The utilization of ventricular assist devices (VADs) 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 the most widely implanted VAD, with more than 10,000 implants worldwide.2 With the increasing numbers of CHF patients and the growing experience gained with extended use of this device, the Food and Drug Administration (FDA) recently approved the HMII for destination therapy.3 Rotary VADs offer the advantages of smaller dimension and simpler structures when compared to pulsatile VADs; however, the continuous, high speed, rotating blood flow patterns generated are a potential risk factor 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 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 1C–F).8–11
Thrombus formation in blood recirculating devices is highly correlated to irregular flow patterns formed within the device. Various methods 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 enables us to predict whether platelets may be driven beyond their activation threshold and identify potential thrombus formation regions. This advanced CFD approach offers the ability to compute the stress levels that blood constituents (e.g., red blood cells 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 current study, we used 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.
The Fluent CFD solver (Ansys Fluent Inc., Lebanon, NH) was used for conducting highly resolved mesh numerical simulations of multiphase 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 1,081 kg/m3, with platelets assumed as neutrally buoyant solid spherical particles (ø = 3 μm; density, 998.2 kg/m3). The HMII VAD components (Figure 2C) include the inlet flow straightener, rear hub (the bearing connecting the stationary flow straightener and the impeller), impeller, front hub (the bearing connecting the impeller and the stationary diffuser), and the diffuser. To simulate the clinical operating condition of the HMII, the impeller spins at 10,000 rpm generating a corresponding cardiac output of 4 L/min. Sliding mesh was employed for the impeller, and the mass flow inlet and pressure outlet were applied as the inlet and outlet boundary conditions, respectively. After conducting mesh independence studies, the highly resolved mesh consisted of 17 × 106 tetrahedral volumetric elements, and an optimized time step of 7 × 10−5 s was carefully selected.14 Approximately 30,000 platelets were seeded and released from a plane located upstream of the VAD. An in-house code was developed to compute and analyze these platelet trajectories with the aim to track the stagnant or entrapped trajectories and the recirculation zones. Approximately 90% of the simulated platelets had a residence time of less than 0.184 seconds while flowing through the device.
Several platelet trajectories depicted the formation of well-defined recirculation zones that spanned approximately 1–2 mm across at the downstream of the flow-straightener blades (Figure 2D, insets i and iv), while other platelet trajectories formed stagnant flow patterns, attaching to the rear hub (Figure 2D, insets ii and iii). Some platelet trajectories were observed to form entrapped circular patterns at the entry of the impeller blades, closely following the rotational motion of impeller (Figure 2E).
These flow patterns correspond geographically to the sites of the thrombus formation that have been directly observed clinically and in analysis of malfunctioning explanted HMII devices (e.g., between rear hub region and entry of impeller blades,8,9,11 Figure 1, C, D, and F, and the flow-straightener blades,10 Figure 1E). Previous DPIV12 and CFD13 studies of HMII lacked the resolution to capture these small eddies and the stagnant trajectories at the rear hub (Figure 1, A and B).12
Discussion and Conclusion
Pump thrombosis has been reported in approximately 6% of continuous-flow VAD recipients regardless of the mandatory long-term anticoagulation/antiplatelet therapy used.7 The current study demonstrates that flow patterns and ensuing platelet trajectories (a time history depicting the trajectory/pathline) are strongly associated with the thrombus formation patterns observed in explanted VADs. The number of simulated platelets (approximately 30,000 platelets released from single surface) was chosen to correspond to a typical physiological platelet count (i.e., 150,000 platelets/μL) for a single passage flowing through the device. Although the platelets that ended up in the stagnant and entrapped trajectories and the recirculation zones were only a small fraction of the platelet population, those represent a single passage through the VAD. As these VADs generate continuous flow, repeated passages through the same platelet trajectories may eventually accumulate at these regions and promote thrombus formation.
Our study clearly indicates that flow-induced device thrombogenicity resulting from certain geometric device characteristics may promote thrombus formation, leading to device malfunction. We have previously performed an optimization study in a similar VAD, in which the thrombogenic potential of the device was reduced by an order of magnitude.14 With the progressive rise of VAD implantation for destination therapy, device optimization could be achieved by using advanced numerical approaches to eliminate the undesired flow patterns that may lead to thrombus formation in a specific device such as those found in the HMII. Using this suggested strategy will further enhance the safety and efficacy of VADs for long-term destination therapy.
All authors have read and approved the manuscript.
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