Effect of Edge-to-Edge Mitral Valve Repair on Chordal Strain: Fluid-Structure Interaction Simulations.

Edge-to-edge repair for mitral valve regurgitation is being increasingly performed in high-surgical risk patients using minimally invasive mitral clipping devices. Known procedural complications include chordal rupture and mitral leaflet perforation. Hence, it is important to quantitatively evaluate the effect of edge-to-edge repair on chordal integrity. in this study, we employ a computational mitral valve model to simulate functional mitral regurgitation (FMR) by creating papillary muscle displacement. Edge-to-edge repair is then modeled by simulated coaptation of the mid portion of the mitral leaflets. in the setting of simulated FMR, edge-to-edge repair was shown to sustain low regurgitant orifice area, until a two fold increase in the inter-papillary muscle distance as compared to the normal mitral valve. Strain in the chordae was evaluated near the papillary muscles and the leaflets. Following edge-to-edge repair, strain near the papillary muscles did not significantly change relative to the unrepaired valve, while strain near the leaflets increased significantly relative to the unrepaired valve. These data demonstrate the potential for computational simulations to aid in the pre-procedural evaluation of possible complications such as chordal rupture and leaflet perforation following percutaneous edge-to-edge repair.

A mechanistic investigation of the EDWARDS INTUITY Elite valve's hemodynamic performance.

OBJECTIVE: Rapid deployment surgical aortic valve replacement has emerged as an alternative to the contemporary sutured valve technique. A difference in transvalvular pressure has been observed clinically between RD-SAVR and contemporary SAVR. A mechanistic inquiry into the impact of the rapid deployment valve inflow frame design on the left ventricular outflow tract and valve hemodynamics is needed. METHODS: A 23 mm EDWARDS INTUITY Elite rapid deployment valve and a control contemporary, sutured valve, a 23 mm Magna Ease valve, were implanted in an explanted human heart by an experienced cardiac surgeon. Per convention, the rapid deployment valve was implanted with three non-pledgeted, simple guiding sutures, while fifteen pledgeted, mattress sutures were used to implant the contemporary surgical valve. In vitro flow models were created from micro-computed tomography scans of the implanted valves and surrounding cardiac anatomy. Particle image velocimetry and hydrodynamic characterization experiments were conducted in the vicinity of the valves in a validated pulsatile flow loop system. RESULTS: The rapid deployment and control valves were found to have mean transvalvular pressure gradients of 7.92 ± 0.37 and 10.13 ± 0.48 mmHg, respectively. The inflow frame of the rapid deployment valve formed a larger, more circular, left ventricular outflow tract compared to the control valve. Furthermore, it was found that the presence of the control valve's sub-annular pledgets compromised its velocity distribution and consequently its pressure gradient. CONCLUSIONS: The rapid deployment valve's intra-annular inflow frame provides for a larger, left ventricular outflow tract, thus reducing the transvalvular pressure gradient and improving overall hemodynamic performance.

Optimized mitral annuloplasty ring design reduces loading in the posterior annulus.

OBJECTIVE: The study objective was to develop a novel annuloplasty ring with regional flexibility and assess its suture force dynamics in healthy ovine subjects compared with fully rigid or fully flexible rings. METHODS: Materially heterogeneous rings were created with rigid anterior and posterior, and flexible commissural segments. These rings were created to match the geometry of the Profile 3D ring (Medtronic, Minneapolis, Minn). Each ring was instrumented with 10 force transducers to measure cyclic suture forces (FC) and undersized annuloplasty was performed in 6 healthy ovine subjects. Each FC was recorded and examined for cardiac cycles reaching a maximum left ventricular pressure of 100, 125, and 150 mm Hg. FC was compared with previously reported values from fully rigid Profile 3D and fully flexible prototype rings. RESULTS: Relative to the fully rigid ring, the heterogeneous ring exhibited 48% reduction in FC at its commissural (rigid vs heterogeneous: 1.80 ± 0.94 N vs 0.95 ± 0.52 N; P < .001) and 32% reduction in posterior (1.90 ± 0.92 N vs 1.29 ± 0.91 N; P < .001) regions, but not in its anterior region (2.45 ± 1.21 N vs 2.23 ± 1.22 N; P = .279). Relative to the fully flexible ring, the heterogeneous ring exhibited no significant differences in FC in any region. CONCLUSIONS: The reduced FC of the heterogeneous ring relative to the fully rigid ring suggests a promising approach to reduce suture loading while preserving the annular remodeling capability of fully rigid rings. Future studies in diseased subjects are necessary to explore repair effectiveness of this ring.

Novel In Vitro Test Systems and Insights for Transcatheter Mitral Valve Design, Part II: Radial Expansion Forces.

Transcatheter mitral valve (TMV) replacement technology has great clinical potential for surgically inoperable patients suffering from mitral regurgitation. An important goal for robust TMV design is maximizing the likelihood of achieving a geometry post-implant that facilitates optimal performance. To support this goal, improved understanding of the annular forces that oppose TMV radial expansion is necessary. In Part II of this study, novel circular and D-shaped Radial Expansion Force Transducers (C-REFT and D-REFT) were developed and employed in porcine hearts (N = 12), to detect the forces required to radially expand the mitral annulus to discrete oversizing levels. Forces on both the septal-lateral and inter-commissural axes (FSL and FIC) scaled with device size. The D-REFT experienced lower FSL than the C-REFT (19.8 ± 7.4 vs. 17.4 ± 10.8 N, p = 0.002) and greater FIC (31.5 ± 14.0 vs. 36.9 ± 16.2 N; p = 0.002), and was more sensitive to degree of oversizing. Across all tests, FIC/FSL was 2.21 ± 1.33, likely reflecting low resistance to radial expansion at the aorto-mitral curtain. In conclusion, the annular forces opposing TMV radial expansion are non-uniform, and depend on final TMV shape and size. Based on this two-part study, we propose that radial force applied at the commissural aspect of the annulus has the most potent effect on paravalvular sealing.

Impact of simulated MitraClip on forward flow obstruction in the setting of mitral leaflet tethering: An in vitro investigation.

OBJECTIVES: We aimed to evaluate diastolic leaflet tethering as a factor that may cause mitral stenosis (MS) after simulated MitraClip implantation, using an in vitro left heart simulator. BACKGROUND: Leaflet tethering commonly seen in functional mitral regurgitation may be a significant factor affecting the severity of MS after MitraClip implantation. METHODS: A left heart simulator with excised ovine mitral valves (N = 6), and custom edge-to-edge clip devices (GTclip) was used to mimic implantation of MitraClip in a variety of positions. Anterior mitral leaflet (AML) tethering severity was varied for each case (leaflet excursion of 75°, 60°, and 45°, consistent with mild, moderate and severe tethering), and the baseline mitral annular area (MAA) was varied across samples (3.6-4.8 cm2 ). The resulting mitral valve area (MVA), and peak/mean mitral valve gradient (MVG) were measured in each case. RESULTS: AML tethering severity was a highly significant factor increasing MVG and decreasing MVA (P < 0.001). When GTclip placement was simulated with severe AML tethering, mean MVG >5 mmHg resulted more frequently than with GTclip placement alone (46% vs. 4%, respectively). However, severe AML tethering alone significantly reduced baseline MVA to 3.6 ± 0.2 cm2 , and increased baseline MVG to 3.0 ± 0.4 mmHg. At MAA above 4.7 cm2 , severe AML tethering did not cause moderate MS, even with placement of two GTclips (95% confidence). CONCLUSIONS: Our results show that diastolic AML tethering may predispose to MS after clip placement, however, MS was not observed when baseline MVA was above 4.0 cm2 . Severity of AML tethering may be an important criterion in selecting patients for edge-to-edge repair.

Mitral annuloplasty ring flexibility preferentially reduces posterior suture forces.

Annuloplasty ring repair is a common procedure for the correction of mitral valve regurgitation. Commercially available rings vary in dimensions and material properties. Annuloplasty ring suture dehiscence from the native annulus is a catastrophic yet poorly understood phenomenon that has been reported across ring types. Recognizing that sutures typically dehisce from the structurally weaker posterior annulus, our group is conducting a multi-part study in search of ring design parameters that influence forces acting on posterior annular sutures in the beating heart. Herein, we report the effect of ring rigidity on suture forces. Measurements utilized custom force sensors, attached to annuloplasty rings and implanted in normal ovine subjects via standard surgical procedure. Tested rings included the semi-rigid Physio (Edwards Lifesciences) and rigid and flexible prototypes of matching geometry. While no significant differences due to ring stiffness existed for sutures in the anterior region, posterior forces were significantly reduced with use of the flexible ring (rigid: 1.95 ±â€¯0.96 N, semi-rigid: 1.76 ±â€¯1.19 N, flexible: 1.04 ±â€¯0.63 N; p < 0.001). The ratio of anterior to posterior FC scaled positively with increasing flexibility (p < 0.001), and posterior forces took more time to reach their peak load when a flexible ring was used (p < 0.001). This suggests a more rigid ring enables more rapid/complete force equilibration around the suture network, transferring higher anterior forces to the weaker posterior tissue. For mitral annuloplasties requiring ring rigidity, we propose a ring design concept to potentially disrupt this force transfer and improve suture retention.

Mitral annuloplasty ring suture forces: Impact of surgeon, ring, and use conditions.

OBJECTIVE: The study objective was to quantify the effect of ring type, ring-annulus sizing, suture position, and surgeon on the forces required to tie down and constrain a mitral annuloplasty ring to a beating heart. METHODS: Physio (Edwards Lifesciences, Irvine, Calif) or Profile 3D (Medtronic, Dublin, Ireland) annuloplasty rings were instrumented with suture force transducers and implanted in ovine subjects (N = 23). Tie-down forces and cyclic contractile forces were recorded and analyzed at 10 suture positions and at 3 levels of increasing peak left ventricular pressure. RESULTS: Across all conditions, tie-down force was 2.7 ± 1.4 N and cyclic contractile force was 2.0 ± 1.2 N. Tie-down force was not meaningfully affected by any factor except surgeon. Significant differences in overall and individual tie-down forces were observed between the 2 primary implanting surgeons. No other factors were observed to significantly affect tie-down force. Contractile suture forces were significantly reduced by ring-annulus true sizing. This was driven almost exclusively by Physio cases and by reduction along the anterior aspect, where dehiscence is less common clinically. Contractile suture forces did not differ significantly between ring types. However, when undersizing, Profile 3D forces were significantly more uniform around the annular circumference. A suture's tie-down force did not correlate to its eventual contractile force. CONCLUSIONS: Mitral annuloplasty suture loading is influenced by ring type, ring-annulus sizing, suture position, and surgeon, suggesting that reports of dehiscence may not be merely a series of isolated errors. When compared with forces known to cause suture dehiscence, these in vivo suture loading data aid in establishing potential targets for reducing the occurrence of ring dehiscence.

Effects of annular contraction on anterior leaflet strain using an in vitro simulator with a dynamically contracting mitral annulus.

Using in vitro models, the mechanics as well as surgical techniques for mitral valves (MV) and MV devices can be studied in a more controlled environment with minimal monetary investment and risk. However, these current models rely on certain simplifications, one being that the MV has a static, rigid annulus. In order to study more complex issues of imaging diagnostics and implanted device function, it would be more advantageous to verify their use for a dynamic environment in a dynamic simulator. This study provides the novel design and development of a dynamically contracting annulus (DCA) within an in vitro simulator, and its subsequent use to study MV biomechanics. Experiments were performed to study the ability of the DCA to reproduce the MV leaflet mechanics in vitro, as seen in vivo, as well as investigate how rigid annuloplasties affect MV leaflet mechanics. Experiments used healthy, excised MVs and normal hemodynamics; contractile waveforms were derived from human in vivo data. Stereophotogrammetry and echocardiography were used to measure anterior leaflet strain and the change in MV geometry. In pursuit of the first in vitro MV simulator that more completely represents the dynamic motion of the full valvular apparatus, this study demonstrated the successful operation of a dynamically contracting mitral annulus. It was seen that the diseased contractile state increased anterior leaflet strain compared to the healthy contractile state. In addition, it was also shown in vitro that simulated rigid annuloplasty increased mitral anterior leaflet strain compared to a healthy contraction.

Suture Dehiscence in the Tricuspid Annulus: An Ex Vivo Analysis of Tissue Strength and Composition.

BACKGROUND: Surgical repair of functional tricuspid regurgitation (FTR) is an increasingly common practice, but annuloplasty suture dehiscence remains a significant problem. Quantitative and mechanistic understanding of annular suture holding strength can support more effective techniques for tricuspid valve device anchoring. METHODS: Suture holding strength of ovine tricuspid annuli (n = 15) was quantified ex vivo by pullout testing at 12 positions around their circumference. Collagen density in additional annuli (n = 7) was quantified at positions above each commissure and midleaflet point by two-photon autofluorescence microscopy, enabling mechanistic assessment of its role in imparting suture holding strength to the tissue. RESULTS: Suture holding strength from pullout testing varied significantly by annular position, with a maximum of 10.0 ± 4.1 N at the septal leaflet (6 o'clock) and a minimum of 4.3 ± 1.3 N at the posterior leaflet (1 o'clock). Leaflet midpoints showed significantly higher annular tissue strength than commissures (7.2 ± 3.4 N versus 5.6 ± 2.1 N, respectively, p = 0.008). Collagen density, measured by a normalized mean pixel intensity, was significantly higher in the septal annulus than in the posterior-septal commissure, posterior annulus, and anterior-posterior commissure. Suture holding strength showed a strong linear correlation with collagen density (R2 = 0.822, p = 0.013). CONCLUSIONS: The clinical predominance of suture dehiscence at the septal annulus, despite its greater ex vivo holding strength, suggests either adverse suture placement techniques in this region or asymmetric tensile loading after implantation. This issue highlights the need to optimize implantation techniques and to carefully assess anchor security in existing and next-generation FTR corrective devices.

Fluid-structure interaction and structural analyses using a comprehensive mitral valve model with 3D chordal structure.

Over the years, three-dimensional models of the mitral valve have generally been organized around a simplified anatomy. Leaflets have been typically modeled as membranes, tethered to discrete chordae typically modeled as one-dimensional, non-linear cables. Yet, recent, high-resolution medical images have revealed that there is no clear boundary between the chordae and the leaflets. In fact, the mitral valve has been revealed to be more of a webbed structure whose architecture is continuous with the chordae and their extensions into the leaflets. Such detailed images can serve as the basis of anatomically accurate, subject-specific models, wherein the entire valve is modeled with solid elements that more faithfully represent the chordae, the leaflets, and the transition between the two. These models have the potential to enhance our understanding of mitral valve mechanics and to re-examine the role of the mitral valve chordae, which heretofore have been considered to be 'invisible' to the fluid and to be of secondary importance to the leaflets. However, these new models also require a rethinking of modeling assumptions. In this study, we examine the conventional practice of loading the leaflets only and not the chordae in order to study the structural response of the mitral valve apparatus. Specifically, we demonstrate that fully resolved 3D models of the mitral valve require a fluid-structure interaction analysis to correctly load the valve even in the case of quasi-static mechanics. While a fluid-structure interaction mode is still more computationally expensive than a structural-only model, we also show that advances in GPU computing have made such models tractable. Copyright © 2016 John Wiley & Sons, Ltd.

Personalized mitral valve closure computation and uncertainty analysis from 3D echocardiography.

Intervention planning is essential for successful Mitral Valve (MV) repair procedures. Finite-element models (FEM) of the MV could be used to achieve this goal, but the translation to the clinical domain is challenging. Many input parameters for the FEM models, such as tissue properties, are not known. In addition, only simplified MV geometry models can be extracted from non-invasive modalities such as echocardiography imaging, lacking major anatomical details such as the complex chordae topology. A traditional approach for FEM computation is to use a simplified model (also known as parachute model) of the chordae topology, which connects the papillary muscle tips to the free-edges and select basal points. Building on the existing parachute model a new and comprehensive MV model was developed that utilizes a novel chordae representation capable of approximating regional connectivity. In addition, a fully automated personalization approach was developed for the chordae rest length, removing the need for tedious manual parameter selection. Based on the MV model extracted during mid-diastole (open MV) the MV geometric configuration at peak systole (closed MV) was computed according to the FEM model. In this work the focus was placed on validating MV closure computation. The method is evaluated on ten in vitro ovine cases, where in addition to echocardiography imaging, high-resolution µCT imaging is available for accurate validation.

Mitral Valve Chordae Tendineae: Topological and Geometrical Characterization.

Mitral valve (MV) closure depends upon the proper function of each component of the valve apparatus, which includes the annulus, leaflets, and chordae tendineae (CT). Geometry plays a major role in MV mechanics and thus highly impacts the accuracy of computational models simulating MV function and repair. While the physiological geometry of the leaflets and annulus have been previously investigated, little effort has been made to quantitatively and objectively describe CT geometry. The CT constitute a fibrous tendon-like structure projecting from the papillary muscles (PMs) to the leaflets, thereby evenly distributing the loads placed on the MV during closure. Because CT play a major role in determining the shape and stress state of the MV as a whole, their geometry must be well characterized. In the present work, a novel and comprehensive investigation of MV CT geometry was performed to more fully quantify CT anatomy. In vitro micro-tomography 3D images of ovine MVs were acquired, segmented, then analyzed using a curve-skeleton transform. The resulting data was used to construct B-spline geometric representations of the CT structures, enriched with a continuous field of cross-sectional area (CSA) data. Next, Reeb graph models were developed to analyze overall topological patterns, along with dimensional attributes such as segment lengths, 3D orientations, and CSA. Reeb graph results revealed that the topology of ovine MV CT followed a full binary tree structure. Moreover, individual chords are mostly planar geometries that together form a 3D load-bearing support for the MV leaflets. We further demonstrated that, unlike flow-based branching patterns, while individual CT branches became thinner as they propagated further away from the PM heads towards the leaflets, the total CSA almost doubled. Overall, our findings indicate a certain level of regularity in structure, and suggest that population-based MV CT geometric models can be generated to improve current MV repair procedures.

Fluid-Structure Interaction Analysis of Ruptured Mitral Chordae Tendineae.

The chordal structure is a part of mitral valve geometry that has been commonly neglected or simplified in computational modeling due to its complexity. However, these simplifications cannot be used when investigating the roles of individual chordae tendineae in mitral valve closure. For the first time, advancements in imaging, computational techniques, and hardware technology make it possible to create models of the mitral valve without simplifications to its complex geometry, and to quickly run validated computer simulations that more realistically capture its function. Such simulations can then be used for a detailed analysis of chordae-related diseases. In this work, a comprehensive model of a subject-specific mitral valve with detailed chordal structure is used to analyze the distinct role played by individual chordae in closure of the mitral valve leaflets. Mitral closure was simulated for 51 possible chordal rupture points. Resultant regurgitant orifice area and strain change in the chordae at the papillary muscle tips were then calculated to examine the role of each ruptured chorda in the mitral valve closure. For certain subclassifications of chordae, regurgitant orifice area was found to trend positively with ruptured chordal diameter, and strain changes correlated negatively with regurgitant orifice area. Further advancements in clinical imaging modalities, coupled with the next generation of computational techniques will enable more physiologically realistic simulations.

Ex Vivo Methods for Informing Computational Models of the Mitral Valve.

Computational modeling of the mitral valve (MV) has potential applications for determining optimal MV repair techniques and risk of recurrent mitral regurgitation. Two key concerns for informing these models are (1) sensitivity of model performance to the accuracy of the input geometry, and, (2) acquisition of comprehensive data sets against which the simulation can be validated across clinically relevant geometries. Addressing the first concern, ex vivo micro-computed tomography (microCT) was used to image MVs at high resolution (~40 micron voxel size). Because MVs distorted substantially during static imaging, glutaraldehyde fixation was used prior to microCT. After fixation, MV leaflet distortions were significantly smaller (p < 0.005), and detail of the chordal tree was appreciably greater. Addressing the second concern, a left heart simulator was designed to reproduce MV geometric perturbations seen in vivo in functional mitral regurgitation and after subsequent repair, and maintain compatibility with microCT. By permuting individual excised ovine MVs (n = 5) through each state (healthy, diseased and repaired), and imaging with microCT in each state, a comprehensive data set was produced. Using this data set, work is ongoing to construct and validate high-fidelity MV biomechanical models. These models will seek to link MV function across clinically relevant states.

How Local Annular Force and Collagen Density Govern Mitral Annuloplasty Ring Dehiscence Risk.

BACKGROUND: Annuloplasty ring dehiscence is a well described mode of mitral valve repair failure. Defining the mechanisms underlying dehiscence may facilitate its prevention. METHODS: Factors that govern suture dehiscence were examined with an ovine model. After undersized ring annuloplasty in live animals (n = 5), cyclic force (FC) that acts on sutures during cardiac contraction was measured with custom transducers. FC was measured at ten suture positions, throughout cardiac cycles with peak left ventricular pressure (LVPmax) of 100, 125, and 150 mm Hg. Suture pullout testing was conducted on explanted mitral annuli (n = 12) to determine suture holding strength at each position. Finally, relative collagen density differences at suture sites around the annulus were assessed by two-photon excitation fluoroscopy. RESULTS: Anterior FC exceeded posterior FC at each LVPmax (eg, 2.8 ± 1.3 N versus 1.8 ± 1.2 N at LVPmax = 125 mm Hg, p < 0.01). Anterior holding strength exceeded posterior holding strength (6.4 ± 3.6 N versus 3.9 ± 1.6 N, p < 0.0001). On the basis of FC at LVPmax of 150 mm Hg, margin of safety before suture pullout was vastly higher between the trigones (exclusive) versus elsewhere (4.8 ± 0.9 N versus 1.9 ± 0.5 N, p < 0.001). Margin of safety exhibited strong correlation to collagen density (R(2) = 0.947). CONCLUSIONS: Despite lower cyclic loading on posterior sutures, the weaker posterior mitral annular tissue creates higher risk of dehiscence, apparently because of reduced collagen content. Sutures placed atop the trigones are less secure than predicted, because of a combination of reduced collagen and higher overall rigidity in this region. These findings highlight the inter-trigonal tissue as the superior anchor and have implications on the design and implantation techniques for next-generation mitral prostheses.

High-resolution subject-specific mitral valve imaging and modeling: experimental and computational methods.

The diversity of mitral valve (MV) geometries and multitude of surgical options for correction of MV diseases necessitates the use of computational modeling. Numerical simulations of the MV would allow surgeons and engineers to evaluate repairs, devices, procedures, and concepts before performing them and before moving on to more costly testing modalities. Constructing, tuning, and validating these models rely upon extensive in vitro characterization of valve structure, function, and response to change due to diseases. Micro-computed tomography ([Formula: see text]CT) allows for unmatched spatial resolution for soft tissue imaging. However, it is still technically challenging to obtain an accurate geometry of the diastolic MV. We discuss here the development of a novel technique for treating MV specimens with glutaraldehyde fixative in order to minimize geometric distortions in preparation for [Formula: see text]CT scanning. The technique provides a resulting MV geometry which is significantly more detailed in chordal structure, accurate in leaflet shape, and closer to its physiological diastolic geometry. In this paper, computational fluid-structure interaction (FSI) simulations are used to show the importance of more detailed subject-specific MV geometry with 3D chordal structure to simulate a proper closure validated against [Formula: see text]CT images of the closed valve. Two computational models, before and after use of the aforementioned technique, are used to simulate closure of the MV.

Novel Method to Track Soft Tissue Deformation by Micro-Computed Tomography: Application to the Mitral Valve.

Increasing availability of micro-computed tomography (µCT) as a structural imaging gold-standard is bringing unprecedented geometric detail to soft tissue modeling. However, the utility of these advances is severely hindered without analogous enhancement to the associated kinematic detail. To this end, labeling and following discrete points on a tissue across various deformation states is a well-established approach. Still, existing techniques suffer limitations when applied to complex geometries and large deformations and strains. Therefore, we herein developed a non-destructive system for applying fiducial markers (minimum diameter: 500 µm) to soft tissue and tracking them through multiple loading conditions by µCT. Using a novel applicator to minimize adhesive usage, four distinct marker materials were resolvable from both tissue and one another, without image artifacts. No impact on tissue stiffness was observed. µCT addressed accuracy limitations of stereophotogrammetry (inter-method positional error 1.2 ± 0.3 mm, given marker diameter 1.9 ± 0.1 mm). Marker application to ovine mitral valves revealed leaflet Almansi areal strains (45 ± 4%) closely matching literature values, and provided radiographic access to previously inaccessible regions, such as the leaflet coaptation zone. This system may meaningfully support mechanical characterization of numerous tissues or biomaterials, as well as tissue-device interaction studies for regulatory standards purposes.