The development of a transcatheter mitral valve

Transcatheter heart valve replacements avoid the main risks associated with conventional open heart surgery and so is the preferred replacement technique for high-risk patients with aortic stenosis. Due to technical challenges, adaptation for the mitral position is still in early stages of research. The aim of this project was to develop the novel UCL transcatheter mitral valve (TMV) based on a prior conceptual design. The UCL TMV is designed to treat mitral regurgitation (MR) and is based on the UCL transcatheter aortic valve (TAV) which is retrievable, repositionable and has enhanced anchoring and sealing. The UCL TMV leaflets, which ensure unidirectional blood flow, are novel because they mimic native mitral valve morphology by having two leaflets, being D-shaped and conical. Their optimal design criterion and two key design parameters were identified using a failure mode and effects analysis and numerical simulations were used to select a design with acceptable stress levels and maximum coaptation area. The optimal leaflets were prototyped as a surgical valve to evaluate their performance against available commercial device designs and were then incorporated in TMV prototypes, and assessed for hydrodynamic performance, both of which exceeded international standard requirements. Durability assessment of the TMV is ongoing and very encouraging; currently withstanding > 80 million cardiac cycles. In conclusion, the results presented and ongoing durability assessments for the UCL TMV indicate it could be a new and effective treatment option for severe MR in high-risk patients whom are declined surgical interventions

A Technical Review of Minimally Invasive Mitral Valve Replacements

Mitral regurgitation is one of the most common forms of heart valve disorder, which may result in heart failure. Due to the rapid ageing of the population, surgical repair and replacement treatments, which have represented an effective treatment in the past, are now unsuitable for about half of symptomatic patients, who are judged high-risk. Encouraged by the positive experience with transcatheter aortic valves and percutaneous reconstructive mitral treatments, a number of research groups are currently engaged in the development of minimally invasive approaches for the functional replacement of the mitral valve. The first experiences have clearly demonstrated that the approach is feasible and promising, though significant progress is still required in the prostheses design and implantation procedures before the treatment can establish as a safe and effective solution. This review analyses the devices currently at a most advanced stage of development, describing their main features and the technical solutions that they adopt in order to respond to the functional requirements of the most challenging of the heart valves

Design, Analysis and Testing of a Novel Mitral Valve for Transcatheter Implantation

Mitral regurgitation is a common mitral valve dysfunction which may lead to heart failure. Because of the rapid aging of the population, conventional surgical repair and replacement of the pathological valve are often unsuitable for about half of symptomatic patients, who are judged high-risk. Transcatheter valve implantation could represent an effective solution. However, currently available aortic valve devices are inapt for the mitral position. This paper presents the design, development and hydrodynamic assessment of a novel bi-leaflet mitral valve suitable for transcatheter implantation. The device consists of two leaflets and a sealing component made from bovine pericardium, supported by a self-expanding wireframe made from superelastic NiTi alloy. A parametric design procedure based on numerical simulations was implemented to identify design parameters providing acceptable stress levels and maximum coaptation area for the leaflets. The wireframe was designed to host the leaflets and was optimised numerically to minimise the stresses for crimping in an 8 mm sheath for percutaneous delivery. Prototypes were built and their hydrodynamic performances were tested on a cardiac pulse duplicator, in compliance with the ISO5840-3:2013 standard. The numerical results and hydrodynamic tests show the feasibility of the device to be adopted as a transcatheter valve implant for treating mitral regurgitation

Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies

The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes

Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences

Efficient processing of information by the central nervous system (CNS) represents an important evolutionary advantage. Thus, homeostatic mechanisms have developed that provide appropriate circumstances for neuronal signaling, including a highly controlled and stable microenvironment. To provide such a milieu for neurons, extracellular fluids of the CNS are separated from the changeable environment of blood at three major interfaces: at the brain capillaries by the blood-brain barrier (BBB), which is localized at the level of the endothelial cells and separates brain interstitial fluid (ISF) from blood; at the epithelial layer of four choroid plexuses, the blood-cerebrospinal fluid (CSF) barrier (BCSFB), which separates CSF from the CP ISF, and at the arachnoid barrier. The two barriers that represent the largest interface between blood and brain extracellular fluids, the BBB and the BCSFB, prevent the free paracellular diffusion of polar molecules by complex morphological features, including tight junctions (TJs) that interconnect the endothelial and epithelial cells, respectively. The first part of this review focuses on the molecular biology of TJs and adherens junctions in the brain capillary endothelial cells and in the CP epithelial cells. However, normal function of the CNS depends on a constant supply of essential molecules, like glucose and amino acids from the blood, exchange of electrolytes between brain extracellular fluids and blood, as well as on efficient removal of metabolic waste products and excess neurotransmitters from the brain ISF. Therefore, a number of specific transport proteins are expressed in brain capillary endothelial cells and CP epithelial cells that provide transport of nutrients and ions into the CNS and removal of waste products and ions from the CSF. The second part of this review concentrates on the molecular biology of various solute carrier (SLC) transport proteins at those two barriers and underlines differences in their expression between the two barriers. Also, many blood-borne molecules and xenobiotics can diffuse into brain ISF and then into neuronal membranes due to their physicochemical properties. Entry of these compounds could be detrimental for neural transmission and signalling. Thus, BBB and BCSFB express transport proteins that actively restrict entry of lipophilic and amphipathic substances from blood and/or remove those molecules from the brain extracellular fluids. The third part of this review concentrates on the molecular biology of ATP-binding cassette (ABC)-transporters and those SLC transporters that are involved in efflux transport of xenobiotics, their expression at the BBB and BCSFB and differences in expression in the two major blood-brain interfaces. In addition, transport and diffusion of ions by the BBB and CP epithelium are involved in the formation of fluid, the ISF and CSF, respectively, so the last part of this review discusses molecular biology of ion transporters/exchangers and ion channels in the brain endothelial and CP epithelial cells