Native Leaflets Research Articles

Biologically Inspired Scaffolds for Heart Valve Tissue Engineering via Melt Electrowriting.

Heart valves are characterized to be highly flexible yet tough, and exhibit complex deformation characteristics such as nonlinearity, anisotropy, and viscoelasticity, which are, at best, only partially recapitulated in scaffolds for heart valve tissue engineering (HVTE). These biomechanical features are dictated by the structural properties and microarchitecture of the major tissue constituents, in particular collagen fibers. In this study, the unique capabilities of melt electrowriting (MEW) are exploited to create functional scaffolds with highly controlled fibrous microarchitectures mimicking the wavy nature of the collagen fibers and their load-dependent recruitment. Scaffolds with precisely-defined serpentine architectures reproduce the J-shaped strain stiffening, anisotropic and viscoelastic behavior of native heart valve leaflets, as demonstrated by quasistatic and dynamic mechanical characterization. They also support the growth of human vascular smooth muscle cells seeded both directly or encapsulated in fibrin, and promote the deposition of valvular extracellular matrix components. Finally, proof-of-principle MEW trileaflet valves display excellent acute hydrodynamic performance under aortic physiological conditions in a custom-made flow loop. The convergence of MEW and a biomimetic design approach enables a new paradigm for the manufacturing of scaffolds with highly controlled microarchitectures, biocompatibility, and stringent nonlinear and anisotropic mechanical properties required for HVTE.

Percutaneous Transcatheter MitralValveReplacement: First-in-Human Experience With a New Transseptal System.

Severe mitral regurgitation (MR) conveys significant morbidity and mortality, and surgical repair or replacement may not be a desirable option. The purpose of this study was to evaluate the feasibility of a percutaneous transseptal transcatheter mitral valve replacement (TMVR) system. This first-in-human study was conducted between August 2017 and August 2018. The system comprises a nitinol dock, which encircles the chordae tendineae, and a balloon-expandable transcatheter heart valve. The dock and transcatheter heart valve form an ensemble, with the native mitral valve leaflets secured in between, thereby abolishing MR. Key inclusion criteria were severe symptomatic MR and high surgical risk; exclusion criteria included left ventricular ejection fraction<30% or screening suggesting unfavorable anatomy. The primary endpoint was technical success as defined by Mitral Valve Academic Research Consortium (MVARC) criteria at completion of the index procedure. The secondary endpoint was freedom from mortality, stroke, and device dysfunction (MR grade >1, mitral gradient >6mmHg, left ventricular outflow tract gradient >20mmHg) at 30days. Ten patients with severe MR of various etiologies (4 degenerative, 4 functional, and 2 mixed) were treated. The device was successfully implanted and the primary endpoint was achieved in 9 of 10 patients (90%). By transesophageal echocardiography, total MR was reduced to≤ trivial in all implanted patients, and mean transmitral gradient was 2.3 ± 1.4mmHg. A pericardial effusion occurred in 1 patient: pericardiocentesis was performed, and the device was not implanted. Median length of hospital stay was 1.5days. At 30days, there was no stroke, myocardial infarction, rehospitalization, left ventricular outflow tract obstruction, device migration, embolization, or conversion to mitral surgery. One patient had recurrent regurgitation due to a paravalvular leak, treated with a closure device. All other treated patients had≤1+ MR. No patients died. Percutaneous transvenous transseptal TMVR is feasible and safe in patients with severe MR who are at high risk for mitral valve surgery. Further evaluation is warranted.

An alternative solution for patient with high risk of coronary obstruction underwent TAVI procedure using a novel second-generation device \u2013 a case series

BackgroundObstruction of the left or right coronary artery is a rare but lethal complication during transcatheter aortic valve implantation (TAVI). The new J-Valve™ prosthesis is a new second generation TAVI device which has several features to avoid the coronary obstruction such as low profile design and clip fixation of the native leaflets. The aim of this study is to report our initial experience of using this valve in treating patient with high risk factors for coronary obstruction during TAVI procedure.Case presentationThree high surgical risk patients (All females with 77, 76, and 75 years old) with symptomatic aortic stenosis were enrolled. All patients have the common feature of low coronary ostium height (< 10 mm) with narrowed aortic sinus (< 30 mm) on CT angiogram and marked leaflet calcification. Three 25 mm J-Valve prostheses were successfully implanted through trans-apical approach. No coronary obstruction was noted for these patients. Effective aortic open area was significantly increased after valve implantation (Preoperative 0.7, 0.7 and 0.65 cm2 – Postoperative 1.8, 1.9 and 2.0 cm2). Only one patient was noted to have trivial degree paravalvular leakage.ConclusionThe new J-Valve prosthesis is a new second generation TAVI device. This system may provide another safety treatment option for patient with high risk factor for coronary obstruction underwent TAVI procedure.

An Ovine Model of Mitral Bioprosthetic Valve Induced Left Ventricular Outflow Tract Obstruction Due to Systolic Anterior Motion of the Fully Retained Native Anterior Leaflet

Aim: Mitral valvular–ventricular interaction includes the following mechanisms. 1. Chordal annulo-papillary connection preventing excessive diastolic dilatation. 2. Systolic closure of the valve during isovolumic left ventricular (LV) contraction causes shortening of the LV long axis. This effect “turbo-charges” the systolic function of the LV. 3. The diastolic baffle effect of the anterior leaflet improves laminar flow through the LV. 4. The dynamic action of the annulus improves diastolic LV filling (“lusitropy”). In chordal-sparing valve replacement the anterior leaflet (AML) is excised or modified, sacrificing the systolic turbo-charging and the diastolic baffle support of LV function. These losses are sufficient to explain equal survival for mitral repair versus replacement in ischaemic cardiomyopathy despite a high recurrence rate of mitral incompetence in the repair group. However, full retention of the native anterior leaflet risks the development of LV outflow tract obstruction (LVOTO).

Behavior of valvular interstitial cells on trilayered nanofibrous substrate mimicking morphologies of heart valve leaflet

Heart valve tissue engineering could be an alternative to the current bioprosthetic heart valve that faces limitations especially in pediatric patients. However, heart valve tissue engineering has remained challenging because leaflets — the primary component of a heart valve — have three layers with three diverse orientations — circumferential, random and radial, respectively. In order to mimic the orientations, we first designed three novel collectors to fabricate three nanofibrous layers with those orientations from a polymeric biomaterial in an electrospinning system. Then, we devised a novel direct electrospinning technique to develop a unified trilayered nanofibrous (TN) substrate comprising those oriented layers. The TN substrate supported the growth and orientations of seeded porcine valvular interstitial cells (PVICs) and their deposited collagen fibrils. After one month culture, the obtained trilayered tissue construct (TC) exhibited increased tensile properties over its TN substrate. Most importantly, the developed TC did not show any sign of shrinkage. Gene expression pattern of the PVICs indicated the developing stage of the TC. Their protein expression pattern was quite similar to that of leaflets. Statement of SignificanceThis manuscript talks about development of a novel trilayered nanofibrous substrate mimicking the morphologies of a heart valve leaflet. It also describes culturing of valvular interstitial cells that reside in a leaflet, in the substrate and compares the behavior of the cultured cells with that in native leaflets in terms cell morphology, protein deposition and its orientation, and molecular signature. This study builds the groundwork for our future trilayered, tissue-engineered leaflet development. This research article would be of great interest to investigators and researchers in the field of cardiovascular tissue engineering especially in cardiac valve tissue engineering through biomaterial-based tissue engineering.

Meta-Analysis Comparing the Incidence of Infective Endocarditis Following Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement

Infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) is a rare but life-threatening complication. Paravalvular regurgitation, compression of native leaflets, and space between transcatheter valve prosthesis and native valves could dispose TAVI recipients at increased risk of IE compared with SAVR. To assess the comparative risk of IE between TAVI and SAVR, we performed a systematic review and meta-analysis. A literature search of PUBMED and EMBASE was performed to identify randomized controlled trials that reported the event rate of IE in both TAVI and SAVR. A Mantel-Haenszel method and a random-effects model was used to calculate the odds ratio (OR) and 95% confidence interval (CI). The studied outcomes were early (at 1-year), late (>1-year), and overall IE (postprocedure to longest follow-up) in TAVI versus SAVR. We performed subgroup analysis based on valve-type (self or balloon-expandable) and surgical risk (high or intermediate). A total of 4 studies with 3,761 (1,895 TAVI and 1,866 SAVR) patients were included. The incidence of early IE, (3 studies, 0.86% vs 0.73%, OR 1.17, 95% CI 0.51 to 2.65, p = 0.71, I2 = 0%), late IE (mean follow-up 2.0 years) (3 studies, 1.3% vs 0.6%, OR 1.85, 95% CI 0.81 to 4.20, p = 0.42, I2 = 0%), and overall IE (mean follow-up 3.4 years) (4 studies, 2.0% vs 1.3%, OR 1.44, 95% CI 0.85 to 2.43, p = 0.18, I2 = 0%) was similar between TAVI and SAVR. Subgroup analysis suggested that in intermediate surgical risk cohort, there was a trend toward increased risk of overall IE in TAVI (2.3% in TAVI and 1.2% in SAVR, OR 1.92, 95% CI 0.99 to 3.72, p = 0.05 I2 = 0%). In this meta-analysis, we did not find an increased risk of IE in TAVI compared with SAVR. Appropriate preventative measure and early recognition of IE in these cohorts are important.

Improved long-term durability of allogeneic heart valves in the orthotopic sheep model.

Frozen cryopreservation (FC) with the vapour phase of liquid nitrogen storage (-135°C) is a standard biobank technique to preserve allogeneic heart valves to enable a preferable allograft valve replacement in clinical settings. However, their long-term function is limited by immune responses, inflammation and structural degeneration. Ice-free cryopreserved (IFC) valves with warmer storage possibilities at -80°C showed better matrix preservation and decreased immunological response in preliminary short-term in vivo studies. Our study aimed to assess the prolonged performance of IFC allografts in an orthotopic pulmonary sheep model. FC (n = 6) and IFC (n = 6) allografts were transplanted into juvenile Merino sheep. After 12 months of implantation, functionality testing via 2-dimensional echocardiography and histological analyses was performed. In addition, multiphoton autofluorescence imaging and Raman microspectroscopy analysis were applied to qualitatively and quantitatively assess the matrix integrity of the leaflets. Six animals from the FC group and 5 animals from the IFC group were included in the analysis. Histological explant analysis showed early inflammation in the FC valves, whereas sustainable, fully functional, devitalized acellular IFC grafts were obtained. IFC valves showed excellent haemodynamic data with fewer gradients, no pulmonary regurgitation, no calcification and acellularity. Structural remodelling of the leaflet matrix structure was only detected in FC-treated tissue, whereas IFC valves maintained matrix integrity comparable to that of native controls. The collagen crimp period and amplitude and elastin structure were significantly different in the FC valve cusps compared to IFC and native cusps. Collagen fibres in the FC valves were less aligned and straightened. IFC heart valves with good haemodynamic function, reduced immunogenicity and preserved matrix structures have the potential to overcome the known limitations of the clinically applied FC valve.

Commissural Alignment of Bioprosthetic Aortic Valve and Native Aortic Valve Following Surgical and Transcatheter Aortic Valve Replacement and its Impact on Valvular Function and Coronary Filling

ObjectivesThe aim of this study was to assess the commissural alignment between bioprosthetic and native aortic valve leaflets following surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) and to investigate its impact on valvular function and coronary filling. BackgroundExpansion and geometry have been shown to affect leaflets of implanted transcatheter aortic bioprosthesis, but commissural alignment has not been studied. MethodsPre- and post-procedural multidetector computed tomography (MDCT) of 28 SAVR patients and 212 TAVR patients were analyzed. Commissural alignment between the bioprosthetic (post) and native (pre) aortic valves was categorized as aligned (0° to 15° angle deviation) or as mild (15° to 30°), moderate (30° to 45°), or severe (45° to 60°) commissural misalignment (CMA). ResultsWith SAVR, 27 of 28 cases (96%) were aligned and 1 had mild CMA. For all types of transcatheter heart valves (THVs), there was random valve implantation with regard to commissural alignment: 22% of THVs were aligned, 25% had mild CMA, 22% had moderate CMA, and 31% had severe CMA. The degree of commissural alignment was not associated with a difference in transvalvular gradient, paravalvular aortic regurgitation, or simulated coronary filling. However, there was a significantly higher rate of mild central aortic regurgitation in those THVs with moderate or greater CMA compared with those THV with mild or less CMA (7.8% vs. 1.1%; p = 0.03). ConclusionsCommissural alignment is excellent in case of SAVR but random in case of TAVR. There is no association between CMA and transvalvular gradient or coronary filling; however, there is a significantly higher rate of mild central aortic regurgitation in case of moderate or greater CMA.

The Rare Complication of Transcatheter Mitral Valve-in-Ring Procedure: Not Only Left Ventricular Outflow Tract Obstruction Counts

The transcatheter mitral valve-in-ring (VIR) procedure can trigger more than just left ventricular outflow tract obstruction from permanent displacement of the native anterior mitral leaflet [(1)][1]. A 74-year-old man was referred for VIR after pulmonary edema due to severe mitral regurgitation.

Templates of flat pericardial patterns for precise aortic cusp extension

Background Aortic cusp extension is a subjective and operator-dependent technique. In order to facilitate surgical correction of aortic cusp retraction and reestablishment of adequate cusp coaptation, we sought to develop new templates that can be used to cut flat pericardial sheets into precise cusp extension patches. Methods Each template was designed as a two-dimensional unwrap of the natural geometry of a complete aortic cusp, and a series of templates were made available to correspond with all potential aortic cusp sizes. Based on these templates, aortic cusp extension was performed in 2 patients (aged 54 and 43 years) with significant retraction of the noncoronary aortic cusps and severe aortic valve insufficiency. In each patient, extension of the retracted native noncoronary cusp was undertaken using a bovine pericardial patch that matched the size of adjacent nondiseased native aortic cusps. Results Achieving geometrically perfect aortic cusp extensions was uncomplicated, and intraoperative transesophageal echocardiography confirmed satisfactory aortic valve repairs (aortic insufficiency < 1+ and low transvalvular gradients). Early follow-up transthoracic echocardiography confirmed that all valve cusps met at similar heights in the aortic root, and that their excursions were virtually identical. Conclusions The newly designed templates can be used to cut flat pericardial sheets into exact cusp extension patches, and initial clinical experience indicates that they are useful in performing precise aortic cusp extension procedures and restoring adequate aortic valve competence.

Biomaterial characterization of off-the-shelf decellularized porcine pericardial tissue for use in prosthetic valvular applications.

Fixed pericardial tissue is commonly used for commercially available xenograft valve implants, and has proven durability, but lacks the capability to remodel and grow. Decellularized porcine pericardial tissue has the promise to outperform fixed tissue and remodel, but the decellularization process has been shown to damage the collagen structure and reduce mechanical integrity of the tissue. Therefore, a comparison of uniaxial tensile properties was performed on decellularized, decellularized‐sterilized, fixed, and native porcine pericardial tissue versus native valve leaflet cusps. The results of non‐parametric analysis showed statistically significant differences (p < .05) between the stiffness of decellularized versus native pericardium and native cusps as well as fixed tissue, respectively; however, decellularized tissue showed large increases in elastic properties. Porosity testing of the tissues showed no statistical difference between decellularized and decell‐sterilized tissue compared with native cusps (p > .05). Scanning electron microscopy confirmed that valvular endothelial and interstitial cells colonized the decellularized pericardial surface when seeded and grown for 30 days in static culture. Collagen assays and transmission electron microscopy analysis showed limited reductions in collagen with processing; yet glycosaminoglycan assays showed great reductions in the processed pericardium relative to native cusps. Decellularized pericardium had comparatively low mechanical properties among the groups studied; yet the stiffness was comparatively similar to the native cusps and demonstrated a lack of cytotoxicity. Suture retention, accelerated wear, and hydrodynamic testing of prototype decellularized and decell‐sterilized valves showed positive functionality. Sterilized tissue could mimic valvular mechanical environment in vitro, therefore making it a viable potential candidate for off‐the‐shelf tissue‐engineered valvular applications.

Implanted In-Body Tissue-Engineered Heart Valve Can Adapt the Histological Structure to the Environment.

Tissue-engineered heart valves (TEHVs) are expected to be viable grafts. However, it is unknown whether they transit their histological structure after implantation. We developed a novel autologous TEHV (named stent biovalve) for transcatheter implantation, using in-body tissue engineering based on a tissue encapsulation phenomenon. In this study, a time-course histological transition of implanted biovalves was investigated in goats. Three types of stent biovalves were prepared by 2 month embedding of plastic molds mounted with metallic stents, in the subcutaneous spaces. After extracting the molds with tissue and removing the molds only, stent biovalves were constituted entirely from the connective tissues. Stent biovalves were implanted in the aortic or pulmonary valve position of other goats with transcatheter technique. In each animal, the stent biovalve was explanted at 1 month step (from 1 to 6 months) or as long as possible. Total 12 goats (five for aortic and seven for pulmonary) were successfully implanted. The maximum duration became 19 months as a result. Even then the leaflets of the biovalves kept their shape and elasticity, and neither calcification nor thrombi were observed in any cases and duration. Histology showed the recipients' cells covering the laminar surface of the leaflets like the endothelium even after 1 month. The cells have also migrated in the leaflets gradually and finally constructed characteristic 3 layered tissues like native leaflets. Implanted stent biovalves can adapt their histological structure to the environment. They have a potential as viable grafts keeping better function and biocompatibility.

Delayed Left Main Narrowing From the Native Left Aortic Valve Leaflet After Transcatheter Aortic Valve Replacement With the Lotus Valve: A Successful Intervention for a Novel Complication

An 89-year-old woman with severe symptomatic aortic valve stenosis and poor surgical candidacy underwent transcatheter aortic valve replacement (TAVR) with a 23-mm Lotus valve (Boston Scientific, Marlborough, Massachusetts). Preoperative computed tomography demonstrated aortic sinuses and coronary

Mid-term function and remodeling potential of tissue engineered tricuspid valve: Histology and biomechanics

ObjectiveTricuspid valve reconstruction using a small intestinal submucosal porcine extracellular matrix (ECM) tube graft is hypothesized to be durable for six months and show signs of recellularization and growth potential. The purpose was to histologically and biomechanically test ECM valves before and after six months of implantation in pigs for comparison with native valves. MethodsTen 60 kg pigs were included, which survived tricuspid valve tube graft insertion. Anterior and septal tricuspid leaflets were explanted from all animals surviving more than one month and examined histologically (n = 9). Endothelialization, collagen content, mineralization, neovascularization, burst strength and tensile strength were determined for native valves (n = 5), ECM before implantation (n = 5), and ECM after six months (n = 5). ResultsCollagen density was significantly larger in ECM at implantation (baseline) compared to native leaflet tissue (0.3 ± 0.02 mg/mm3 vs. 0.1 ± 0.03 mg/mm3, p < .0001), but collagen density decreased and reached native leaflet collagen content, six months after ECM implantation (native vs. ECM valve at six months: 0.1 ± 0.03 mg/mm3 vs. 0.2 ± 0.05 mg/mm3, p = .8).Histologically, ECM valves showed endothelialization, host cell infiltration and structural collagen organization together with elastin generation after six months, indicating tissue remodeling and -engineering together with gradual development of a close-to-native leaflet structure without foreign body response. ConclusionsECM tricuspid tube grafts were stronger than native leaflet tissue. Histologically, the acellular ECM tube grafts showed evidence of constructive tissue remodeling with endothelialization and connective tissue organization. These findings support the concept of tissue engineering and recellularization, which are prerequisites for growth.

Clinical outcomes of coronary occlusion following transcatheter aortic valve replacement: A systematic review.

Coronary occlusion (CO) is a rare but serious complication following transcatheter aortic valve replacement (TAVR) with limited published data. We sought to evaluate the immediate and short-term outcomes of CO complicating TAVR. Studies, including case reports, case series and original articles published from 2002 to 2016 describing CO following TAVR were identified with a systematic electronic search using the PRISMA Statement. Only studies reporting data on demographic and procedural characteristics, management and follow up outcomes were analyzed. A total of 40 publications describing 96 patients (86 native, 10 bioprosthetic) were identified. Mean age was 83±7years and most (81%) were females. The mean logistic EuroSCORE and STS score was 23.5±14.6% and 9.1±3.2% respectively. TAVR access site was transfemoral in 73% and a balloon expandable valve was used in 78%. Among those with LCA occlusion, the mean LCA ostium height was 10.1±1.8mm while the mean RCA ostium height was 10.4±2.0mm among those with RCA occlusion. CO frequently involved the left main coronary artery (80%) and the most common mechanism was displacement of native valve leaflet (60%), and most cases occurred within 1-hour post-implantation (88%). Percutaneous coronary intervention was attempted in 82 patients and successful in 89%. Procedural death was 10.4%. CO following TAVR in native aortic valve stenosis was associated with a 30-day mortality rate of 35.3%. CO following TAVR is associated with a high procedural and 30-day mortality rate despite aggressive resuscitative measures including percutaneous coronary intervention.

Fully-coupled fluid-structure interaction simulation of the aortic and mitral valves in a realistic 3D left ventricle model.

In this study, we present a fully-coupled fluid-structure interaction (FSI) framework that combines smoothed particle hydrodynamics (SPH) and nonlinear finite element (FE) method to investigate the coupled aortic and mitral valves structural response and the bulk intraventricular hemodynamics in a realistic left ventricle (LV) model during the entire cardiac cycle. The FSI model incorporates valve structures that consider native asymmetric leaflet geometries, anisotropic hyperelastic material models and human material properties. Comparison of FSI results with subject-specific echocardiography data demonstrates that the SPH-FE approach is able to quantitatively predict the opening and closing times of the valves, the mitral leaflet opening and closing angles, and the large-scale intraventricular flow phenomena with a reasonable agreement. Moreover, comparison of FSI results with a LV model without valves reveals substantial differences in the flow field. Peak systolic velocities obtained from the FSI model and the LV model without valves are 2.56 m/s and 1.16 m/s, respectively, compared to the Doppler echo data of 2.17 m/s. The proposed SPH-FE FSI framework represents a further step towards modeling patient-specific coupled LV-valve dynamics, and has the potential to improve our understanding of cardiovascular physiology and to support professionals in clinical decision-making.

INFLUENCE OF LEAFLET’S MATRIX STIFFNESS AND FIBER ORIENTATION ON THE OPENING DYNAMICS OF A PROSTHETIC TRILEAFLET HEART VALVE

Biological valves are employed for aortic valve substitution since a long time but there is a growing effort toward the development of new engineered tissues, in which the complex mechanical response of native leaflets is replicated using composite materials consisting of a soft matrix with embedded reinforcing fibers. The main goal of the present study is to investigate the influence that variations on fiber orientation and matrix stiffness may have on valve dynamics. To this aim, a fluid–structure interaction (FSI) model of a trileaflet valve was implemented in which the opening phase was simulated and leaflet matrix stiffness and fiber orientation were varied in the framework of an anisotropic hyperelastic strain energy function. Results show that both parameters may affect significantly transvalvular pressure gradient and effective orifice area (EOA). For the opening phase of the valve examined, less favorable flow conditions were found when preferred fiber orientation is circumferential, due to lower maximum EOA achievable. Such configuration in combination with stiffer matrix may result in significant degradation of valve performances. Overall fiber orientation can potentially be taylored to optimize valve dynamics, provided also structural aspects that may be prominent in the closure phase, are considered.

Fabrication of a matrigel–collagen semi-interpenetrating scaffold for use in dynamic valve interstitial cell culture

The study of heart valve homeostatic and disease mechanisms are often limited by the challenges in simulating the in vivo milieu, where valve cells are surrounded by the extracellular matrix in a three-dimensional (3D) environment and experience multiple dynamic mechanical forces. Type I collagen is typically the most common 3D matrix used to culture valve cells in vitro. Unfortunately, this material has poor mechanical behavior due to an inherent propensity to compact significantly, unlike native valve leaflets. We hypothesized that incorporation of matrigel, which contains other heart valve-relevant matrix components such as type IV collagen and sulfated proteoglycans, to type I collagen would provide an appropriate physiological milieu for in vitro valve interstitial cell culture. Different semi-interpenetrating mixtures of collagen type I and matrigel were prepared and a thorough characterization of their physical, mechanical and biocompatibility properties was performed. We observed that the matrigel–collagen hydrogel was porous and degradable with tunable swelling behavior. Incorporation of matrigel not only enhanced the mechanical behavior of the composite hydrogel but also presented the cultured valve interstitial cells with a more enriched extracellular matrix network for in vitro culture. We showed that cells cultured in the composite hydrogel had comparable viability, proliferation and cell phenotype as compared with those in a collagen only gel. Importantly, the composite hydrogel was also amenable to in vitro cyclic stretching culture for 48 h. Overall, we report here the potential use of the matrigel–collagen hydrogel as a three dimensional scaffold for the dynamic mechanical culture of valve interstitial cells in vitro.

The Fluid Mechanics of Transcatheter Heart Valve Leaflet Thrombosis in the Neosinus.

Transcatheter heart valve (THV) thrombosis has been increasingly reported. In these studies, thrombus quantification has been based on a 2-dimensional assessment of a 3-dimensional phenomenon. Postprocedural, 4-dimensional, volume-rendered CT data of patients with CoreValve, Evolut R, and SAPIEN 3 transcatheter aortic valve replacement enrolled in the RESOLVE study (Assessment of Transcatheter and Surgical Aortic Bioprosthetic Valve Dysfunction With Multimodality Imaging and Its Treatment with Anticoagulation) were included in this analysis. Patients on anticoagulation were excluded. SAPIEN 3 and CoreValve/Evolut R patients with and without hypoattenuated leaflet thickening were included to study differences between groups. Patients were classified as having THV thrombosis if there was any evidence of hypoattenuated leaflet thickening. Anatomic and THV deployment geometries were analyzed, and thrombus volumes were computed through manual 3-dimensional reconstruction. We aimed to identify and evaluate risk factors that contribute to THV thrombosis through the combination of retrospective clinical data analysis and in vitro imaging in the space between the native and THV leaflets (neosinus). SAPIEN 3 valves with leaflet thrombosis were on average 10% further expanded (by diameter) than those without (95.5±5.2% versus 85.4±3.9%; P<0.001). However, this relationship was not evident with the CoreValve/Evolut R. In CoreValve/Evolut Rs with thrombosis, the thrombus volume increased linearly with implant depth (R2=0.7, P<0.001). This finding was not seen in the SAPIEN 3. The in vitro analysis showed that a supraannular THV deployment resulted in a nearly 7-fold decrease in stagnation zone size (velocities <0.1 m/s) when compared with an intraannular deployment. In addition, the in vitro model indicated that the size of the stagnation zone increased as cardiac output decreased. Although transcatheter aortic valve replacement thrombosis is a multifactorial process involving foreign materials, patient-specific blood chemistry, and complex flow patterns, our study indicates that deployed THV geometry may have implications on the occurrence of thrombosis. In addition, a supraannular neosinus may reduce thrombosis risk because of reduced flow stasis. Although additional prospective studies are needed to further develop strategies for minimizing thrombus burden, these results may help identify patients at higher thrombosis risk and aid in the development of next-generation devices with reduced thrombosis risk.

MitraClip removal: surgical techniques to preserve native mitral valve leaflets.

Transcatheter valve procedures are wide-spreading techniques for the treatment of heart valves pathologies. In case of implantation failure, the transcatheter device often needs to be removed. This procedure, which can alter the biological structure integrity, can limit the option available for the subsequent traditional surgery. One of the most popular devices for transcatheter mitral valve repair is the MitraClip system. In this work, we describe 2 different techniques for the surgical removal of MitraClip. These techniques aim to preserve the valve leaflets integrity, to allow for subsequent mitral valve surgical repair.