Dr. Maximilian Kütting (MK) is Director R&D at New Valve Technology, a company that is “dedicated to developing and marketing innovative technologies for the minimally invasive treatment of all heart valves”. Founded in September 2007, New Valve Technology Headquarters are in Muri, Switzerland, with Production & Development in Hechingen, Germany. Dr. Kütting recently spoke with Rob Fraser (RF), Lab and General Manager at ViVitro Labs, about his work, Transcatheter aortic valve implantation (TAVI) valves, and future projects.
RF: Congratulations on receiving the CE mark for your Allegra Transcatheter Aortic Valve. How are things at New Valve Technology going?
MK: Basically New Valve Technology is a small medical company. Our aim was set up a company with expertise in heart valve development and manufacturing. The Allegra was a product that we built, but the aim was always to build a company around Allegra and use this product to learn and to establish the processes that we need to be a company that, in the long run, has the capability to develop new and exciting innovative heart valve technologies.
The Allegra is just the tip of the iceberg. There’s more to come. The first product that we developed was a TAVI device. We saw what was on the market and we said, well there are a couple of features that we feel could still be integrated into TAVI. We decided to put these features into one device and bring an alternative to the market compared to already established valves.
Allegra TAVI valve Photo credit: NVT AG
A feature that we integrated into the Allegra is the supra-annular design because one of our focuses is always flow. When you’re treating aortic stenosis the idea is to create the lowest resistance for flow that you can because you’re treating a disease which means the patient doesn’t get enough flow. It has too high resistance and you want to get the resistance down as far as possible. Low gradients are really the key to effectively treating the patient -especially in small anatomies. This is why Allegra has the supra-annular design.
One of the other flow aspects is that during the implantation of the Allegra we never occlude the flow. When we position the valve, first we retract the retaining catheter, but the valve is still crimped on the front and the back of the catheter. Then in one movement we release the valve and so we immediately have flow again. This is another area where we just respect the flow of the anatomy of the patient and we try to make the implantation basically as natural as possible without the need for rapid pacing. So the design of the valve and the catheter doesn’t mean that we need rapid pacing.
RF: What kind of reactions are you getting to the valve?
MK: The reaction that we’re getting to the work is quite positive because these are things that are scientific aspects we incorporated into design which many other manufacturers didn’t really incorporate. There are other TAVI devices that you can implant without occlusion, but their concepts are a little bit different. Another concept we integrate into the Allegra is having stent post movement of the valve, a design feature successfully used in surgical valves. This means that the commissures of the valve is attached to a part of the stent which is more flexible than the anchoring part of the stent.
Because of the supra-annular design we have a section which anchors in the annulus which has a higher radial force. At the top part of the valve we have a more flexible area where the valve is attached. This provides some flexibility which is well known from surgical valves through studies from the 80s and 90s. This is the design feature that led to the durability aspects of biological valves which really improved the durability and lowered the mechanical failure rate and the calcification rate of biological heart valves allowing this tissue to have less stress during the diastolic phase.
RF: How did ViVitro equipment help your team?
MK: The SuperPump pulsatile pump we had was really essential in getting the stents designed to a stage where we had the flexibility that we were aiming for. We went through a lot of design iterations and if you come here to Hechingen and you have a look at our R&D building, then just outside my office, there is a long line of valve prototypes that led up to the Allegra — maybe 15 to 20 designs. A lot of the final tweaking work was really getting the flexibility right on the stent frame to make sure that in diastole we have the right amount of stent post movement to lower the leaflet stress to a level where it needs to be to really get the durability of the valves where we want it to be in the long term.
Using the SuperPump pulsatile pump we were able to really analyze exactly how much movement of the stent posts we have. In literature this was described as ideally between one to one point five millimeters of movement. There’s an interesting publication by GW Christie and BG Barratt-Boyes from the 90s where they said if you get this level, leaflet stresses will go down significantly. That is what we were aiming for and our tool in getting us there was the SuperPump pulsatile pump.
RF: I’m glad to hear the SuperPump pulsatile pump helped. It’s interesting you mentioned you’re taking lessons learned from surgical valves and it seems a lot of people have sort of thrown all those lessons away and started from scratch with TAVI valves. Do you feel that a TAVI valve will ever have the same durability as a surgical valve?
MK: I think it’s definitely possible if we respect what we’ve learned from surgical heart valves. It’s not a secret. All of these things are out there. You can read the publications and there’s a lot of work that has been done on this. If you look at the failure mechanisms of TAVI valves, a lot of them look similar to what we’ve experienced in the phases with biological surgical valves. I think that looking at the people who also designed these TAVI valves, they didn’t come from a cardiovascular or a cardiac surgeon background or a field where all this knowledge was well known because it wasn’t the big heart valves manufacturers that originally developed these valves. Companies like Edwards Lifesciences and Medtronic may have a lot of heart valve knowledge, but the concepts of the valves that they use are from CoreValve or smaller engineering groups like the PVT group from Israel that developed a first Cribier valves. They took more of their inspiration from interventional devices like vascular stents.
Their focus was really how we can crimp it down. How can we expand it? How we get into this position? Flex, as in stent post movement, is not a feature that you need to have with a coronary stent, but it is a feature that you need to have with a heart valve. I think that the approach was a little bit different. The first engineer that worked at New Valve Technology, Marcos Centola was originally the Director of Development for Braile in Brazil, a company that also built surgical heart valves. He knew about these factors of heart valve design. It is interesting to think about that these companies that now sell TAVI valves have tremendous heart valve experience but these TAVI valves they’ve built are not logical continuations of their surgical valves.
RF: And you feel that the Allegra valve is more along those lines. Not that New Valve Technology had a predecessor that was surgical, but you’re at least following those design elements.
MK: I mean the design and design ideas that went into it definitely respected is the experience from the field. And I think that only time will tell what durability is with these TAVI devices. We know that we gave it these design features and we’ll see what 10 year, 15 year, 20 year data on durability tells us about these devices.
Honestly, it’s difficult to get this data now for these kind of devices because the patients we’re treating are so old that they often die of co-morbidities. If you’re treating an 80 year old patient or let’s say an 89 year old patient you’re not going to get 20 year follow up for this patient. But now, especially in Europe, you’re seeing a trend to younger patients. With this trend to younger patients we’ll also need to have devices that can be more durable. What we really did was set out to build a TAVI valve which respects what we’ve learned from surgical valves. If this actually works out we’ll see, because in the early tests we see that it holds and it lasts, so we don’t have mechanical failure. But durability tests are one thing. The calcification potential is difficult to assess, especially in vitro, just because there are so many other mechanisms going into it.
RF: One issue that came to light recently that affects both surgical and TAVI valves is subclinical leaflet thrombosis. What are your thoughts on this phenomenon?
MK: My thoughts are that it’s a flow phenomenon. What we also see in the published data is that you have less of an issue with this with supra-annular valves. I think it might be also less of an issue in patients with maybe larger sinuses because of the different flow fields. You’re taking a region of flow that was basically designed perfectly by nature and took millions of years to get it to this design and where it needs to be. And you’re putting something inside to replace the function of the valves. But you’re not really respecting the entire anatomy.
You’re not really thinking about OK what happens to creating a low flow zone over here and creating an area where there might be poor wash out. And so with these intra-annular designs we see this seems to be more of a problem- at least from how I interpret the data. We’ve seen it less with supra annular designs just because the flow is different at the region of the leaflets. Also, because behind the leaflets, the stent is open so there’s flow that can go through there. I think we’ll see less of an issue with that. But, it’s just a question of anticoagulation really in the end. It’s just like questions of pacemaker rate, stroke rate and generally anticoagulation. These things are questions which will be more in the forefront when we’re talking about younger TAVI patients.
You can anticoagulate a patient who is older, maybe not as active in his lifestyle or maybe is already on anticoagulation because he already has some kind of atrial fibrillation or another prosthesis which already means that he’s on warfarin or some kind of other anticoagulation therapy. But looking forward looking at the TAVI patients that we feel we want to treat in 10-15 years, I think that this will also be an issue which we’ll have to look into more.
RF: You mentioned a few issues there. What keeps you up most at night?
MK: I would really like to know what’s going to be the main strategy of the heart team to treat the patient effectively in the future.
This is really where I see the need for durability data on TAVI valves and for complication rates to go down. It’s interesting what’s going to happen next year in two years, but what’s going to happen next 15, 20 years? Are we going to have TAVI as an outpatient procedure where you can just go into the hospital and get a TAVI valve, then maybe leave the same day? Is that going to be a possibility? Is TAVI going to be a possibility for the 60 year old patient where first you implanted TAVI valves, and the second treatment would be to do a surgery, take out the TAVI valve, put in a biological surgical valve, and have that for another 15 years. Then a valve in valve with the TAVI device? Is that going to be something that’s interesting?
That’s something that we’re thinking about just as a company which is also oriented more towards the long run. What you need to know about New Valve technology is that we are not venture capital owned. We have private owners who set out to develop a company which will still be here building out in the next 20, 30, 40, 50 years. So we’re really thinking about where we’re going to be then.
RF: That’s a good segue to the next question. I know you know you must be careful what you say, but can you highlight your plans for the future beyond your TAVI device?
MK: As a company entirely focused on building heart valves we’d be stupid not to look at the other valves that are in the heart. So we’re definitely looking at all four valves and we currently have development projects for all positions.. We’ve presented the First in Man with our tricuspid concept at PCR London Valves.. We have now treated 3 patients successfully with this and it’s a technology that is sort of out of the box. It’s a device which is a stent graft spanning from the inferior to the superior vena cava with a bicuspid lateral valve element which we developed also using our pulse duplicator technology here in-house.
We had to build custom fixtures for the pulse duplicator to mimic the anatomy of the right atrium and to incorporate an insufficient tricuspid valve. But that really also helped design this entire concept. That’s something we’re excited about because it’s out of the box, it’s new. It seems to work well. Very well. At least from the first three patients that we treated. But we’re far away from being able to say “look this is going to be the technology for the next 20 years, because we need to treat not three patients but maybe 3000 patients, and then we’ll see how that works out.
Same thing with the mitral. I’m not sure how much we should talk about this concept at this stage, but I think every heart valve company that is looking to the future is also going to look at the mitral valve and we have a concept which is our own intellectual property which we’re excited about. Again it’s out of the box. It’s not like other mitral valves which are more based on what people know from TAVI. It’s a different kind of concept, a mix between repair and replacement. But it’s just what we feel a mitral treatment option could be. With everything else going into it – respecting the patient, respecting the anatomy, respecting the kind of disease that we have -that is something we feel passionate about and we’re going to go forward and see if we can get it into the clinical stage.
RF: Which valve do you think presents the most challenges?
MK: I think that every valve presents different challenges. I think the thing about the mitral valve (or mitral and tricuspid) is that often it’s a disease also of the ventricles and not only of the valves, and the valves are more secondary. If we’re talking about mitral stenosis or mitral annular calcification, I think it’s going to be more like a TAVI-type treatment. But the large patient base that we’re really seeing is more functional mitral insufficiency. I think to develop an effective treatment, you need to be smarter, respect the entire disease and really think about why this valve is the way that it is and what can we do to recreate the function of the valve.
I think that’s where concepts which are similar to TAVI are not going to be directly transferable the mitral valve. You really need to think differently. Mitral and tricuspid are definitely challenging. I think pulmonary is also challenging. For a company to develop a pulmonary valve is difficult because of the market size and because of the diversity of the disease that you see and because these are very often young patients requiring multiple re- operations. It’s difficult to have a product that you can give to the doctor that he can have on a shelf like you see with the Medtronic Melody valve. They did first in man with basically the same device in 2000 and you still have the first generation of this device on the market. There’s hardly any development work going into it just because the market is difficult.
So it’s a different challenge. Not an anatomical challenge, but it’s a question of what is the entire field around the patient, treatment strategy and market that makes it possible or impossible to give a product to the physician who is trying to treat this patient. Basically, we give the doctor a toolbox and he uses this toolbox to fix a disease. Maybe it’s just not possible or financially attractive compared to other therapies at this stage to give them a tool for the pulmonary. We think that there are options if you are clever enough in the development. So we’re thinking about developing something for this. We are actually doing this, but it’s more challenging to convince everybody that it’s the right thing to do because there aren’t so many patients and they are very diverse.
RF: Those are great points. That brings us to our last question. Do you have any advice for our readers?
MK: Don’t be afraid to think outside the box. Try to look at the mechanisms of the disease. Why things are the way that they are and what is the basis of this disease which you are really trying to treat?
If you look at this and if you really think about for instance mitral insufficiency as a disease of the entire ventricle, and what actually happened or what happens generally when you have these patients who are first having aortic stenosis, then high left ventricular pressure and then a failing mitral valve and then they have a failing tricuspid valve. Think about how you could help this patient as a whole. Think more basically about the mechanisms leading to this, because these thoughts about the mechanisms led us to our concepts for the aortic valve that led us to our concept also for the mitral and the tricuspid valves because we didn’t think about what others are trying.You know there’s a saying which is “If you have a hammer everything looks like a nail”. And if you have something like a TAVI valve then maybe you think we’ll take the TAVI valves and put this in here and there, just because these doctors are used to stents, which you can use in a lot of positions. They know that “I can put a stent here, I can inflate it, and it going to be there and that’s going to solve the problem.”
But that’s not really the case for complex heart valve diseases. I think you really need to think about the mechanisms. Why do we have this disease? What led to the disease? And what do I need to do to help this patient? So with the tricuspid valve just as an example, we’re not treating the tricuspid valve itself. We’re putting a fifth heart valve into the right atrium. This means that the tricuspid valve itself is still insufficient but there’s no back flow into the venous system. So there’s no congestion of the venous system. There’s better liver function. There is better renal function. These patients feel better. And so we’re you know we’re treating the disease we’re not treating the valve so we took a step back, before we went forward and said “this is what we need to do to treat tricuspid insufficiency”. I think that applies to a lot of things.
RF: That’s good advice, thank you for taking the time to speak with me.
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