Rick Schreurs

130 Chapter 7 the optimal AV-delay in a manner that is relatively independent of IAD and IVD, especially when corrected for the heart rate. Therefore, the mean effective AV-delay may be a useful measure for pacemaker optimization in the future. After showing the importance of an optimal AV-delay in chapter 3 and chapter 4 , we focused on how to optimize the optimal AV-delay for CRT using intracardiac derived accelerometer signals and in particular the first heart sound (SonR1). In chapter 5 we showed that the SonR1 amplitude strongly correlates with LV and RV contractility in a canine LBBB model. In animals that responded successfully to CRT, the SonR1 signal could be used to predict the LV dP/dt max -based optimal AV-delay. This study showed that the SonR1 amplitude is influenced by changes in cardiac contractility and time interval between atrial and ventricular contraction, while interventricular dyssynchrony plays a minor role. Placement of the SonR sensor in the RA seems to assess cardiac function better than an RV-placed sensor. Finally, in chapter 6 we combined data from a canine LBBB model with computer simulations to show that the LV and RV respond in an opposite manner to variations in the amount of LV or RV pre-excitation. Pre-exciting the LV leads to an improvement in LV contractility (dP/dt max ) and a decrease in RV dP/dt max . An opposite pattern was observed with pre-excitation of the RV. The simulations extended these observations by showing that changes in steady-state BiV cardiac output differed from changes in both LV and RV dP/dt max . In this general discussion the results presented in the previous chapters will be placed in a broader perspective. Finally, the impact of this thesis on the clinic as well as on society will be discussed. POTENTIAL NEW INDICATION FOR PACING THERAPY First degree AV-block is commonly considered a benign conduction disorder, however it is known to increase the rate of atrial fibrillation [1], diastolic MR [2] and worse clinical outcome [3] in heart failure patients. The guidelines of the European Society of Cardiology state that restoring AV-coupling using pacemaker therapy should only be considered for patients with persistent symptoms, similar to those of pacemaker syndrome and attributable to a PR-interval >300ms [4]. These guidelines are based on a few small uncontrolled and non-randomized studies, which have suggested that normalization of the AV-delay using conventional DDD pacemakers could reduce diastolic MR and increase cardiac output and LV ejection fraction [5-8]. However, all these studies were performed using permanent RV pacing, which is known to create pacing-induced heart failure due to dyssynchronous activation of the ventricles. More recently, substudies of the randomized RethinQ [9], MADIT-CRT [10] and COMPANION [11] trials have indicated that non-LBBB patients with prolonged PR-interval do benefit from BiV pacing when compared to unpaced controls.