Effect of myocardial heterogeneity on ventricular electro-mechanical responses: a computational study

BACKGROUND: The heart wall exhibits three layers of different thicknesses: the outer epicardium, mid-myocardium, and inner endocardium. Among these layers, the mid-myocardium is typically the thickest. As indicated by preliminary studies, heart-wall layers exhibit various characteristics with regard to electrophysiology, pharmacology, and pathology. Construction of an accurate three-dimensional (3D) model of the heart is important for predicting physiological behaviors. However, the wide variability of myocardial shapes and the unclear edges between the epicardium and soft tissues are major challenges in the 3D model segmentation approach for identifying the boundaries of the epicardium, mid-myocardium, and endocardium. Therefore, this results in possible variations in the heterogeneity ratios between the epicardium, mid-myocardium, and endocardium. The objective of this study was to observe the effects of different thickness ratios of the epicardium, mid-myocardium, and endocardium on cardiac arrhythmogenesis, reentry instability, and mechanical responses during arrhythmia. METHODS: We used a computational method and simulated three heterogeneous ventricular models: Model 1 had the thickest M cell layer and thinnest epicardium and endocardium. Model 2 had intermediate layer thicknesses. Model 3 exhibited the thinnest mid-myocardium and thickest epicardium and endocardium. Electrical and mechanical simulations of the three heterogeneous models were performed under normal sinus rhythm and reentry conditions. RESULTS: Model 1 exhibited the highest probability of terminating reentrant waves, and Model 3 exhibited to experience greater cardiac arrhythmia. In the reentry simulation, at 8 s, Model 3 generated the largest number of rotors (eight), while Models 1 and 2 produced five and seven rotors, respectively. There was no significant difference in the cardiac output obtained during the sinus rhythm. Under the reentry condition, the highest cardiac output was generated by Model 1 (19 mL/s), followed by Model 2 (9 mL/s) and Model 3 (7 mL/s). CONCLUSIONS: A thicker mid-myocardium led to improvements in the pumping efficacy and contractility and reduced the probability of cardiac arrhythmia. Conversely, thinner M cell layers generated more unstable reentrant spiral waves and hindered the ventricular pumping.