Rick Schreurs

12 Chapter 1 found a significant increase in maximum oxygen uptake only patients with a prolonged PR-interval (>180ms) [21]. However, the acute hemodynamic improvements and underlying mechanisms of restoration of AV coupling in patients or animals with prolonged PR-interval have not been studies prospectively. Optimization of CRT Unfortunately, a vast number of patients does not show any significant response to CRT, although they completely fulfill the strict criteria [22, 23]. The response to CRT depends on multiple factors like the underlying pathology and the mode of delivery. Optimization of CRT is multifactorial as well and can be divided into the following three parts [24]: • Pre-implantation: better patient selection and optimizing imaging techniques. • Implantation: optimal PM lead placement and focus on acute improvement. • Post-implantation: program pacemaker settings for better timing of atrial and ventricular activation and improved follow-up. This thesis focuses mainly on the optimization of pacemaker settings. All modern pacemakers possess the ability to individually program the delay between atrial and ventricular activation (AV-delay) and the delay between RV and LV pacing (VV-delay, in case of CRT). Numerous studies have shown that optimizing the AV-delay improves ventricular filling, while optimizing the interventricular delay significantly reduces dyssynchrony and improves ventricular activation patterns [25, 26]. Several studies using single, in rest AV optimization were not able to show a long- term benefit of CRT as compared to using a default setting [27-29]. However, acute hemodynamic studies have shown benefit of CRT optimization and that the optimal AV- delay varies from one patient to another and may change between rest and exercise [30- 33]. Most dynamic, automated algorithms for AV optimization are based on electrical signals like electrograms or electrocardiography. The Adaptive CRT algorithm provides LV-only pacing timed with native RV activation, optimizing AV and VV-delay on the basis of periodic automatic evaluation of intrinsic conduction intervals [28, 34, 35]. The SyncAV algorithm provides a concept of BiV pacing by periodically measuring intrinsic conduction and dynamically adjusting AV-delays 50ms shorter than the intrinsic AV-interval, allowing paced BiV wavefronts to fuse with intrinsic conduction (triple wavefront fusion) [36, 37]. The QuickOpt optimization algorithm examines the conduction properties of the heart during various spontaneous and paced rhythms and calculates the optimal AV and VV delays that achieve the best electromechanical resynchronization of the LV [38, 39]. The SonR signal, or peak endocardial acceleration, is the only algorithm that is based on a mechanical sensor. The signal, which is derived from intracardiac accelerometers, is related to the amplitude of the first heart sound and shows a strong correlation with cardiac contractility [40]. An automated algorithm based on the SonR signal has been proven to be non-inferior to echocardiography-based optimization in terms of clinical outcome in