Assessment of left ventricular mechanics in right ventricular overload using in silico rat models

BACKGROUND: To preserve cardiac function in overload conditions, the RV adapts by developing muscular hypertrophy through progressive tissue remodelling. This process may lead to a vicious cycle with detrimental effects on RV diastolic and systolic function, as seen in pulmonary arterial hypertension (PAH) patients [1]. However, how RV overload affects LV function and remodelling remains an open question [2]. Computational models of cardiac physiology offer an opportunity for investigating mechanisms difficult or impossible to analyse otherwise due to the existence of overlapping factors and technical limitations. AIM: This study aims to assess the acute effects of RV overload and increased myocardial passive stiffness on the LV mechanical properties in an anatomically-based computational model of healthy rat heart. METHODS: A computational simulation pipeline of cardiac mechanics based on the Holzapfel-Ogden model has been implemented using MR images from a healthy rat. Whereas LV function was modelled realistically using catheter measurements conducted on the same subject than the MR imaging, RV function was based on representative literature values for healthy and PAH rats with RV overload. The following cases were defined (Fig. 1): CTRL, with normal RV function; PAH1, with 30% increase in RV ESV (end-systolic volume) and 15% increase in RV ESP (end-systolic pressure) in comparison to CTRL; and PAH2, with 60% increase in RV ESV and 30% increase in RV ESP compared to CTRL. The cardiac cycle was simulated for all cases whilst fitting the experimentally measured LV pressure and volume values from a healthy rat, which allowed quantifying the effects of RV overload on LV function. RESULTS: The increase of average circumferential strain in the LV correlated with the degree of RV overload simulated (CTRL: −8.7%, PAH1: −8.9%, PAH2: −9.2%), whilst average radial (CTRL: 35.2%, PAH1: 34.8%, PAH2: 30.3%) and longitudinal strains decreased (CTRL: −7.7%, PAH1: −7.4%, PAH2: −6.6%), as seen in Fig.2. However, regional differences in strain were significant: under RV overload conditions, circumferential strain increased in the septum (−3.5% difference in PAH2 vs. CTRL) but lower values were observed in the lateral wall (+1.7% difference in PAH2 vs. CTRL). Cardiac function of case PAH2 was simulated also with increased myocardial passive stiffness (2.67 kPa instead of 1.34 kPa) which presented a mild strain increase in the mid LV ventricle in comparison to PAH2 with normal stiffness (circumferential strain: −0.8%, radial strain: +0.5%, longitudinal strain: −0.2%). CONCLUSION: Our study provides mechanistic evidence on how RV overload and increased passive myocardial stiffness causes a redistribution of strain and fibre stress in the LV, which may play a significant role in LV remodelling and function. FUNDING ACKNOWLEDGEMENT: Type of funding sources: Public Institution(s). Main funding source(s): K.G. Jebsen Center for Cardiac Research