Rick Schreurs

52 Chapter 3 attenuated by ventricular desynchronization due to RV pacing. These results indicate that the 2013 guidelines [14] on pacing and CRT may need revision, because the lower limit of PR-interval for recommending pacing therapy may be decreased (from >300ms to >230ms), whereas the use of RV pacing should be discouraged and that of biventricular pacing recommended. In order to avoid ventricular desynchronization, besides BiV pacing, also recently proposed modes of physiological ventricular pacing, such as His bundle, left bundle branch and LV septum pacing [23,24] may be used to this purpose. Restoring atrioventricular coupling provides hemodynamic improvement A few studies in the 1990s used DDD RV pacing to restore AV-coupling [6–8]. These studies showed beneficial effects of normalization of AV-coupling in terms of reduction of diastolic MR [6,7], longer filling times and larger cardiac output [7] and higher LVEF and arterial blood pressure [8]. Notably, these studies were performed in small (12-24 patients) cohorts with variable baseline characteristics (wide and narrow QRS complex, normal and depressed cardiac function). The results from the present study not only corroborate these findings using state-of-the-art measurements, but also extend them and provide a comprehensive understanding of mechanisms involved. The complicated interaction between (intrinsic or paced) AV-delay and ventricular dyssynchrony on hemodynamics may explain why other (unpublished) studies were not able to reproduce these results, in particular when single site pacing was used. Improving AV-coupling is an integral part of “conventional CRT” in patients with LBBB and/ or QRS duration >150ms (class I CRT indication) and its benefit can therefore be considered as evidence-based. Interestingly, recent analysis using the same computer model as used in the present study, and data from CRT patients indicated that improving AV-coupling in “conventional” CRT may be responsible for more than two-thirds of the benefit of this therapy while only one third was accounted for by ventricular resynchronization [25]. However, the feasibility, safety, and long-term efficacy of pacing-based AV-coupling in patients without LBBB and with narrow QRS complex requires further investigation in prospective clinical trials. Such studies should also provide a more precise definition of the category patients that qualify for this therapy, such as the optimal cut-off of PR-interval, degree of separation of E and A wave on the mitral valve Doppler velocity recording, NYHA class, ischemic or non-ischemic cardiomyopathy and LVEF. In addition, duration of the (intrinsic and paced) P-wave may be important to take into account, because large interatrial delay may safeguard LV filling in the presence of a long PR-interval. Hemodynamic improvement relates to better ventricular filling The crucial finding of the present study is that improving AV-coupling leads to increased LV filling, thereby increasing cardiac output at unchanged (patients) or increased (simulations, animals) blood pressure. These improvements are likely explained by the length-dependent activation of the myocardium, the cellular basis of the well-known Frank-Starling mechanism. Notably, LV dP/dt max was hardly affected, whereas this is a very sensitive