Leaflet Strain Research Articles

Tricuspid valve leaflet strains in the beating ovine heart.

The tricuspid leaflets coapt during systole to facilitate proper valve function and, thus, ensure efficient transport of deoxygenated blood to the lungs. Between their open state and closed state, the leaflets undergo large deformations. Quantification of these deformations is important for our basic scientific understanding of tricuspid valve function and for diagnostic or prognostic purposes. To date, tricuspid valve leaflet strains have never been directly quantified in vivo. To fill this gap in our knowledge, we implanted four sonomicrometry crystals per tricuspid leaflet and six crystals along the tricuspid annulus in a total of five sheep. In the beating ovine hearts, we recorded crystal coordinates alongside hemodynamic data. Once recorded, we used a finite strain kinematic framework to compute the temporal evolutions of area strain, radial strain, and circumferential strain for each leaflet. We found that leaflet strains were larger in the anterior leaflet than the posterior and septal leaflets. Additionally, we found that radial strains were larger than circumferential strains. Area strains were as large as 97% in the anterior leaflet, 31% in the posterior leaflet, and 31% in the septal leaflet. These data suggest that tricuspid valve leaflet strains are significantly larger than those in the mitral valve. Should our findings be confirmed they could suggest either that the mechanobiological equilibrium of tricuspid valve resident cells is different than that of mitral valve resident cells or that the mechanotransductive apparatus between the two varies. Either phenomenon may have important implications for the development of tricuspidvalve-specific surgical techniques and medical devices.

Modeling Impaired Coaptation Effects on Mitral Leaflet Homeostasis Using a Flow-Culture Bioreactor

Mitral valve (MV) regurgitation constitutes an increasing burden of adult and pediatric cardiac disease tending to worsen over time. Whether altered mechanical forces on leaflets cause valve disease is unknown. Here we show that MV leaflet coaptive strain disruption alters expression of genes critical to leaflet homeostasis. We used a flow-culture bioreactor of rat MVs with flow-induced cyclic coaptation (cycling valve group; n= 4) or in a sustained open state (open valve group; n= 4). After 3 days of culture, leaflet RNA expression was profiled. More than 48 genes exhibited markedly changed expression when coaptive leaflet strain was disrupted for 3 days (change >fourfold; p < 0.05; cycling vs open valves). Genes exhibiting highly altered expression included Angpt2, Vegf, Cd74, RT1-Da (HLA-DRA), and Igfbp3. Pathway analysis indicated the most significant signaling pathways regulating the expression changes were Hif1α and Tnfα when MV closure was disrupted. Disruption of normal MV coaptive strain markedly alters the expression of leaflet genes, demonstrating that cyclic strain is critically important to leaflet homeostasis. We demonstrate a pattern of MV gene expression changes in which hypoxia signaling is prominently increased in response to disrupted strain cycles. Coaptive strain regulation of MV leaflet homeostasis implicates altered strain as a mechanism potentially initiating valve disease. Early repair may prevent progression of disease driven by altered coaptation.

A noninvasive method for the determination of in vivo mitral valve leaflet strains.

Assessment of mitral valve (MV) function is important in many diagnostic, prognostic, and surgical planning applications for treatment of MV disease. Yet, to date, there are no accepted noninvasive methods for determination of MV leaflet deformation, which is a critical metric of MV function. In this study, we present a novel, completely noninvasive computational method to estimate MV leaflet in-plane strains from clinical-quality real-time three-dimensional echocardiography (rt-3DE) images. The images were first segmented to produce meshed medial-surface leaflet geometries of the open and closed states. To establish material point correspondence between the two states, an image-based morphing pipeline was implemented within a finite element (FE) modeling framework in which MV closure was simulated by pressurizing the open-state geometry, and local corrective loads were applied to enforce the actual MV closed shape. This resulted in a complete map of local systolic leaflet membrane strains, obtained from the final FE mesh configuration. To validate the method, we utilized an extant in vitro database of fiducially labeled MVs, imaged in conditions mimicking both the healthy and diseased states. Our method estimated local anisotropic in vivo strains with less than 10% error and proved to be robust to changes in boundary conditions similar to those observed in ischemic MV disease. Next, we applied our methodology to ovine MVs imaged in vivo with rt-3DE and compared our results to previously published findings of in vivo MV strains in the same type of animal as measured using surgically sutured fiducial marker arrays. In regions encompassed by fiducial markers, we found no significant differences in circumferential(P = 0.240) or radial (P = 0.808) strain estimates between the marker-based measurements and our novel noninvasive method. This method can thus be used for model validation as well as for studies of MV disease and repair.

Left-Ventricular Assist Device Impact on Aortic Valve Mechanics, Proteomics and Ultrastructure

Aortic regurgitation is a prevalent, detrimental complication of left ventricular assist devices (LVADs). The altered hemodynamics of LVADs results in aortic valves (AVs) having distinct mechanical stimulation. Our hypothesis was that the altered AV hemodynamics modulates the valve cells and matrix, resulting in changes in valvular mechanical properties that then can lead to regurgitation. AVs were collected from 16 LVAD and 6 non-LVAD patients at time of heart transplant. Standard demographic and preoperative data were collected and comparisons between the two groups were calculated using standard statistical methods. Samples were analyzed using biaxial mechanical tensile testing, mass spectrometry-based proteomics, and transmission electron microscopy to assess ultrastructure. The maximum circumferential leaflet strain in LVAD patients was less than in non-LVAD patients (0.35 ± 0.10MPa versus 0.52 ± 0.18 MPa, p= 0.03) with a trend of reduced radial strain (p= 0.06) and a tendency for the radial strain to decrease with increasing LVAD duration (p= 0.063). Numerous proteins associated with actin and myosin, immune signaling and oxidative stress, and transforming growth factor β were increased in LVAD patients. Ultrastructural analysis showed a trend of increased fiber diameter in LVAD patients (46.2 ± 7.2 nm versus 45.1 ± 6.9 nm, p= 0.10), but no difference in fiber density. AVs in LVAD patients showed decreased compliance and increased expression of numerous proteins related to valve activation and injury compared to non-LVAD patients. Further knowledge of AV changes leading to regurgitation in LVAD patients and the pathways by which they occur may provide an opportunity for interventions to prevent and/or reverse this detrimental complication.

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.

Surface Strains of Porcine Tricuspid Valve Septal Leaflets Measured in Ex Vivo Beating Hearts.

Quantification of the tricuspid valve (TV) leaflets mechanical strain is important in order to understand valve pathophysiology and to develop effective treatment strategies. Many of the traditional methods used to dynamically open and close the cardiac valves in vitro via flow simulators require valve dissection. Recent studies, however, have shown that restriction of the atrioventricular valve annuli could significantly change their in vivo deformation. For the first time, the porcine valve leaflets deformation was measured in a passive ex vivo beating heart without isolating and remounting the valve annuli. In particular, the right ventricular apexes of porcine hearts (n = 8) were connected to a pulse-duplicator pump that maintained a pulsatile flow from and to a reservoir connected to the right atrium and the pulmonary arteries. This pump provided a right ventricular pressure (RVP) waveform that closely matched physiological values, leading to opening and closure of the tricuspid and pulmonary valves (PVs). At the midsection of the valve leaflets, the peak areal strain was 9.8 ± 2.0% (mean±standard error). The peak strain was 5.6 ± 1.1% and 4.3 ± 1.0% in the circumferential and radial directions, respectively. Although the right ventricle was beating passively, the leaflet peak areal strains closely matched the values measured in other atrioventricular valves (i.e., the mitral valve (MV)) in vivo. This technique can be used to measure leaflet strains with and without the presence of valve lesions to help develop/evaluate treatment strategies to restore normal valve deformation.

Molecular Mechanism of Ionic-Liquid-Induced Membrane Disruption: Morphological Changes to Bilayers, Multilayers, and Vesicles.

The application of ionic liquids (ILs) in many industrially relevant processes provides an urgent need to better understand their molecular interactions with biological systems. A detailed understanding of the cytotoxicity mechanism of ILs can be helpful in facilitating the molecular design of nontoxic ILs. Using coarse-grained molecular dynamics (MD) simulations, we investigate the effects of imidazolium-based ILs on several lipid bilayer morphologies. Our results demonstrate that the asymmetric insertion of IL cations into one side of a lipid bilayer leaflet enhances the leaflet strain, which upon reaching a critical value triggers a morphological disruption in the bilayer. Consistently, the bending modulus of the bilayer is reduced by 1 to 2 orders of magnitude relative to that of an IL-free planar bilayer prior to the disruption event. Our results suggest that ILs that can easily insert into the lipid bilayer without diffusing across or inducing lipid flip-flop can be more disruptive to a lipid biomembrane.

Heterogeneity of Mitral Leaflet Matrix Composition and Turnover Correlates with Regional Leaflet Strain.

To determine how extracellular matrix and contractile valvular cells contribute to the heterogeneous motion and strain across the mitral valve (MV) during the cardiac cycle, regional MV material properties, matrix composition, matrix turnover, and cell phenotype were related to regional leaflet strain. Radiopaque markers were implanted into 14 sheep to delineate the septal (SEPT), lateral (LAT), and anterior and posterior commissural leaflets (ANT-C, POST-C). Videofluoroscopy imaging was used to calculate radial and circumferential strains. Mechanical properties were assessed using uniaxial tensile testing and micropipette aspiration. Matrix composition and cell phenotypes were immunohistochemically evaluated within each leaflet region [basal leaflet (BL), mid-leaflet (ML), and free edge]. SEPT-BL segments were stiffer and stronger than other valve tissues, while LAT segments demonstrated more extensibility and strain. Collagens I and III in SEPT were greater than in LAT, although LAT showed greater collagen turnover [matrix metalloprotease (MMP)-13, lysyl oxidase] and cell activation [smooth muscle alpha-actin (SMaA), and non-muscle myosin (NMM)]. MMP13, NMM, and SMaA were strongly correlated with each other, as well as with radial and circumferential strains in both SEPT and LAT. SMaA and MMP13 in POST-C ML was greater than ANT-C, corresponding to greater radial strains in POST-C. This work directly relates leaflet strain, material properties, and matrix turnover, and suggests a role for myofibroblasts in the heterogeneity of leaflet composition and strain. New approaches to MV repair techniques and ring design should preserve this normal coupling between leaflet composition and motion.

TCT-673 Transcatheter Aortic Valve Oversizing: A Comparison of Leaflet Stress and Strain Distribution

TCT-673 Transcatheter Aortic Valve Oversizing: A Comparison of Leaflet Stress and Strain Distribution

Isolated effect of geometry on mitral valve function for in silico model development

Computational models for the heart's mitral valve (MV) exhibit several uncertainties that may be reduced by further developing these models using ground-truth data-sets. This study generated a ground-truth data-set by quantifying the effects of isolated mitral annular flattening, symmetric annular dilatation, symmetric papillary muscle (PM) displacement and asymmetric PM displacement on leaflet coaptation, mitral regurgitation (MR) and anterior leaflet strain. MVs were mounted in an in vitro left heart simulator and tested under pulsatile haemodynamics. Mitral leaflet coaptation length, coaptation depth, tenting area, MR volume, MR jet direction and anterior leaflet strain in the radial and circumferential directions were successfully quantified at increasing levels of geometric distortion. From these data, increase in the levels of isolated PM displacement resulted in the greatest mean change in coaptation depth (70% increase), tenting area (150% increase) and radial leaflet strain (37% increase) while annular dilatation resulted in the largest mean change in coaptation length (50% decrease) and regurgitation volume (134% increase). Regurgitant jets were centrally located for symmetric annular dilatation and symmetric PM displacement. Asymmetric PM displacement resulted in asymmetrically directed jets. Peak changes in anterior leaflet strain in the circumferential direction were smaller and exhibited non-significant differences across the tested conditions. When used together, this ground-truth data-set may be used to parametrically evaluate and develop modelling assumptions for both the MV leaflets and subvalvular apparatus. This novel data may improve MV computational models and provide a platform for the development of future surgical planning tools.

In Vitro Mitral Valve Simulator Mimics Systolic Valvular Function of Chronic Ischemic Mitral Regurgitation Ovine Model

This study was undertaken to evaluate an in vitro mitral valve (MV) simulator's ability to mimic the systolic leaflet coaptation, regurgitation, and leaflet mechanics of a healthy ovine model and an ovine model with chronic ischemic mitral regurgitation (IMR). Mitral valve size and geometry of both healthy ovine animals and those with chronic IMR were used to recreate systolic MV function in vitro. A2-P2 coaptation length, coaptation depth, tenting area, anterior leaflet strain, and MR were compared between the animal groups and valves simulated in the bench-top model. For the control conditions, no differences were observed between the healthy animals and simulator in coaptation length (p = 0.681), coaptation depth (p = 0.559), tenting area (p = 0.199), and anterior leaflet strain in the radial (p = 0.230) and circumferential (p = 0.364) directions. For the chronic IMR conditions, no differences were observed between the models in coaptation length (p = 0.596), coaptation depth (p = 0.621), tenting area (p = 0.879), and anterior leaflet strain in the radial (p = 0.151) and circumferential (p = 0.586) directions. MR was similar between IMR models, with an asymmetrical jet originating from the tethered A3-P3 leaflets. This study is the first to demonstrate the effectiveness of an in vitro simulator to emulate the systolic valvular function and mechanics of a healthy ovine model and one with chronic IMR. The in vitro IMR model provides the capability to recreate intermediary and exacerbated levels of annular and subvalvular distortion for which IMR repairs can be simulated. This system provides a realistic and controllable test platform for the development and evaluation of current and future IMR repairs.

Evidence of adaptive mitral leaflet growth

Ischemic mitral regurgitation is mitral insufficiency caused by myocardial infarction. Recent studies suggest that mitral leaflets have the potential to grow and reduce the degree of regurgitation. Leaflet growth has been associated with papillary muscle displacement, but role of annular dilation in leaflet growth is unclear. We tested the hypothesis that chronic leaflet stretch, induced by papillary muscle tethering and annular dilation, triggers chronic leaflet growth. To decipher the mechanisms that drive the growth process, we further quantified regional and directional variations of growth. Five adult sheep underwent coronary snare and marker placement on the left ventricle, papillary muscles, mitral annulus, and mitral leaflet. After eight days, we tightened the snares to create inferior myocardial infarction. We recorded marker coordinates at baseline, acutely (immediately post-infarction), and chronically (five weeks post-infarction). From these coordinates, we calculated acute and chronic changes in ventricular, papillary muscle, and annular geometry along with acute and chronic leaflet strains. Chronic left ventricular dilation of 17.15% (p<0.001) induced chronic posterior papillary muscle displacement of 13.49mm (p=0.07). Chronic mitral annular area, commissural and septal–lateral distances increased by 32.50% (p=0.010), 14.11% (p=0.007), and 10.84% (p=0.010). Chronic area, circumferential, and radial growth were 15.57%, 5.91%, and 3.58%, with non-significant regional variations (p=0.868). Our study demonstrates that mechanical stretch, induced by annular dilation and papillary muscle tethering, triggers mitral leaflet growth. Understanding the mechanisms of leaflet adaptation may open new avenues to pharmacologically or surgically manipulate mechanotransduction pathways to augment mitral leaflet area and reduce the degree of regurgitation.

Mitral valve leaflet strain imaging with echocardiography opens new windows to mitral valve study

Mitral valve leaflet strain imaging with echocardiography opens new windows to mitral valve study

On the In Vivo Deformation of the Mitral Valve Anterior Leaflet: Effects of Annular Geometry and Referential Configuration

Alteration of the native mitral valve (MV) shape has been hypothesized to have a profound effect on the local tissue stress distribution, and is potentially linked to limitations in repair durability. The present study was undertaken to elucidate the relation between MV annular shape and central mitral valve anterior leaflet (MVAL) strain history, using flat annuloplasty in an ovine model. In addition, we report for the first time the presence of residual in vivo leaflet strains. In vivo leaflet deformations were measured using sonocrystal transducers sutured to the MVAL (n = 10), with the 3D positions acquired over the full cardiac cycle. In six animals a flat ring was sutured to the annulus and the transducer positions recorded, while in the remaining four the MV was excised from the exsanguinated heart and the stress-free transducer positions obtained. In the central region of the MVAL the peak stretch values, referenced to the minimum left ventricular pressure (LVP), were 1.10 ± 0.01 and 1.31 ± 0.03 (mean ± standard error) in the circumferential and radial directions, respectively. Following flat ring annuloplasty, the central MVAL contracted 28% circumferentially and elongated 16% radially at minimum LVP, and the circumferential direction was under a negative strain state during the entire cardiac cycle. After valve excision from the exsanguinated heart, the MVAL contracted significantly (18 and 30% in the circumferential and radial directions, respectively), indicating the presence of substantial in vivo residual strains. While the physiological function of the residual strains (and their associated stresses) are at present unknown, accounting for their presence is clearly necessary for accurate computational simulations of MV function. Moreover, we demonstrated that changes in annular geometry dramatically alter valvular functional strains in vivo. As levels of homeostatic strains are related to tissue remodeling and homeostasis, our results suggest that surgically introduced alterations in MV shape could lead to the long term MV mechanobiological and microstructural alterations that could ultimately affect MV repair durability.

Rigid, Complete Annuloplasty Rings Increase Anterior Mitral Leaflet Strains in the Normal Beating Ovine Heart

Annuloplasty ring or band implantation during surgical mitral valve repair perturbs mitral annular dimensions, dynamics, and shape, which have been associated with changes in anterior mitral leaflet (AML) strain patterns and suboptimal long-term repair durability. We hypothesized that rigid rings with nonphysiological three-dimensional shapes, but not saddle-shaped rigid rings or flexible bands, increase AML strains. Sheep had 23 radiopaque markers inserted: 7 along the anterior mitral annulus and 16 equally spaced on the AML. True-sized Cosgrove-Edwards flexible, partial band (n=12), rigid, complete St Jude Medical rigid saddle-shaped (n=12), Carpentier-Edwards Physio (n=12), Edwards IMR ETlogix (n=11), and Edwards GeoForm (n=12) annuloplasty rings were implanted in a releasable fashion. Under acute open-chest conditions, 4-dimensional marker coordinates were obtained using biplane videofluoroscopy along with hemodynamic parameters with the ring inserted and after release. Marker coordinates were triangulated, and the largest maximum principal AML strains were determined during isovolumetric relaxation. No relevant changes in hemodynamics occurred. Compared with the respective control state, strains increased significantly with rigid saddle-shaped annuloplasty ring, Carpentier-Edwards Physio, Edwards IMR ETlogix, and Edwards GeoForm (0.14 ± 0.05 versus 0.16 ± 0.05, P=0.024, 0.15 ± 0.03 versus 0.18 ± 0.04, P=0.020, 0.11 ± 0.05 versus 0.14 ± 0.05, P=0.042, and 0.13 ± 0.05 versus 0.16 ± 0.05, P=0.009), but not with Cosgrove-Edwards band (0.15 ± 0.05 versus 0.15 ± 0.04, P=0.973). Regardless of three-dimensional shape, rigid, complete annuloplasty rings, but not a flexible, partial band, increased AML strains in the normal beating ovine heart. Clinical studies are needed to determine whether annuloplasty rings affect AML strains in patients, and, if so, whether ring-induced perturbations in leaflet strain states are linked to repair failure.

In vivo dynamic strains of the ovine anterior mitral valve leaflet

Understanding the mechanics of the mitral valve is crucial in terms of designing and evaluating medical devices and techniques for mitral valve repair. In the current study we characterize the in vivo strains of the anterior mitral valve leaflet. On cardiopulmonary bypass, we sew miniature markers onto the leaflets of 57 sheep. During the cardiac cycle, the coordinates of these markers are recorded via biplane fluoroscopy. From the resulting four-dimensional data sets, we calculate areal, maximum principal, circumferential, and radial leaflet strains and display their profiles on the averaged leaflet geometry. Average peak areal strains are 13.8±6.3%, maximum principal strains are 13.0±4.7%, circumferential strains are 5.0±2.7%, and radial strains are 7.8±4.3%. Maximum principal strains are largest in the belly region, where they are aligned with the circumferential direction during diastole switching into the radial direction during systole. Circumferential strains are concentrated at the distal portion of the belly region close to the free edge of the leaflet, while radial strains are highest in the center of the leaflet, stretching from the posterior to the anterior commissure. In summary, leaflet strains display significant temporal, regional, and directional variations with largest values inside the belly region and toward the free edge. Characterizing strain distribution profiles might be of particular clinical significance when optimizing mitral valve repair techniques in terms of forces on suture lines and on medical devices.

Effect of Geometry on the Leaflet Stresses in Simulated Models of Congenital Bicuspid Aortic Valves

The aim of the study was to assess the effect of geometric variations on the stresses developed in the leaflets of congenital bicuspid aortic valves (CBAV). We developed a model for the human tri-leaflet aortic valve based on the geometry and dimensions published in the literature. We also developed simulated CBAV geometry based on the most common geometry present in patients with CBAV that is published in the literature. We employed a constitutive relationship for the leaflet material from the previously published experimental data of fresh porcine aortic valve leaflet specimens for the analysis. We performed dynamic finite element (FE) structural analysis of the valves in the aortic position in order to compute the strain and stress distribution on the leaflets of the tri-leaflet valve and the CBAV models. Our results showed that large changes in the computed in-plane leaflet strain and stress occurred with variations in the geometry of the simulated CBAV whereas changes due to alterations in material constants were correspondingly less. The valve orifice area in the fully open position was significantly reduced in CBAV compared to that for the tri-leaflet valve. The changes in geometry of CBAV resulted in large changes in in-plane strain and stress and our results suggest that geometrical variations may be a potential risk factor inducing calcific aortic stenosis frequently present in patients with CBAV.

A novel approach to in vivo mitral valve stress analysis

Three-dimensional (3-D) echocardiography allows the generation of anatomically correct and time-resolved geometric mitral valve (MV) models. However, as imaged in vivo, the MV assumes its systolic geometric configuration only when loaded. Customarily, finite element analysis (FEA) is used to predict material stress and strain fields rendered by applying a load on an initially unloaded model. Therefore, this study endeavors to provide a framework for the application of in vivo MV geometry and FEA to MV physiology, pathophysiology, and surgical repair. We hypothesize that in vivo MV geometry can be reasonably used as a surrogate for the unloaded valve in computational (FEA) simulations, yielding reasonable and meaningful stress and strain magnitudes and distributions. Three experiments were undertaken to demonstrate that the MV leaflets are relatively nondeformed during systolic loading: 1) leaflet strain in vivo was measured using sonomicrometry in an ovine model, 2) hybrid models of normal human MVs as constructed using transesophageal real-time 3-D echocardiography (rt-3DE) were repeatedly loaded using FEA, and 3) serial rt-3DE images of normal human MVs were used to construct models at end diastole and end isovolumic contraction to detect any deformation during isovolumic contraction. The average linear strain associated with isovolumic contraction was 0.02 ± 0.01, measured in vivo with sonomicrometry. Repeated loading of the hybrid normal human MV demonstrated little change in stress or geometry: peak von Mises stress changed by <4% at all locations on the anterior and posterior leaflets. Finally, the in vivo human MV deformed minimally during isovolumic contraction, as measured by the mean absolute difference calculated over the surfaces of both leaflets between serial MV models: 0.53 ± 0.19 mm. FEA modeling of MV models derived from in vivo high-resolution truly 3-D imaging is reasonable and useful for stress prediction in MV pathologies and repairs.

Biomechanics of the Aortic Valve in the Continuous Flow VAD-Assisted Heart

The biomechanics of the aortic valve are altered in patients with ventricular assist devices (VADs). During high VAD flow and low cardiac function, transvalvular pressure is high, and the aortic valve remains closed throughout the cardiac cycle. This condition has been linked to the development of aortic valve fusion and incompetence during VAD use. Thus, physicians try to maintain pulsatile flow to assure periodic valve opening. The aim of this study was to determine the extent of aortic valve opening and alterations in valve leaflet strain before and during VAD support using a specially designed mock loop. The results showed that diastole is prolonged during VAD use. In addition, there is a reduction in valve opening area, producing a VAD-related functional stenosis. The average leaflet strain increased during VAD support, primarily due to an increase in the minimum strain, during systole, rather than the maximum strain during diastole. The findings support our hypothesis that altered biomechanics in the VAD-assisted heart results in increased strain in the aortic valve leaflets, which can stimulate soft tissue remodeling. The implication for clinical use is that valve opening during parallel VAD flow is reduced compared with normal flow conditions. Consequently, current clinical practice for VAD patients may not be achieving sufficient valve opening to prevent changes such as fusion and incompetence.

152 Towards a Noninvasive Assessment of Valve Biology: Echocardiographic Measures of Mitral Leaflet Distensibility

Changes in mitral valve (MV) elasticity or distensibility occur in disease and directly affect MV function, contributing to MV prolapse (MVP) or flail vs restricted coaptation of stiffer leaflets in functional mitral regurgitation (FMR) and MV stenosis (MS). Recent studies suggest MV distensibility may be modified to reduce MR, but distensibility has only been measured in excised MVs. Our aim was to test the feasibility of obtaining a noninvasive measure of MV distensibility in patients by measuring systolic change in anterior leaflet length (ALL) or anterior leaflet strain; and to test the hypothesis that these measures vary in diseases with known altered MV elasticity. ALL was quantified in a long-axis view standardized by 3D echo in 80 patients: 20 each with normal hearts, MVP, FMR and MS. Distensibility was measured as end-systolic (ES) – end-diastolic (ED) total ALL normalized to an ED reference; and alternatively as mid-leaflet strain measured by tracking echo features. ALL was greater in all disease groups vs normal (p<.001). The maximum systolic increase in ALL relative to ED was 7.9 ± 7.4% in normals vs >2-fold higher (17.6 ± 11.2%) in MVP; it was 63-76% lower (2.9 ± 3.0%, 1.9 ± 3.1%) in FMR and MS, with comparable results for segmental AL strain (Table). Noninvasive echocardiographic measures of MV distensibility based on systolic changes in total length or segmental strain are feasible. Results are consistent with excised valve biomechanics, showing increased distensibility in MVP and decreased values in FMR and MS. Ultimately, these techniques have the potential to monitor response to new therapies that aim to improve MV biology and mechanics to reduce MR.ParameterunitNormMVPFMRMSALL systolemm.26.6 ± 2.739.7 ± 5.6*32.7 ± 4.1*33.4 ± 5.0*ALL diastolemm.24.5 ± 3.133.5 ± 3.2*32.0 ± 4.2*32.8 ± 4.9*ALL (sys-dia)/dia%7.9 ± 7.417.6 ± 11.2*2.9 ± 3.0*1.9 ± 3.1*SegL (ES-ED)/ED%9.1 ± 4.819.6 ± 10.9*3.2 ± 2.6*2.7 ± 3.7**P < 0.05 vs. Normals P < 0.05 vs. Normals