Rick Schreurs

41 Cardiac pacing in first degree AV-block dyssynchrony as a result of pacing and compared to the simulation of synchronous activation: 1) a BiV-pacing activation pattern and 2) a RV-only pacing activation pattern. Simulated paced activation sequences were based on invasive and non-invasive electrocardiographic mapping studies during pacing [16–20]. Animal experiments Animal handling was performed in compliance with the Guide for the Care and Use of Laboratory Animals and in accordance with the European Community recommendations. The protocol was approved by the Dutch National Ethical Committee for Animal Handling. Experiments were performed in seven female landrace pigs weighing 61±3kg. Animals were pre-medicated with intramuscular Zoletil (5 mg/kg). After induction with intravenous sodium thiopental (5-15 mg/kg), anesthesia was maintained by continuous infusion of Propofol (10 mg/kg/h), Sufentanyl (5 µg/kg/h) and Rocuronium (0.1 µg/kg/h). Details of the experimental model are provided in figure 1 . Complete AV-block was created by radiofrequency ablation of the AV-node. Subsequently, the animals were paced at the right atrial appendage and at the RV apex and left ventricular (LV) epicardial lateral wall. A 7Fr conductance catheter (CD Leycom, Zoetermeer, The Netherlands) was introduced into the LV cavity via the femoral artery. A 4Fr Millar Mikro-Tip pressure catheter (Millar, Houston, Texas, USA) was used to measure left atrial (LA) pressure. A vascular flow probe (Transonic Europe B.V., Elsloo, the Netherlands) was mounted around the ascending aorta to assess aortic flow and subsequently calculate cardiac output. Measurements were performed after instrumentation and hemodynamic stabilization using BiV pacing at 10 beats per minute (bpm) above intrinsic atrial rhythmwith an AV-delay of 300ms, mimicking prolonged PR-interval, as baseline condition. Subsequently, during BiV pacing the AV-delay was programmed between 50 and 250ms in randomized steps of 50ms. Baseline recordings were performed before every step. Each recording lasted for at least two respiratory cycles. Patient studies The patient study was performed according to the principles of the Declaration of Helsinki and the study protocol was approved by the ethics committee of the Maastricht University Medical Center+ (registration number NL60764.068.17/METC 171013). All patients gave written informed consent prior to investigation, and the study was monitored by the Clinical Trial Center Maastricht. The study has been registered at clinicaltrials.gov (https:// clinicaltrials.gov/ct2/show/NCT03973944). Patients were included in the Maastricht University Medical Center+ (n=20), the University Medical Center Utrecht (n=5) and the Amsterdam University Medical Center (n=1) from June 2018 to February 2020. The cut-off value for PR-interval of 230ms was chosen based on the subanalysis of the MADIT-CRT study [21]. Patients were implanted with a CRT-D and LV lead for this study, considering that this additional implantation creates minimal additional risk to the patient while the option to provide CRT therapy was offered after the 3