Biomedical Engineering

Design Optimization of a Mechanical Heart Valve forReducing Valve Thrombogenicity—A Case Study

with ATS Valve

YARED ALEMU,* GAURAV GIRDHAR,* MICHALIS XENOS,* JAWAAD SHERIFF,* JOLYON JESTY,† SHMUEL EINAV,*AND DANNY BLUESTEIN*

Patients implanted with mechanical heart valves (MHV) orwith ventricular assist devices that use MHV require manda-tory lifelong anticoagulation for secondary stroke prevention.We recently developed a novel Device Thrombogenicity Em-ulator (DTE) methodology that interfaces numerical andexperimental approaches to optimize the thrombogenic per-formance of the device and reduce the bleeding risk associ-ated with anticoagulation therapy. Device ThrombogenicityEmulator uses stress-loading waveforms in pertinent plateletflow trajectories that are extracted from highly resolved nu-merical simulations and emulates these flow conditions in aprogrammable hemodynamic shearing device (HSD) bywhich platelet activity is measured. We have previously com-pared two MHV, ATS and the St. Jude Medical, and demon-strated that owing to its nonrecessed hinge design, the ATSvalve offers improved thrombogenic performance. In thisstudy, we further optimize the ATS valve thrombogenic per-formance, by modifying various design features of the valve,intended to achieve reduced thrombogenicity: 1) optimizingthe leaflet-housing gap clearance; 2) increasing the effectivemaximum opening angle of the valve; and 3) introducing astreamlined channel between the leaflet stops of the valvethat increases the effective flow area. We have demonstratedthat the DTE optimization methodology can be used as testbed for developing devices with significantly improved thom-bogenic performance. ASAIO Journal 2010; 56:389–396.

Flow past mechanical heart valves (MHV) in mechanicalcirculatory support devices, including total artificial hearts andventricular assist devices (VADs), is primarily implicated inthromboembolism.1 The newer valve designs, although morehemodynamically efficient, pose a significant thromboembolicrisk owing to nonphysiological flow conditions at which theelevated stresses and exposure times are sufficiently high to

cause platelet activation and thrombus formation.2–5 Mitiga-tion of this risk requires lifelong anticoagulation therapy,4,6

and less thrombogenic MHV designs should therefore be de-veloped by device manufacturers.

Design-specific thrombogenic effects of MHV with emphasison flow fields around the hinges have been investigated with laservelocimetry7 and computational fluid dynamics (CFD).8,9 Com-parison between St. Jude Medical (SJM, St. Paul, MN) and Car-boMedics (CM, Austin, TX) valve hinges revealed higher velocityand shear stress magnitudes in the CM valve.7 In another study,the open pivot design (ATS Medical, Minneapolis, MN) hadsuperior hemodynamics and lower peak stresses than the re-cessed hinge design (SJM).8 The effect of leaflet-housing gaps inSJM valve on peak stresses was investigated numerically10 andexperimentally.11 In these studies, optimized intermediate gapclearances (�100 �m) were concluded to be the least thrombo-genic based on reduced peak stresses and the expected reducedplatelet activation, while having a minimal effect on regurgitantvolumes. However, these studies did not correlate numerical orflow measurements with thrombogenic markers such as plateletactivation to validate the reduced thrombogenicity of the partic-ular valve designs.

Our group has extensively investigated platelet activation indevices within a left ventricular assist device (LVAD) setup12–14

and conducted advanced numerical simulations to elucidate theeffect of specific flow phases on platelet activation.2,15,16 Wedeveloped a new methodology entitled Device Thromboge-nicity Emulator (DTE) that interfaces advanced numericalsimulations with experimental measurements.17 We recentlyapplied DTE to compare the thrombogenic performance of twocommercial bileaflet MHV—the SJM regent and the ATSAP—in forward and regurgitant flow phases.17 The main dif-ference between these valves is the hinge region design. Thevalve design-dependent resultant platelet activity was found tobe higher in the SJM valve, particularly during regurgitation, inagreement with our previous results using fluid structure inter-action (FSI) approach.16 Motivated by these findings and not-ing that the ATS valve is less thrombogenic than the widelyimplanted SJM MHV, we apply the DTE methodology to fur-ther optimize the original ATS design.

Methods

The DTE is used for optimizing cardiovascular device throm-bogenicity by optimizing its design in the virtual numerical

From the *Department of Biomedical Engineering and †Division ofHematology/Oncology, School of Medicine, Stony Brook University,Stony Brook, New York.

Submitted for consideration December 2009; accepted for publica-tion in revised form April 2010.

The first three authors contributed equally to this work.Corresponding Author: Danny Bluestein, PhD, Department of Bio-

medical Engineering, Stony Brook University, HSC T18-030, StonyBrook, NY 11794-8181. Email: danny.bluestein@sunysb.edu.

DOI: 10.1097/MAT.0b013e3181e65bf9

ASAIO Journal 2010

389

domain and interfacing it to an experimental apparatus thatemulates the flow conditions within the device.17 Device-specific probability density function (PDF) of stress accumula-tion (SA) of multiple trajectories is computed in the numericaldomain to establish a “thrombogenic footprint” of the device.The DTE then uses stress-loading waveforms in localized high-stress regions, or “hot-spots,” extracted from the numericalsimulations and emulates these flow conditions in a program-mable hemodynamic shearing device (HSD) by which theresultant platelet activity is measured.17–19

The original ATS valve has an open pivot configuration withopen and closed leaflet stops protruding into the flow field (Figure1). We use the DTE to assess the thrombogenic effects of designchanges in several ATS valve features—valve-housing gap clear-ances, valve opening angles, and hinge modification (Figure 1). Aregion-specific PDF was mapped and iteratively optimized. Plate-let activation measurements were performed with an innovativeprothrombinase assay20 by exposing platelets in the HSD toprogrammed stress-loading waveforms in pertinent flow trajecto-ries that were extracted from the numerical simulations after eachdesign change. A description of the methodology follows.

Simulation Methods

Numerical simulations were conducted for the forward (up to300 msec from peak systole, with the valve in fully open posi-tion17) and the regurgitant flow phases. A two-phase Newtonianfluid was used to represent the blood, with platelets considered asneutrally buoyant solid spherical particles (3 �m diameter). Thesimulations were discretized within a range of 5–9 million finitevolume cells and 15,000–30,000 platelets seeded upstream. Thesimulations were performed using high mesh density approachingdirect numerical simulations (DNS)21 resolution, which enablesto capture flow effects in the smallest confines of complex MHVgeometries while liberating from the use of turbulence models(mesh resolution within the Kolmogorov scales in MHV flows:20–70 �m).22,23 Grid independence studies were conducted us-ing three different grid sizes, 2, 9, and 17 � 106 cells. The

difference between 9 and 17 million elements was found to be�5%. Similar optimization for time step, dt, was established at5 � 10�4 s and was used for all simulations.

SA Model

Stress loading history of the seeded platelets was computedby incorporating the combined effect of stress and exposuretime according to the well-established shear induced plateletactivation (SIPA) concept.24 The stress tensor was extractedfrom the simulations along the corresponding platelet trajec-tories and rendered into a scalar stress value as previouslydescribed.2,25 The extremely refined DNS mesh used in thisstudy can capture the smallest turbulent Kolmogorov scales.Thus, there is no need for turbulent modeling and inclusion ofthe approximated turbulent Reynolds stresses. Accordingly,only viscous stresses are present in the stress tensor and con-sidered in the SA formulation. We further developed our for-mulation of the SA of a platelet (the linear product of stress, �,and exposure time, texp) to include the stress-loading rate �̇�t�26

according to the following equation:

SA � � � texp � �t0

texp

��t�dt � �t0

texp

t �̇�t�dt

� �i�1

N

�i � �t � �i�1

N

ti � ��i � �i�1�. (1)

where �i, i � 1, 2, . . ., N, is the nodal scalar value extractedfrom the total stress tensor described above and �t the corre-sponding time step between successive nodal points.

PDF of SA

The PDF is representative of the overall thrombogenic po-tential of the valve17 or specific valve modification. To ensurethat the SA is independent of number of seeded platelets(15,000–30,000) and spatiotemporal variations, we have used

Figure 1. Modifications to the original ATS valve.A: Three valve-housing gap clearances (38, 130,and 250 �m). B: Two maximum opening angles(80° and 85°). C: Original geometry and hingemodifications—insertion of a channel between theleaflet stops.

390 ALEMU ET AL.

bootstrapping statistics16,17 to compare localized PDF of dif-ferent valve designs. Those were calculated in respect to asphere of interest (SOI) located at the middle of the hinge andwith a radius r � 2.5 mm.17

Platelet Activation Measurement

Specific high-stress trajectories identified from the SOI wereprogrammed into a HSD (Figure 2), a computer-controlled

cone-plate-Couette viscometer capable of accurately emulat-ing shear stress conditions found in devices, as previouslydescribed.18,19,27 Thirty milliliters of citrated blood was ob-tained from healthy adult volunteers in accordance with StonyBrook University Institutional Review Board regulations. Gel-filtered platelets were prepared and diluted (2 � 107/ml) inmodified Tyrode’s buffer.20 Viscosity was adjusted to 3.5–6.5cP with the addition of high-molecular-weight Dextran (500kDa, Sigma, St. Louis, MO) to achieve the desired peak shearstresses in stress-loading waveforms. Platelet activation wasmeasured corresponding to 600 repeats of each stress-loadingwaveform with a modified prothrombinase assay20 at the be-ginning and end of the experiments (n � 5). The difference inactivation was normalized to maximum activation determinedby sonication17,27 and was reported for each trajectory. One-way analysis of variance was used to statistically infer activa-tion differences between design changes and the control.

Design Changes of ATS Valve

In our previous studies, we compared the effects of thehinges of two MHV designs, ATS AP and the SJM Regent, onplatelet activation.16,17 In this study, we explore design opti-mization changes in the ATS valve intended to achieve animproved thrombogenic performance.

Changes in Leaflet-Housing Gap Clearance. In the originalATS valve, the gap clearance (distance between the leaflet andhousing) near the hinge region is 38 �m. This distance wasincreased to 130 and 250 �m, correspondingly, to establishthe contribution of gap clearance to the flow stresses experi-enced by platelets and find an optimal distance that wouldminimize platelet activation (Figure 1A).

Figure 3. Effect of valve-housing clearance gap.Probability density function (PDF) of the stress ac-cumulation during (A) forward and (B) regurgitantflow. (C) Velocity contour plots during forward andregurgitant (inset) flow phases close to the hingesvicinity.

Figure 2. Schematic of the hemodynamic shearing device (HSD)and an example of accurate emulation of a platelet shear stress-loading waveform that was extracted from a numerical simulation.

391THROMBO-OPTIMIZATION OF THE ATS VALVE DESIGN

Changes in Opening Angle. According to the valve man-ufacturer, the maximum opening angle for the ATS valve is85°. Experimentally measured values however are closer to80°, indicating that the leaflets of the ATS valve do not alwaysreach its fully opening angle.16,28 To investigate the role of theeffective maximum opening angle on SA distribution andplatelet activation, maximum opening angles of 80° and 85°were investigated (Figure 1B).

Hinge Region Modification. The ATS valve has sphericalconvex pivots facilitating rotation of the leaflets. Three convexpivot stops on the inner circumference of the orifice ring oneach side arrest the leaflets in open and closed positions. Thegeometry below the convex leaflet stops was modified, and astreamlined flow channel was carved along the edges of thesestops (Figure 1C). Probability density function and plateletactivation measurements for this modification were comparedwith the original valve design.

Results

Velocity contour plots, PDF, and platelet activation mea-surements resulting from the design modifications measured in“hot spot” trajectories are presented in Figures 3–8. The ve-locity contour plots show regions of flow separation and re-circulation during forward flow for the valve-housing gapclearance and opening angle cases. Strong jets emanating fromthe hinges were observed during regurgitant flow.

The secondary flow for the original and modified valvesconsisted of a pair of counter-rotating vortices emanating fromthe jet flow that is generated in the hinge regions. The forma-

tion of these vortices seems to entrain a significant number ofplatelets toward elevated shear stress regions.17 Elevated shearstresses particularly during regurgitant phase, experienced byplatelets because of pathological flow conditions, play a majorrole in SA that may lead to platelet activation.

Leaflet-Housing Gap Clearance

Simulations were performed for three hinge gap clearances:38, 130, and 250 �m. Stress accumulation was determinedfor all particle trajectories in the hinge SOI (PDF: Figure 3A,forward flow; Figure 3B, regurgitant flow). A significant shiftin the mean SA to lower values was observed as the gapclearance was increased. The hinge SA in forward flow for the250 �m gap clearance (9.8 dyne � s/cm2) was lower than the38 �m (14.97 dyne � s/cm2) and 130 �m (9.98 dyne � s/cm2)gap clearances (p � 0.01). The velocity contour plots depictstronger jets in the smallest gap clearance. Shed vorticeswere observed near the leaflet tip during forward flow(Figure 3C). The hinge SA in regurgitant flow for the 130 �mgap clearance (80.9 dyne � s/cm2) was lower than the 38�m (85.6 dyne � s/cm2).

Hot-spot platelet trajectories and their corresponding stress-loading waveforms (Figure 4, A and C) were programmed into theHSD for platelet activation measurements (Figure 4, B and D). Inthe forward flow, the activation was significantly higher (p �0.05) for the 38 �m case compared with the two larger gapclearances (130 and 250 �m). The mean platelet activation forthe three groups was calculated as follows: a) 0.0208 0.0023(38 �m), b) 0.0079 0.0007 (130 �m), and c) 0.0063 0.0005

Figure 4. Platelet activation in hemodynamic shearing device (HSD). A: Stress-loading waveforms extracted from 38 (1 and 2), 130 (3 and4) and 250 �m (5 and 6) gap clearances during forward flow. B: Platelet activation corresponding to 600 repeats of each trajectory. C:Stress-loading waveforms extracted from 38 (1–3) and 130 �m (4–6) gap clearances in regurgitant flow and D: corresponding plateletactivation measurements.

392 ALEMU ET AL.

(250 �m). The lowest platelet activation value was established forthe two larger gaps but was not significantly lower for the largestone. In regurgitant flow, mean activation was significantly higher(p � 0.05) for the 38 �m case (0.0438 0.0035) compared withthe 130 �m gap clearance (0.0186 0.0008).

To estimate the effect of increased flow volumes passingthrough the larger clearance gaps and the effect that this mayhave on the platelet activation potential, we have calculatedthe exact amount of platelets passing through the hinges for thethree different gap clearances. We found out that 1,232 plate-lets passed from the hinges for the control gap clearance (38�m), 1,354 platelets (10% increase) passed from the hinges forgap clearance of 130 �m, and 1,155 platelets (6.25% de-

crease) passed from the hinges for gap clearance of 250 �m.The number of platelets does not change drastically when gapclearance increases and actually decreases in the larger gap(250 �m). Moreover, the peak velocity at the hinge vicinity wasmuch higher (higher SA could result in more platelet activation)for the smallest gap clearance (u38�m � 1.59m/s) and decreasesfor the 130 �m gap clearance (u130�m � 1.46m/s). The peakvelocity at the hinge vicinity increases again for the 250-�m gapclearance (u250�m � 1.48m/s). Although a larger volume of bloodpasses through the larger pivot gaps, our simulations indicate thatit does not necessarily translate into a larger number of particlespassing through these regions. In addition, the PDFs indicate thatthe larger volumes are compensated by localized velocity reduction.

Figure 5. Effect of ATS valve open-ing angle. A: Probability density func-tion (PDF) of the stress accumulationfor the two opening angles. B: Veloc-ity contours for 80° and 85° maxi-mum opening angles.

Figure 6. Platelet activation inHSD. A: Hinge trajectories extractedfrom 80° (1–3) and 85° (4–6) openingangles. B: Stress-loading waveformscorresponding to trajectories 1–6. C:Platelet activation corresponding to600 repeats of each trajectory.

393THROMBO-OPTIMIZATION OF THE ATS VALVE DESIGN

Valve Opening AngleLarge areas of flow separations were observed for the 80°

opening angle case (Figure 5B). This angle produced signifi-cantly higher mean values (p � 0.01) of platelet SA (15.16dyne � s/cm2) than the 85° opening angle (14.97 dyne �s/cm2, Figure 5A). Maximum velocities were found in the

central jet at the leaflets’ leading edge and are in agreementwith earlier studies.16,29

Hot-spot platelet trajectories (Figure 6A) and their co-rresponding stresses (Figure 6B) were programmed intothe HSD for platelet activation measurements (Figure 6C).Significantly higher (p � 0.05) mean platelet activation

Figure 7. Effect of the modified hinge region. Probability density function (PDF) of the stress accumulation for the modified and the originalATS valves during (A) forward and (B) regurgitant flow phases.

Figure 8. Platelet activation in hemodynamic shearing device (HSD). A: stress-loading waveforms extracted from the original (1–3)and modified hinge region design (4 – 6) during forward flow. B: platelet activation corresponding to 600 repeats of each trajectory.C: Stress-loading waveforms extracted from the modified hinge region design (1–3) during regurgitant flow and D: correspondingplatelet activation measurements [note: platelet activation for control design is shown in Figure 4D (corresponding to trajectories 1–3in Figure 4C)].

394 ALEMU ET AL.

was found for the 80° opening angle case (0.0593 0.0041) compared with the 85° angle case (0.0056 0.0006).

Hinge Modifications

The hinge regions were modified to introduce a channelbetween the leaflet stops. The resulting channels are intendedto increase the flow area near the hinge regions and to reducethe elevated flow stresses generated in the narrow gap clear-ance between the stops and the leaflets. The hinge SA (PDF:Figure 7A, forward flow; Figure 7B, regurgitant flow) for themodified valve (forward flow: 11.31 dyne � s/cm2; regurgitantflow: 76.7 dyne � s/cm2) was found to be significantly lower(p � 0.01) than the control case (forward flow: 14.97 dyne �s/cm2; regurgitant flow: 85.6 dyne � s/cm2).

Hot-spot platelet trajectories and their corresponding shearstress-loading waveforms (Figure 8A, forward flow; Figure 8C,regurgitant flow) were programmed into the HSD for plateletactivation measurements (Figure 8B, forward flow; Figure 8D,regurgitant flow). The mean platelet activation for the modifiedvalve (Figure 4B, forward: 0.0104 0.0013; Figure 4D, re-gurgitant: 0.0438 0.0035) was statistically lower (p � 0.05)than that for the original valve (Figure 8B, forward: 0.0241 0.0020; Figure 8D, regurgitant: 0.0248 0.0015) in both flowphases.

Discussion

In this study, an optimization of the ATS AP valve thrombo-genic performance was carried out with our novel DTE meth-odology. The ATS leaflet-housing gap clearance studies showthe contribution of the hinge regions in imparting high stress toplatelets. The flow fields are almost identical for the larger gapclearances of 130 and 250 �m, however with weaker jets andcounter-rotating vortices in the leaflet-housing region com-pared with the 38 �m case in forward flow. This smallest gapclearance generates the strongest jets, increasing shear stresslevels and the platelet residence time in the counter-rotatingvortices emanating from the hinges, subsequently producinghigher SA values. In regurgitant flow, higher stresses were alsofound for the smallest gap clearance. The resultant plateletactivity measurements in the HSD were in complete agree-ment with the numerical PDF. Although the ATS valve is notrecessed, optimized gap clearance is essential for reducedstresses and regurgitant flow.30 An intermediate gap clearancewould be the optimal choice for minimized thrombogenic risk.A larger gap clearance does not produce significantly lower SAand may impair the valve functionality by increasing regurgi-tant flow volume through enhanced leakage jets formed withinthe hinge recess, as reported before for the SJM.7

Previous studies suggest that bileaflet MHV with larger openingangles are preferred for reduced thrombogenicity.29 Larger flowseparation in the 80° opening angle accelerates the flow becauseof reduced cross sectional flow area, which produces higherlocalized velocity gradients and stresses. Exposure of platelets toincreased stresses shifts the PDF to a higher mean value for the80° opening angle. Measured platelet activation was significantlyhigher for the 80° opening angle trajectories, in agreement withthe PDF. A larger opening angle would improve the thrombo-genic performance of the ATS valve. The ATS MHV does not

necessarily open fully under various operating conditions,16,28

and extra care is mandated during the design of the MHV movingparts to guarantee that the leaflets can meet their full excursion.However, individual flow patterns are influenced by valve pivotgeometries and the introduction of sinuses downstream, whichcan dissipate stresses11 and may affect the fully open angle.

A streamlined channel was introduced in the hinge regionbetween the leaflet and the stops intended to reduce flowinduced stresses by increasing the effective flow area. A PDF ofSA for the modified and the original designs shows that themodified valve has a significantly lower SA and is in completeagreement with measured platelet activation values in forwardand regurgitant flow phases. Although the ATS open pivothinge design already offers a significant improvement over theSJM MHV cavity pivot hinge design,16,17 it is clear that anadditional improvement may optimize this successful designand make it less thrombogenic.

The simulations were performed during the forward andregurgitant flow phases to study the effect of stress-inducedplatelet activation that may lead to thromboembolic compli-cations.31 Flow disturbances caused by leaflet motion andassociated transient effects during the rapid closing phase thatmay further add to the platelet activation potential were notincluded in this study. Its very short duration (10–30 msec)offers only a modest contribution to platelet activation—unlesscavitation is generated during this phase.32,33 Moreover, it isonly marginally related to the design optimization methodol-ogy presented in this study, which focused on the optimization ofthe MHV recesses and gap clearances within the valve super-structure. Physiological geometrical features such as the sinusregions were not considered. More realistic near-valve regionsand valve misalignment may additionally enhance the stress lev-els observed in this study.2,13 Physiological, non-Newtonianblood properties13 also influence the size of the recirculationzones, which may result in increased stress-exposure time. Wewill address some of these issues in our future studies using theDTE methodology.

Our studies demonstrate the robustness of the DTE method-ology for optimizing the thrombogenic performance of MHV.In this study, we optimized the ATS valve design and concludethat the following changes to the original valve may signifi-cantly reduce thrombogenicity: 1) increasing the effectivemaximum opening angle of the valve to 85°, 2) optimizing thegap clearance between the valve and the housing to be atapproximately 130 �m, and 3) modifying the hinge region bycarving a streamlined flow channel in the leaflet stops at theedges facing the leaflets. We note that a combination of designchanges described above could additionally improve the valvethromboresistance. The excellent agreement between numer-ical simulations and experimental results, and the ability tointerface the two, demonstrates the efficacy of DTE for esti-mating the effects of design parameters on device thromboge-nicity. We envision that this methodology will be adopted bycardiovascular device manufacturers to optimize their devicedesigns for achieving improved thrombogenic performance.This may reduce or even eliminate the need for anticoagula-tion that is mandated for most of these devices.

Acknowledgment

Supported by NIH Grant 1R01 EB008004-01 (to D.B.).

395THROMBO-OPTIMIZATION OF THE ATS VALVE DESIGN

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