Quantitative reconstruction of cardiac electromechanics in human myocardium: regional heterogeneity

Regional heterogeneity of electrophysiologic properties within the human ventricles is based on changes in ion channel kinetics and density inside the wall. The heterogeneity not only influences the electrophysiologic properties but also cellular force development. In this study, the influence of heterogeneity was investigated using mathematical models.

An overview of measurements of the heterogeneity of electrophysiology and force development is presented. This knowledge is transferred to an electromechanical heart model composed of a human ionic cell model describing electrophysiologic properties and a model for the development of forces. Heterogeneity is included in the ionic model by changing ion channel kinetics and density. The characteristics and dependencies of the electromechanical model are demonstrated in a single-cell environment and a multicell environment. In the single-cell environment, the effects of heterogeneity on electrical activity are demonstrated. The notch in the action potential decreases from epicardium to endocardium, and action potential duration is longest in the mid-myocardium. The developed forces are largest in the subendocardial cells and decrease continuously toward the epicardium. The multicell environment describes a transmural line of cells in the left ventricular free wall using a bidomain approach. The transmural ECG shows typical characteristics with a positive monophasic T wave.

This work demonstrates the need to incorporate regional heterogeneity in order to model human cardiac electromechanics. The results of electrophysiologic simulations correspond to measured data. The dependencies of regional heterogeneity on force development need to be validated in experiments, because little is known about the influence of heterogeneity on electromechanical coupling.