Rick Schreurs

76 Chapter 4 Pacing induced pre-excitation of the LV leads to a significantly shorter LA-LV interval compared to RA-RV interval. Also the LA-LV interval is shorter during LV pacing than during RV or BiV pacing. In other words, atrial pacing leads to a delayed activation of the LA compared to the RA (RA pre-excitation), while LV pacing (LV pre-excitation) shortens the left effective AV-delay compared to the right heart. In our study, it leads to a longer optimal programmed AV-delay during LV pacing in A-P mode. Similar results might be present during RV pacing, however RV apex pacing did not lead to significant amounts of interventricular dyssynchrony in our porcine study. It is important to realize that the present study has been performed in pigs after creation of complete AV-block, eliminating the possibility of fusion of the pacing-induced and intrinsic activation. Such fusion pacing is frequently employed, because it may lead to even better resynchronization than BiV pacing [15-17]. Mean effective AV-delay as predictor for optimal hemodynamic response The results discussed in the previous paragraphs indicate that it is important to take both atrial pacing mode and ventricular pacing site into account when defining the optimal AV- delay for an individual. From this perspective we calculated the ventricle-specific effective AV-delay. However, in previous animal studies and computer simulations about optimizing interventricular delays we have shown that optimal LV function was reached using LV pre-excitation while RV function was better during RV pre-excitation and that the best overall cardiac output was achieved using a setting in between the optimal settings for the LV and RV [7] (see also chapter 6 ). Along the same lines, we hypothesized that a mean effective AV-delay would provide an even better estimation of the optimal AV-delay in a given setting. This idea has meanwhile been supported by simulations in the CircAdapt computer model [18]. One important implication of these results is that, while most research focusses on left- sided AV-optimization, this study shows that filling of both ventricles should be taken into account. Commonly the golden standard in AV-optimization uses echocardiography- derived mitral flow patterns. The optimal AV-delay is considered the shortest AV-delay with A-wave truncation in the absence of E and A-wave fusion [19]. This technique focusses on left-sided optimization and this might be one of the reasons why long-term benefits of AV- optimization have not been observed in clinical trials, and consequently, not implemented in the guidelines. Other optimization algorithms use electrograms [20] or accelerometer signals [21], but it is unclear how these relate to the mean effective AV-delay. The mean effective AV-delay concept was further finetuned by normalizing AV-delay for RR-interval. This idea was based on several patient studies. Rafie et al have shown that the optimal AV-delay decreased when patients receiving CRT were paced at a higher frequency. Pacing at this shorter optimal AV-delay improved diastolic filling time, mitral inflow VTI, systolic ejection time and NYHA class compared to a fixed AV-delay [22]. These findings