Rick Schreurs

154 Appendices failure patients with first-degree AV-block (PR-interval >230ms) and QRS duration <150ms. Using invasive pressure-volume loops, we find that the improvements in hemodynamics are achieved by better LV filling, which is the result of a combination of increased forward flow over the mitral valve and a reduction in diastolic mitral regurgitation. These results are replicated using the CircAdapt computer model. In the patient study we show that restoring AV coupling using BiV pacing increases stroke volume and stroke work, but that these improvements are absent when using right ventricular (RV) pacing. This adverse effect of RV pacing, caused by increased ventricular dyssynchrony, is also seen in CircAdapt simulations. These results indicate that restoration of AV-coupling may provide considerable benefit to patients, as long as an increase in ventricular dyssynchrony is avoided. The aim of chapter 4 is to get a better understanding of the diastolic filling patterns during various AV-delays. Furthermore, it explores how variations in interatrial delay (IAD) and various ventricular pacing sites with changes in IVD influence the optimal AV-delay. The ultimate goal is to better predict the optimal AV-delay using parameters based on effective AV-delays of the right and left heart. Experiments were performed in a porcine total AV- block model in which atrial pacing was compared to atrial sensing for RV, LV and BiV pacing at various AV-delays. Our findings are that the optimal AV-delay is a function of both atrial sensing or atrial pacing and of the ventricular pacing site, so a function of both IAD and IVD. To combine these influences in finding the optimal AV-delay the mean effective AV-delay is introduced, which is a parameter that takes into account both right and left sided effective AV-delay. The new parameter corrects for variances in atrial and ventricular activation and for effective AV-delay in the right and left heart. The use of the mean effective AV-delay may improve automated algorithms for AV-delay optimization. Chapter 5 focuses on the SonR1 signal, which is an accelerometer derived parameter reflecting the first heart sound, used for automated AV- and VV-delay optimization. The objective is to better understand the role of ventricular contractility, AV-coupling and IVD on the amplitude of SonR1 using canines with synchronous and dyssynchronous hearts. First, we show that during infusion of increasing concentrations of dobutamine the amplitude of SonR1 strongly correlates to RV and LV dP/dt max­ . Next, the SonR signal was compared to various hemodynamic parameters during a large range of AV-delays. Starting from long AV-delays, SonR1 amplitude increases at intermediate AV-delays and is largest during the shortest AV-delays, possibly caused by atrial contraction against closed AV-valves. The optimal AV-delay, defined as the AV-delay with the largest increase in LV dP/dt max , occurs at AV-delays just longer than those where the SonR1 amplitude starts to increase. Finally, the SonR1 values do not greatly vary between BiV and LV pacing, which indicates that IVD is not a major determinant of SonR1. The SonR1 amplitude is larger when measured in the RV than in the RA, but the relative increases at the shortest AV-delays were larger in the RA. We conclude that the SonR1 amplitude is influenced by changes in cardiac contractility