Interventional cardiology is one of the most dynamic medical device markets, witnessing a surge in new product development with accompanying mergers, investments, and acquisitions. Dozens of companies, both new and established, are developing interventional structural heart devices, such as transcatheter aortic valves, mitral valves, occlusion and heart failure treatment devices. Following in the success of companies like Medtronic and Edwards, new product development is focused on achieving superior clinical outcomes through improving product delivery, performance, and durability. This article takes a “look under the hood” at some of the development plans likely for next-generation devices.
Aortic transcatheter heart valves (THV) are among the more established interventional structural heart implants. In simple terms, THV devices feature a metal frame and tissue-derived valve, either with or without a seal or skirt around the base and wall of the frame. Yet this apparent simplicity veils highly complex devices, featuring hundreds of components between the implant and the delivery system. New designs continue to push the boundaries, in order to simplify the procedure, reduce the risk of complications, improve outcomes, and widen applicability.
Next-Generation Delivery Systems
Creative design in both implant and delivery, is facilitating lower profile delivery systems, with improved functionality. The original Edwards LifeSciences SAPIEN valve had a 22 and 24 French (F) delivery sheath, while the Medtronic CoreValve was mounted in an 18 French system. The latest iterations from both companies are now using the much smaller 14 French or equivalent systems. A reduction in profile increases the potential to treat a wider patient population, while improving patient comfort. Correct implant positioning is essential in order to avoid periprosthetic aortic regurgitation, a concern that was noted on earlier generation devices. As a result, the latest devices feature steerable delivery systems, with controlled positioning and repositioning capabilities, improving procedural outcomes while facilitating ease of use. Edward’s CENTERA, for example, is supported by a motorized low-profile system for single hand deployment and retrieval. Next-generation delivery systems will continue to improve performance in this way, adding advanced functionality and control, particularly in device handles.
Seal and Skirt Design
Polyethylene terephthalate (PET) textiles have been widely used as a skirt or seal around transcatheter valve frames, in order to inhibit paravalvular leakage. Woven or knitted PET fabric offers a versatile solution, with an established clinical history of use in vascular indications. However, textiles, by their nature, have a level of porosity and cannot offer an entirely impermeable barrier. In order to improve performance, there are a number of possible solutions. For example, companies are working to provide coated textiles (See Figure 1) and integrate alternative biomaterial coverings (See Figures 2 and 3) or hybrid material solutions.
Utilizing PET fabric and an ultra-thin coating, either resorbable or nonresorbable, could help reduce shortterm paravalvular leakage, while improving surrounding blood flow and durability. Non-textile biomaterials, such as polytetrafluoroethylene (PTFE) or certain polyurethane grades may also offer a distinct advantage, in that they do not necessarily have to be sutured onto the valve frame.
Due to the complexity of these devices, manufacturing is labor intensive and highly skilled, so methods that afford functional improvements, while facilitating ease and cost of manufacture are highly advantageous. The Colibri Heart Valve, for example, has addressed this issue using a biologic skirt, which the company claims reduces the number of sutures from 1,500 to less than 200, while increasing durability and functionality.
In terms of design evolution, it is likely that we’ll see greater use of hybrid materials or composites that incorporate both textile and non-textile biomaterials. This takes the best attributes of both to maximize functional performance at the lowest possible profile, where the textile can act as a reinforcement layer or facilitate tissue ingrowth.
This type of concept is already being used in other structural heart devices, such as Coherex Medical’s WaveCrest left atrial appendage (LAA) occlusion device. PTFE creates an impermeable anti-adhesive barrier on the blood facing surface, while a PET textile facilitates tissue ingrowth on the reverse side.
Other novel biomaterials are being used effectively within the structural heart area. Thoratec Corporation, acquired by St. Jude Medical in 2015, developed a proprietary material known as Thoralon® several years ago, from poly(etherurethane urea) (PEUU) blended with a siloxanebased surface modifying additive (SMA) to minimize blood clotting and inflammation. The material is used on their percutaneous ventricular assist device (PVAD). The company’s latest transcatheter ventricular assist device (VAD) for the treatment of heart failure, known as the HeartMate PHP (Percutaneous Heart Pump) System, features a covered Nitinol cannula, and an inner collapsible impeller pump. It received the European CE Mark in July 2015 and is currently undergoing FDA investigational device exemption clinical trials.
While a wider range of biomaterials are being considered within the structural heart space, most of these materials are borrowed from other vascular indications where they have an established clinical history of use. As designers continue to push the boundaries, it will be interesting to see whether more novel biomaterials will gain traction. Of particular interest would be the use of hydrogels and other agents that swell in vivo and may offer addition benefits in terms of conforming to irregular anatomy and reducing paravalvular leakage.
Implant Frame Design
Another exciting development in next-generation heart implants is the use of inflatable components. TriVascular Technologies, which recently merged with Endologix, successfully implemented this concept for endovascular use, by integrating an inflatable seal on its Ovation Abdominal Stent Graft Platform. The seal is inflated post deployment and acts as a means of reducing potential endoleak, while supporting fixation of the graft. By employing a sophisticated design feature such as this, the delivery profile for its device is one of the lowest on the market, at 14F.
Direct Flow Medical has employed a similar concept, but has gone one step further, effectively removing the requirement for a metal frame on its THV implant. During deployment, saline is injected into the frame through hollow positioning wires, inflating the frame, while also allowing it to be repositioned. Once in position, the saline is replaced with a quick-curing polymer for permanent implantation.
An inflatable component is also being developed for use in mitral valve repair by Cardiosolutions. The company’s Mitra-Spacer system, currently under development, is a balloon-like device, implanted as a means to bridge the gap between mitral valve leaflets that can cause mitral regurgitation. It is likely that a greater number of implants featuring inflatable components will be seen in the future, as a means to provide effective solutions, with reduced delivery profiles that can treat challenging environments.
Future Valve Development
It is difficult to consider the future of structural heart devices without addressing valve materials innovation. The majority of transcatheter valves on the market and in development, whether for aortic or mitral indications, use a bioprosthetic valve that is either porcine or bovine pericardium derived. Significant development has been made in recent years to improve performance and durability and many contemporary models, treated with an anti-mineralization agent can last for 10 to 15 years. However, bioprosthetic valves need extensive processing to make them fit for use and, in general, they can be expensive to source, challenging to optimize, and cumbersome to store.
There is a clear desire in the market to develop valves from synthetic materials, with improved durability, similar mechanical function to native valves, while reducing dependency on anticoagulant and antithrombotic therapy. Indicating a potential direction for future valve development, a novel bioresorbable valve is being developed by a Swiss company, Xeltis AG, made from electrospun polymeric materials. By a process described as endogenous tissue restoration, the valve is designed to be replaced by native tissue, leaving new healthy functioning valves over time.
Improvements in next-generation devices are leading to lower delivery profiles, more controlled placement, improved valve function, reduced paravalvular regurgitation, increased durability, and lower cost. Product innovation has helped expand this market, to treat a greater patient population, while achieving superior clinical outcomes. Despite considerable progress in recent years, interventional structural heart treatment remains a nascent market full of potential. Clever design, new technologies and novel use of biomaterials, continue to push the boundaries in new product development, ensuring that these devices will remain at the forefront of interventional product innovation for many years to come.
This article was written by Stephen Duffy, Business Development Manager, Proxy Biomedical Ltd., Galway, Ireland. For more information, Click Here .