Rick Schreurs

133 General discussion be noticed that in the majority of studies and in clinical care only attention is paid to the delay between the RA and the RV or LV. In chapter 4 we show that true RA-RV (right effective AV-delay) and LA-LV (left effective AV-delay) delays depend on both IAD and IVD. Because we were aiming at the functional (or mechanical) consequences, we employed the time of maximum rate of rise of each of the chambers to define these effective delays. As expected, RA appendage pacing prolonged IAD (defined as the time difference between RA and LA dP/dt max ), leading to a longer optimal AV-delay (defined as the delay providing the highest cardiac output). This finding is in line with previous experiments studying the difference between atrial pacing and atrial sensing [19-22]. Interestingly, in our study the difference in optimal AV-delay between atrial pacing and atrial sensing was the same as the difference in IAD during BiV and RV pacing. In contrast, during LV pacing the difference between the optimal AV-delay between atrial pace and atrial sense mode was larger, which coincided with a greater IVD than during RV and BiV pacing. This might demonstrate that the optimal AV-delay is not only dependent on IAD, but also on IVD. The largest differences in optimal AV-delay were found between RV pacing in atrial sense mode and LV pacing in atrial pace mode. RA pacing leads to delayed activation of the LA, while the LV is pre-excited during LV pacing leading to delayed activation of the RV, creating a long RA-RV delay and a short LA-LV delay. In contrast, during RV pacing in atrial sense mode left and right effective AV-delay are comparable, because the delay of LA activation is corrected by pre-excitation of the RV. In order to generate an overarching index for optimal AV-delay, accounting for IAD, IVD and the function of both ventricles, we developed the mean effective AV-delay ( chapter 4) . It turned out that the mean effective AV-delay was better in predicting the optimal AV-delay in pigs than the right or left effective AV-delay alone. The mean effective AV- delay is derived from changes in blood pressures in all four heart chambers and therefore reflects mechanical instead of electrical actions. It represents the time interval between the average time of atrial and average time of ventricular contraction, and by doing so takes into account both the left and the right heart. We believe that the mean effective AV-delay is a way to correct for abnormalities in IAD and IVD in patients and hypothesize that it may be able to improve the CRT effect. NOVEL OPTIMIZATION STRATEGIES Sub-optimal timing of atrial and ventricular activation is one of the causes of ineffective CRT. Optimizing the AV-delay improves ventricular filling and thereby cardiac output and stroke work and there are two ways of doing this. The first is acute optimization, which is performed during or early after the implantation procedure. The golden standard is based on echocardiography, with the optimal AV-delay being considered the shortest AV-delay without truncation of the A-wave. Other optimization strategies use invasively measured pressure-volume loops or first derivative of LV pressure pulse (LV dP/dt), finger 7