Arteriovenous fistulae for haemodialysis: the role of the flow field and three-dimensional geometry in the development of neointimal hyperplasia

Abstract

Native arteriovenous fistulae (AVF) for haemodialysis are susceptible to early failure and non-maturation. This is believed to occur due to the formation of juxtaanastomotic neointimal hyperplasia. Local geometry and features of the flow field are implicated in the formation of vascular disease. However, little is known about the correlates that lead to the development of adverse pathology and clinical outcomes in AVF, in particular the role of three-dimensional (non-planar) geometry. In this thesis, a mechanistic hierarchy is proposed where geometry influences the local flow field, in turn leading to the development of neointimal hyperplasia and ultimately non-maturation. This concept is explored using a variety of approaches: in vitro flow visualisation, an observational cohort study and a pre-clinical model. Flow visualisation work identifies the importance of vessel geometry, with an outer arterial curvature anastomosis appearing to suppress local flow instability as compared to straight or inner curvature. Using imaging on the day of surgery, an observational cohort study demonstrates significant geometric heterogeneity in surgically created AVF. Greater arterial curvature and non-planarity appear to be associated with improved rates of maturation. The association between the spectral estimates of the AVF bruit and outcome are also explored. Finally, placement of a prototype device derived from an idealised geometry suppresses flow instability, using changes in the bruit as a surrogate for the local flow field, though the effect on neointimal hyperplasia is less clear. Insights obtained from this work, with particular reference to arterial curvature and non-planarity, will provide the basis for future work designed to investigate the effect of idealised geometries on the development of vascular pathology and ultimately clinical trials aimed at improving outcomes associated with AVF surgery.