Rick Schreurs

14 Chapter 1 myocardial scarring on the effect of CRT. And finally, the optimization of AV- and VV-delays in patients and animals are discussed. The first-degree AV-block as a new indication for CRT has been studied in chapter 3 . The chapter is a combination of clinical, computational and animal experiments. It describes the acute hemodynamic improvements in patients with reduced LV ejection fraction and prolonged PR-intervals. The same has been done in a porcine model of first-degree AV- block. Additionally, these experiments were replicated using the CircAdapt computer model. Overall, special attention has been paid to the improvements in cardiac function and the optimization of cardiac filling pressures using invasive measurements. In chapter 4 a porcine model of total AV-block was used to study whether atrial sensing or atrial pacing was superior to the other in cardiac pacing and how the variance in interatrial delay (IAD) led to differences in the optimal AV-delay. Additionally, the interventricular dyssynchrony was varied by changing ventricular pacing sites in order to study its influence on the right and left effective, mechanical AV-delay. Main goal was to find a new parameter to better predict the optimal AV-delay irrespective of IAD or ventricular pacing. In chapter 5 a canine LBBB model was used to gain more information on the pathophysiology of the SonR signal and the aim was to find new insights in how to further improve the algorithm to optimize the AV-delay Finally, a combined experimental-computational approach was chosen in chapter 6 to examine the response of the LV and RV to various pacing delays in CRT. Data from experiments in canine LBBB hearts were simulated using CircAdapt to study the differences between LV and RV hemodynamic response and linked to find the optimal overall settings. To conclude, chapter 7 integrates the major finding of the above-mentioned studies and discusses them in a broader scientific and clinical perspective.