Rick Schreurs

155 Summary and time interval between atrial and ventricular contraction, while IVD plays a minor role. Placement of the SonR sensor in the RA seems to assess overall cardiac function better than an RV-placement. In chapter 6 we used a canine AV-block model and CircAdapt computer simulations to study the effect of a large variation of AV- and VV-delays on RV and LV contractility. In the dogs we show that RV pre-excitation results in the largest LV total activation time and vice- versa, while during simultaneous pacing two electrical wavefronts fuse and resynchronize the heart, indicated by the lowest LV total activation time. Additionally, RV function is best during RV pre-excitation, while LV pre-excitation results in the highest LV dP/dt max and decreases RV dP/dt max . In contrast to changes in VV-delay, alterations in AV-delay have less effect on measured LV and RV dP/dt max . These observations were replicated using a dog- specific version of the the CircAdapt model. We conclude that the LV and the RV respond in a opposite manner to variation in the amount of LV or RV pre-excitation. Computer simulations capture LV and RV behavior during pacing delay variation and may be used in the design of new CRT optimization studies. In order to find an explanation for the different behavior of cardiac output and RV and LV dP/ dt max , the time course of these parameters during the first beats after the start of a certain setting were compared. We find that stroke volume of both ventricles stabilizes after three beats and are the same for the RV and LV. However, the differences between LV and RV dP/dt max remain present, accompanied by opposite changes in RV and LV end-diastolic volume. This study demonstrates that improving LV function can reduce RV function. Furthermore, cardiac output is not necessarily increasing when LV dP/dt max increases. Hence, an exclusive focus on the LV might not lead to the best overall outcome. Finally, chapter 7 integrates the major findings of the above summarized chapters and discusses them in a broader scientific and clinical perspective. Based on this thesis we can conclude that restoring AV-coupling using BiV pacing results in acute hemodynamic improvements in both pigs and patients with heart failure and first-degree AV-block. The mechanism of action is due to better ventricular filling because of increased transmitral forward flow and a decrease of diastolic mitral regurgitation. This may lead to a novel indication for pacemaker therapy in patients with prolonged PR-interval, although additional research needs to further unravel which pacing modality is most suitable and which patient category has the highest benefits. Furthermore, the fact that restoring AV-coupling in first-degree AV-block improves hemodynamics, once again suggests that AV-delay optimization remains an important factor in improving the efficacy of pacemaker therapies like CRT. We describe that the optimal AV-delay is influenced by changes in interatrial delay and ventricular dyssynchrony and that AV-delay optimization should therefore not only focus on the left side of the heart, but also consider the right side. Novel parameters like the mean effective AV-delay and S