation, and the total sum of dimensions of the great arteries is similar to controls. Methods: We performed a single-center retrospective study of all fetuses with TOF (2014-2020) and gestational age-matched controls. We compared sums of diameters, circumferences, and cross-sectional areas of the aorta and PA and evaluated the Ao:PA across gestation in TOF with pulmonary stenosis (TOF-PS) and atresia (TOF-PA). We analyzed data with two-tailed t-tests and Pearson's correlation. Results: There were 100 fetuses with TOF (36% TOF-PA) with median gestational age of 31 weeks [IQR 26.5, 34.4] and median maternal age of 34 years [IQR 30, 37]. There were no differences in sums of great artery dimensions between TOF-PS and controls. In TOF-PA, sums were significantly lower than controls. The Ao:PA was stable throughout gestation. Conclusions: The aorta in fetal TOF is large but grows proportionally throughout gestation, with a sum of great artery dimensions similar to controls. TOF-PA appears to be distinct from TOF-PS (with overall smaller dimensions), and is a group that warrants further investigation. In conclusion, our findings do not support the flow-mediated model of aortic dilation in TOF, and instead suggest an intrinsic developmental mechanism.

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“…In a 3-point-analysis (septal annulus, lateral annulus, apex) endocardial borders of every cardiac cavity were defined (endocardial tracing). This methodology of offline analysis was previously described for the assessment of myocardial deformation properties in fetal humans [ 27 , 28 ] and lamb hearts [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

Evaluation of right ventricular myocardial deformation properties in fetal hypoplastic left heart by two-dimensional speckle tracking echocardiography

Enzensberger

Graupner

Fischer

et al. 2023

Arch Gynecol Obstet

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Purpose Right ventricular (RV) function influences the outcome of hypoplastic left heart (HLH) patients. This study aimed to confirm the assumption of prenatal RV remodeling and possible influencing factors of myocardial restructuring using two-dimensional speckle tracking echocardiography (2D STE). Methods This is a retrospective cross-sectional cohort study including HLH fetuses and gestational age-matched controls. Based on a four-chamber view, cine loops were stored with 60 frames per second. Global longitudinal peak systolic strain (GLPSS) of the RV was retrospectively determined and compared to healthy controls. Furthermore, HLH subgroups were built according to the presence of left ventricular endocardial fibroelastosis (LV-EFE) and restrictive foramen ovale (FO) to investigate the effect of these compromising factors on myocardial deformation. Results A total of 41 HLH fetuses and 101 controls were included. Gestational age at fetal assessment was similarly distributed in both groups (controls: 26.0 ± 5.6 weeks vs. HLH: 29.1 ± 5.6 weeks). Relating to RV-GLPSS values, fetuses with HLH demonstrated lower mean values than healthy control fetuses (− 15.65% vs. − 16.80%, p = 0.065). Cases with LV-EFE (n = 11) showed significantly lower mean values compared to such without LV-EFE (n = 30) (RV-GLPSS: − 12.12% vs. − 16.52%, p = 0.003). No significant differences were observed for cases with FO restriction (n = 10). Conclusions In HLH the RV undergoes prenatal remodeling, leading to an adaptation of myocardial function to LV conditions. Further explorations by STE should expand knowledge about RV contraction properties in HLH and its impact on surgical outcome.

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Induction of left ventricular hypoplasia by occluding the foramen ovale in the fetal lamb

Cited by 14 publications

References 37 publications

Fluid Mechanics of Fetal Left Ventricle During Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome

Fluid Mechanics of Fetal Left Ventricle During Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome

Thinking Outside the “Flow-Mediated” Box: An Analysis of Aortic Dilation in 100 Fetuses with Tetralogy of Fallot Compared to Matched Controls

Evaluation of right ventricular myocardial deformation properties in fetal hypoplastic left heart by two-dimensional speckle tracking echocardiography

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