Rick Schreurs

45 Cardiac pacing in first degree AV-block Figure 3 depicts that in the computer simulations and the animal studies, the largest increase in LV end-diastolic volume was observed at the AV-delay leading to the LV filling pattern with most pronounced E-A wave separation (175ms in the simulations, 157±7ms in the animals) and leading to minimal diastolic MR. At this setting, MAP and cardiac output were also increased (both ~15% in simulations and ~10% in animals). Importantly, in the animal studies the largest increase in LVEDV (at AV-delay 150ms) was achieved without a significant change in mean LA pressure compared to the baseline condition with long AV-delay ( Table 1 ). 50 100 150 200 250 BL -10 0 10 20 * * * * * 50 100 150 200 250 BL AV-delay (ms) -10 0 10 20 50 100 150 200 250 BL -20 0 20 40 * * * 50 100 150 200 250 BL -10 0 10 20 * * * 50 100 150 200 250 BL AV-delay (ms) -20 0 20 40 50 100 150 200 250 BL AV-delay (ms) -10 0 10 20 Δ MAP (%) Δ LVEDV (%) Δ Stroke volume (%) Experimental data Computer simulations f(x) Figure 3. Hemodynamic response to improving atrioventricular (AV) coupling in pig experiments and computer simulations during biventricular pacing. Relative changes in hemodynamic function by shortening AV-delay in all pig experiments ( Top panel ) and simulations ( Bottom panel ) as compared to a baseline PR-interval of 300ms. MAP: mean arterial pressure, LVEDV: left ventricular end diastolic volume. For the pig experiments mean±SD are presented. * indicates p<0.05 as compared to baseline. Both the computer simulations and animal studies showed that the increased filling at intermediate AV-delays was achieved by a dual effect: larger forward flow over the mitral valve (area under the E- and A-waves) and a reduction in diastolic MR ( Table 1 ). Modulating effects of ventricular dyssynchrony: computer simulations While the aforementioned study results concerned manipulation of AV-coupling in normal hearts at a constant degree of ventricular dyssynchrony, a next step was to investigate how different degrees of pacing-induced ventricular dyssynchrony would influence the hemodynamic response to changes of AV-coupling in the failing heart. The amount of hemodynamic improvement obtained with recovery of AV-coupling depended on the degree of pacing-induced ventricular dyssynchrony. The largest hemodynamic improvement was predicted with the simulations with synchronous ventricular activation, while RV pacing simulations showed the smallest improvement, in terms of stroke volume ( Figure 4A ), 3