As a result, in 1999, I began developing what is now the ReValving system stent. After developing the initial steps of this concept, I decided to stop surgery and devote all my time to CoreValve, because I knew that if we could achieve a successful percutaneous procedure, we could change the face of how patients were treated. I felt myself to be more useful in developing this system than operating on patients everyday.

Can you describe the design of the device and its various components?
When I started all this, I knew definitely that surgeons would not be using the device, considering surgeons are unlikely to adopt noninvasive procedures. I tried to develop a device that the interventional cardiologist could use easily, a technique close to what they were using every day, but also, on the other hand, starting from a surgical point of view in regards to the characteristics of the implantation in other words, trying to mimic what I was doing every day. I knew very well that the clinical essence of the device would be both the stent and what we put in the stent, the new valve. Once the stent is applied correctly, then what is left is the valve in the vascular flow, which is left for the whole life of the patient. We came up with the design as a result of the basic concept of homograft implantation. I developed the frame that hosts the tissue valve as a three-layer (or three-story) structure:

a) The lower part applies itself on the aortic annulus and has a high radial force. It can mimic the shape of the annulus, whether it is oval, circular or irregular. This is very important to assure the absence of para-valvular leaks around the newly implanted prosthesis.
b) The middle part, which is constrained to a given size, carries the new valve. As we all know, a tissue valve is designed with a specific size diameter that cannot be altered, so the middle portion of the stent has a very precise and stable diameter. Finally, the upper stent area was given its concave shape to oppose the convex shape of the coronary sinus and the coronaries.
c) This higher part of the stent, which ends in the ascending aorta, has two additional functions. It helps to increase the fixation of the whole system and it serves to properly orient the prosthesis parallel to the flow.

The next step consisted of developing the percutaneous delivery system that would permit the implantation under standard cath lab conditions.

How do you implant the valve?
What we tried to do is to develop a technology that was as simple as possible, straightforward, and easily adaptable by the cardiologist without extensive training.

The first-generation ReValving device requires a surgical cut down on one of the inferior limb arteries. Then, after placing an extra stiff guidewire into the left ventricle, the delivery system is pushed over the wire and is positioned in the aortic annulus. Then progressively, the outer catheter wall is pulled back, and the valved frame auto-expands and pushes the native valve aside while anchoring in place. If the valve is heavily calcified, a single predilatation is recommended. The heart valve prosthesis is inventoried in its open shape, as with a standard tissue valve. Prior to delivery, it needs to be compressed onto the catheter. The nitinol is temperature-sensitive, and when you cool it down, it becomes soft and compressible. It is in this state that it can be loaded onto the delivery system.

The most important factor of our frame is that it is self-expanding. We chose self-expanding for a number of reasons. First, if we had used a balloon-expandable stent, we would have to balloon inside the flow, and therefore interrupt blood flow to the brain for the time of expansion. Secondly, when the balloon is inflated, it would compress the tissue valve against the metallic frame, creating some degree of trauma to the valve tissue and possibly decreasing its durability. The third issue is that a self-expanding stent can adapt itself to any shape of annulus, and this considerably reduces the possibility of para-valvular leaks, which have been a problem with other devices. Finally, once you have implanted a self-expanding stent, there is substantial residual radial force pushing on the tissue, assuring not only proper seating but also compression of the calcified part of the native valve. It is important to keep in mind that a balloon-expandable stent would not offer this advantage because it does recoil to a certain degree, which is unfavorable in front of calcified tissue.

Once implanted, how stable and durable is the valve?
The radial force of the stent is sufficient in ensuring a solid and stable anchoring of the new prosthesis. During the course of experimentation on more than 80 animals, no migration was ever noted. Cadaver studies reinforced our belief that the anchoring is absolute. The limited clinical data that we have from the feasibility study also shows no migration.

Before implanting our device in humans, we completed substantial durability testing, as you would do with any new valve. This work was performed by Professor Reul in Aachen, Germany. We also tested whether or not compressing this valve inside the frame for the duration of the delivery cycle would traumatize the valve. A testing protocol that compressed and decompressed the valve in a manner similar to the delivery manipulation showed no trauma to the valve leaflets by microscopy, scanning electron microscopy and histology.

Can you explain what type of tissue is used for the valve?
The tissue used is of the same type, and undergoes the same preparation processes as the tissue from valves used for surgical implantation. There are many different tissue types in use today, but the predominant ones are mainly porcine valves or valves engineered from bovine pericardium. We are currently using bovine pericardium, because its thickness and flexibility characteristics allow for optimal mounting in our stent design. The tissue is sewn into the frame using the same surgical stitching techniques employed in the manufacture of standard surgical tissue valves.

Two patients have undergone the ReValving procedure.
Aortic valves can be either stenotic or regurgitant. If they are stenotic, the flow cannot exit the heart correctly. If they are regurgitant, once the flow has exited, it comes back into the heart. We were fortunate enough to be able to treat patients with the two different diseases during our first cases. The first patient had a highly stenotic calcified valve. We predilated the native valve and implanted our device without procedural complications. Post implantation, we observed good and immediate valve function without para-valvular leakage and with good gradients.
The second patient exhibited severe aortic valve regurgitation. No pre-dilatation was required and post implantation of our device, we again observed good and immediate valve function, without para-valvular leakage and with good gradients. It was very gratifying to see confirmation that we can treat the whole span of aortic valve disease.

What are your current plans in terms of doing further testing or trials?
We plan to conclude our feasibility trials in Asia. We will also initiate additional feasibility trials in Europe on high-risk patients. Actually, we received our first European IRB approval at Dr. Grube's center, the Heart Center Siegburg in Germany. During 2005, we will begin our pivotal trial in Europe to obtain CE marking. This trial will include all types of patients, contraindications to surgery as well as standard patients that would otherwise go to surgery. We will be treating both regurgitant valves and stenotic valves. In the meantime, we will be discussing the U.S. pivotal trial requirements with the FDA.

It should also be noted that this summer we opened a new facility in Irvine, California. The intent is to be totally independent in terms of having full control over all aspects of manufacturing all parts of our ReValving System.

Who are the physicians involved in working on the procedure?
We have a very distinguished scientific advisory board, comprised of both North American and European interventionalists. The U.S. and Canadian medical community is represented by Dr. Peter Block, Dr. Gregg Stone, Dr. Maurice Buchbinder and Dr. Raoul Bonan. From Europe, we have Patrick Serruys, Alec Vahanian, Jean-Claude Laborde and Eberhard Grube. Drs. Grube and Laborde were instrumental in our first two cases. Dr. Laborde from Toulouse, France performed all the animal implants, and has cooperated closely with the company in designing the system and achieving the result that we have today.

What do you feel is particularly unique about the ReValving system?
The most unique aspect is the self-expansion and the tri-level design of the CoreValve frame. Other aspects that differentiate us from PVT (now owned by Edwards Lifesciences) include the fact that we are targeting all aortic valve patients and not just very high risk and compassionate cases. Finally, together with PVT/ Edwards, we are well ahead of other percutaneous aortic developmental programs which have not progressed beyond the concept or animal experimentation stage.

How do you treat patients post procedure?
The device is essentially a stent and a valve, not much different from surgically implanted tissue valves. So, following the implantation, we protect the patient and his/her new valve in the same way as post-surgical ones. A stent typically requires ticlopidine or Plavix in the short term and aspirin long term. A tissue valve typically needs coumadin for three months and then aspirin long term. Standard interventional protocols apply and the patient remains in the hospital overnight, to be discharged the next day.

How large is the catheter?
Any delivery system is always too large. The first-generation devices are 24 Fr. We are working hard on reducing the size to 20 Fr in the near future. As we get our device even smaller in future generational iterations, we are optimistic it will be technically possible to make it purely percutaneous, with its own closure system.
At present, however, the current size does mean that when we implant the device, it is through a surgical cut down. We are creating a discipline that is medical-surgical or surgical-medical the old war between surgeons and cardiologists has subsided and we are confident that the two specialties will cooperate in the best interest of the patient. We are definitely seeing procedures being done by both in the same room. Probably, in the future, there will be a new type of specialty physician that will able to perform hybrid surgical-interventional procedures.

How long does the procedure take?
From the moment you insert the catheter to the moment you retrieve the catheter is approximately 45 minutes. Deployment of the system itself takes about three to four minutes.
Following traditional surgery, the patient stays about 12“24 hours in the intensive care unit and four to five days in the hospital. It takes the patient about one month to recover and two months to go back to work, if they are relatively young. However, following the ReValving procedure, the patient requires only an overnight stay, and the overall procedural costs are likely to be half those incurred with traditional surgery.

We have tried since the beginning design efforts to make things as simple as possible and as close to what the cardiologist is doing already: putting in a guidewire, pushing a delivery system, positioning the device, delivering the device and retrieving the access tools. ReValving training will be minimal. The biggest lab prep change will be that they need to rinse the tissue valve before they load it. Also, cardiologists need to acknowledge that they are now treating valves, and must treat the patient as a valve patient.