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

Abstract

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.

Fluid Mechanical Effects of Fetal Aortic Valvuloplasty for Cases of Critical Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome

“… AV – aortic valve; MV – mitral valve; RV – right ventricle; SV – stroke volume; LV – left ventricle; EDV – end-diastolic volume; EF – ejection fraction; MR – mitral regurgitation; AR – aortic regurgitation. Disease cohort data from the current study were combined with pre-FAV and healthy cohort data from Wong et al 35 All data are presented as mean ± standard deviation. † p < 0.05 comparing diseased pre-FAV to healthy and post-FAV to healthy; ‡ p < 0.05 comparing diseased pre-FAV and corresponding post-FAV cases.…”

“…Vorticity dynamics were generally quiescent in pre-FAV LVs due to low flow rates, but there was a wide variability from case to case.

Figure 2 Flow visualisation at different time points of the cardiac cycle using the lambda2 vortex criterion iso-surfaces and wall shear stress color contour plots for two representative healthy LVs and five FAS LVs pre- and post-FAV with data combined from Wong et al 35 Further results are shown in Supplementary Figure S2 and Supplementary Videos S1–12.

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“…The spatial distributions of time-averaged WSS (TAWSS) and OSI for two age groups (21–22 weeks, 28–31 weeks) are shown for the two representative healthy cases, 35 and two pre-FAV cases and their corresponding post-FAV cases in Fig. 4 .…”

“…1 and was described in our previous study, where all model parameters are given. 35 The model was originally proposed by Pennati et al , 21 , 22 but was recalibrated to match more recent human fetal clinical measurements, including fetal abdominal aortic pulse pressures across gestational ages, and systolic and diastolic LV pressure across gestational ages. 9 , 30

Figure 1 Scheme of the human fetal circulation lumped parameter model coupled to the CFD model of the left ventricle, adapted from Pennati et al 21 AA: Ascending aorta, AO1: aortic arch, AO2: thoracic descending aorta, AO3: abdominal descending aorta, AO4: femoral descending aorta, BR: brain, CA: cerebral arteries, HE: liver, INTE: intestinal circulation, IVC: inferior vena cava, KID: kidney, LA: left atrium, LEG: lower limbs, LUNG: lungs, PA1: main pulmonary artery, PA2: pulmonary arteries, PLAC: placenta, RA: right atrium, RV: right ventricle, SVC: superior vena cava, UB: upper body, UV: umbilical vein.

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“…We have previously characterized the fluid mechanics of diseased FAS LV and found altered vorticity dynamics, wall shear stress (WSS) spatial patterns, excessive flow energy losses, and poor turnover of blood. 35 However, a detailed investigation of the biomechanical impact of FAV has not been conducted, and our current understanding of its impact is limited to echocardiographic measurements with limited resolution.…”