Rick Schreurs

39 Cardiac pacing in first degree AV-block INTRODUCTION Atrioventricular (AV) conduction delay (or: AV dromotropathy), as evidenced by a prolonged PR-interval (>200ms) on the electrocardiogram (ECG), is present in 15-51% of patients with heart failure [1–4]. A prolonged PR-interval in these patients increases the risk of atrial fibrillation [5], diastolic mitral regurgitation (MR) [6] and worse clinical outcome [4]. A few small studies in the 1990s suggested that shortening the AV-delay by ventricular pacing could improve cardiac pump function [7–9]. These studies were among the first to use ventricular pacing as a treatment for heart failure. Notably, these studies employed right ventricular (RV) pacing, because these were performed before the era of biventricular (BiV) pacing. In subsequent years, the attention for treatment of a prolonged PR-interval faded as it became overruled by cardiac resynchronization therapy (CRT). However, recent sub-analyses of clinical trials investigating the benefit of CRT revitalized the interest in this topic [10]. While patients without left bundle branch block (LBBB) generally show little clinical improvement from CRT, a significant benefit was observed in non-LBBB patients with prolonged PR-interval [11,12]. Similarly, in a sub-study of the ReThinQ trial, which investigated the benefit of CRT in patients with QRS duration <130ms, only patients with a prolonged PR-interval (>180ms) showed a significant increase in maximum oxygen uptake [13]. The 2013 ESC guidelines on pacing and CRT recommend the use of RV pacing in patients with PR-interval >300ms and find no indication to use biventricular pacing [14]. Therefore, we hypothesized that restoring proper AV-coupling by pacing significantly improves cardiac pump function. We investigated this hypothesis and revealed the mechanisms of action using a three-step approach. First, the hemodynamic benefits of restoring AV-coupling were studied in a porcine model and a computational model of the non-failing heart with prolonged PR-interval. Second, the confounding effect of pacing- induced ventricular dyssynchrony and heart failure on the potential hemodynamic benefit of restoring AV-coupling was studied in the computational model. Third, a proof-of-principle clinical study was performed in patients with heart failure and a prolonged PR-interval. METHODS Studies were performed in the CircAdapt computer model of the human heart and circulation, in a porcine model of AV-block and in patients with heart failure and a prolonged PR-interval (>230ms). Computer simulations The CircAdapt closed-loop cardiovascular system model enables real time simulation of hemodynamical and mechanical interactions between the left and right ventricles, between the atria and their distal ventricle, and between the heart and the systemic and pulmonary circulations. In CircAdapt, blood flow through the four cardiac valves is assumed to have a nonlinear flow pattern, to be unsteady and to be non-viscous [15,16]. Pressure 3