Right Ventricular Fiber Structure as a Compensatory Mechanism in Pressure Overload: A Computational Study

Abstract

Right ventricular failure (RVF) is a lethal condition in diverse pathologies. Pressure overload is the most common etiology of RVF, but our understanding of the tissue structure remodeling and other biomechanical factors involved in RVF is limited. Some remodeling patterns are interpreted as compensatory mechanisms including myocyte hypertrophy, extracellular fibrosis, and changes in fiber orientation. However, the specific implications of these changes, especially in relation to clinically observable measurements, are difficult to investigate experimentally. In this computational study, we hypothesized that, with other variables constant, fiber orientation alteration provides a quantifiable and distinct compensatory mechanism during RV pressure overload (RVPO). Numerical models were constructed using a rabbit model of chronic pressure overload RVF based on intraventricular pressure measurements, CINE magnetic resonance imaging (MRI), and diffusion tensor MRI (DT-MRI). Biventricular simulations were conducted under normotensive and hypertensive boundary conditions using variations in RV wall thickness, tissue stiffness, and fiber orientation to investigate their effect on RV pump function. Our results show that a longitudinally aligned myocardial fiber orientation contributed to an increase in RV ejection fraction (RVEF). This effect was more pronounced in response to pressure overload. Likewise, models with longitudinally aligned fiber orientation required a lesser contractility for maintaining a target RVEF against elevated pressures. In addition to increased wall thickness and material stiffness (diastolic compensation), systolic mechanisms in the forms of myocardial fiber realignment and changes in contractility are likely involved in the overall compensatory responses to pressure overload.

In-silico assessment of the effects of right ventricular assist device on pulmonary arterial hypertension using an image based biventricular modeling framework

“…As shown in this study, the image-based computational framework can help evaluate patientspecific effects of PAH and RVAD implantation not only on ventricular hemodynamics, deformation and myofiber stresses but also on arterial hemodynamics and wall stresses when coupled with a FE model of the vasculature as we have done previously [36]. Previous computational heart models [9,10,12] developed to investigate PAH in humans do not consider the bi-directional coupling between the heart and both the pulmonary and systemic circulation. On the other hand, a computational study that investigate the effects of RVAD in PAH patients [3] is based entirely on a lumped parameter modeling framework, which cannot be used to evaluate regional ventricular stresses and deformation (e.g., septal curvature).…”

“…In Eqn. (10), P is the first Piola Kirchhoff stress tensor and F is the deformation gradient tensor. The variations of the displacement field, Lagrange multiplier for enforcing incompressibility and volume constraint, zero mean translation and rotation are denoted by δu, δp, δP LV , δP RV , δc 1 , and δc 2 , respectively.…”

“…Mechanical behavior of the myocardial tissue was described by an active stress formulation in which the first Piola stress tensor P in Eqn. (10) was additively decomposed into a passive and an active component, i.e.…”

“…Computational models are increasingly developed to improve our understanding on the effects of PAH on RV mechanics, although the number of models is significantly lesser compared to those developed to study left ventricular (LV) mechanics [5][6][7][8]. While able to produce insights of PAH, existing computational heart models developed to investigate this disease currently suffer from one or more of the following limitations: (a) not calibrated based on human data [9,10], (b) focusing only on RV passive mechanics and ignore active mechanics [11], and (c) do not couple both systemic and pulmonary circulatory systems [9,10,12]. Specifically, the latter limitation places a restriction on our ability to fully assess how alterations in the pulmonary circulation consisting of the RV, such as by RVAD implantation, can impact the systemic circulation (including LV mechanics), and vice versa.…”

Interactions Between Structural Remodeling and Hypertrophy in the Right Ventricle in Response to Pulmonary Arterial Hypertension

“…Image-based computational models of PAH, including both biventricular cardiac models as well as hemodynamic models of the pulmonary vasculature, hold promise to advance our understanding of cardiac and vascular remodeling under PAH, and there has been growing interest in developing such models [13][14][15][16]. As computational cardiac models have elucidated the marked effect of myofiber orientation in the load distribution in the myocardial wall [17][18][19][20], remodeling in fiber structure alone is expected to influence the overall contractile function of the ventricle.…”