Rick Schreurs

146 Appendices can, besides BiV pacing, also be achieved by His-bundle, left bundle branch area, or LV septum pacing as well. Scientific impact In chapter 3 and chapter 4 the hemodynamic changes that occurred due to AV-delay optimization were thoroughly studied. As known from basic physiology, better filling of the ventricles leads to pre-stretching of the cardiac myocytes which in response leads to improved contraction, conform the Frank-Starling mechanism [5]. Our studies in chapter 3 showed that in case of first-degree AV-block LV filling was improved due to a combination of increased forward flow over the mitral valve and a reduction in the amount of diastolic mitral regurgitation (MR). Therefore, also in future studies both these processes require attention. Chapter 4 expanded these findings, by investigating the AV-coupling for both the right and left heart. In this regard it should be noticed that conventionally the AV-delay is defined by the time between stimulating (or sensing activity) the RA and stimulation of one or two of the ventricles. We showed that there are considerable differences in “effective” AV-delay between the right and left side of the heart (RA-RV vs. LA-LV delays) and that these delays also strongly depend on the site of ventricular pacing. The mean effective AV-delay takes into account the right and left side of the heart, and was able to more accurately predict the optimal AV-delay. Implication for future research is that both atrial (interatrial delay) and ventricular (interventricular dyssynchrony) activation sequences should be taken into account when searching for new algorithms for optimization of AV- and VV-delays. In chapter 5 we studied the SonR signal which is derived from intracardiac accelerations and gives mechanical information of cardiac contractility. We proved that the amplitude of this signal is not only sensitive for ventricular contraction, but also changes with alterations in ventricular filling at various AV-delays. On the contrary, we proved that the influence of interventricular dyssynchrony on the amplitude of the signal is small. Chapter 6 shows that LV pre-excitation improves LV function but impairs RV function, while RV pre-excitation causes an improvement in RV function and a reduction of LV function. This indicates again that both ventricles should be taken into account while optimizing the AV-delay. Societal impact Part of the potential societal impact of this work relates to the ideas about improving pacemaker therapies. Doing so we believe that health care costs may be reduced due to less symptoms and decreased hospitalization rate. However, as mentioned above, there are several steps to be taken before this benefit can be proven. This thesis also demonstrates how clinical and animal experiments can be enhanced through computer simulations. In chapter 3 computer simulations aided in better understanding the hemodynamic improvements caused by AV-coupling restoration. In