Interview: Philippe Pibarot on transcatheter valve therapy, valve durability

Philippe Pibarot, D.M.V., Ph. D., FAHA, FACC, FESC, FASE, FCCS, is Directeur de la recherche en cardiologie / Head of Cardiology Research at the Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ) – Université Laval, Professeur titulaire, Département de médecine / Professor, Department of Medicine, Chaire de recherche du Canada sur les maladies valvulaires cardiaques / Canada Research Chair in Valvular Heart Diseases  Université Laval

His twitter account, @PPibarot, describes him as “Proud father, husband, rock and ice climber, and clinical scientist and professor passionate about valvular heart disease and cardiovascular imaging”. Rob Fraser, ViVitro Labs Applications Manager, recently spoke with Dr. Pibarot about his work.

Rob Fraser Please tell us about your current work that’s going on.

Dr. Philippe Pibarot We are very busy work with the transcatheter valve therapy, which is really a revolution in the field in the way we treat valvular disease. If you would have told me when I started my career, 30 years ago, that we would one day implant a valve that as a diameter of about, 25 mm inside of the heart, without opening the chest, without opening the heart, just through a catheter percutaneously. And with the patient going back home the next day, or in some institutions, the same day.

I think transcatheter valve replacement in particular, and all the other type of transcatheter valve therapies have been a revolution. And this has been an opportunity for scientists in the field to rediscover how they feel about the disease and this has brought more people, more money as well, into research.

And it has brought people together. Before, the cardiac surgeons, the majors, the interventional cardiologists, the basic scientists, the engineers, were not talking to each other much. Whereas now, we all work together.

I think the concept of a heart team is important. In our current work we have a lot of imaging activities to document with computer tomography, before and after transcatheter therapy, how the valve performs in the short term and in the long term. Because the durability of the devices, of course, is an important concern. We serve as the core echocardiography core laboratory for several large trials in the field. This has brought us a lot of activity, questions, and data as well.

Rob Fraser You mentioned that the heart team is working well and that it’s bringing people together, I hear in some cases it can be a bit the opposite too, where, if interventional cardiologists are moving on the turf of what was traditionally seen as cardiac surgeons, there can be a bit of animosity there. Have you seen that in your experience?

Dr. Philippe Pibarot Well, it’s an excellent point that you raised. I think, for the surgeons, it’s like the history of PCI (Percutaneous Coronary Intervention) versus CABG (coronary artery bypass graft surgery) that comes back again. It’s an old nightmare coming back. So yes, it’s a volume of activity that the surgeons do which is eventually transferred to interventional cardiologists. The heart team will work well in an institution where there is a relatively good balance between cardiac surgeons and interventional cardiologists and mutual respect and good communication.

Keep in mind that at the end of the day, we want to help the patient. In our institution at the Quebec Heart and Lung Institute, it works very well because the cardiac surgeons and interventional cardiologists sit together and try to see, first, is the valve replacement really indicated for this patient? And then, what is the best type of replacement valve for this patient, given the data that we have, given the surgical risk, given the demonstrated durability of the device, given the life expectancy of the patient, and given the desire of the patient?

I think it’s really this concept of shared decision and shared decision is shared between not only the cardiac surgeons and interventional cardiologists, but also the patients and the family. You’re right to say that it is not working as well in all institutions.

It’s generally when you a history of one group being more powerful than the others, either the cardiac surgeons or the interventional cardiologists. Therefore the heart team is kind of unbalanced and the power of the decision is not really well shared. This is something that we still have to achieve and to improve in some institutions. But I think the concept of heart team and upstream of the heart team in the heart valve clinic as well and heart valve Center of Excellence are all important things to better serve the patients without the disease.

Rob Fraser You’ve brought up about valve durability a few times. That’s sort of the big question is will TAVI ever match the surgical durability that’s already been well-established? Given the data that you’re seeing, what are your thoughts?

Dr. Philippe Pibarot That is still a big question mark. Will this TAVR valve be as durable as a surgical valve. And why this is a very important question to answer is because we started the TAVR validation in the extreme risk, high risk population, then intermediate. In this population the durability of the valve was important. But it’s more like short term, mid term durability, because these patients unfortunately have a relatively short life expectancy anyway.

But nowadays, with a low surgical risk trial being completed and the valve now approved for the low surgical risk population, these are younger patients with a much longer life expectancy. And in these patients, we cannot afford having a device that is not durable. So that’s an important question. And so far, we don’t have long term data. We have midterm data. We have good five year data.

We just published an article in JACC about the five year durability of the TAVI in the context of the PARTNER II trial, which was intermediate risk. But still we have a good number of patients who have reached the five year follow up. There was good and bad news. The bad news is that the second generation of balloon expandable valves or the SAPIEN XT, has a high incidence of structural valve deterioration and re-intervention compared to the gold standard, which is the SAVR.

But on the other hand, the SAPIEN 3 (the third generation, the most recent one) has similar durability as the surgical valve. This is the one that is used nowadays. The SAPIEN XT is no longer used. We have similar data with the self-expanding CoreValve showing relatively good durability until five years. Demonstrated durability until 5 years.  But five years is still very young in the life of a bioprosthetic valve. I think we will be able to say, well, OK, durability, long term durability, is as good as a surgical valve when we’ll have good ten year data. We still have to wait for some time before getting that data. But this is indeed the important question.

And in parallel we are doing some in vitro studies in the Pulse Duplicator in order to maybe have a projection of what might happen in the future. The mechanical stress on the leaflet is one of the main determinants of the durability.  If you have higher mechanical stress on the leaflet, or region of the leaflet, and it’s repeated billions of times during the lifetime of the patient, you may anticipate and guess that this valve will not be very durable.

This is the type of study that we are doing, comparing surgical valves with different type of transcatheter valves in different conditions. Some more favorable, some more hostile, because, if the valve is implanted in a smaller annulus, oval, or irregular annulus, you may have higher mechanical stress. There may be some signs that are telling us that mechanical stress may be somewhat higher in some type of transcatheter valve in some kind of condition. Therefore we may have shorter durability compared to surgical valves. We need the clinical data to confirm that.

Rob Fraser You’re using the pulse duplicator to look at the stresses and not necessarily putting it in an accelerated wear tester and seeing the failure modes over time. You’re being proactive to look for what might cause the failure modes as opposed to waiting a few months to see what’s going to fail.

Dr. Philippe Pibarot I like the HiCycle tester. That’s important piece of information, but it’s not very physiological. Of course, you want to accelerate the process by having a HiCycle. I prefer more physiological conditions both in terms of anatomy, the pulse duplicator that we have has a compliant aorta, and also things like flow, heart rate, and the systolic duration, et cetera, that are more physiological. And then, measure the stress using different methods. It’s a more an indirect measure of using a high speed camera. But we are able to compute the mechanical stress on the leaflets.  There is quite a bit of information that you need to know a priori, but it’s pretty reliable and it connects very well with what we see clinically.

For example, the region of the leaflets where we see the biomechanical stress are those that generally we will see fail in vivo. I think it’s complementary information from the HiCycle tester and it may be providing more accurate information on the long term durability. Also, it gives us some insight, in terms of the TAVR valve, we tend to do some mild to moderate over sizing to address this issue of paravalvular leak of course. But by doing so, the valve is somewhat a little bit under deployed, meaning that the leaflets may have some been pin wheeling and higher mechanical stress.

So in this pulse duplicator, we will assess the different sizing strategy, positioning strategy and see how it might impact the mechanical stress to give some info to the interventional cardiologist. And indeed, if you oversize the valve too much, clearly, this increases the mechanical stress.

Rob Fraser You have your own in-house built pulse duplicator system?

Dr. Philippe Pibarot We have an in house built system that was developed more than 30 years ago. It started with a collaboration with Alain Carpentier who was a pioneer in the field and the University of Aix-Marseilles, and my good friend and colleague, Professor Regis Rieu. We have made some improvements and upgrades over the years. I think now we have achieved an excellent, very physiological system.

Having said that, I’m using the ViVitro system indirectly because I have some other studies and other collaboration ongoing with my former student, who is now a professor at Concordia University, Professor Lyes Kadem, who is using the ViVitro, and some collaborators also of Regis Rieu are using the ViVitro system.

Part of the experiments that were done in Marseilles on this pulse duplicator may have also been done or some of the experiments have been done on the ViVitro system. I should say, it’s an excellent system. And I could not even dream that one day one company will commercialize the system. And that’s probably the reason why we are using a custom made. It’s because at the time there was nobody commercializing this. So we did our own system. When they say, well, it’s probably very easy to reproduce what the heart is doing, but, my God, you know, it’s many years of work and it takes a lot of equipment and the room to do what the small thing like a heart is doing. You know, it’s fascinating.

Rob Fraser Your heart is an incredible piece of machinery, and to try and do our best to recreate it is a humbling process, very challenging. You’ve talked quite a bit about sizing transcatheter valves. Another hot topic is sizing surgical valves. You’re involved in that on a few fronts. Do you want to bring us up to speed on the latest there?

Dr. Philippe Pibarot The sizing of the surgical valve that’s been has been a matter of controversy and probably of confusion because, the size that is provided by the company and that the surgeon uses as information to select the valve that they will put in the patient. When I started my career, they were not very well standardized. And then the ISO committee and task force attempted to standardize the sizing algorithm. And a recent edition of the ISO that has revisited the standardization of the sizing. There is a sort of task force from the different surgical societies working on that. And they have published several position statement papers.

To me, the most important thing is that the different companies report the same thing. And what is a twenty five millimeter is a true twenty five millimeter for everybody. It looks simple, but it’s much more complicated than they expected. If we refer to the stentless valve, generally the external diameter of the stentless valve is what is reported. And if you take a sizer of a stentless valve and measure it with a caliper and it says twenty five. When there is a stent it gets more complicated because there are some valves that are implanted more intra-annular, supra-annular, et cetera. Essentially the sizing remains, the main determinant is the external diameter is really the portion that goes into the annulus or just above.

And I would dream one day, but I’m not sure it’s going to happen, to have a universal sizer. Similar to what the surgeon calls the Hegar sizer where it’s the same for everybody. And maybe we should not even call it the size of a millimeter, because as soon as you talk about twenty five twenty three, maybe it should be A, B, C, D, E and then, if the sizer “A” fits, so you take the valve a from this company or another company that you think is the best for the patient. That is maybe the future. We are not there yet, but maybe that’s the way to go.

The other thing we tried to improve with the task force is valve labeling that goes beyond the size per say. It doesn’t mean that the valve is large, that it has a good hemodynamic performance.  And at the end of the day, for the patient, what counts is the EOA (effective orifice area), What is the available orifice? What is the orifice area of the valve that is available for blood flow? Because if you have a smaller area, you’re going to have a higher residual gradient and therefore higher residual afterload on the left ventricle. And then what?

Rob Fraser You said you wouldn’t have thought 30 years ago that a transcatheter valve would have been approved, and then you also didn’t think a pulse duplicator would ever get commercialized. So hopefully you can have one more miracle in your career in the surgical size out figured out.  Last question, do you have any advice for our readers?

Dr. Philippe Pibarot My most important advise that is very timely, is it to believe in science, to believe in the scientist, to listen to scientists in every field. We are talking here about medicine. In this COVID-19 era, we know that there is a lot of fake news and fake scientific news.

I am concerned, that maybe the government has decided to not listen well to the science, and the proportion of our population not believing anymore in science. And this is something that has changed during my career. I see some deterioration recently.

And I think that the work that we do, that you do with ViVitro, and that the scientists in universities do, I think is very important. Our goal, I think, is to provide accurate, robust data on, our field is medicine, but the same with climate change and other fields. I think to be able to inform the population, to be able to inform the government as long as they listen to this data. I think probably many of your readers are scientists.

They will not be difficult to convince, but I encourage them to to become scientific preachers. We have a responsibility as scientists to also educate and to spend time and energy not only in publishing papers. Publishing papers is great, and that’s what eventually your university will require. And that’s how they will judge you and give you advancement and your professorship. And once you have published and presented, you think that the work is done. But no, I think it’s just starting.

I think we have to have knowledge translation. And when I say knowledge translation, it is at every level. Not only to the healthcare providers, to the believers who are already convinced. We need to go beyond that. We need to go to the public. We need to talk more to the patients themselves to do more patient oriented research and to communicate this research and our results to the patient and the general population., Because the people outside are the patients of the future. So if they are pre-educated, preconditioned it is going to be easier to treat them.

I think it’s a challenge. Maybe it’s wishful thinking that I’m doing here, but I think as scientists we have to jump into the arena and work with the population, educate the population, not only the healthcare providers. I think we have to do this effort of knowledge, translation and accurate knowledge translation.

Rob Fraser Very timely advice for these unfortunate times.

Read about other Cardiovascular Pioneers here.

Read Dr. Pibarot’s published articles citing ViVitro equipment here.