Randy Lane has over 20 years experience in the cardiovascular medical device field with the majority of his time spent developing both surgical and transcatheter heart valves at Sorin Group (now LivaNova) and NeoVasc, most recently serving as V.P. of R&D and Intellectual Property. Randy currently holds numerous granted and pending patents in the cardiovascular field, most notably being the primary inventor of the Tiara TMVR technology. Rob Fraser, Applications Manager at ViVitro Labs, recently interviewed Randy about industry changes, the Tiara valve, and his consulting company, Cx3 – Core Cardiovascular Consulting.
You’ve been in the heart valve industry for over two decades, tell us how the industry has changed.
There has been significant progress and evolution in the valve space over the last 20 years. However, a significant amount has remained the same. In the 90’s, refinements to mechanical valves and bioprosthetic valves were: anti-calcification treatments for bioprosthetic valves, pivot refinements for mechanical valves and efforts to develop polymer heart valves. Root valves, stented bio-prostheses and surgical mitral valve repair versus replacement were hot topics. In the early 2000’s the concept of minimally invasive aortic valve implantation was pursued pretty heavily and some efforts were successful. Those efforts also morphed into the early development of transcatheter aortic valves (TAVR).
The years 2000 to 2010 were a busy time for the development of TAVR technology. Dozens of programs were active in the space as well as a significant amount of activity in the mitral repair space. Around 2010, the success and failures of the TAVR and repair space influenced the mitral valve space. Over the last ten years, refinements to transcatheter aortic valves include incorporating dry tissue and anti-calcification treatments. The development of polymer valves continues. The industry now makes safer, more effective, more durable, easier to implant valves. Today there are over 50 TMVR, TMVr, TTVR and TTVr therapies in development.
What has changed in testing surgical valves compared to trans-catheter valves?
With so much development in the valve space, a lot has changed; utilizing new materials, new delivery routes, new imaging guidance and new measurement methods, the standards development has had to try to keep up. We’ve seen ISO-5840 evolve over the years, incorporating new testing requirements, imaging guidance, clinical protocol requirements and guidance that were not previously present. This evolution has given rise to many new test methods. It forced existing test houses to either modify their equipment to accommodate the new technology or create new equipment giving opportunity for new test facilities to be established.
Simulator development is one of the biggest differences between what was present for testing and training 20 years ago to now. Being able to demonstrate that your device can be safely and effectively implanted into the target anatomy without having to sacrifice countless animals, and utilize the imaging guidance within the operating room to train physicians to accurately and reliably implant the device, has been immeasurable in the advancement of heart valve development.
You led the heart valve consulting and development group at Neovasc, helping clients develop TAVR, TMVR and TTVR technologies. Can you talk about the unique challenges with each of these implant locations, and where you see the markets heading?
Transcatheter Aortic Valves was the first child. There were a lot of unknowns during the initial phases of development. The introduction of new materials, new implant pathways, new imaging guidance, new failure modes were a steep learning curve for physicians and an untreated population now having an option for treatment. A lot of road was paved by the pioneers of the TAVR efforts and many could be followed by those developing TMVR technology, which was the logical next step in development once the TAVR space became crowded.
However, TMVR has its own challenges; a much larger valve to treat with a complex geometry, a dynamic landing zone and variable adjacent anatomy. In addition to this, an entirely new imaging guidance was required to facilitate new and complex delivery pathways and large anatomical variability. Transcatheter tricuspid valves may be the third child, slightly easier to implant as the transfemoral route has been heavily researched for TMVR. Many of the materials, technologies, imaging guidance and physician experiences can be leveraged. However the valve is different again in its own way and lessons will need to be learned.
I think the TAVR market is stabilizing with younger and lower risk patients being treated. Refinements are going to continue to be made and we will very likely see a polymer TAVR valve hit the market and shake things up. The TMVR space is going to continue to evolve to address many of the shortcomings and lessons learned thus far. Hopefully a technology suitable for both Functional Mitral Regurgitation (FMR) and Degenerative Mitral Regurgitation (DMR) patients will be developed. I think the TTVR space is going to evolve in parallel with the TMVR space and many of the TMVR technologies will become suitable for the TTVR space. Many patients previously treated with medical therapy, or considered too high risk for surgical intervention, may have an option for TTVR and TMVR soon.
Two billions dollars was spent acquiring TMVR programs back in 2015. The mitral space was not the same slam dunk as the aortic space. We have also seen growth in repair technologies like the Mitraclip. What are your thoughts on repair vs replacement?
You’re right, the mitral space wasn’t the same slam dunk as the aortic space. I think that comes down to the fact that the mitral space is much more complicated with a lot more variability in patient anatomy, etiology and complexity. DMR patients have a generally normal annulus and ventricle, with defective or deficient subvalvular apparatuses which result in the leaflets not functioning properly, possibly flailing or prolapsing. FMR patients have normally intact leaflets, chordae and papillaries but their ventricles are dilated, causing leaflet tenting and insufficient leaflet coaptation.
As long as I have been in the heart valve industry, there has been debate over the superiority/inferiority of repair versus replacement. I have not yet seen a single perfect solution to treat the gamut of variability in mitral valve disease, regardless of surgical or transcatheter approaches. I think there is a time and place (patient and disease state) where one technology is superior to the other. I think the debates will continue until the ideal device/therapy has been developed.
You were responsible for the Tiara program. What was that like and what made the Tiara valve so unique?
The early days of Tiara development were exciting. We were in a race to develop what we thought was the best idea for a transcatheter mitral valve. The idea of being involved in the development of one of the first technologies to treat an untreated patient population was invigorating. Working in a fast paced environment is exciting. Encountering new challenges every day and troubleshooting those problems while working alongside brilliant people is always rewarding.
The unique aspect of the Tiara device is that it was one of the first (if not the first) transcatheter valves specifically designed for the mitral anatomy. Some of the other technologies at the time were simply aortic valves turned upside down. It was the first valve to incorporate a D shape geometry intended to restore the shape of native mitral valve anatomy as well as incorporate anchoring methods utilized in traditional surgical mitral valve implantations. I believe the technology has proven to be quite successful. To my knowledge, the longest surviving patient (+6.5 years) with a TMVR technology implanted, happens to be sporting a Tiara valve, with many other successfully treated patients following.
If you had a company looking to get acquired today, what would it need to stand out?
If I had a valve company looking to get acquired, I think it would need a unique concept to treat a large inadequately treated patient population with a short procedure time, a small crossing profile that is easy to use and accurately place, and excellent clinical results. It would also need a very strong intellectual property portfolio with great coverage, a team built on experience, and a willingness to think outside of the box. For this company to stand out, it needs to have a unique concept that is well protected, has some proven performance and is something the large device companies (likely acquirers) do not already have in their arsenal or pipeline.
Most of your work has been based in Canada (Vancouver). What are the pros and cons of working in Canada, and your thoughts on global medical device development?
I’m a proud Canadian and I have resided in Vancouver, British Columbia for most of my professional life. One of the pros for me is living in one of the most beautiful places in the world. Once you are done with your workday, the outdoor activities are ever-present year-round on the West Coast. We don’t get the harsh winters, making it a dream for sports enthusiasts.
Working in the heart valve industry in Canada (specifically British Columbia) has its challenges, even more so now with a pandemic going on. However, over the last 20 years, the industry in BC has grown, and more resources are becoming available. I believe BC is becoming Canada’s center for heart valve development, similar to how Minnesota and California are the centers for heart valve development in the United States.
Vancouver’s St. Paul’s Hospital houses some of the world leaders in heart valve procedures. There are a handful of companies developing and manufacturing valve technologies. The Universities have heart valve development labs and ViVitro is either a nice ferry ride or a beautiful float plane flight from Vancouver.
Being able to take advantage of the technology we have available to us today makes global development seamless. The only real challenge upon us today, due to COVID19, is face to face meetings and essential travel., However, we’re finding our way through these issues and will come out making global collaboration even better.
How has ViVitro helped you?
ViVitro has helped me throughout my entire heart valve career. From working with Larry and David in the 90’s with ViVitro Systems to design, build and qualify an in-process hydrodynamic test system. I relied on ViVitro Labs to conduct hydrodynamic and durability testing for clients during my time working with TAVR, TMVR and TTVR clients, then collaborating with ViVitro Labs on designing and developing a Real Time Durability Tester for the Tiara valve. Now, I am collaborating with ViVitro in assisting clients looking to develop novel heart valve therapies.
You now have a consulting company, will you please tell us about that endeavour?
My consulting company, CX3 – Core Cardiovascular Consulting Ltd., emerged as a way for me to ease back into industry. After working on the Tiara program, I had a life changing accident that required me to take some time off to go through surgeries and rehabilitation. The time off forced me to think about what I wanted to work on next. Starting CX3 seemed like the most natural progression. It was a way for me to continue to live in British Columbia, work with various groups around the world to provide my knowledge and expertise compiled over the last 23 years in a format that suited their company and or program needs. It has been incredibly satisfying to get back to work in the valve arena.
This venture has also given me the opportunity to dedicate more time to the development of both ISO-5840 and ISO-5910 standards, gain a better understanding of the inner workings of the standards development and share those learnings with clients to help them navigate the pathways of valve development.
Do you have any advice for our readers?
Find your passion and follow it, don’t be the norm, don’t be afraid to ask questions, work hard and stay humble. Innovation means we need to question the norm, accept our failures and learn from them and have the motivation to find the answers to the difficult questions.
Read about other Cardiovascular Pioneers here.