A calcified polymeric valve for valve-in-valve applications

The prevalence of aortic valve stenosis (AS) is increasing in the aging society. More recently, novel treatments and devices for AS, especially transcatheter aortic valve replacement (TAVR) have significantly changed the therapeutic approach to this disease. Research and development related to TAVR require testing these devices in the calcified heart valves that closely mimic a native calcific valve. However, no animal model of AS has yet been available. Alternatively, animals with normal aortic valve that are currently used for TAVR experiments do not closely replicate the aortic valve pathology required for proper testing of these devices. To solve this limitation, for the first time, we developed a novel polymeric valve whose leaflets possess calcium hydroxyapatite inclusions immersed in them. This study reports the characteristics and feasibility of these valves. Two types of the polymeric valve, i.e., moderate and severe calcified AS models were developed and tested by deploying a transcatheter valve in those and measuring the related hemodynamics. The valves were tested in a heart flow simulator, and were studied using echocardiography. Our results showed high echogenicity of the polymeric valve, that was correlated to the severity of the calcification. Aortic valve area of the polymeric valves was measured, and the severity of stenosis was defined according to the clinical guidelines. Accordingly, we showed that these novel polymeric valves closely mimic AS, and can be a desired cost-saving solution for testing the performance of the transcatheter aortic valve systems in vitro.     

High resolution three-dimensional strain mapping of bioprosthetic heart valves using digital image correlation

Transcatheter aortic valve replacement (TAVR) is a safe and effective treatment option for patients deemed at high and intermediate risk for surgical aortic valve replacement. Similar to surgical aortic valves (SAVs), transcatheter aortic valves (TAVs) undergo calcification and mechanical wear over time. However, to date, there have been limited publications on the long-term durability of TAV devices. To assess longevity and mechanical strength of TAVs in comparison to surgical bioprosthetic valves, three-dimensional deformation analysis and strain measurement of the leaflets become an inevitable part of the evaluation. The goal of this study was to measure and compare leaflet displacement and strain of two commonly used TAVs in a side-by-side comparison with a commonly used SAV using a high-resolution digital image correlation (DIC) system. 26-mm Edwards SAPIEN 3, 26-mm Medtronic CoreValve, and 25-mm Carpentier-Edwards PERIMOUNT Magna surgical bioprosthesis were examined in a custom-made valve testing apparatus. A time-varying, spatially uniform pressure was applied to the leaflets at different loading rates. GOM ARAMIS® software was used to map leaflet displacement and strain fields during loading and unloading. High displacement regions were found to be at the leaflet belly region of the three bioprosthetic valves. In addition, the frame of the surgical bioprosthesis was found to be remarkably flexible, in contrary to CoreValve and SAPIEN 3 in which the stent was nearly rigid under a similar loading condition. The experimental DIC measurements can be used to characterize the anisotropic materiel behavior of the bioprosthetic heart valve leaflets and validate heart valve computational simulations.     

In vitro assessment of the influence of aortic annulus ovality on the hydrodynamic performance of self-expanding transcatheter heart valve prostheses

Background

Although CT-studies as well as intraoperative analyses have described broad anatomic variations of the aortic annulus, which is predominantly found non-circular, commercially available transcatheter aortic heart valve prostheses are circular. In this study, we hypothesize that the in vitro hydrodynamic function of a self-expanding transcatheter heart valve (Medtronic CoreValve^®) assessed in an oval compartment representing the aortic annulus will differ from the conventionally used circular compartment.

Methods

Medtronic CoreValve^® prostheses were tested in specifically designed and fabricated silicone compartments with three degrees of defined ovalities. The measurements were performed in a left heart simulator at three different flow rates. In this setting, regurgitation flow, effective orifice area, and systolic pressure gradient across the valve were determined. In addition, high speed video recordings were taken to investigate leaflet kinematics.

Results

The pressure difference across the prosthesis increased with rising ovality. The effective orifice areas were only slightly impacted. The analyses of the regurgitation showed minor changes and partially lower regurgitation when switching from round to slightly oval settings, followed by strong increases for further ovalization. The high speed videos show minor central leakage and impaired leaflet apposition for strong ovalities, but no leaflet/stentframe contact in any setting.

Conclusion

This study quantifies the influence of oval expansion of transcatheter heart valve prostheses on their hydrodynamic performance. While slight ovalities were well tolerated by a self-expanding prosthesis, more significant ovality led to worsening of prosthesis function and regurgitation.     

Outcome of transcatheter aortic valve replacement in patients over 85 years of age versus patients aged 85 and younger

IntroductionThe Dutch general population is aging rapidly. Many of these patient are fit and eligible for TAVR. However, studies on outcome in older versus younger patients are scant.Material and methodsA single-centre retrospective study comparing patients older and younger than age 85 on outcome.Results190 patients underwent TAVR: 136 were aged 85 or younger (U85), 54 were older than 85 (O85). The U85 group had more men (U85: 71 [52.2%] vs O85: 19 [35.2%]; p = 0.034), a higher incidence of diabetes (U85: 36 [26.5%] vs O85: 3 [5.6%]; p = 0.001) and atrial fibrillation (U85: 35 [25.7%] vs O85: 5 [9.3%]; p = 0.03) and a higher body mass index (U85: 27.5 [± 5.24] vs O85: 26 [± 3.78]; p = 0.027). In the O85 group there was a lower estimated glomerular filtration rate (O85: 50.28 [± 15.32] ml/min vs U85: 65.25 [± 29.97] ml/min; p = 0.012). There was no difference in 30-day mortality (U85: 6 [4.4%] vs O85: 3 [5.6%]) and 1‑year mortality (U85 9 [6.6%] vs O85 3 [5.6%]) (p = 0.521). There was an equal amount of new onset permanent left bundle branch block (U85: 38 [27.9%] vs O85: 14 [25.9%]; p = 0.896) and permanent pacemaker implantation (U85: 28 [20.6%] vs O85: 28 [20.6%]; p = 0.748). There was no difference in bleeding events (p = 0.469), vascular complications (p = 0.195) or moderate/severe regurgitation (p = 0.972). The U85 group had a slightly longer admission duration (U85 6.29 [± 5.289] days vs O85 5.98 [± 3.328] days (p = 0.037)).ConclusionTAVR in patients over 85 years of age has excellent outcome, comparable to those aged 85 and younger.     

Physical activity,dietary intake and quality of life during COVID-19 lockdown in patients awaiting transcatheter aortic valve implantation

BackgroundThe COVID-19 pandemic has led to a national lockdown in the Netherlands, which also affected transcatheter aortic valve implantation (TAVI) patients. The objective of the study was to describe physical activity, dietary intake and quality of life (QoL) in patients on the waiting list for TAVI pre-lockdown and during lockdown.MethodsConsecutive patients awaiting TAVI at the Amsterdam University Medical Centers, the Netherlands were included. Measurements were self-reported effect of lockdown, physical activity, dietary intake and QoL.ResultsIn total, 58 patients (median age 80, interquartile range (IQR) 76–84, 45% female) were observed pre-lockdown and 16 patients (median age 78, IQR 76–82, 25% female) during lockdown. Ten of the 16 patients during lockdown reported a decline in physical activity. However, we observed a median number of 5861 steps a day (IQR 4579–7074) pre-lockdown and 8404 steps a day (IQR 7653–10,829) during lockdown. Median daily protein intake was 69 g (IQR 59–82) pre-lockdown and 90 g (IQR 68–107) during lockdown. Self-rated health on a visual analogue scale was 63 points (IQR 51–74) pre-lockdown and 73 points (IQR 65–86) during lockdown.ConclusionsMore than half of the patients during lockdown reported less physical activity, while we observed a higher number of steps a day, a similar dietary intake and a higher QoL. Therefore, patients on the TAVI waiting list appeared to be able to cope with the lockdown measures.     

An in vitro model quantifying the effect of calcification on the tissue–stent interaction in a stenosed aortic root

Transcatheter Aortic Valves rely on the tissue-stent interaction to ensure that the valve is secured within the aortic root. Aortic stenosis presents with heavily calcified leaflets and it has been proposed that this calcification also acts to secure the valve, but this has never been quantified. In this study, we developed an in vitro calcified aortic root model to quantify the role of calcification on the tissue-stent interaction. The in vitro model incorporated artificial calcifications affixed to the leaflets of porcine aortic heart valves. A self-expanding nitinol braided stent was deployed into non-calcified and artificially calcified porcine aortic roots and imaged by micro computed tomography. Mechanical tests were then conducted to dislodge the stent from the aortic root and it was found that, in the presence of calcification, there was a significant increase in pullout force (8.59 ± 3.68 N vs. 2.84 ± 1.55 N p = 0.045), stent eccentricity (0.05 ± 0.01 vs. 0.02 ± 0.01, p = 0.049), and coefficient of friction between the stent and aortic root (0.36 ± 0.12 vs. 0.09 ± 0.05, p = 0.018), when compared to non-calcified roots. This study quantifies for the first time the impact of calcification on the friction between the aortic tissue and transcatheter aortic valve stent, showing the role of calcification in anchoring the valve stent in the aortic root.     

Population-specific material properties of the implantation site for transcatheter aortic valve replacement finite element simulations

Patient-specific computational models are an established tool to support device development and test under clinically relevant boundary conditions. Potentially, such models could be used to aid the clinical decision-making process for percutaneous valve selection; however, their adoption in clinical practice is still limited to individual cases. To be fully informative, they should include patient-specific data on both anatomy and mechanics of the implantation site. In this work, fourteen patient-specific computational models for transcatheter aortic valve replacement (TAVR) with balloon-expandable Sapien XT devices were retrospectively developed to tune the material parameters of the implantation site mechanical model for the average TAVR population.Pre-procedural computed tomography (CT) images were post-processed to create the 3D patient-specific anatomy of the implantation site. Balloon valvuloplasty and device deployment were simulated with finite element (FE) analysis. Valve leaflets and aortic root were modelled as linear elastic materials, while calcification as elastoplastic. Material properties were initially selected from literature; then, a statistical analysis was designed to investigate the effect of each implantation site material parameter on the implanted stent diameter and thus identify the combination of material parameters for TAVR patients.These numerical models were validated against clinical data. The comparison between stent diameters measured from post-procedural fluoroscopy images and final computational results showed a mean difference of 2.5 ± 3.9%. Moreover, the numerical model detected the presence of paravalvular leakage (PVL) in 79% of cases, as assessed by post-TAVR echocardiographic examination.The final aim was to increase accuracy and reliability of such computational tools for prospective clinical applications.     

Transcatheter aortic valve replacement: impact of pre-procedural FEops HEARTguide assessment on device size selection in borderline annulus size cases

ObjectivesThe aim of this study is to evaluate device size selection in patients within the borderline annulus size range undergoing transcatheter aortic valve replacement (TAVR) and to assess if pre-procedural patient-specific computer simulation will lead to the selection of a different device size than standard of care.BackgroundIn TAVR, appropriate device sizing is imperative. In borderline annulus size cases no standardised technique for tailored device size selection is currently available. Pre-procedural patient-specific computer simulation can be used, predicting the risk for paravalvular leakage (PVL) and need for permanent pacemaker implantation (PPI).MethodsIn this multicentre retrospective study, 140 patients in the borderline annulus size range were included. Hereafter, device size selection was left to the discretion of the operator. After TAVR, in 24 of the 140 patients, patient-specific computer simulation calculated the most appropriate device size expected to give the lowest risk for PVL and need for PPI. In these 24 patients, device size selection based on patient-specific computer simulation was compared with standard-of-care device size selection relying on a standardised matrix (Medtronic).ResultsIn a significant proportion of the 140 patients (26.4%) a different device size than recommended by the matrix was implanted. In 10 of the 24 patients (41.7%) in whom a computer simulation was performed, a different device size was recommended than by means of the matrix.ConclusionsDevice size selection in patients within the borderline annulus size range is still ambiguous. In these patients, patient-specific computer simulation is feasible and can contribute to a more tailored device size selection.     

Effect of zooplankton availability on the rates of photosynthesis, and tissue and skeletal growth in the scleractinian coral Stylophora pistillata

This work investigated the effect of light and feeding on tissue composition as well as on rates of photosynthesis and calcification in the zooxanthellae (zoox) scleractinian coral, Stylophora pistillata. Microcolonies were maintained at three different light levels (80, 200, 300 μmol m⁻² s⁻¹) and subjected to two feeding regimes (starved and fed) over 9 weeks. Corals were fed both natural plankton and Artemia salina nauplii four times a weeks and samplings were made after 2, 5, and 9 weeks. Results confirmed that feeding enhances coral growth rate and increases both the dark and light calcification rates. These rates were 50-75% higher in fed corals (FC; 60±20 and 200±40 nmol Ca²⁺ cm⁻² h⁻¹ for dark and light calcification, respectively) compared to control corals (CC; 30±9 and 124±23 nmol Ca²⁺ cm⁻² h⁻¹). The dark calcification rates, however, were four times lower than the rates of light calcification (independent of trophic status). After 5 weeks, chlorophyll a (chl-a) concentrations were four to seven times higher in fed corals (7-21 μg cm⁻²) than in control corals (2-5 μg cm⁻²). The amount of protein was also significantly higher in fed corals (2.11-2.50 mg cm⁻²) than in control corals (1.08-1.52 mg cm⁻²). Rates of photosynthesis in fed corals were 2-10 times higher (1.24±0.75 μmol O₂ h⁻¹ cm⁻²) than those measured in control corals (0.20±0.08 μmol O₂ h⁻¹ cm⁻²).     

Identification and characterization of cells with high angiogenic potential and transitional phenotype in calcific aortic valve

Recent data suggest that angiogenesis plays an important role in the pathogenesis of valvular disease. However, the cellular mechanisms underlying this process remain unknown. This study aimed at identifying and characterizing the cellular components responsible for pathological neovascularization in calcific aortic valves (CAV). Immunohistochemical analysis of uncultured CAV tissues revealed that smooth muscle alpha-actin (alpha-SMA)-positive cells, which coexpressed Tie-2 and vascular endothelial growth factor receptor-2 (VEGFR-2), can be identified prior to the initiation of capillary-like tube formation. In a second step, leaflets of CAV and non-calcific aortic valves (NCAV) were cultured and the cells involved in capillary-like tube formation were isolated. The majority of these cells displayed the same phenotype as non-cultured cells identified in CAV tissues, i.e., expression of alpha-SMA, Tie-2, and VEGFR-2. In comparison to cells isolated from cultures of NCAV leaflets, these cells showed enhanced angiogenic activity as demonstrated by migration and tube assays. The coexpression of VEGFR-2 and Tie-2 together with alpha-SMA suggests both endothelial and mesenchymal properties of the angiogenically activated cells involved in valvular neovascularization. Hence, our findings might provide new insights into the process of pathological angiogenesis in cardiac valves.     

The effect of aortic valve replacement on quality of life in symptomatic patients with severe aortic stenosis

Background

Although symptomatic patients with severe aortic stenosis have a high disease burden and guidelines recommend aortic valve replacement, many are treated conservatively. This study describes to what extent quality of life is changed by aortic valve replacement relative to conservative treatment.

Methods

This observational study followed 132 symptomatic patients with severe aortic stenosis who were subjected to an SF-36v2TM Health Survey.

Results

At baseline 84 patients were treated conservatively, 48 were referred for aortic valve replacement. In the conservatively treated group 15 patients died during a mean follow-up of 18 months (Kaplan-Meier survival was 85 % and 72 % at one and 2 years respectively) and 22 patients crossed over to the surgical group. Of the resulting 70 patients in the surgical group 3 patients died during a mean follow-up of 11 months (survival 95 % at 1 year). Physical functioning, vitality and general health improved significantly 1 year after aortic valve replacement. In conservatively treated patients physical quality of life deteriorated over time while general health, vitality and social functioning showed a declining trend. Mental health remained stable in both groups.

Conclusions

Aortic valve replacement improves physical quality of life, general health and vitality in patients with symptomatic severe aortic stenosis. Besides having a low life expectancy, conservatively treated patients experience deterioration of physical quality of life. Health surveys such as the SF-36v2TM can be valuable tools in monitoring the burden of disease for an individual patient and offer additional help in treatment decisions.     

Three-dimensional macro-scale assessment of regional and temporal wall shear stress characteristics on aortic valve leaflets

The aortic valve (AV) achieves unidirectional blood flow between the left ventricle and the aorta. Although hemodynamic stresses have been shown to regulate valvular biology, the native wall shear stress (WSS) experienced by AV leaflets remains largely unknown. The objective of this study was to quantify computationally the macro-scale leaflet WSS environment using fluid–structure interaction modeling. An arbitrary Lagrangian–Eulerian approach was implemented to predict valvular flow and leaflet dynamics in a three-dimensional AV geometry subjected to physiologic transvalvular pressure. Local WSS characteristics were quantified in terms of temporal shear magnitude (TSM), oscillatory shear index (OSI) and temporal shear gradient (TSG). The dominant radial WSS predicted on the leaflets exhibited high amplitude and unidirectionality on the ventricularis (TSM>7.50 dyn/cm², OSI < 0.17, TSG>325.54 dyn/cm² s) but low amplitude and bidirectionality on the fibrosa (TSM < 2.73 dyn/cm², OSI>0.38, TSG < 191.17 dyn/cm² s). The radial WSS component computed in the leaflet base, belly and tip demonstrated strong regional variability (ventricularis TSM: 7.50–22.32 dyn/cm², fibrosa TSM: 1.26–2.73 dyn/cm²). While the circumferential WSS exhibited similar spatially dependent magnitude (ventricularis TSM: 1.41–3.40 dyn/cm², fibrosa TSM: 0.42–0.76 dyn/cm²) and side-specific amplitude (ventricularis TSG: 101.73–184.43 dyn/cm² s, fibrosa TSG: 41.92–54.10 dyn/cm² s), its temporal variations were consistently bidirectional (OSI>0.25). This study provides new insights into the role played by leaflet–blood flow interactions in valvular function and critical hemodynamic stress data for the assessment of the hemodynamic theory of AV disease.     

Effect of natural zooplankton feeding on the tissue and skeletal growth of the scleractinian coral<Emphasis Type="Italic"> Stylophora pistillata</Emphasis>

Laboratory experiments were designed to estimate the ingestion rates of the scleractinian coral Stylophora pistillata under varying prey concentrations and feeding regimes and to assess the effect of feeding on the tissue and skeletal growth. Six sets of corals were incubated under two light (80 and 300 µmol photons m^–2 s^–1) and three feeding levels (none, fed twice, and fed six times per week) using freshly collected zooplankton. Results showed that the number of prey ingested was proportional to prey density, and no saturation of feeding capability was reached. Capture rates varied between 0.5 and 8 prey items 200 polyp^–1 h^–1. Corals starved for several days ingested more plankton than did fed corals. Fed colonies exhibited significantly higher levels of protein, chlorophyll a, and chlorophyll c₂ per unit surface area than starved colonies. Feeding had a strong effect on tissue growth, increasing it by two to eight times. Calcification rates were also 30% higher in fed than in starved corals. Even moderate levels of feeding enhanced both tissue and skeletal growth, although the processes involved in this enhancement remain to be determined.     

三维超声心动图评价不同年龄段和性别主动脉瓣二叶畸形

目的:三维超声心动图评估不同年龄段和性别主动脉瓣二叶畸形(bicuspid aortic valve malformation,BAV)的应用价值。方法:超声心动图检测我院2012年6月至2014年9月70例BAV患者,根据年龄段分为4组,≤20岁年龄组7例,21-40岁年龄组14例,41-60岁年龄组30例,≥60岁年龄组19例;根据性别分为2组,男性42例,女性28例。测量不同病例分组的主动脉窦部及升部内径、室间隔厚度、左心功能及左房横径,比较主动脉瓣狭窄、关闭不全、钙化及脱垂四个合并症发生率。结果:在心脏结构指标方面,年龄段分组室间隔厚度≥60岁年龄组12.37±1.64 mm高于≤20岁年龄组10.43±2.22 mm和21-40岁年龄组11.00±1.92 mm;左房横径41-60岁年龄组38.73±7.95 mm和≥60岁年龄组40.05±9.71 mm高于≤20岁年龄组29.86±1.86 mm。性别分组左心功能女性64.18±6.04%高于男性58.71±11.28%。在合并症发生率方面年龄段分组主动脉瓣狭窄41-60岁年龄组80%、≥60岁年龄组84%高于21-40岁年龄组50%,性别分组狭窄男性81%大于女性54%,关闭不全女性79%大于男性50%。结论:三维超声心动图诊断BAV可获得更加全面、具体、直观的诊断信息,BAV的超声表现与患者年龄段和性别密切相关。     

The impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Singapore

The National University Hospital (NUH) Tissue Bank was established in October 1988. The National University of Singapore (NUS) was officially appointed by IAEA to be the IAEA/NUS Regional Training Centre (RTC) for RCA Member States for training of tissue bank operators on September 18, 1996. In the first five years since its establishment the National University Hospital Tissue Bank concentrated its work on the sterile procurement and production of deep frozen femoral heads and were used in patients for bone reconstruction. The cost of producing these tissues were about SGD$ 250 per femoral head although cost fees were initially charged at SGD$ 50 per femoral head. The most important activity carried out by Singapore within the IAEA was training. Between November 1997 and April 2007, a total of nine courses were conducted by RTC with a total of 180 tissue bank operators registered, 133 from Asia and the Pacific region (13 countries, including 2 from Iran), 14 from Africa (Zambia, Libya, Egypt, Algeria, and South Africa), 6 from Latin America (Brazil, Chile, Cuba, Peru, and Uruguay), 9 from Europe (Greece, Slovakia, Poland, and Ukraine), and 2 from Australia. The last batch (ninth batch) involved 20 students registered in April 2007 and will be due to sit for the terminal examination in April 2008.     

The impact of the International Atomic Energy Agency (IAEA) program on radiation and tissue banking in Cuba

The first multi-tissue bank was founded at Havana in 1958. At that time, freeze-drying was used at the bank as a method of preserving, as well as Cobalt 60 irradiation to sterilise bone tissue, heart valves and others. The impact of the IAEA program in tissue banking activities in Cuba can be summarised as follows: (a) Increase in the production of sterilised tissues using ionising radiation (bone, pig skin and amnion) for medical treatment in the tissue bank of the Hospital Frank Pais; (b) increase of the quality of the productions of bone tissues, pig skin and amnion; (c) reduction in the import of tissues by increasing the local production of tissues; (d) sustainability in the number of donors through the implementation of a public and professional awareness campaign; (e) training of six persons in the Regional Training Centre of Buenos Aires; (f) qualification of one person in the administration of a tissue bank and in the implementation of a Quality System. The amount of tissues produced and sterilised using the ionising radiation techniques in the established banks was 25,510 units. The amount of patients treated with sterilised tissues produced by the established banks was 2,448.     

Applied tissue engineering in the closure of severe burns and chronic wounds using cultured human autologous keratinocytes in a natural fibrin matrix

Whereas in severe burns cultured human epithelial cells may well serve as a life saving method, the true value of tissue-engineered skin products in chronic wound care has yet to be clearly defined. Among other well-known clinical problems, the engraftment rate of commercially available multilayered "sheet grafts" has been shown to vary extremely. Adherence of transplanted cells to the wound bed--especially in the presence of potential wound contamination-- is one of the crucial aspects of this technique. Keratinocyte suspensions in a natural fibrin sealant matrix can potentially treat a variety of skin defects. In acute burn wounds, as well as in chronic wounds the clinical application of this type of tissue-engineered skin substitute demonstrates the capacity of cultured human autologous keratinocytes in a fibrin sealant matrix to adhere to wound beds, attach and spread over the wound resulting in reepithelialization of both acute and chronic wounds. In full thickness burns the combination of this new tool with allogenic dermis is a promising option to achieve complete dermal-epidermal reconstitution by means of tissue engineering and guided tissue repair. When transferring this technique into the treatment of chronic wounds we found an optimal preparation of such recipient wound beds to be crucial to the success. The additional application of continuous negative pressure (vacuum therapy) and preliminary chip skin grafting to optimally prepare the recipient site may be helpful tools to achieve such well-prepared and graftable surfaces. Prospective controlled comparative studies should be designed to further assess the clinical efficacy of this technique.