Rick Schreurs

54 Chapter 3 of pacing-induced ventricular dyssynchrony. In the present study, BiV pacing was able to acutely increase cardiac pump function in 19 out of 22 patients, indicating that the functional gain achieved by improving AV-coupling is relatively large compared to the loss of function due to BiV pacing-induced ventricular dyssynchrony. On the other hand, severe ventricular dyssynchrony, as occurs during RV pacing abrogates the hemodynamic benefits of restoring AV-coupling. Interestingly, shortening the AV-delay using RV pacing did not improve filling either, due to a lack of reduction in diastolic MR and no increase in diastolic filling time or diastolic forward flow. These observations may be explained by a combination of factors, such as prolonged isovolumic contraction due to desynchronization and dyssynchronous contraction of the papillary muscles which increases the risk of diastolic MR. Our study also suggests that the presence of LV filling abnormalities, such as E-A wave fusion and diastolic MR, may be important selection criteria for the use of BiV pacing in patients with prolonged PR-interval. The results from the present study may also explain the lack of benefit of algorithms aiming at minimization of ventricular pacing. After all, these algorithms do so by prolonging the AV-delay, thus inducing AV dromotropathy [36]. Our study supports the idea that too aggressive prolongation of PR-interval may have adverse effects on pump function and possibly clinical outcome. Limitations The present patient study has all the characteristics of a proof-of-principle study, showing acute hemodynamic effects in a small cohort. For ethical reasons, patients in this study all had the indication for ICD implant, so that the implant of the LV lead was only a minor extension of the medically indicated procedure. Clearly, studies in a wider population (also non-ICD indicated patients) and using long term outcome as endpoint are required to provide further evidence for the benefit of improving AV-coupling in patients with a prolonged PR-interval. Promising is that subanalyses in non-LBBB patients of the randomized MADIT-CRT [21], COMPANION [12] and RethinQ [13] trials also indicate that patients with long PR-interval can benefit from BiV pacing when compared to their unpaced “control group” counterparts. The preclinical studies were performed in porcine hearts. While this species is frequently used for cardiovascular research, a limitation is that the amount of dyssynchrony induced by (single site) ventricular pacing is small. Therefore, for this study only BiV pacing was used to demonstrate the effect of AV-coupling at unchanged ventricular activation (BiV pacing being used for all AV-delays). Moreover, the lack of intrathoracic negative pressure in these open-thorax experiments may have interfered with the effect of AV-interval on filling.