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Pulmonary arterial hypertension (PAH) presents a significant challenge to right ventricular (RV) function due to progressive pressure overload, necessitating adaptive remodeling in the form of increased wall thickness, enhanced myocardial contractility and stiffness to maintain cardiac performance. However, the impact of these remodeling mechanisms on RV mechanics in not clearly understood. In addition, there is a lack of quantitative understanding of how each mechanism individually influences RV mechanics. Utilizing experimental data from a rat model of PAH at three distinct time points, we developed biventricular finite element models to investigate how RV stress and strain evolved with PAH progression. The finite element models were fitted to hemodynamic and morphological data to represent different disease stages and used to analyze the impact of RV remodeling as well as the altered RV pressure. Furthermore, we performed a number of theoretical simulation studies with different combinations of morphological and physiological remodeling, to assess and quantify their individual impact on overall RV load and function. Our findings revealed a substantial 4-fold increase in RV stiffness and a transient 2-fold rise in contractility, which returned to baseline by week 12. These changes in RV material properties in addition to the 2-fold increase in wall thickness significantly mitigated the increase in wall stress and strain caused by the progressive increase in RV afterload. Despite the PAH-induced cases showing increased wall stress and strain at end-diastole and end-systole compared to the control, our simulations suggest that without the observed remodeling mechanisms, the increase in stress and strain would have been much more pronounced. Our model analysis also indicated that while changes in the RV’s material properties–particularly increased RV stiffness - have a notable effect on its mechanics, the primary compensatory factor limiting the stress and strain increase in the early stages of PAH was the significant increase in wall thickness. These findings underscore the importance of RV remodeling in managing the mechanical burden on the right ventricle due to pressure overload.
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Computational models of ventricular mechanics and adaptation in response to right-ventricular pressure overload
Pulmonary arterial hypertension (PAH) is associated with substantial remodeling of the right ventricle (RV), which may at first be compensatory but at a later stage becomes detrimental to RV function and patient survival. Unlike the left ventricle (LV), the RV remains understudied, and with its thin-walled crescent shape, it is often modeled simply as an appendage of the LV. Furthermore, PAH diagnosis is challenging because it often leaves the LV and systemic circulation largely unaffected. Several treatment strategies such as atrial septostomy, right ventricular assist devices (RVADs) or RV resynchronization therapy have been shown to improve RV function and the quality of life in patients with PAH. However, evidence of their long-term efficacy is limited and lung transplantation is still the most effective and curative treatment option. As such, the clinical need for improved diagnosis and treatment of PAH drives a strong need for increased understanding of drivers and mechanisms of RV growth and remodeling (G&R), and more generally for targeted research into RV mechanics pathology. Computational models stand out as a valuable supplement to experimental research, offering detailed analysis of the drivers and consequences of G&R, as well as a virtual test bench for exploring and refining hypotheses of growth mechanisms. In this review we summarize the current efforts towards understanding RV G&R processes using computational approaches such as reduced-order models, three dimensional (3D) finite element (FE) models, and G&R models. In addition to an overview of the relevant literature of RV computational models, we discuss how the models have contributed to increased scientific understanding and to potential clinical treatment of PAH patients.
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- Award ID(s):
- 2046259
- PAR ID:
- 10385026
- Date Published:
- Journal Name:
- Frontiers in Physiology
- Volume:
- 13
- ISSN:
- 1664-042X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3389/fphys.2022.948936
