An exploratory assessment of stretch-induced transmural myocardial fiber kinematics in right ventricular pressure overload

Figures

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  Figure 1. Stretch-induced deformations experienced by RV myocardium during diastolic filling and the IVC phase of early-systole. During diastole, ventricular filling results in passive stretch of the RVFW. IVC follows tricuspid valve closure at end-diastole, during which active myocardial contraction increases chamber pressures (while both tricuspid and pulmonary valves remain closed) and results in increased wall stress (afterload) and stretching of the RVFW. Both active contraction and stretching happen simultaneously during this phase, as reflected in increased ventricular pressures6,13 in addition to ventricular wall thinning13,14 and fiber stretch13 during early-systole. This is followed by pulmonary valve opening and systolic ejection, which results in negative RVFW contractile strains. The current study focuses on stretch-induced deformations of RV myocardium during the end-diastolic and early-systolic phases of a cardiac cycle, without considering the effects of cardiomyocyte contraction. ECM extracellular matrix, RV right ventricle, RVFW right ventricular free wall, IVC isovolumetric contraction.

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  Figure 2. The ultrasound image processing framework used to detect transmural RV myofiber orientations. (a) Development of the HFU imaging framework. Basal anterior zone RVFW specimens were scanned while the ultrasound probe was aligned with the apex-to-base direction, normal to the transmural axis. High noise in the acquired high-frequency B-mode images were reduced via multi-scale decomposition using NLADF, followed by establishing myofiber connectivity by CEDF. Skeleton extraction was performed on the resulting image, followed by fiber detection using the Hough transform and fitting a normal PDF to the fiber distributions. (b) Algorithm verification by comparing HFU measurements with histological staining (H&E). Error bars demonstrate fiber spread (standard deviation of the distribution of fiber orientations; measure of fiber dispersion) at each transmural section. Fiber angles are normalized to 0° at the epicardial layer, to better demonstrate the transmural change in fiber angles and facilitate comparison with previous studies42. Dotted lines between HFU measurements are for visualization purposes only. TV Tricuspid valve, Epi Epicardium, Endo endocardium, HFU high-frequency…

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  Figure 3. The finite element modeling framework used to study biaxial RV fiber kinematics. (a) Loading and boundary condition calculations. In order to keep the computational burden tractable, simulations were performed on a representative volume element (RVE; shown in black in dotted box), and effects of the 3D RV geometry were modeled as loading and boundary conditions based on an extension of the law of Laplace for ellipsoidal geometries. Measurements were performed on porcine hearts to acquire the geometrical parameters required for modeling. (b) The RVE in the circumferential-longitudinal and longitudinal-transmural planes, showing the transmural stack of fibers from epi to endocardium and distribution of myofibers, collagen and ECM at each transmural section. Transmural fiber architectures (measured via HFU) and porcine RVFW material properties/volume fractions were used to generate the RVE. The calculated boundary conditions (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\upsigma…

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  Figure 4. Uniaxial myofiber kinematics under a stretch ratio of λ = 1.35. (a) Representative transmural HFU images before and after loading. (b) Quantification of fiber angles using the developed framework. Uniaxial loading results in fiber reorientation towards the loading direction (0°). Experimental measurements demonstrate good agreement with theoretical approximations of affine fiber kinematics for an incompressible transversely isotropic solid (R2 = 0.92). (c) Effects of loading on RVFW helix slope. Loading results in decreased RVFW helix slope, which does not show any statistically significant differences with theoretical affine approximations. Error bars show standard error of the mean (SEM). *Indicates p < 0.01. One-way repeated measures ANOVA with post-hoc testing performed using Tukey’s test. Epi epicardium, Endo endocardium, US Probe ultrasound probe, Exp experimental, RV right ventricle, RVFW right ventricular free wall.

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  Figure 5. Effects of different loading scenarios on biaxial fiber kinematics of RV myocardium. (a) Effects of loading on end-diastolic fiber kinematics, indicating increased proportion of oblique fibers only for the CPO scenario without concentric hypertrophy (single-cycle simulations). (b) Effects of loading on early-systolic fiber kinematics, demonstrating elevated proportion of oblique fibers under both CPO scenarios with amplified proportions for CPO without concentric hypertrophy (single-cycle simulations). (c) Multi-cycle simulations of RV fiber reorientation towards the longitudinal direction (± 90°) under CPO and (d) CPO without concentric RV hypertrophy. Error bars demonstrate fiber spread (standard deviation of the distribution of fiber orientations) at each transmural section. (e) Proportion of oblique fibers for the normotensive scenario compared to CPO with and without concentric hypertrophy. Fiber proportions for the CPO cases are plotted following 4 cycles of remodeling simulations, while normotensive loading quits the remodeling algorithm following the first cycle of loading. Both CPO scenarios result in significant increases in the proportion of oblique fibers compared to…

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  Figure 6. Effects of fibrosis on biaxial RV fiber kinematics under chronic pressure overload with concentric and eccentric hypertrophy. (a) Parametric increase in RV collagen content. Red: Myofibers, Blue: Collagen. (b) Effects of fibrosis on end-diastolic and (c) Early-systolic fiber kinematics. RV fibrosis did not demonstrate any statistically significant alteration in fiber proportions at end-diastole or early-systole. Chi-squared tests. Circ circumferential, RV right ventricle.