Improving the Prediction of 1-Year Right Ventricular Failure After Left Ventricular Assist Device Implantation.

Previous predictive models for postimplant right heart failure (RHF) following left ventricular assist device (LVAD) implantation have demonstrated limited performance on validation datasets and are susceptible to overfitting. Thus, the objective of this study was to develop an improved predictive model with reduced overfitting and improved accuracy in predicting RHF in LVAD recipients. The study involved 11,967 patients who underwent continuous-flow LVAD implantation between 2008 and 2016, with an RHF incidence of 9% at 1 year. Using an eXtreme Gradient Boosting (XGBoost) algorithm, the training data were used to predict RHF at 1 year postimplantation, resulting in promising area under the curve (AUC)-receiver operating characteristic (ROC) of 0.8 and AUC-precision recall curve (PRC) of 0.24. The calibration plot showed that the predicted risk closely corresponded with the actual observed risk. However, the model based on data collected 48 hours before LVAD implantation exhibited high sensitivity but low precision, making it an excellent screening tool but not a diagnostic tool.

Shear Histories Alter Local Shear Effects on Thrombus Nucleation and Growth.

Our goal was to determine the impact of physiological and pathological shear histories on platelet nucleation and thrombus growth at various local shear rates. We designed and characterized a microfluidic device capable of subjecting platelets to shear histories reaching as high as 6700 s - 1 in a single passage. Time-lapse videos of platelets and thrombi are captured using fluorescence microscopy. Thrombi are tracked, and the degree of thrombosis is evaluated through surface coverage, platelet nucleation maps, and ensemble-averaged aggregate areas and intensities. Surface coverage rates were the lowest when platelets deposited at high shear rates following a pathological shear history and were highest at low shear rates following a pathological shear history. Early aggregate area growth rates were significantly larger for thrombi developing at high shear following physiological shear history than at high shear following a pathological shear history. Aggregate vertical growth was restricted when depositing at low shear following a pathological shear history. In contrast, thrombi grew faster vertically following physiological shear histories. These results show that physiological shear histories pose thrombotic risks via volumetric growth, and pathological shear histories drastically promote nucleation. These findings may inform region-based geometries for biomedical devices and refine thrombosis simulations.

A homogenized two-phase computational framework for meso- and macroscale blood flow simulations.

BACKGROUND AND OBJECTIVE: Owing to the complexity of physics linked with blood flow and its associated phenomena, appropriate modeling of the multi-constituent rheology of blood is of primary importance. To this effect, various kinds of computational fluid dynamic models have been developed, each with merits and limitations. However, when additional physics like thrombosis and embolization is included within the framework of these models, computationally efficient scalable translation becomes very difficult. Therefore, this paper presents a homogenized two-phase blood flow framework with similar characteristics to a single fluid model but retains the flow resolution of a classical two-fluid model. The presented framework is validated against four different sets of experiments. METHODS: The two-phase model of blood presented here is based on the classical diffusion-flux framework. Diffusion flux models are known to be less computationally expensive than two-fluid multiphase models since the numerical implementation resembles single-phase flow models. Diffusion flux models typically use empirical slip velocity correlations to resolve the motion between phases. However, such correlations do not exist for blood. Therefore, a modified slip velocity equation is proposed, derived rigorously from the two-fluid governing equations. An additional drag law for red blood cells (RBCs) as a function of volume fraction is evaluated using a previously published cell-resolved solver. A new hematocrit-dependent expression for lift force on RBCs is proposed. The final governing equations are discretized and solved using the open-source software OpenFOAM. RESULTS: The framework is validated against four sets of experiments: (i) flow through a rectangular microchannel to validate RBC velocity profiles against experimental measurements and compare computed hematocrit distributions against previously reported simulation results (ii) flow through a sudden expansion microchannel for comparing experimentally obtained contours of hematocrit distributions and normalized cell-free region length obtained at different flowrates and inlet hematocrits, (iii) flow through two hyperbolic channels to evaluate model predictions of cell-free layer thickness, and (iv) flow through a microchannel that mimics crevices of a left ventricular assist device to predict hematocrit distributions observed experimentally. The simulation results exhibit good agreement with the results of all four experiments. CONCLUSION: The computational framework presented in this paper has the advantage of resolving the multiscale physics of blood flow while still leveraging numerical techniques used for solving single-phase flows. Therefore, it becomes an excellent candidate for addressing more complicated problems related to blood flow, such as modeling mechanical entrapment of RBCs within blood clots, predicting thrombus composition, and visualizing clot embolization.

Effect of Artificial Lung Fiber Bundle Geometric Design on Micro- and Macro-scale Clot Formation.

The hollow fiber membrane bundle is the functional component of artificial lungs, transferring oxygen and carbon dioxide to and from the blood. It is also the primary location of blood clot formation and propagation in these devices. The geometric design of fiber bundles is defined by a narrow range of parameters that determine gas exchange efficiency and blood flow resistance, such as fiber packing density, path length, and frontal area. However, these parameters also affect thrombosis. This study investigated the effect of these parameters on clot formation using 3-D printed flow chambers that mimic the geometry and blood flow patterns of fiber bundles. Hollow fibers were represented by an array of vertical micro-rods (380 micron diameter) arranged with varying packing densities (40, 50, and 60%) and path lengths (2 and 4 cm). Blood was pumped through the device corresponding to three mean blood flow velocities (16, 20, and 25 cm/min). Results showed that (1) clot formation decreases dramatically with decreasing packing density and increasing blood flow velocity, (2) clot formation at the outlet of fiber bundle enhances deposition upstream, and consequently (3) greater path length provides more clot-free fiber surface area for gas exchange than a shorter path length. These results can be used to create less thrombogenic, more efficient artificial lung designs. Translational Impact Sentence: Fiber bundle parameters, such as decreased packing density, increased blood flow velocity, and a longer path length, can be used to design a less thrombogenic, more efficient artificial lung to extend functionality.

In Vitro and In Silico Characterization of the Aggregation of Thrombi on Textured Ventricular Cannula.

The unacceptably high stroke rate associated with HeartMate 3 ventricular assist device (VAD) without signs of adherent pump thrombosis is hypothesized to be the result of the emboli produced by the inflow cannula, that are ingested and ejected from the pump. This in vitro and numerical study aimed to emulate the surface features and supraphysiological shear of a ventricular cannula to provide insight into their effect on thrombogenesis. Human whole blood was perfused at calibrated flow rates in a microfluidic channel to achieve shear rates 1000-7500 s-1, comparable to that experienced on the cannula. The channel contained periodic teeth representative of the rough sintered surface of the HeartMate 3 cannula. The deposition of fluorescently labeled platelets was visualized in real time and analyzed with a custom entity tracking algorithm. Numerical simulations of a multi-constituent thrombosis model were performed to simulate laminar blood flow in the channel. The sustained growth of adherent platelets was observed in all shear conditions ( p <  0.05). However, the greatest deposition was observed at the lower shear rates. The location of deposition with respect to the microfluidic teeth was also found to vary with shear rate. This was confirmed by CFD simulation. The entity tracking algorithm revealed the spatial variation of instances of embolic events. This result suggests that the sintered surface of the ventricular cannula may engender unstable thrombi with a greater likelihood of embolization at supraphysiological shear rates.

Exploratory Simulation of Thrombosis in a Temporary LVAD Catheter Pump within a Virtual In-vivo Left Heart Environment.

Percutaneous catheter pumps are intraventricular temporary mechanical circulatory support (MCS) devices that are positioned across the aortic valve into the left ventricle (LV) and provide continuous antegrade blood flow from the LV into the ascending aorta (AA). MCS devices are most often computationally evaluated as isolated devices subject to idealized steady-state blood flow conditions. In clinical practice, MCS devices operate connected to or within diseased pulsatile native hearts and are often complicated by hemocompatibility related adverse events such as stroke, bleeding, and thrombosis. Whereas aspects of the human circulation are increasingly being simulated via computational methods, the precise interplay of pulsatile LV hemodynamics with MCS pump hemocompatibility remains mostly unknown and not well characterized. Technologies are rapidly converging such that next-generation MCS devices will soon be evaluated in virtual physiological environments that increasingly mimic clinical settings. The purpose of this brief communication is to report results and lessons learned from an exploratory CFD simulation of hemodynamics and thrombosis for a catheter pump situated within a virtual in-vivo left heart environment.