Rick Schreurs

115 Left and right ventricular response to CRT the other conditions, illustrates that dP/dt max was largely independent of preload, whereas stroke volume depended on it, most likely due to the length dependent activation, implemented in the CircAdapt model (see methods). Computer simulations Δ Caridac output (%) Effect of changing VV-delay Effect of changing AV-delay -10 -5 5 10 0 50 50 90 90 130 130 170 170 210 210 50 210 90 170 130 130 170 90 210 50 A-LV A-RV (ms) (ms) Increase in AV-delay LV first | RV first 50 230 50 230 A-RV (ms) -11% 9% A-LV (ms) Simulations Δ Caridac output (%) A Figure 5. Relative change in simulated steady-state cardiac output with a change in pacing delay settings. Depicted are the changes relative to baseline (see text). Δ Stroke volume (%) Δ EDV (%) Δ LV dP/dt max (%) 10 5 0 -5 6 3 0 -3 -6 20 10 0 -10 -20 Baseline A-RV 125ms Direct mechanical effect Right ventricle Left ventricle Pacing change A-LV 70ms, A-RV 190ms 1 2 3 4 5 6 7 8 SS Δ Stroke volume (%) Δ EDV (%) Δ LV dP/dt max (%) - - - - - li i i l i i l i l Balancing LV/RV preload i , Figure 6. Time courses of the relative change of stroke volume (top), end-diastolic volume (EDV, mid) and dP/dt max of the LV (black circles) and RV (red squares) after changing pacing delay from baseline (A-RV 125ms) to LV pre-excitation (A-LV 70ms, A-RV 190ms) in computer simulations. The black dashed line indicates the start of the change in pacing delay. The numbers on the horizontal axis indicate the number of simulated cardiac cycles. SS: steady state. 6