Abstract—Timing of biventricular pacing devices employed in cardiac resynchronization therapy (CRT) is a critical determinant of efficacy of the procedure. Optimization is done by maximizing function in terms of arterial pressure (BP) or cardiac output (CO). However, BP and CO are also determined by the hemodynamic load of the pulmonary and systemic vasculature. This study aims to use a lumped parameter circulatory model to assess the influence of the arterial load on the atrio-ventricular (AV) and inter-ventricular (VV) delay for optimal CRT performance. The model consists of variable elastance components to simulate both left and right ventricles as well as the interventricular septum. The pulmonary and systemic circulations are modeled by lumped parameter Windkessel elements using resistors, inductors and capacitors to represent vascular resistance, blood inertia and arterial and venous compliance, including the coronary circulation. Optimal CRT performance was determined by varying AV and VV delay and the critical delay was obtained for the maximum value of CO. The maximal (optimal) central systolic blood pressure (SBP) was also used to assess the potential use of non-invasive continuous pressure for CRT optimization Model calculations were made for maximal (optimal) CO and SBP with changes in systemic compliance (Cas) and peripheral resistance (Ras). Simulations with the circulatory model indicate that arterial loading parameters have an intrinsic effect on the timing for optimal CRT performance, with a greater relative impact on VV compared to that on AV delay. Load parameter changes for SBP give similar results to using CO as an optimizing parameter, although differences occur with changes in Ras. I. INTRODUCTION Cardiac resynchronization therapy (CRT) is a device based procedure using biventricular pacing in conditions of heart failure associated with asynchronous contraction of left and right ventricles. Setting of optimum atrio-ventricular (AV) and inter-ventricular (VV) conduction times is often done using echocardiography to maximize atrial inflow [1] and so maximizing cardiac output, or using peripheral pulse measures to maximize arterial pulse pressure [2-4]. However, even with attempts at optimizing timing parameters, not all subjects obtain benefits in terms of increased ejection fraction and improved ventricular function from the different optimal delay strategies [5]. * This work was supported in part by a grant from the Australian Research Council (MB; ARC Discovery DP110101134) and by Macquarie University Research Postgraduate Scholarship (KX) K. Xu, M. Butlin and A.P. Avolio are with Australian School of Advanced Medicine, Macquarie University, Sydney, NSW, AUSTRALIA. phone: +61 2 9812 3500; fax +61 2 9812 3600; e-mails: ke.xu1@students.mq.edu.au; mark.butlin@mq.edu.au; alberto.avolio@mq.edu.au. In addition to the optimum time delays for atrial and ventricular filling and contraction to achieve maximal cardiac output (CO), cardiac ejection is also influenced by the arterial load from both the pulmonary and systemic vasculature. The arterial load is determined by the steady component comprising peripheral resistance, and a pulsatile component related to the elastic properties of the large conduit arteries [5]. Hence, with a given set of AV and VV delay times optimized for particular values of load parameters, CRT performance would be altered with changes in either peripheral resistance or arterial compliance or both. To investigate the relationship of changes in load parameters with AV and VV delays to achieve maximal CRT performance, a closed loop model of the pulmonary and systemic circulation was constructed using lumped parameter representation of the arterial load and variable elastance for cardiac chambers and interventricular septum with addition of the Frank-Starling law. II. METHODS A. Arterial Section of Circulatory Model The arterial system in this simulation was constructed by use of the classic 4 element Windkessel model with inductor (Las, blood inertia) in series with characteristic impedance (Zas, vascular resistance) (WK4s), in which the two hemodynamic parameters as variables are systemic arterial compliance (Cas) and systemic peripheral resistance (Ras) (Fig. 2a). The contractile function of the atria, ventricle and septum was simulated by variable capacitors in the electric circuit using time-varying elastance characteristics [6]. Intrinsic relationships of the Frank-Starling mechanism and VV delay associated with ventricular inotropy were also simulated. This feedback was made by the addition of functions that describe the relationships: (1) the increase in venous return flow causes the elevation in maximum and minimum ventricular contractility; (2) the VV delay resulting in a lag for ventricular contraction (Fig. 1) is associated with decreases in maximum ventricular contractility. RV +VV AV sinus node LV LV -VV RV Figure 1. Diagram of AV and VV delay and ventricular contraction. A positive VV delay indicates left ventricle (LV) contracts after the right ventricle (RV). Assessment of hemodynamic load components affecting optimization of cardiac resynchronization therapy by lumped parameter model* Ke Xu, Mark Butlin and Alberto P Avolio 34th Annual International Conference of the IEEE EMBS San Diego, California USA, 28 August - 1 September, 2012 6661 978-1-4577-1787-1/12/$26.00 ©2012 IEEE