Rick Schreurs

118 Chapter 6 In agreement with our observations, other studies in patients have shown that the lowest electrical dyssynchrony does not necessarily lead to the highest LV contractility or better clinical outcome [17,32]. Optimization based on minimization of electrical dyssynchrony alone might therefore not be sufficient. Even if the optimal electrical activation for LV contractility is known, further clinical studies are required to investigate whether the gain in LV contractility outweighs the loss of RV contractility, especially since cardiac output might not match either or both but be a combination/compromise. CircAdapt simulations capture both LV and RV contractile response to pacing delay changes The present study demonstrates that the CircAdapt model can capture pacing-induced changes to both LV and RV contractile function. It is especially the response of the RV to pacing that has been less well studied, both by our group and by others. The use of experimental measurements electrical activation of the paced dog heart, derived from canine experiments, coupled to the simulation of the entire circulation, resulted in changes in RV and LV dP/dt max that closely mimicked values measured in dog experiments. Earlier studies have shown that CircAdapt enables realistic simulation of cardiac response to CRT, mostly focusing on LV function [15–17]. In one of those studies, it was demonstrated that the RV plays an important role in the improvement of LV function during LV-only pacing [17]. The present study extends the mechanistic insight in the working action of CRT in the context of pacing delay optimization, where the complex mechanical and hemodynamic interactions between the four cardiac cavities and the surrounding circulations are found to be important. As demonstrated in this study, the CircAdapt model can capture the complexity of different LV and RV responses to CRT by incorporating several relevant components of cardiovascular interaction. Firstly, it realistically incorporates direct mechanical interaction between the three ventricular walls [23]. Secondly, it allows realistic simulation of regional myocardial mechanics in the ventricular walls of the asynchronously activated heart [21,26], thereby enabling experimentally measured activation times to be imposed and the related intraventricular heterogeneities in mechanical myofiber behavior to be simulated. Thirdly, it is a closed-loop system allowing for indirect (serial) hemodynamic interaction between the left and right side of the heart through the systemic and pulmonary circulations [22,33]. Fourthly, its four-chamber heart captures the dynamics of hemodynamic atrioventricular interactions [34]. Lastly, it includes the mechanical interaction through pericardial constraint, with an increase in the volume of a chamber altering the pressure in the other chambers and, hence, diastolic filling and septal position [35].