Modeling cardiac electromechanics and mechanoelectrical coupling in dyssynchronous and failing hearts: insight from adaptive computer models

Abstract

Computer models have become more and more a research tool to obtain mechanistic insight in the effects of dyssynchrony and heart failure. Increasing computational power in combination with increasing amounts of experimental and clinical data enables the development of mathematical models that describe electrical and mechanical behavior of the heart. By combining models based on data at the molecular and cellular level with models that describe organ function, so-called multi-scale models are created that describe heart function at different length and time scales. In this review, we describe basic modules that can be identified in multi-scale models of cardiac electromechanics. These modules simulate ionic membrane currents, calcium handling, excitation-contraction coupling, action potential propagation, and cardiac mechanics and hemodynamics. In addition, we discuss adaptive modeling approaches that aim to address long-term effects of diseases and therapy on growth, changes in fiber orientation, ionic membrane currents, and calcium handling. Finally, we discuss the first developments in patient-specific modeling. While current models still have shortcomings, well-chosen applications show promising results on some ultimate goals: understanding mechanisms of dyssynchronous heart failure and tuning pacing strategy to a particular patient, even before starting the therapy.

Fig. 1

Schematic overview of the CircAdapt model. Cardiac hemodynamics was modeled by placing the ventricles in a systemic and pulmonary circulation including atria, valves, arteries, organs, and veins. Properties of the right ventricular wall (RW), septal wall (SW), and left ventricular wall (LW) can be modified independently in order to simulate left bundle branch block. Adapted from Lumens et al. [49]

Fig. 2

Schematic overview of the model of electrical remodeling proposed by Kuijpers et al. [42, 43]. Cardiac electromechanics was described by a single fiber composed of 300 segments. Left ventricular pressure and volume were related to fiber stress and strain. Cardiac hemodynamics was modeled by placing the left ventricle in a systemic circulation describing the left atrium, valves, arteries, organs, and veins. Electrical activation was started by activating one (normal, LBBB) or both (CRT) fiber ends. Mechanoelectrical feedback (MEF) was incorporated by adjusting segmental L-type calcium current (I _CaL) to obtain target myofiber external work

Fig. 3

Membrane potential (V _mem), calcium transient ([Ca²⁺]_i), and strain for three segments located at the endocardium, midwall, and epicardium of the ventricular wall. Results are shown for all five subsequent simulations, representing the transition from the healthy to the chronically diseased state in left bundle branch block (LBBB) and its response to cardiac resynchronization therapy (CRT) on the short and long term. Modified from Kuijpers et al. [43]

Fig. 4

Dispersion in external work (W _ext), action potential duration (APD_− 60mV), and repolarization (t _repol) during left bundle branch block (LBBB) and cardiac resynchronization therapy (CRT). Modified from Kuijpers et al. [43]