“New generation TAVI devices will push complication rates down”


Alain Cribier implanted the first transcatheter aortic valve in a patient at the University Hospital of Rouen, France, on 16 April 2002. Ten years after the first case, transcatheter aortic valve implantation (TAVI) shows similar results to surgery in high-risk patients and superior results to medical therapy in inoperable patients. At EuroPCR, where Cribier spoke about the 10 years of TAVI, he told Cardiovascular News how it all began, how he dealt with criticism in the early days, complications with the procedure and the changes to the concept of the heart team. Cribier believes that, in another 10 years, TAVI will be available to the majority of patients with aortic stenosis.

How did you develop the idea of fitting an artificial valve inside the aortic valve to correct stenosis?

I wanted to develop this valve because I had to face a real issue with balloon aortic valvuloplasty. The history of TAVI began in 1985 with the first case of balloon aortic valvuloplasty, which we did in patients who were contraindicated for surgery. The story of balloon aortic valvuloplasty is fascinating because, in 1985, age per se was a barrier to valve replacement surgery. Almost no one aged over 75 underwent valve replacement surgery. Therefore, with balloon aortic valvuloplasty, there was an explosion of technology that could be used to treat patients who were not candidates for surgery.

After two or three years, because of huge registries, we realised that there was a very high restenosis rate of the valve that had been dilated. I thought, “If there is valvular restenosis, can we do something to maintain the valve open after balloon valvuloplasty?” Then came the idea of using a mechanical device to prevent valvular restenosis after balloon valvuloplasty. The problem was to find the right device. But at that time, in 1987, the peripheral stent, with Palmaz, was coming into focus. Suddenly, we had the possibility of using large stents that did not exist previously. So placing a stent within the valve after dilatation was potentially the solution. My work was to do something absolutely dedicated to calcified aortic stenosis. We had to confirm that a stent would be able to maintain the calcified aortic stenosis valve open after dilatation. This was what we did. I went to the autopsy lab and started implanting the Palmaz stent inside the aortic stenosis. I was stupefied to see that the stent was able to open the vast majority of patients’ valves with calcified aortic stenosis. I also used this crucial demonstration to determine what would be the ideal dimension of the stent, because it is not enough to keep the valve open, you have to preserve the coronary arteries, the mitral valve and the septum. I came to the conclusion that if we had various dimensions of the stent that could be adapted to this technology, 14 to 16mm in height, 23mm in diameter, we could then prevent coronary occlusion, mitral involvement and septal crossing. Also, I observed that removing the stent after implantation required a very strong force. This brought an answer to the potential issue of having an embolisation of the stent with the contraction of heart. This was also demonstrated by Renu Virmani, just before the first human case. Her group did the exact same experiment in the United States and came to the same conclusion: that first of all, the stent was able to open the valve; secondly, you could not remove it. So this was the start.

What happened next?

The next step was to find a company that would be able to design a specific stent and place the valve inside it. I went to every active biomedical company, and it was a complete flop – mainly because the assessment of the experts brought in turned out to be extremely negative. With two engineers as well as the world-renowned cardiologist Martin Leon of the United States, we created a start-up, Percutaneous Valves Technologies, with the goal of producing the required device ourselves. The technology was developed by ARAN R&D in Israel. There we found capable engineers who produced the first prototypes of the percutaneous aortic valve. We then did a lot of experimental work and improved the device before performing the first-in-man implantation.

The first patient was a dying patient who had all the contraindications for TAVI: he was only 57, the contraction of the heart was down to almost zero, with 10% ejection fraction, there was a thrombus inside in the left ventricle, and we did not have any femoral access because the arteries were occluded. We had to improvise, with a transseptal approach, coming from the femoral veins, to implant the valve.

The feeling during the first case was great. The patient resuscitated on the table. Before that, he was practically dead; he had had several episodes of cardiac arrest before entering the cathlab. Immediately after the valve was implanted, the colour came back his face and he was speaking. We could observe a true resuscitation! Unfortunately, he died four months later. When he came to us, he had ischaemia of the leg, with occlusion of the femoral arteries. After four months, his heart was stable but his leg got worse. His leg developed gangrene, we had to amputate it and it did not heal. So it was an extra cardiac cause.

People criticised you at the beginning. When did people start to realise that your idea was going to be a breakthrough in interventional cardiology?

The criticism started with the idea itself. When you have an idea, you have to find a company that will sponsor it and invest a lot of money to develop the concept. All the experts were against the project because they thought it would be impossible to make the valve and, if ever the valve was made, it would be impossible to implant it, and then that it would be impossible to prevent coronary occlusion. My argument at the time was that all I was saying had been checked and proved. I was not using only words, but facts, but nothing worked. So I had a lot of criticism before the first case.

After the first case, I still faced criticism over the next 40 patients. We treated a series of 40 patients in my department, all on a compassionate basis. I was having meetings, speaking to engineers, surgeons, experts, and bringing results showing that the patients were alive and that they had no coronary occlusion, no embolisation, and that they were doing very well. Some of these patients survived five to six years, even though they had been close to death before the procedure. Despite this, all the experts kept their opinion unchanged for almost two years. It was only when we moved to the retrograde approach, when Edwards Lifesciences acquired Percutaneous Valve Technologies and sponsored the development of the transfemoral retrograde and transapical approach that finally, slowly, and because of the involvement of the surgeons in the transapical approach, the criticism stopped. After that it was the opposite; there was a lot of enthusiasm and everybody wanted to start TAVI.

Some issues, such as paravalvular leaking, still need improvement. Is the new generation of devices going to be successful in addressing these problems?

Absolutely! TAVI started 10 years ago and is the only interventional cardiology technique, besides coronary stenting, that has survived 10 years, and we will see continuous expansion in the next decade. Of course, nothing is perfect.

We have had, in the open registry, as well as in the PARTNER trial, some complications. But these complications are not that big. We had some issues concerning aortic regurgitation and long-term mortality, and vascular complications, which are obviously higher with the transfemoral approach than with surgery. We have the stroke rate, which is still around 2–3%. But this is normal. We are just reaching a point where we can say “We have to improve this and that”. We are confident that not only new devices, but better screening of patients and better delivery systems will reduce this already acceptable percentage of complications in the coming years. New valves, which address aortic regurgitation, will be available this year. We also have protection devices for the carotid arteries to be used in association with the valves. The size of the valves has been incredibly reduced – we will have 14F arterial introducers this year. With new valves becoming available, the rate of complications is going to fall.

What is your analysis of PARTNER Cohort A two-year results? Was it a surprise for you that the stroke rate was similar at two years?

I was expecting this. The stroke rate was significantly higher in the acute phase and during one year. After that it got more similar as we had more strokes with surgery and less with TAVI. The stroke rate in PARTNER is surprisingly much higher than in any previous TAVI registry. There are several explanations to that. The large size first-generation of Edwards Sapien devices was used in the study. Also, operators were at the beginning of their learning curve with this device. Many interventional cardiologists were using the Sapien device for the first time when they included the first series of patients. Manipulating the device in the aortic arch can dislodge plaques, and crossing the aortic valve, positioning it, deploying it, require a significant learning phase. With new devices, more experienced investigators, and a better understanding of the optimal antiplatelet treatment strategy after TAVI, I am sure the stroke problem will be nearly solved in the acute phase.

Regarding standard risk patients, what is still needed to evaluate the performance of TAVI?

I am more cautious about the evolution of TAVI in all surgical candidates. At the present time we are decreasing the level of risk. If we look at the European registries, the Euroscore and STS score are decreasing with time. So we have moved from a Euroscore of 20% to a score of 15%. We have to investigate if this technique can be really compared to surgery in lower risk, younger patients. But we cannot go directly to that. We have to be extremely cautious because there is an ethical aspect to keep in mind. Today, surgery in good surgical candidates offers the best results. We have to take time and move very cautiously. The SURTAVI trial, which will start in Europe, and the PARTNER II trial, in the USA, will give us some answers. Only after that will we be able to say “OK, we can now include average risk patients”. In 10 years, I think TAVI will be offered to the majority of patients with aortic stenosis.

In your opinion, what is the ideal team for a centre to achieve excellence in TAVI?

There has been a small change in the concept of the heart team. The heart team is essential in screening the patients, and this demands a strong team. During the procedures, things are moving faster as we have new strategies, using conscious sedation, local anaesthesia, the Prostar technique etc. The change I refer to is that we do not need to have all the people together in the same room as it was done at the beginning. This is not the way we work in my department. We are moving to a stent-like strategy in the cathlab. During the transfemoral procedure, the cardiac surgeon, echocardiographers, are advised that we are doing a case but they do not have to be in the cathlab; they have to be ready to do something if necessary. Actually, with experience, better patient screening and advanced technologies, conversion to heart surgery has become particularly rare. 

What is your advice to interventional cardiologists and cardiac surgeons who are starting to perform TAVI?

Follow an official training. These are offered by both companies, Edwards and Medtronic. Also, get additional training by going to an experienced centre, do 10 to 15 cases and follow them closely. Start your experience with a proctor. But when I say training and proctoring, it does not concern only the investigator, but the whole heart team. At that point, the first patients can be treated with very good results.

Is it better to be very good with one valve or learn how to use more than one device?

I think the best is to start with one valve, and when you get enough experience with this device, you can then move to another device. Do not start with two devices at the same time because you will be spreading your experience in different directions.

What questions about TAVI would you like to see answered?

Are the technical advances enough to eliminate all the complications? I look forward to seeing the onset of new TAVI devices. I am also interesting in knowing whether surgeons and interventional cardiologists will have common training in the future, in a subspecialty of structural heart disease.