Rick Schreurs

117 Left and right ventricular response to CRT DISCUSSION In this study we investigated the influence of LV and RV pacing delay settings on LV and RV electrical activation and contractility in animal studies and computer simulations. Both studies showed that LV TAT is smallest during synchronous RV and LV stimulation and increases when VV-delays increase. RV TAT becomes larger in particular during LV pre- excitation. LV and RV contractility vary most, and in opposite direction, with changes in VV-delay settings. After demonstrating the realistic simulations in the model, we used the model to calculate cardiac output changes and to explain why changes cardiac output differed from both RV and LV contractility. The latter findings demonstrate how a model like CircAdapt can extend mechanistic understanding of circulatory changes due to a device therapy. LV and RV contractility respond in opposite manner to variations in VV pacing delays A key finding in the present study is that LV and RV dP/dt max change in opposite direction when changing the VV pacing delay. Sciaraffia et al previously demonstrated that RV and LV dP/dt max identify different ‘optimal’ VV-delays in most of the patients included in their study [12]. Furthermore, Houston et al recently showed that in patients with dyssynchronous heart failure, RV-only pacing leads to higher RV dP/dt max than LV-only or simultaneous LV+RV pacing [29]. In an experimental study in pigs, different VV-delays were tested at different pacing locations [30]. Similar to our study, these investigators found that RV pre-excitation led to a higher RV dP/dt max than LV pre-excitation. The fact that findings were consistent in patients, animals and a computer model implies that the opposing changes in hemodynamics, caused by varying VV pacing delays, are caused by a universal mechanism. Another key finding is that ventricular specific pre-excitation is required for a good contractile function in both the LV and RV. This is illustrated by LV pre-excitation increasing LV dP/dt max and RV pre-excitation leading to the largest RV dP/dt max values. In contrast, changes in AV-delay have less effect on measured and simulated LV and RV dP/dt max . In a previous study, in which we evaluated the relative importance of interventricular and intraventricular dyssynchrony for contractile response to CRT (change in LV dP/dt max ), it was demonstrated that interventricular dyssynchrony during intrinsic rhythm is the dominant electrical substrate driving response to CRT [15]. In contrast, intraventricular dyssynchrony showed little effect on LV dP/dt max , which is in line with experimental observations that reducing LV TAT by multipoint pacing does not improve LV dP/dt max [31]. However, results in this study suggest that intraventricular dyssynchrony might still play a modulating role since increase in LV TAT, with large LV pre-excitation, led to a decrease in LV dP/ dt max compared to slight LV pre-excitation. Because RV TAT increases concurrently with decreases in VEU we cannot distinguish if either intra- or interventricular dyssynchrony has a larger effect on RV contractility. 6