Analyses of the redistribution of work following cardiac resynchronisation therapy in a patient specific model

Abstract

Regulation of regional work is essential for efficient cardiac function. In patients with heart failure and electrical dysfunction such as left branch bundle block regional work is often depressed in the septum. Following cardiac resynchronisation therapy (CRT) this heterogeneous distribution of work can be rebalanced by altering the pattern of electrical activation. To investigate the changes in regional work in these patients and the mechanisms underpinning the improved function following CRT we have developed a personalised computational model. Simulations of electromechanical cardiac function in the model estimate the regional stress, strain and work pre- and post-CRT. These simulations predict that the increase in observed work performed by the septum following CRT is not due to an increase in the volume of myocardial tissue recruited during contraction but rather that the volume of recruited myocardium remains the same and the average peak work rate per unit volume increases. These increases in the peak average rate of work is is attributed to slower and more effective contraction in the septum, as opposed to a change in active tension. Model results predict that this improved septal work rate following CRT is a result of resistance to septal contraction provided by the LV free wall. This resistance results in septal shortening over a longer period which, in turn, allows the septum to contract while generating higher levels of active tension to produce a higher work rate.

Figure 1. Patient specific model mesh geometry.

Cubes show the regional variation in the fibre orientation in the A) mid LV lateral free wall, B) apex LV lateral free wall, C) LV posterior wall, D) LV anterior wall, E) septum and F) RV free wall. The mesh is dissected into labeled regions of the heart.

Figure 2. Plot of changes in global metrics of cardiac function following LV pacing. Panel A), B) and D) show the change in left ventricle pressure, rate of pressure development and volume, respectively, on pacing.

Panel D) shows the phase plot of pressure and volume, where the area enclosed beneath the lines is equal to the work performed.

Figure 3. Plot of local work (A) pre- and (B) post-CRT, yellow spheres correspond to regions of scar that perform no work.

Blue spheres and red spheres correspond to regions performing positive and negative work, respectively and the size of the sphere corresponds to the magnitude of the work rate. Panels A) and B) show in the first row the local work in the whole heart at 100 ms intervals, and in the second row a close up of the septum at 50 ms intervals.

Figure 4. Plots the relative volumes of the A) RV, B) LV and C) septum performing zero work (red lines), positive work that can contribute to pump function (yellow lines) and negative work that opposes pump function (blue lines) for sinus rhythm (solid lines) and LV paced case (dashed lines).

Figure 5. Plot of regional work rates for the LV (yellow lines), RV (red lines), septum (blue lines) and the whole heart (black lines) for sinus rhythm (solid lines) and for LV pacing (dashed lines).

Panel A) compares the total work density. Panels B–E) separates Panel A) into regional plots of Septum, RV, LV and whole heart work densities individually for sinus rhythm and LV pacing. Similarly Panel F–J) compares the total work density in volumes of the heart that are performing positive work and Panel L–O) compares the regional work performed in volumes of the heart performing negative work.

Figure 6. Plot of the average A) active-tension and B) fibre SR in the LV (yellow lines), RV (red lines), septum (blue lines) and the whole heart (black lines) for sinus rhythm (solid lines) and for LV pacing (dashed lines).

Panels C–F) show the individual plots from Panel B) for clarity. Panels G) and H) show the average work rate and the average SR, respectively, in the posterior (black), apex (blue), lateral (yellow) and anterior (red) LV free wall for sinus (solid) and paced (dashed) stimulation.

Figure 7. Plot off the regional work rate calculated in the LV (yellow lines), RV (red lines), septum (blue lines) and the whole heart (black lines).

The regional work rate was calculated using the SR from the sinus and paced model for the left and right plots, respectively and the tension from the sinus and paced models for the top and bottom plots, respectively.