An electromechanical left ventricular wedge model to study the effects of deformation on repolarization during heart failure

Abstract

Heart failure is a major and costly problem in public health, which, in certain cases, may lead to death. The failing heart undergo a series of electrical and structural changes that provide the underlying basis for disturbances like arrhythmias. Computer models of coupled electrical and mechanical activities of the heart can be used to advance our understanding of the complex feedback mechanisms involved. In this context, there is a lack of studies that consider heart failure remodeling using strongly coupled electromechanics. We present a strongly coupled electromechanical model to study the effects of deformation on a human left ventricle wedge considering normal and hypertrophic heart failure conditions. We demonstrate through a series of simulations that when a strongly coupled electromechanical model is used, deformation results in the thickening of the ventricular wall that in turn increases transmural dispersion of repolarization. These effects were analyzed in both normal and failing heart conditions. We also present transmural electrograms obtained from these simulations. Our results suggest that the waveform of electrograms, particularly the T-wave, is influenced by cardiac contraction on both normal and pathological conditions.

Figure 1

Coupled electromechanical TNNP + Rice cell model: (a) normalized transmembrane potential and active force and (b) intracellular calcium concentration.

Figure 2

HF changes: (a) steady state calcium transient; (b) transmembrane potential for endo, M, and epi myocytes.

Figure 3

Action potential, calcium transient, and active force for cell types under normal (solid line) and failing heart (dashed line) conditions.

Figure 4

Spatial distribution of the transmembrane potential v in the coupled electromechanical simulation. Panels (e) to (h) show the transmural stretch of the LV wedge. v varies from −90 mV (blue) to 20 mV (red).

Figure 5

Comparisons of simulations with and without deformation (pure electrophysiology). (a) Repolarization time and (b) action potential duration in a transmural line of the domain. The dashed red line in (b) represents the single cell APD. (c) Simulated electrogram obtained with the extracellular potential u _e from the bidomain model.

Figure 6

Transmural electrograms computed from simulations with and without (w/o) deformation for the HF case considering a hypertrophic LV wedge. On the right panel, the graph shows a zoom on the T-wave region.

Figure 7

Comparison of the electrograms for the simulations considering HF conditions. Control denotes the HF simulation without deformation; HF-case  1 is the full HF remodeling with changes on both single cell and tissue properties; HF-case  2 is the HF remodeling case without changing the properties of the HO constitutive model.