Ramji Iyer Ph.D. (RI) is Director of R&D at LivaNova (Caisson Interventional). His expertise includes tissue heart valve and delivery system design, soft tissue biomechanics, and computational modeling. He recently spoke with ViVitro General Manager (acting), Rob Fraser (RF) about Caisson Interventional’s fully percutaneous, transvascular mitral valve replacement (TMVR) implant and the unique challenges and opportunities for TMVR.
RF: Caisson had their First in Man in September 2016. How is that going?
RI: It’s been good. We have had several successful implants and some challenging ones. I think everyone knows the TMVR field is a little bit more challenging in comparison to TAVR. We’ve been going steady and cautious, learning along the way, identifying, solving and overcoming some issues.
RF: Given the initial success with TAVI, there was a lot of excitement as people transitioned into the TMVR space. Pretty quickly people realized TMVR was a lot more challenging. What are some of the learnings or most challenging aspects of the mitral space?
RI: I think you probably heard about this pretty much at any of the big meetings that you go to. Between aortic and mitral transcatheter procedures, aortic is relatively less complex and that was perhaps one of the reasons why it was addressed first despite the mitral market being 2-3 times bigger than the aortic market. Perhaps people always tend to solve the complex problems last. But I think we’re there. In terms of specific challenges unique to mitral, I can keep going on and on. You have calcified leaflets on the aortic side and on the mitral side there is no real substrate. Then there is LVOT obstruction. Deliverability from a transeptal standpoint that is not easy at all. You almost have to take a 180 degree turn that is off planar. Then there is the back pressure acting on the valve itself which is substantially higher on the mitral side compared to the aortic side. All these make it challenging to design a bio prosthesis for mitral compared to aortic.
Specific to us, I think we don’t have some of the issues that other valves might have – specifically LVOT obstruction. The biggest limitation we had before was the size. Before we were offering only one. Now we are offering three valve sizes. That should help substantially in terms of improving the patient screening rate.
RF: What sort of reactions have you gotten from doctors using this device?
RI: Very encouraging reactions from the doctors overall. There has been some feedback of it being complex, but learnable. The way to solve a complex problem is methodically or, for lack of a better word, algorithmically, defining the sequence specifically the procedural implantation.
There are multiple steps involved in getting the valve deployed or delivered. But having said that I think that it can be systematically defined, which is exactly what we’re doing. If you systematically split a complex problem into smaller simpler steps, you can always get there. The reactions have been very similar.
RF: So you’re finding that part of your value add is a better delivery system and some very clear instructions for doctors on how to deploy this device.
RI: It is a complex path or trajectory to get to the mitral valve from a transeptal standpoint. You need a delivery system that offers substantial degrees of freedom and I think ours does. We have made design improvements since the first clinical implant, but in general the basic premise of the delivery system and the degrees of freedom it offers hasn’t changed. It’s more about getting physicians familiarized with our devices as well as developing the IFU so that they can follow it step by step. So we have been focusing heavily on these aspects.
RF: Right. There’s a big debate at every conference about whether it is a valve repair or a valve replacement. I know you’ve got a bit of a biased view, but do you think there’s a future for both technologies?
RI: You don’t get complete elimination of MR from Mitral repair solutions. Previously, before valve replacement or TMVR, I think there was no other option. So even with a small improvement in mitral regurgitation a patient receives substantial clinical benefits. I think if you can completely eliminate MR that’s going to be even better. Having said that, I think the challenge from the TMVR standpoint is to accurately position the device in a safe manner – which is what everyone is working on and trying to get it better.
From a transeptal standpoint compared to transapical, you are making the safety profile even better. If we can achieve good procedural success rate, I think replacement would take over repair. Until all of the procedural efficacies have been ironed out and improved, I think there will be some scope for repair.
Additionally, if you look at valve repairs specifically, the biggest one is MitraClip. One of the issues or concerns with MitralClip is that once you have a MitraClip there you cannot go and re-operate. That is an issue that is not the case in most TMVR implants.
RF: In both cases do you think in terms of functional mitral regurgitation do you think you’re really just treating the symptom and not necessarily the underlying heart failure?
RI: Treating the MR vs treating the Left-ventricle for functional MR is an ongoing saga. Irrespective of what started the functional MR, if you eliminate MR, I believe the patients would do well. From some of the initial learnings, all patients with a good implant seem to do really well long term. We have treated both functional and degenerative MR patients and both of them seem to do well.
RF: How has ViVitro Labs helped you with your work?
RI: We’ve used the ViVitro duplicator extensively. It’s worked out pretty good so far. There is always room for improvements and enhancements particularly when you operate in a cardiovascular medtech space. I think you have been easily reachable and talk to us quite frequently; so that has been very helpful.
RF: Are you able to share any of your plans for the future?
RI: Currently we are in an early feasibility trial and are also enrolling in our CE Mark trial (INTERLUDE). That’s going to be our current primary focus. We will then get to the randomized trial in the US.
RF: Do you have any advice (based on personal work/career experience) for our readers?
RI: PhD gave me a good start. In a nutshell, the biggest learning that I got from my PhD was to be able to sequentially or methodically solve a complex problem. You could apply that to pretty much any field or any problem. I also soon realized there was a world of difference between academia and industry specifically with regard to developing solutions that work in a timely fashion.
I have worked in a big company (St. Jude), and then a startup (Caisson Interventional), and now at LivaNova. It’s not as big as some of the other companies, but it’s not a startup either. I think the startup experience was definitely my best time. It gave me a very in depth understanding of how a company or different functions in a company work. This is when I was given several opportunities spanning a breadth of functions; ultimately a fun experience to be able to wear multiple hats.
RF: That’s great. I’m sure your comments will be helpful to our readers. Thank you for taking the time to talk with us.
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