Global sensitivity analysis of a model for venous valve dynamics

Chronic venous disease is defined as dysfunction of the venous system caused by incompetent venous valves with or without a proximal venous obstruction. Assessing the severity of the disease is challenging, since venous function is determined by various interacting hemodynamic factors. Mathematical models can relate these factors using physical laws and can thereby aid understanding of venous (patho-)physiology. To eventually use a mathematical model to support clinical decision making, first the model sensitivity needs to be determined. Therefore, the aim of this study is to assess the sensitivity of the venous valve model outputs to the relevant input parameters. Using a 1D pulse wave propagation model of the tibial vein including a venous valve, valve dynamics under head up tilt are simulated. A variance-based sensitivity analysis is performed based on generalized polynomial chaos expansion. Taking a global approach, individual parameter importance on the valve dynamics as well as importance of their interactions is determined. For the output related to opening state of the valve, the opening/closing pressure drop (dp_valve,0) is found to be the most important parameter. The venous radius (r_vein,0) is related to venous filling volume and is consequently most important for the output describing venous filling time. Finally, it is concluded that improved assessment of r_vein,0 and dp_valve,0 is most rewarding when simulating valve dynamics, as this results in the largest reduction in output uncertainty. In practice, this could be achieved using ultrasound imaging of the veins and fluid structure interaction simulations to characterize detailed valve dynamics, respectively.