Mechanical discoordination increases continuously after the onset of left bundle branch block despite constant electrical dyssynchrony in a computational model of cardiac electromechanics and growth

Abstract

To test whether a functional growth law leads to asymmetric hypertrophy and associated changes in global and regional cardiac function when integrated with a computational model of left bundle branch block (LBBB). In recent studies, we proposed that cardiac myocytes grow longer when a threshold of maximum fibre strain is exceeded and grow thicker when the smallest maximum principal strain in the cellular cross-sectional plane exceeds a threshold. A non-linear cardiovascular model of the beating canine ventricles was combined with the cellular growth law. After inducing LBBB, the ventricles were allowed to adapt in shape over time in response to mechanical stimuli. When subjected to electrical dyssynchrony, the combined model of ventricular electromechanics, haemodynamics, and growth led to asymmetric hypertrophy with a faster increase of wall mass in the left ventricular (LV) free wall (FW) than the septum, increased LV end-diastolic and end-systolic volumes, and decreased LV ejection fraction. Systolic LV pressure decreased during the acute phase of LBBB and increased at later stages. The relative changes of these parameters were similar to those obtained experimentally. Most of the dilation was due to radial and axial fibre growth, and hence altered shape of the LVFW. Our previously proposed growth law reproduced measured dyssynchronously induced asymmetric hypertrophy and the associated functional changes, when combined with a computational model of the LBBB heart. The onset of LBBB leads to a step increase in LV mechanical discoordination that continues to increase as the heart remodels despite the constant electrical dyssynchrony.