Tissue- engineered implantable heart valves (CryoLife SG)

[Jim]

Here is an artical about the CryoLife SG valves:


CryoLife receives 'CE Mark' approval for distribution of Model 700 synergraft tissue-engineered pulmonary heart valves in Europe
April 19, 2001
A Correspondent, Atlanta

CryoLife Inc, a life- science company involved in the development and commercialisation of tissue- engineered implantable heart valves, vascular and orthopaedic grafts and surgical adhesives, has received a "CE" (product certification) Mark allowing for the commercial distribution of its Model 700 SynerGraft tissue-engineered pulmonary heart valves within the European Community.

CryoLife's Model 700 SynerGraft pulmonary heart valve represents a major development in tissue-engineered replacement biologic devices for repair of damaged or diseased human tissues. The technology incorporates the use of a porcine pulmonary heart valve that has been depopulated of its porcine cells, leaving a collagen matrix that has the potential to repopulate with the recipient's own cells, providing a bioengineered human heart valve with structure and biodynamics similar to the recipient's own heart valve. It is anticipated that the tissue-engineered valve will have the capability to grow with the maturing of a child, thus potentially avoiding a series of heart valve replacement procedures.

Steven G. Anderson, President and Chief Executive Officer, CryoLife, Inc., said, "The addition of the Model 700 SynerGraft pulmonary heart valve demonstrates the potential for expansion of the SynerGraft technology platform. CryoLife now provides two tissue-engineered heart valves for patients requiring heart valve replacement, the SynerGraft Model 500 aortic valve and the Model 700 pulmonary valve, thus making CryoLife a technology leader in tissue-engineered products. In advanced animal studies, both of these valves have been repopulated with the recipient's own cells."

The CE Mark for the SynerGraft Model 700 tissue-engineered pulmonary heart valve, granted by Lloyd's Register Quality Assurance Limited (LRQA) of Coventry, England, represents the sixth CE Mark designation awarded for CryoLife products. CryoLife was awarded its CE Mark for the SynerGraft Model 500 heart valve last year. CryoLife was awarded CE Marks for its stentless porcine aortic and pulmonary heart valves in 1996 and 1998, respectively. CryoLife was also awarded CE Marks in 1998 and 1999 for its BioGlue surgical adhesive for applications in both vascular and pulmonary repairs.

Domestically, CryoLife scientists and regulatory personnel are working on the development of additional SynerGraft Model 500 and 700 clinical data relating to an IDE (Investigational Device Exemption) application to the U.S. Food and Drug Administration to use SynerGraft Model 500 and 700 pulmonary heart valves in human clinical trials. These IDE applications are expected to be made in the fourth quarter of 2001.

 

[srwieland]

Thanks, Jim, for suggesting this new forum and for getting it started. Perhaps we could transfer Peter Easton's discussion of biological vs. mechanicals over here, since it is really a discussion about new advancements and directions in valve options.

By the way, the CryoValve-SG valve that I received was a human (homograft) pulmonary valve that replaced my aortic valve. The animal tissue valves referred to in that article are for use in Europe, whereas my surgeon had access to the human valves being implanted here in the U.S. I'm not sure who else has access to it, although there are a few of the principal surgeon developers of it listed on the CryoLife website.

I am really busy catching up with work now that I'm back and nobody is cutting me any slack at work (or at home for that matter) anymore! The downside of such a quick and good recovery is that you lose all that good sympathy and TLC with it! But, I will put together a description of my story and post it here soon. Actually I have sketched out and somewhat drafted my personal story for permanent posting in that section of this site, but haven't had time yet to finish it.

Hope others push the envelope in this new forum with us too. I don't usually experiment on myself, but now that I have I'm truly eager to discuss it with others!

Thanks again Jim and let's talk to Peter Easton and get him over here in this section too.

 

[BillC]

A Question..

A Question..

Hi Steve ... just curious why you replaced your aortic valve with the CryoLife SG pulmonary valve.... why didn't you replace it with their aortic valve instead? Did it have to do with valve size or what?

 

[srwieland]

Don't know for sure. Just read it in the operative report. I do know that my valve size was relatively large, but I'll have to ask my surgeon to clarify it.

My understanding from various indirect things that I've read and heard is that aortic valves undergo much more pressure than pulmonary valves, and so aortic valves are not considered as good for 'harvesting', if you know what I mean. In other words, pulmonary valves are considered to be in generally better condition due to having undergone less stress in the donor's body and therefore are the preferred replacement valves even for the aortic valve location.

As far as the CryoValve-SG that I received, it is an aortic valve in the sense that it is prepared for aortic valve and not mitral valve replacements. However, it is a pulmonary valve by source.

Hope that helps. I'll pass on anything else I can find out about it.

P. S. Now you've really got me wondering! I just reflected that I also had the aortic root and part of the ascending aorta replaced, and I know that it was all one piece, so it doesn't make sense that it was a pulmonary valve. The operative report that I got a copy of was not the definitive one, which wasn't ready yet at that time, just the draft from the resident with spelling errors still in it. I'm going to check this out for sure and get back to you, because something is definitely wrong with my information.

 

[srwieland]

Clarification about the CryoValve-SG

Clarification about the CryoValve-SG

Wow! Got an incredible clarification from my surgeon about Bill's question regarding the CryoValve-SG being a pulmonary valve.

Indeed, the CryoValve-SG that I received was a pulmonary valve. He explained that CryoLife has not yet been able to successfully flush aortic valves of their living (i.e., genetic or DNA containing) cells because of their thickness. CryoLife has succeeded with pulmonary valves because they are thinner. Hence, they are providing altered pulmonary valves to replace aortic valves.

I asked if the thinner valve would have less structural integrity, and he replied that, normally, it would be somewhat less strong and durable. However, he quickly added that, in this case, because of the SynerGraft treatment, my new valve would be histilogically the same as a native aortic valve within a year (going by the results in the animal studies). He said that, since the pulmonary valve has no distinctly pulmonary cells left, my body would populate the valve with aortic cells and thicken and reform it to be just like a normal aortic valve.

Hope this clears things up, Bill, and feel free to ask more questions. Although I had thought I had pretty much understood what was going on, you truly had me stumped.

By the way, I also asked my surgeon another question about the rate of return of my heart to a normal size, since it was the symptoms such as atrial fibriallation resulting from my heart enlargement that precipitated my need for surgery at this time. He replied that it normally takes 1-3 years for enlarged hearts to return to normal.

However, about 15 minutes later, he called me back and reported that he had just reviewd my echocardiogram done about 4 weeks ago and, amazingly, my heart had indeed returned to normal size. From the echo I had just before surgery, my diastolic left ventricle size was 60 mm (56 mm is the upper limit of normal) and on the most recent echo (6 weeks after surgery and 4 weeks ago) it measured only 52 mm. Also, my systolic left ventricle size was 40 mm before surgery (40 mm is the upper limit of normal) and 36 mm after. My thickness hasn't changed much but it was at the upper limit of normal before surgery and so is not a big concern. He says that the diastolic size is the primary indicator of trouble and that it is very significant that mine has reduced so quickly to well within the normal range so soon after surgery. I'm sure that's a major reason why I am recovering so well.

Thanks for all your interest and encouragement and keep in touch.

 

[BillC]

Wow ..

Wow ..

Steve ... that is an incredible tale that you tell! It must be exciting to be part of this new technology. And it's that very thing that convinced me to go with the Homograph (and not mechanical)... I'm hoping in another 15-20 years when my probable re-op comes about, I'll be part of the grow-your-own generation.

Sorry to cause confusion about the pulmonary valve. After you clarified it, it makes perfect sense.

Take care and please stay in touch ~

 

[srwieland]

I will certainly stay in touch and thanks very much for your interest. I agree fully that, even if I too need another surgery in 15 years or so, or whatever, that the options will be greatly improved with every passing year. We need to all stay tuned as much as possible and share what we discover with all our heart buddies.

I wish you the best.

 

[Peter Easton]

More on Cryolife SG

More on Cryolife SG

Steve, Bill and friends --

As briefly related over on the "making the choice" thread of the Heart Forum, I had a further telephone conversation with Dr. Tom Martin of Shands yesterday about tradeoffs between the Cryolife SG valve and the CE Pericardium one in preparation for my upcoming operation (9/4). His analysis largely repeated and confirmed what Steve wrote above, with the following possible additional wrinkles.

I asked what the life expectancy would be for the Cryolife SG as a pulmonary homograft to the aortic position if it does not turn out to repopulate with my own cells, as hoped. He said "unclear" but probably a bit lower than an aortic-origin homograft or standard bovince/porcine replacement, since alien (is that the word?) pulmonary tissue in the aortic position has turned out to calcify a bit more quickly than the other varieties. The Ross Procedure uses, of course, a pulmonary valve to replace the aortic one, but in that case it is the patient's OWN pulmonary valve, not a donated one. So though the Cryolife SG is a perfenctly viable valve on its own independently of any native cell repopulation (which is, I guess, why it has already been approved by the FDA), its durability absent that outcome would seem to be on the lower end of the spectrum. In short, as said before, implantation of the Cryolife SG is at this point something of a roll of the dice, though a pretty good one, given the theoretical arguments for the technique, the results in animal trials and the piecemeal indications from examination of human recipients who have died of other causes.

In addition, Dr. Martin says that Cryolife has announced they will shortly be coming out with an aortic valve version of the genetically washed replacement, once they iron out final technical difficulties (mentioned by Steve) in washing out the thicker tissue of the AV. Martin says, though, that he doesn't really expect anything for another year or so. Now if I could postpone my operation that long .... Nah.

Peter

 

[Peter Easton]

A question for Steve

A question for Steve

Hi Steve --

A quesiton for you (or anyone else with the requisite experience) -- one I forgot to ask Dr. Martin.

In "regular" or classic homografts, one consideration or concern is the age of the donor relative to the age of the recipient. Is that an issue with the Cryolife SG, or does the reprocessing and washing that it undergoes change the issue? Did you happen to be aware/apprised of the age of your donor -- or did it make any difference?

Peter

 

[srwieland]

When I asked Dr. Martin about the donor, he replied that very strict selection criteria and protocol are in place for the procurement of donor tissue and that the donated valve has to be absolutely free of stuctural or other defect. Specifically, he said that donated valves must be completely absent of calcification or plaque or any kind of buildup on the tissues. Although I don't know anything about the donor, he seemed to agree with me that donors are probably young adults who died for reasons other than heart problems.

There is some interesting information about the procurement of CyroValves on the CryoLife website. There, they explain that they are supplied with the entire heart, and that only their own surgeon/technicians extract the valves from it. They further explain that they have arrangements to receive these donated hearts even before autopsies are performed, so that they're really 'fresh', with the agreement that they send back the 'remnants' for the medical examiner to autopsy.

To be honest, these discussions make me feel a bit 'creepy', but I certainly appreciate those who donate their organs for these purposes, even if I don't know anything specific about the donor in my case.

 

[Peter Easton]

Heart donors and donated hearts

Heart donors and donated hearts

We are all more intimately linked than we realize! I guess your answer also means that the "age" of a donor is relatively immaterial as long as the valve proves, on appropriate inspection, to be healthy and free of calcium and whatnot.

Coincidentally, I have a student who is doing his research on the development of professional and community education functions in Florida's "OPO's" (organ procurement organizations). It's a growing field.

Peter

 

[Jennie]

I may be signing up soon....

I may be signing up soon....

I met with a surgeon at Mayo Clinic in mid-December, and he suggested that I consider CryoLife's aortic SynerGraft homograph as the replacement for my aortic valve (provided he is unable to repair it). He said that these valves are being released in a month (mid-January?) exclusively to Mayo Clinic and another medical center in Oklahoma (I suspect U of O); they will not be available elsewhere at this time. He said I would be a prime candidate. A no-drug tissue with the hope of longevity!! It MUST be Christmas!! I received the literature from CryoLife, now I need to sit down and read it all....

 

[Chris Green]

Okay, can we get a few things clear?

Are we saying here that in the near future an aortic tissue valve that regenerates the recipients cells will be commercially available?

If so then this combined with non-intrusive surgery means that we could be looking at the holy grail in the next decade?

I don't want my chest ripped open.
I don't want this operation more than once.
I don't want to limit my lifestyle with drugs.
I hopefully have a number of years prior to the day.

How hopeful should I be?

 

[Jennie]

Hi Chris,

I am still trying to wade through my thoughts on this myself. From the literature, it seems that this valve has two things going for it (in my own layman's terms):

1. Decelluarization of the donor cells. I thought the big benefit of this was the replacement of those cells by the recipient's cells. Yes, true, but the literature seems to focus more on the concept that the removal of the foreign donor cells reduces the recipient's production of antibodies that attack foreign cells; thus the valve is less of a threat, is less attacked, and thus lasts longer.

2. Cryopreservation of the valve. They get a fresh tissue valve, straight from the donor, and supercool it, so that it is still "living". A living item tends to last longer that a dead one.

How hopeful to be? I wish I knew. There are no guarantees, there isn't a large quantity of data available yet, and certainly not long-term data. This valve is being presented to me as a "valve still under evaluation". Before they offer it to me, they will have to determine whether they believe it is ethical to offer such a product without first going through a trial. The surgeon tells me that hopefully it will last at least as long as a regular homograph, hopefully longer. Time will tell, huh.

Steve in Florida, on this site, and Mara too, have gotten CryoValves. I believe Steve's was a pulmonary valve that was placed in his aortic position, and I think Mara had a pulmonary valve placed in her pulmonary position as part of the Ross Procedure.

Your four hopes, these are mine too. Or, they were.

1. I don't want my chest ripped open. I can't stress this enough! But the surgeon is telling me this is big time stuff here, and he needs room to move. I say I want to be alive and have everything go well, so baby, take all the room you need.

2. I don't want this more than once either. Will a CryoValve last me forever? Don't know. I just need to make the best choice that I can, with what I know, and place myself in the hands of a capable surgeon and my all-powerful God, and trust that His good and perfect will be done in my life.

3. I don't want to limit my lifestyle with drugs, either. This is what I'm having to decide, do I want to risk a tissue?

4. I have no real choice over when the surgery occurs in my life - I would like to push it off indefinitely (and believe me, I've been trying to!), yet I would also like to stay alive and actually recover after surgery, and I've come to the point where I say, I don't know when I'm gonna hit the point of no return, so I should have it done sooner rather than later. I don't know that I have much of a choice here.

Anyway. I think the CryoValve has great promise. "A new hope for the future" says my surgeon. This could be the answer to one lifetime surgery and no drugs. As far as minimally invasive, I am doubtful, though I know others here would disagree. But, I think the chest split is something that you move on from to a degree, it becomes a thing of the past, relatively speaking when compared to your valve. And, let's hope that you have many years ahead of you before you come to surgery. Enjoy them, live them to the full, and don't worry too much about the future - don't let it spoil your present. "Each day has enough troubles of their own"!

hope this helps
Jennie

 

[Tom]

Hi Jennie,

Who is your surgeon at Mayo? I was operated on by Dr. Schaff in 8/99. I had an aortic homograft. He was great and I now feel great. St. Mary's is also a very nice hospital. I think you picked a good place. Best of luck to you.

Tom

 

[Jennie]

Hi Tom,

The surgeon I met with is Dr. Kenton Zehr. I have no doubts about his capabilities - he struck me as extremely competent. My wafflings right now are cold feet I suppose - do I REALLY need to get this done NOW?? Am I being an idiot to go with a valve that's still under evaluation?? Should I just go for the long haul with a mechanical? Should I get another opinion from another surgeon? These sorts of things. I will probably go with the current offerings, I just want to be sure!!

I'm glad to hear you're doing well! I've heard of Schaff before, somewhere on this board - maybe it was you. I'm curious as to your age and how long they estimated your homograph would last?

I finally called my Mayo doctor (several weeks late) yesterday, to discuss my questions. He was out, so I guess I'll talk to him on Monday.... Will keep you posted! Thanks for the encouraging words.

-Jennie

 

[Tom]

Hi Jennie,

It is a very tough decision. I received three opinions before I had my surgery. I had a bicuspid valve, moderate-severe AI, and a benign tumor in my ventricular outflow tract that was a major risk factor for embolus and stroke, so I could not put my surgery off. I went to Houston where I was told I should only have a mechanical. I sent my echos to another well-known surgeon who told me that I should only consider a biological valve, either a homograft or Ross procedure. At Mayo I was told they would try to repair my valve. If it was irrepairable, my surgeon would put in either a homograft or mechanical, depending on my wishes. I went with a homograft and was 45 when I had my surgery in '99. So far I am doing great and continue to snow ski and mountain bike. I was told that my valve should last about 15 years. I would recommend getting at least a couple of opinions. Whatever decision you make is the right one. There are no definitive answers, and all choices have their own benefits and drawbacks. You have to decide what fits your lifestyle the best. Can't say enough good things about Mayo and St. Marys.
Keep in touch,
Tom