Effect of infarct stiffness on non-infarcted left and right ventricular tissue remodeling: a computational study based on myocardial mechano-transduction

Abstract

Abstract Background/Introduction The mechanical properties of infarcted myocardium are important determinants of cardiac pump function and risk of developing heart failure following myocardial infarction (MI). Purpose To better understand the effects of infarct stiffness on compensatory hypertrophy and dilation of non-infarcted tissue in the left (LV) and right ventricle (RV), by using a computational model. Methods The CircAdapt computational model of the human heart and circulation was applied to simulate an acute MI involving 20% of LV wall mass. The simulation was validated using previously published experimental data. Subsequently, two degrees of increased infarct stiffness were simulated. In all three simulations, a model of structural myocardial adaptation of the non-infarcted tissue was applied, based on sensing of mechanical loading of myocytes and extracellular matrix (ECM). Results Mild and severe stiffening of the infarct reduced the increase of LV end-diastolic volume (EDV) from +23 mL to +17 mL and +16 mL, respectively, and the increase of LV non-infarcted tissue mass from +31% to +21% and +18%. RV EDV decreased after adaptation, and mild and severe infarct stiffening reduced the decrease of RV EDV from −21 mL to −12 mL and −10 mL, respectively. Increase of RV tissue mass was reduced from +13% to +8% and +7% with mild and severe infarct stiffening. In the LV, reduced dilation and hypertrophy were driven mainly by a reduction of maximum stress in the ECM and a higher stress between the myocytes and ECM following infarct stiffening. The decreased RV hypertrophy, but not EDV reduction, was caused by a reduction of maximum RV ECM stress and maximum RV active myofiber stress. Conclusions Model simulations predicted that a stiffened LV infarct reduces both LV and RV non-infarcted tissue hypertrophy as well as LV dilation. In LV remodeling, maximum ECM stress and stress between myocyte and ECM played a more prominent role than in RV remodeling, while maximum active stress was more important in the RV. Overview of all model simulations Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was funded by the Netherlands Organisation for Scientific Research and the Dutch Heart Foundation.