Rick Schreurs

78 Chapter 4 Limitations This study concerns experiments in a small number of porcine hearts. While this species is frequently used for cardiovascular research, a limitation is that the degree of dyssynchrony induced by LV and RV pacing is smaller than in other species like man and dog. We hypothesize that the concept of mean effective AV-delay works better in humans, due to a greater amount of interventricular dyssynchrony, which was also the case in the CircAdapt computer model [18]. A model of total AV-block was used because this allowed observing the isolated effect of changes in AV-delay, while in many patients AV-conduction might be present. In such situation fusion of intrinsic conduction and paced activation waves may occur, thereby changing the amount of interventricular dyssynchrony. Furthermore, the optimal AV-delay was based on acute hemodynamic improvements while an autonomic regulatory response characterized by changes in peripheral arterial resistance and pressure might be likely to occur. Beat-to-beat measurements in patients have shown though, that the initial increment in cardiac output would sustain throughout a longer period [31], but acute hemodynamic improvements may not (fully) translate into clinical improvements. CONCLUSION This experimental animal study has identified interatrial delay and interventricular dyssynchrony as important influencers for the optimal AV-delay to be programmed. The optimal AV-delay increases with greater interatrial delay due to RA pre-excitation and with pre-excitation of the LV. Furthermore, the mean effective AV-delay corrected for heart rate seems a good and widely applicable predictor for the optimal hemodynamic effect of pacing since it takes into account both RV and LV function. Additional research should be performed to examine how this parameter can be implemented to optimize atrioventricular optimization in patients.