Biomechanics of Human Fetal Hearts with Critical Aortic Stenosis

Chi Wei Ong,Citra Nurfarah Zaini Mattar,Choon Hwai Yap,Wei Xuan Chan,Meifeng Ren,Andreas Tulzer,Joy Mojumder,Martin Lindsay Buist,Hadi Wiputra,Lik Chuan Lee,Gerald Tulzer

doi:10.1007/s10439-020-02683-x

Abstract

Critical aortic stenosis (AS) of the fetal heart causes a drastic change in the cardiac biomechanical environment. Consequently, a substantial proportion of such cases will lead to a single-ventricular birth outcome. However, the biomechanics of the disease is not well understood. To address this, we performed Finite Element (FE) modelling of the healthy fetal left ventricle (LV) based on patient-specific 4D ultrasound imaging, and simulated various disease features observed in clinical fetal AS to understand their biomechanical impact. These features included aortic stenosis, mitral regurgitation (MR) and LV hypertrophy, reduced contractility, and increased myocardial stiffness. AS was found to elevate LV pressures and myocardial stresses, and depending on severity, can drastically decrease stroke volume and myocardial strains. These effects are moderated by MR. AS alone did not lead to MR velocities above 3 m/s unless LV hypertrophy was included, suggesting that hypertrophy may be involved in clinical cases with high MR velocities. LV hypertrophy substantially elevated LV pressure, valve flow velocities and stroke volume, while reducing LV contractility resulted in diminished LV pressure, stroke volume and wall strains. Typical extent of hypertrophy during fetal AS in the clinic, however, led to excessive LV pressure and valve velocity in the FE model, suggesting that reduced contractility is typically associated with hypertrophy. Increased LV passive stiffness, which might represent fibroelastosis, was found to have minimal impact on LV pressures, stroke volume, and wall strain. This suggested that fibroelastosis could be a by-product of the disease progression and does not significantly impede cardiac function. Our study demonstrates that FE modelling is a valuable tool for elucidating the biomechanics of congenital heart disease and can calculate parameters which are difficult to measure, such as intraventricular pressure and myocardial stresses.

Highlights

Congenital aortic stenosis (AS) carries a prevalence of 0.2–0.5 per 1000 live births.[14]
We developed and calibrated Finite Element (FE) models of healthy fetal hearts from 4D ultrasound images and Doppler velocity measurements, and used them to investigate biomechanical changes during disease conditions associated with fetal AS
We could successfully calibrate the FE models, where healthy heart models showed stroke volume, chamber sizes, and left ventricular (LV) geometry that agreed well with the same data obtained from clinical images

Summary

INTRODUCTION

Congenital aortic stenosis (AS) carries a prevalence of 0.2–0.5 per 1000 live births.[14]. We believed that 60 kPa to be an appropriate estimate for Tmax in our fetal heart models of all ages This was corroborated by difficulty in matching the target stroke volume and pressures in our simulations of the 32 week old fetal heart when we had assumed a higher peak active tension of 80 kPa or 100 kPa. We did not assume a variability of Tmax with gestational age due to the paucity of data. We estimated the thickness of the aortic and mitral valves of fetal heart by first obtaining literature value of newborn heart valve leaflet thicknesses,[44] and scaling them down assuming a direct linear relationship with cardiac diameter.[19] Thickness values used were 0.25 and 0.27 mm for the mitral and aortic valves These thickness values were assumed to be the axial length of the stenotic / regurgitant valve orifices. Equation (5) was solved with a simple gradient descent algorithm as follows (Eq 6), and its results were manually verified

RESULTS

DISCUSSION

CONFLICT OF INTEREST