Matteo Nobili

Platelet Activation Due to Hemodynamic Shear Stresses: Damage Accumulation Model and Comparison to in vitro Measurements

The need to optimize the thrombogenic performance of blood recirculating cardiovascular devices, e.g., prosthetic heart valves (PHV) and ventricular assist devices (VAD), is accentuated by the fact that most of them require lifelong anticoagulation therapy that does not eliminate the risk of thromboembolic complications. The formation of thromboemboli in the flow field of these devices is potentiated by contact with foreign surfaces and regional flow phenomena that stimulate blood clotting, especially platelets. With the lack of appropriate methodology, device manufacturers do not specifically optimize for thrombogenic performance. Such optimization can be facilitated by formulating a robust numerical methodology with predictive capabilities of flow-induced platelet activation. In this study, a phenomenological model for platelet cumulative damage, identified by means of genetic algorithms (GAs), was correlated with in vitro experiments conducted in a Hemodynamic Shearing Device (HSD). Platelets were uniformly exposed to flow shear representing the lower end of the stress levels encountered in devices, and platelet activity state (PAS) was measured in response to six dynamic shear stress waveforms representing repeated passages through a device, and correlated to the predictions of the damage accumulation model. Experimental results demonstrated an increase in PAS with a decrease in “relaxation” time between pulses. The model predictions were in very good agreement with the experimental results.

Numerical simulation of the dynamics of a bileaflet prosthetic heart valve using a fluid-structure interaction approach

The main purpose of this study is to reproduce in silico the dynamics of a bileaflet mechanical heart valve (MHV; St Jude Hemodynamic Plus, 27mm characteristic size) by means of a fully implicit fluid-structure interaction (FSI) method, and experimentally validate the results using an ultrafast cinematographic technique. The computational model was constructed to realistically reproduce the boundary condition (72 beats per minute (bpm), cardiac output 4.5l/min) and the geometry of the experimental setup, including the valve housing and the hinge configuration. The simulation was carried out coupling a commercial computational fluid dynamics (CFD) package based on finite-volume method with user-defined code for solving the structural domain, and exploiting the parallel performance of the whole numerical setup. Outputs are leaflets excursion from opening to closure and the fluid dynamics through the valve. Results put in evidence a favorable comparison between the computed and the experimental data: the model captures the main features of the leaflet motion during the systole. The use of parallel computing drastically limited the computational costs, showing a linear scaling on 16 processors (despite the massive use of user-defined subroutines to manage the FSI process). The favorable agreement obtained between in vitro and in silico results of the leaflet displacements confirms the consistency of the numerical method used, and candidates the application of FSI models to become a major tool to optimize the MHV design and eventually provides useful information to surgeons.

Platelet damage accumulation: In vitro and mathematical models

A phenomenological model for platelet cumulative damage was developed to express the platelet activation state (PAS) in response to a specific shear stress loading waveform. genetic algorithms (GAs) were used for model identification. The model was fine-tuned using parameters obtained in vitro by application of a shear stress loading waveform to a Hemodynamic Shearing Device (HSD). The PAS was measured temporally using a modified prothrombinase method. The proposed analytical model and PAS prediction agree well with and follow the same trend as the experimental results.

Prediction of Shear Induced Platelet Activation in Prosthetic Heart Valves by Integrating Fluid–Structure Interaction Approach and Lagrangian-Based Blood Damage Model

Altered haemodynamics are implicated in the blood cells damage that leads to thromboembolic complications in presence of prosthetic cardiovascular devices, with platelet activation being the underlying mechanism for cardioemboli formation in blood flow past mechanical heart valves (MHVs). Platelet activation can be initiated and maintained by flow patterns arising from blood flowing through the MHV, and can lead to an enhancement in the aggregation of platelets, increasing the risk for thromboemboli formation. Hellums and colleagues compiled numerous experimental results to depict a locus of incipient shear related platelet activation on a shear stress – exposure time plane, commonly used as a standard for platelet activation threshold [1]. However, platelet activation and aggregation is significantly greater under pulsatile or dynamic condition relative to exposure to constant shear stress [2]. Previous studies do not allow to determine the relationship existing between the measured effect — the activation of a platelet, and the cause — the time-varying mechanical loading, and the time of exposure to it as might be expected in vivo when blood flows through the valve. The optimization of the thrombogenic performance of MHVs could be facilitated by formulating a robust numerical methodology with predictive capabilities of flow-induced platelet activation. To achieve this objective, it is essential (i) to quantify the link between realistic valve induced haemodynamics and platelet activation, and (ii) to integrate theoretical, numerical, and experimental approaches that allow for the estimation of the thrombogenic risk associated with a specific geometry and/or working conditions of the implantable device. In this work, a comprehensive analysis of the Lagrangian systolic dynamics of platelet trajectories and their shear histories in the flow through a bileaflet MHV is presented. This study uses information extracted from the numerical simulations performed to resolve the flow field through a realistic model of MHV by means of an experimentally validated fluid-structure interaction approach [3]. The potency of the device to mechanically induce activation/damage of platelets is evaluated using a Lagrangian-based blood damage cumulative model recently identified using in vitro platelet activity measurements [4,5].Copyright

Identification of a mathematical model for the prediction of platelet damage accumulation in artificial organs: a preliminary study

Platelets are the pre-eminent cell involved in hemostasis and thrombosis. In recent years it has been demonstrated that flow-induced platelet activation is a major cause for the relatively high incidence of thromboembolic complications in mechanical heart valves (MHVs) [1,2].The platelet activation state (PAS) assay has proved to be a reliable technique for the experimental measurement of procoagulant activity [3]. A Predictive numerical model for platelets damage accumulation could provide critical information for thrombogenicity optimization of implantable prosthetic devices. This would lead to improving the safety and efficacy of implantable devices. Reliable models able to predict this phenomenon are still lacking. The aim of this work is an attempt to bridge this gap. A model for describing the activation of formed elements in blood requires establishing a correlation between mechanical loading, exposure time and the phenomenological response of these elements to it. A physically consistent phenomenological model is used [4] and genetic algorithms (GAs) [5], have been successfully applied to the tuning of the model parameters by correlating its predictions to PAS measurements conducted in a Hemodynamic Shearing Device (HSD) by exposing platelets to prescribed shear stress loading waveforms.Copyright

Evaluation of the Dynamics of a Bileaflet Heart Valve: Physical and Numerical Experiments

Clinical reports indicate that mechanical heart valves are still unable to eliminate problems mainly related to a non physiological fluid dynamics like thrombosis and coagulation complications [1]. Advanced experimental technique such as laser doppler anemometry (LDA) and particle image velocimetry (PIV), used to investigate the fluid dynamics of these devices, suffer from some intrinsic limitations (eg. access difficulties, light reflection, low resolution) [2]. In parallel with the increased performance at computing, the use of computational fluid dynamics has gained relevance as a powerful tool able to provide meaningful information of clinical and design aspects [3]. Key parameters in the assessment of blood damage potency (velocity patterns and turbulence, among them) are related to the behaviour of the valve in the flow field. The application of fluid structure interaction (FSI) models moves in the direction of greater accuracy in the reproduction of realistic flow condition in order to reach more in-depth insight into the hemodynamic of the virtual prototypes. The aim of this study is the investigation, in silico, of the bileaflet mechanical valve dynamics during the whole systolic phase. A 3D direct numerical simulation (DNS) was performed and an implicit fluid structure interaction model was used [4,5]. The results of the dynamics of the valve were validated with an experimental counterpart.Copyright

Magnetic Vascular Positioner for Automatic Coronary Artery Bypass Grafting does not Significantly Increase the Risk of Failure Related to Local Fluid Dynamics. A Numeric Study

Anastomotic devices have been recently introduced in cardiac surgery, in order to make the anastomosis procedure more quick, automatic and efficient. The Ventrica magnetic vascular positioner (MVP) constitutes an attractive anastomotic option that significantly shortens the ischemic time when creating the coronary anastomosis on the beating heart [1]. However, the implantation of the MVP connector modifies the graft configuration, consistently affecting the hemodynamics usually found in the traditional anastomosis. As local fluid dynamics could play a significant role on the onset of vessels’ wall pathologies, in this study a computational approach was designed to investigate the flow patterns in presence of the MVP. To do this, a model of standard hand-sewn anastomosis and a model of automated anastomosis were constructed, and CFD was used to simulate realistic graft hemodynamics. Synthetic analytical methods were calculated and compared for the quantitative assessment of the role played by the fluid dynamics in the activation of mechanotransduction pathways at the vessel wall, i.e., time-averaged wall shear stress (TAWSS), oscillating shear index (OSI) [2], and the very recent helical flow index HFI [3, 4]. This allowed to evaluate if the use of the MVP design increases the risks of failure related to the local bypass fluid dynamics.© 2007 ASME