A novel polymeric prosthetic heart valve: design, manufacture, and testing

In this thesis a flexible leaflet polymeric prosthetic aortic heart valve was designed, manufactured, and tested. The prosthesis was designed with the aim of overcoming the need for anticoagulant therapy, which is required for current mechanical prostheses; while also having lifelong durability, which current bioprosthetic heart valves are not able to achieve. Inspired by the anisotropic architecture of collagen in the natural valve, a shortlist of polystyrene based block copolymers (BCPs), which can be processed to yield mechanically anisotropic materials, was proposed. The shortlist was evaluated based upon processability, biostability, ex vivo haemocompatibility, and a novel material performance index comprising the flexural modulus and the cyclic fatigue stress predicted by fracture mechanics methods. Polystyrene-block-polyethylene-polypropylene-block-polystyrene with 22 mol% polystyrene (SEPS22) was selected for further testing and use in the design. Haemocompatibility and calcification of the BCPs was assessed against reference materials. In measures of coagulation and thrombogenicity the BCPs were better than polyester, but worse than expanded polytetrafluoroethylene and pericardium graft materials. In measures of inflammation, the BCPs and polytetrafluoroethylene were better than polyester and pericardium. A durable heparin coating gave SEPS22 superior haemocompatibility compared to all the reference materials. The BCPs calcified less than pericardium, but calcification still accelerated failure. The technique of injection moulding discs of the BCP from a point was used to create a novel biaxial structure of cylindrical polystyrene domains. A combination of modelling and bench-scale injection moulding was used to select a point from which the prosthetic heart valve injection tool cavity should be filled. By simultaneously injecting at a point at the centre of the free edge of each leaflet, a bioinspired orientation was produced. Based upon hydrodynamic testing, a spherical form leaflet design was selected. The hydrodynamic performance of the complied with the ISO 5840 standard for cardiac valve prostheses, but the fatigue performance was inadequate due to the leaflets being thinner than specified due to manufacturer error. Fatigue prediction and finite element analysis were used to conjecture that correctly manufactured polymeric valves could theoretically reach the ISO limit, indicating that there is potential for polymeric prostheses to overcome the issues of durability and need for anticoagulation

Feasibility of a Mitral Annuloplasty With the Capability for Peri- and Postoperative Adjustment

Abstract Surgical repair with implantation of a mitral annuloplasty ring is the gold standard treatment for mitral regurgitation. However, outcomes are variable and recurrent mitral regurgitation is not uncommon. A REshapeable Mitral Annuloplasty DevIce (REMADI) is proposed, which consists of a fully encapsulated low melting temperature alloy. The alloy is solid and rigid at body temperature and provides traction force to shape the annulus. When heated using a noncontact method, the alloy melts and the REMADI becomes malleable. The REMADI is engaged with the mitral valve annulus using anchors which automatically deploy upon contact. A passive beating porcine heart model was used to demonstrate the feasibility of the REMADI device, which was deployed, engaged, and used to reduce the diameter of the mitral valve annulus.Armstrong Trus

Fluid dynamic characterization of a polymeric heart valve prototype (Poli-Valve) tested under continuous and pulsatile flow conditions.

PURPOSE: Only mechanical and biological heart valve prostheses are currently commercially available. The former show longer durability but require anticoagulant therapy; the latter display better fluid dynamic behavior but do not have adequate durability. New Polymeric Heart Valves (PHVs) could potentially combine the hemodynamic properties of biological valves with the durability of mechanical valves. This work presents a hydrodynamic evaluation of 2 groups of newly developed supra-annular, trileaflet prosthetic heart valves made from styrenic block copolymers (SBC): Poli-Valves. METHODS: 2 types of Poli-Valves made of SBC and differing in polystyrene fraction content were tested under continuous and pulsatile flow conditions as prescribed by ISO 5840 Standard. A pulse duplicator designed ad hoc allowed the valve prototypes to be tested at different flow rates and frequencies. Pressure and flow were recorded; pressure drops, effective orifice area (EOA), and regurgitant volume were computed to assess the behavior of the valve. RESULTS: Both types of Poli-Valves met the minimum requirements in terms of regurgitation and EOA as specified by the ISO 5840 Standard. Results were compared with 5 mechanical heart valves (MHVs) and 5 tissue heart valves (THVs), currently available on the market. CONCLUSIONS: Based on these results, PHVs based on styrenic block copolymers, as are Poli-Valves, can be considered a promising alternative for heart valve replacement in the near future.This work was funded by the British Heart Foundation, New Horizons grant NH/11/4/29059.This is the final version of the article. It first appeared from Wichtig Publishing via http://dx.doi.org/10.5301/ijao.500045

A bio-inspired microstructure induced by slow injection moulding of cylindrical block copolymers.

It is well known that block copolymers with cylindrical morphology show alignment with shear, resulting in anisotropic mechanical properties. Here we show that well-ordered bi-directional orientation can be achieved in such materials by slow injection moulding. This results in a microstructure, and anisotropic mechanical properties, similar to many natural tissues, making this method attractive for engineering prosthetic fibrous tissues. An application of particular interest to us is prosthetic polymeric heart valve leaflets, mimicking the shape, microstructure and hence performance of the native valve. Anisotropic layers have been observed for cylinder-forming block copolymers centrally injected into thin circular discs. The skin layers exhibit orientation parallel to the flow direction, whilst the core layer shows perpendicularly oriented domains; the balance of skin to core layers can be controlled by processing parameters such as temperature and injection rate. Heart valve leaflets with a similar layered structure have been prepared by injection moulding. Numerical modelling demonstrates that such complex orientation can be explained and predicted by the balance of shear and extensional flow.This is the author-accepted manuscript. It will be under embargo for 12 months after publication. The final version of this article is published by RSC in Soft Matter and can be found here: http://pubs.rsc.org/en/Content/ArticleLanding/2014/SM/C4SM00884G#!divAbstract

A Newly Developed Tri-Leaflet Polymeric Heart Valve Prosthesis.

The potential of polymeric heart valves (PHV) prostheses is to combine the hemodynamic performances of biological valves with the durability of mechanical valves. The aim of this work is to design and develop a new tri-leaflet prosthetic heart valve (HV) made from styrenic block copolymers. A computational finite element model was implemented to optimize the thickness of the leaflets, to improve PHV mechanical and hydrodynamic performances. Based on the model outcomes, 8 prototypes of the designed valve were produced and tested in vitro under continuous and pulsatile flow conditions, as prescribed by ISO 5840 Standard. A specially designed pulse duplicator allowed testing the PHVs at different flow rates and frequency conditions. All the PHVs met the requirements specified in ISO 5840 Standard in terms of both regurgitation and effective orifice area (EOA), demonstrating their potential as HV prostheses.This work was funded by the British Heart Foundation (New Horizons NH/11/4/29059).This is the final published version. It first appeared at http://www.worldscientific.com/doi/abs/10.1142/S0219519415400096?src=recsys

Quantifying the Shift Toward Transcatheter Aortic Valve Replacement in Low-Risk Patients: A Meta-Analysis.

BACKGROUND: In recent years, use of transcatheter aortic valve replacement has expanded to include patients at intermediate- and low-risk cohorts. We sought to determine disease prevalence and treatment distribution including transcatheter aortic valve replacement eligibility in low-risk patients across 37 advanced economies. METHODS AND RESULTS: Four systematic searches were conducted across MEDLINE, EMBASE, and the Cochrane database for studies evaluating disease prevalence, severity, decision making, and survival in patients with aortic stenosis. Estimates of disease prevalence and treatment eligibility were calculated using stochastic simulation and population data for the 37 countries comprising the International Monetary Fund's advanced economies index. Fifty-six studies comprising 42 965 patients were included across 5 domains: prevalence, severity, symptom status, treatment modality, and outcome. The pooled prevalence in the general population aged 60 to 74 years and >75 years was 2.8% (95% confidence interval [CI], 1.4%-4.1%) and 13.1% (95% CI, 8.2%-17.9%), respectively-corresponding to an estimated 16.1 million (95% CI, 12.2-20.3) people in 37 advanced economies. Of these, an estimated 3.2 million (95% CI, 2.2-4.4) patients have severe aortic stenosis with 1.9 million (95% CI, 1.3-2.6) eligible for surgical aortic valve replacement. There are ≈485 230 (95% CI, 284 550-66 7350) high-risk/inoperable patients, 152 690 (95% CI, 73 410-263 000) intermediate-risk patients, and 378 890 (95% CI, 205 130-610 210) low-risk patients eligible for transcatheter aortic valve replacement. CONCLUSIONS: With a prevalence of 4.5%, an estimated 16.1 million people aged ≥60 years across 37 advanced economies have aortic stenosis. Of these, there are ≈1.9 million patients eligible for surgical aortic valve replacement and 1.0 million patients eligible for transcatheter aortic valve replacement.British Heart Foundation Translational Award TG/15/4/31891 (Drs De Sciscio, Brubert, and Moggridge) and British Heart Foundation Special Project Grant SP/15/5/31548 (Drs Serrani, Stasiak, and Moggridge)

Hemocompatibility of styrenic block copolymers for use in prosthetic heart valves.

Certain styrenic thermoplastic block copolymer elastomers can be processed to exhibit anisotropic mechanical properties which may be desirable for imitating biological tissues. The ex-vivo hemocompatibility of four triblock (hard-soft-hard) copolymers with polystyrene hard blocks and polyethylene, polypropylene, polyisoprene, polybutadiene or polyisobutylene soft blocks are tested using the modified Chandler loop method using fresh human blood and direct contact cell proliferation of fibroblasts upon the materials. The hemocompatibility and durability performance of a heparin coating is also evaluated. Measures of platelet and coagulation cascade activation indicate that the test materials are superior to polyester but inferior to expanded polytetrafluoroethylene and bovine pericardium reference materials. Against inflammatory measures the test materials are superior to polyester and bovine pericardium. The addition of a heparin coating results in reduced protein adsorption and ex-vivo hemocompatibility performance superior to all reference materials, in all measures. The tested styrenic thermoplastic block copolymers demonstrate adequate performance for blood contacting applications.The authors would like to thank Michaela Braun for her laboratory support, BHF New Horizons Grant no. NH/11/4/29059 for providing financial support to this project and the Armstrong Fund (Cambridge) for a studentship. X-ray photoelectron spectra were obtained at the National EPSRC XPS User's Service (NEXUS) at Newcastle University, an EPSRC Mid-Range Facility.This is the final version of the article. It was first available from Springer via http://dx.doi.org/10.1007/s10856-015-5628-

How to prevent infective endocarditis in 2020? Practical issues

The incidence of infective endocarditis (IE) continues to rise in many populations and is typically accompanied by a shift to healthcare‑associated staphylococcal species. Despite efforts with aggressive antibiotic therapy and increasing rates of surgical intervention, little progress has been made to reduce mortality. Disease prevention is therefore a crucial part of limiting its effects. Prevention should target each point in the pathogenic triad of IE: initiating bacteremia, adhesion to substrate, and proliferation of pathogenic species. Preventative strategies should focus on at‑risk patients undergoing high‑risk procedures, and these patients and procedures can now be identified by quantitative risk estimates. The attendant risk resulting from a procedure must then be placed in the perspective of the day‑to‑day risk, and the resulting balance can inform the benefit of prophylactic antibiotics. Implantable devices are a major risk factor for IE, and novel coatings and designs may be effective in risk reduction. Guidelines differ worldwide and a consensus has yet to be reached on who should receive pre‑ and periprocedural antibiotics

Jak zapobiegać infekcyjnemu zapaleniu wsierdzia w 2020 roku? Aspekty praktyczne

Częstość występowania infekcyjnego zapalenia wsierdzia (IZW) stale wzrasta w wielu populacjach. Chorobętę coraz częściej wywołują gronkowce, a zakażenia są związane z opieką zdrowotną. Mimo podejmowanychprób agresywnej antybiotykoterapii oraz coraz częściej podejmowanych interwencji chirurgicznychobserwuje się jedynie niewielki postęp w zakresie redukcji śmiertelności. Zapobieganie chorobie stanowizatem kluczowy element strategii ograniczania jej skutków. W prewencji powinno się uwzględnić każdyelement triady patogenezy IZW: początkową bakteriemię, adhezję do podłoża oraz proliferację gatunkówpatogennych. W strategiach prewencyjnych należy się skupić na pacjentach z grup ryzyka poddawanychprocedurom wiążącym się z dużym ryzykiem zakażenia. Zarówno tę grupę, jak i wspomniane zabiegimożna obecnie identyfikować za pomocą ilościowej oceny ryzyka. Decyzja o profilaktycznej antybiotykoterapiipowinna być wynikiem oceny bilansu pomiędzy określanymi w codziennej obserwacji ryzykiem infekcjiokołozabiegowej i korzyściami oraz zagrożeniem wynikającym z profilaktycznej antybiotykoterapii.Urządzenia wszczepialne stanowią główny czynnik ryzyka IZW, a ich nowoczesne osłony oraz konstrukcjemogą skutecznie to ryzyko redukować. Wytyczne znacznie się różnią w zależności od kraju i do tej porynie osiągnięto konsensusu dotyczącego wskazań do antybiotykoterapii przed- i okołozabiegowej