Constrained mixture models of growth and remodelling in an infarct left ventricle: A modelling study

Abstract

Myocardial infarction (MI), characterized by the death of myocytes in the myocardium, leads to high morbidity and mortality rates worldwide. The persistent imbalance of biomechanical stress and strain within the myocardium is a critical factor contributing to adverse growth and remodelling (G&R) following MI, such as wall thinning and chamber dilation. This study investigates the structural and functional adaptations of a left ventricle (LV) after MI through the application of a constrained mixture model of G&R. We further examine the effects of fibre dispersion on LV pump performance using this G&R model. Our model successfully reproduces key characteristics of post-MI G&R, including scar thinning, LV cavity dilation and wall stiffening. Pure myofibre G&R after scar maturation could lead to excessive LV dilation with slightly reduced stroke volume. In contrast, pure collagen G&R would result in a significantly reduced stroke volume that will not meet the blood demand of a patient. A moderate increase in fibre dispersion could prevent significant LV dilation and maintain LV stroke volume, which might be beneficial in preserving normal LV pump function. Whereas excessive dispersion could severely impair active contractility, leading to a much-reduced stroke volume, and ultimately progressing towards heart failure. Future investigations should incorporate the complex interplays between mechanical triggers, biochemical environment and pathological pathways using this constrained mixture theory framework. This approach has the potential to enhance our understanding of cardiac tissue G&R following myocardial infarction, predict LV pump failure due to adverse remodelling, and aid in the assessment of therapeutic strategies in the future.