Post-implant device thrombosis remains a life-threatening complication and limitation of continuous-flow

Post-implant device thrombosis remains a life-threatening complication and limitation of continuous-flow ventricular assist devices (VADs). leading to enhanced safety and efficacy of VADs for long-term destination therapy. Keywords: Thrombosis CFD HeartMate II VAD Introduction The utilization of ventricular assist devices (VADs) Ioversol as a means of stabilizing congestive heart failure (CHF) patients as a bridge-to-transplant has increased dramatically over the past few years.1 The HeartMate II? (HMII Thoratec Corp. Pleasanton CA) VAD is currently MLT the most widely implanted VAD with more than 10 0 implants worldwide.2 With the increasing numbers of CHF patients and the growing experience gained with extended use Ioversol of this device the FDA recently approved the HMII for destination therapy.3 Rotary VADs offer the advantages of smaller dimension and simpler structures as compared to pulsatile VADs; however the continuous high speed rotating blood flow patterns generated are a potential risk factor Ioversol for adverse events including thrombus formation thromboembolic complications and device malfunction. Pump thrombosis is one of the main causes for device malfunction and patients are exposed to the risk of sudden death or the risks involved in complex device replacement surgery.4 5 In recent Ioversol years various cases of pump thrombosis in patients implanted with the HMII were reported in the clinical literatures despite the anticoagulation regimens mandated for device recipients. The incidence reported was approximately 6% with some cases being fatal.6 7 Specifically since the FDA has approved the HMII for bridge-to-transplant and for destination therapy in 2008 and 2010 respectively the incidence of pump thrombosis has grown steadily.4-7 In most of these cases thrombus formation was observed at the flow-straightener and the rear hub bearing (between the flow-straightener and the impeller of the device). Typical cases are shown in explanted devices (Figure 2 (C)8 (D)9 (E)10 & (F)11). Figure 2 Clinical Observations of Thrombus Formation in HMII Thrombus formation in blood recirculating devices is highly correlated to irregular flow patterns formed within the device. Various methods Ioversol such as digital particle image velocimetry (DPIV)12 and computational fluid dynamic (CFD)13 had been employed for visualizing or predicting the streamlines of blood flow through these devices. Thrombus formation arises from the combined effect of elevated shear stress levels and recirculating flow patterns in specific regions within a device. Advanced CFD methodology which was developed by our group and refined over the years combined with recently developed algorithms tuned for capturing thrombus formation patterns enable us to predict whether platelets may be driven beyond their activation threshold and identify potential thrombus formation regions. Briefly this Ioversol advanced CFD approach offers the ability to compute the stress levels that blood constituents (e.g. RBCs or platelets) are exposed to while flowing through these pathological flow patterns and estimate the thrombogenicity which may lead to thrombus formation within the device. This is achieved by computing the trajectories of multiple particles and the dynamic stresses they are exposed to within the device flow field. A detailed description of the methodology – applied to the optimization of a VAD appears in our recent PLoS One publication.14 In the present study we utilized advanced CFD simulations to predict the stress exposure and flow trajectories of platelets flowing through the HMII VAD and leading to observed thrombus formation locations within the device. Methods The Fluent CFD solver (Ansys Fluent Inc. Lebanon NH) was utilized for conducting highly resolved mesh numerical simulations of multi-phase FSI (Fluid Structure Interaction)URANS (Unsteady Reynolds Averaged Navier-Stokes) blood flow using the two equation k-ω turbulence model.14 Blood was modeled as a two-phase Newtonian fluid with viscosity of 0.0035 kg/m-s and density of 1 81 kg/m3 with platelets assumed as neutrally buoyant solid spherical particles (? = 3 μm; density: 998.2 kg/m3). The HMII VAD components (Figure 1B) include the inlet flow-straightener rear hub (the bearing connecting the stationary flow-straightener and the impeller) impeller front hub (the bearing.