When Edwards' INSPIRIS RESILIA Valve will be market available in US?

[Nocturne]

I'll also repost something I posted earlier about CAC score growth. A shocking number of docs are completely ignorant about this -- even my current doc actually told me that the statin she gave me will freeze CAC growth! Nonsense. Anyway:

* * * * *

I've recently been doing some more reading and figuring on CAC scores, and I've come to the conclusion that there may be a bit of wowsering and fear-mongering coming from some circles.

I'm not saying that the CAC score is an invalid measure of CHD risk or anything -- far from it! But a couple of things have made me think in the last day or so, and I'm going to share them here.

First, this:

http://www.ajronline.org/doi/pdf/10.....181.3.1810743

This is a fairly old paper from 2003 discussing the use of CAC scores to stratify risk in patients. Nothing particularly new here, except I noticed some of the graphs that are located down just a bit where they plot average CAC score by age and percentile rank. If you scroll down a bit, you'll find them. When I saw them, it struck me that it appeared that CAC grew rather quickly early on but growth seemed to taper off as score and/or age rose. You can clearly see this with every percentile rank -- so it's not just a matter of the top 1% showing "less growth" where that could potentially be confounded by people simply dying of heart disease once their CAC scores got above a certain threshold.

Today, I went to the MESA website and closely examined their data for CAC scores by age and percentile rank. You can find the website here:

https://www.mesa-nhlbi.org/Calcium/input.aspx

I wrote down and made a rough graph of my own for CAC score by age and percentile rank for caucasian men. Then I calculated yearly percentage growth of CAC for ten year spans of time from ages 45-55, 55-65, 65-75, and 75-84 (the MESA data does not go above age 84).

What I found was very interesting. It would seem that across percentile ranks, CAC growth rate (in the form of percent growth per year) DOES slow down as scores and age get higher. Again, this is true across percentile ranks, so it's not just a matter of this being an illusion caused by people at the top of the range dying off when their scores get above a certain point.

We've all heard the statistics about CAC growing at "an average of 20% per year," or "up to 30% per year," and similar scary information. And this analysis (which you can do for yourself with the MESA data if you have the time) reveals these statements to be true -- for certain age groups and percentile ranks. Between the ages of 55 and 65, caucasian men in the 50th percentile rank for CAC do indeed see a rise in CAC of 27% per year. But this shifts to an average of only 13% per year between the ages of 65-75, and slows down again to 9% per year between the ages of 75-84.

It's impossible to calculate growth for the bottom 25% of the caucasian male cohort's range until they reach 65, as they have no measurable CAC until just before this point, but between 65 and 75 they show an average growth of 26% per year, which slows to 12% per year between the ages of 75 and 84.

At the 75th percentile, there is growth of a whopping 53% per year from the age of 45-55, but this again slows to 17% per year from 55-65, 10% per year from 65-75, and 7% per year from 75-84.

And at the 90th percentile rank, CAC growth is 21% per year on average from 45-55, 13% per year from 55-65, 10% per year from 65-75, and only 6.5% per year from 75-84.

I even ran the numbers for the top 99th percentile rank, which is sadly where I am at, and found growth of 13% per year from the ages 45-55, 13% per year from 55-65, 9% per year from 65-75, and 3.5% per year from 75-84 -- although I am sure that at this far end of the bell curve, there MUST be at least some confounding of the data by people simply dying off at ultra-high CAC scores and causing people with lower scores to become the "new top 1%".

What does this mean?

Well, consider a caucasian man of 55 who learns that his CAC score is a whopping 234 (placing him at the 90th percentile rank for caucasian men of his age). He does some reading and learns that typical CAC growth is 20% per year, and that a score of 1000 is considered "crazy-go-nuts high". He whips out his calculator to learn with horror that at a normal growth rate his score will be 1448 by age 65, 8970 by age 75, and an impossible 55,546 by age 85. He concludes that he'll never live to see 85, and will probably be dead by his late 60s -- if he's LUCKY!

But that's not necessarily true, even if his progression is simply average from then on in. In reality, his CAC score will likely be about 802 by age 65, 2030 by age 75, and 3848 by age 84.

Now those ARE terrible scores, and he'd be best off doing whatever he can to slow down CAC growth as much as he can -- but he isn't doomed to die young, even if he has typical CAC progression.

Now for me, personally, in the top 1% bracket -- it's still pretty damned ugly, but not as ugly as it might seem at first. If I progress at about 20% per year until age 45, I'll be about 260 by then, and then the average progression rates from that point on would put me at 913 by age 55, 3099 by age 65, and 7336 by age 75. If I somehow lived to 84, I'd be pushing 10,000 -- what I consider "critical mass" because we never hear of anyone actually reaching that point, and because the MESA data doesn't go above 9999. So I have EVERY reason to try to slow my CAC growth by as much as possible! But even if I can't, and I progress at the "average" rates -- I don't hit "critical mass" at 65 or so, like a flat 20% per year progression would have me do.

This information is important to the average Joe, who may factor at age 55, CAC score 10, and progression rate of 27% on a repeat scan that he's doomed to have a score of 7800 by age 85 and no hope of ever seeing 90. That's not the case at all. He should still take steps to improve his health and his odds, but he can relax a bit and let go of some unhealthy anxiety.

 

[hx77]

Thanks "Doctor" Nocturne! You are so knowledgeable in this topic, you deserve the title!

I felt so terrible about myself that I did not push for a cardiac catheterization exam. I knew my CAC was out of range but I didn't know it's so extreme. Last February, I met a doctor and a retired nurse on a cruise ship. Both of them were very worried after learning my CAC scores.

AV calcification might not be a big issue for me. I have done three echo tests and all three mentioned "mildly calcified leaflets". I believe my valve is bicuspid as it was reported on all three echo reports and the recent MRA. I will talk to my family doctor to get the Lpa tested in a few weeks at my annual physical exam.

You are lucky that you know your CAC score and its implications so you could deal with it. You might want to do an angiogram or a similar test to evaluate your coronary arteries at some point. Good luck to you!

Thank you very much for the links for the Lpa. I will read and digest during the weekend. Ionis's new drug looks promising and hopeful to me.

 

[Nocturne]

Thanks "Doctor" Nocturne! You are so knowledgeable in this topic, you deserve the title!

Well, I'm no Pellicle, but I try.

I felt so terrible about myself that I did not push for a cardiac catheterization exam. I knew my CAC was out of range but I didn't know it's so extreme. Last February, I met a doctor and a retired nurse on a cruise ship. Both of them were very worried after learning my CAC scores.

AV calcification might not be a big issue for me. I have done three echo tests and all three mentioned "mildly calcified leaflets". I believe my valve is bicuspid as it was reported on all three echo reports and the recent MRA. I will talk to my family doctor to get the Lpa tested in a few weeks at my annual physical exam.

You are lucky that you know your CAC score and its implications so you could deal with it. You might want to do an angiogram or a similar test to evaluate your coronary arteries at some point. Good luck to you!

Thank you very much for the links for the Lpa. I will read and digest during the weekend. Ionis's new drug looks promising and hopeful to me.

Yeah, this stuff is scary as heck, and it's scarier because few people really know about it. Most cardio docs I talk to about it are either ignorant or lying to make me feel better; I'm never absolutely sure which. When a doc tells you that a statin will "freeze" your CAC growth, they are flat out wrong. When they tell you not to worry about sky-high Lp(a) because it "doesn't change your treatment", they are handing you a line. It's not out of malice, they just genuinely don't know much about the threat or do know and don't know what to do about it. Barring an Esselstyn type diet, which would leave you jealous of the dietary freedoms of diabetics who also have Celiac disease, and which may or may not work anyway, there isn't much you can do about Lp(a) or CAC growth.

There is a researcher named Budoff who I have gotten email responses from twice, who does research with CAC growth and Kyolic aged garlic extract. He claims it can slow CAC growth significantly, but the only person I have met who has taken it for an extended period of time (a fellow over on the Lp(a) Foundation forums) hasn't seen any reduction in CAC growth. I take the stuff anyway, because hey, my life is on the line, but the truth is there just isn't any established treatment for extremely high CAC score or Lp(a) other than the standard "eat a Mediterranean diet and get your exercise" routine that everyone else gets. Here's what I see: they know you're screwed, they just don't know what to do about it. And maybe they'd rather be dealing with patients that they actually know how to help.

That being said, it's not like you are doomed to die young. I have one grandfather, no doubt a carrier of the gene that raises my Lp(a), who had a stroke in his late 40s and died of a heart attack in his early 50s. I have another grandparent (not sure if it was my grandmother or grandfather, one had a stroke and the other suffered more than one heart attack) who had to have also been a carrier, and they both lived to be 89. What were their CAC scores like? I don't know.

Interesting that you have "mildly calcified leaflets". I have that on my first ECHO as well, along with a vague note about my leaflets being -- not bicuspid, but "odd". "Structurally tricuspid but functionally bicuspid" or some such. That, I do not understand.

I would be far less worried if I could see that I was unlikely to ever reach a CAC score that was beyond what other people have been known to get to, before reaching an unrealistically high age like 100. But I see the MESA and other studies top out around 10,000, and I know I'll be there before 85 with an average progression, and I am not sure for certain what that means but I know it can't be good.

Get your Lp(a) checked and maybe get a 23andme genetic test run and see what you can learn. I sort of feel like for me, the damage to my heart is already done, but it isn't too late for my kids or yet-to-be-born grandkids, so I'd better stay on top of it for their sake. I don't want any of them having to wake up at 41 to a knock on the door and a telegram announcing that their 40s are now effectively their 60s, like I got. Not for them.

Good luck and don't be a stranger!

 

[ozsky]

Welcome to this forum hx77. One thing is for sure......advances in the science of heart valve replacement will continue, so any treatments of yesterday and today will be replaced by the advances of tomorrow......and , as the old saying goes, "tomorrow never comes". Make the decision that you, with the help of your docs, makes the most sense in your situation. As many have posted in the past........"there are no bad choices" and no choice of today cannot be undone in the future, if or when, the magic forever fix is found.

Hi ****, your mechanical valve is different from valves nowadays right? It requires higher INR or the same as today's valves, as 2.0 ?
thank you

 

[dick0236]

Hi ****, your mechanical valve is different from valves nowadays right? It requires higher INR or the same as today's valves, as 2.0 ?
thank you

Yes, it is quite different from the leaflet valves of today. It is "a little free floating plastic ball that moves up and down (opens and closes) within a metal cage". It is the same valve as the one introduced by Edwards Lifesciences iin 1960 and was manufactured by Edwards until 2007 without major redesign. It does require a slightly higher INR range (2.5-3.5).....not a big deal. My Cardio says these old Starr-Edwards ball valves are like the Sherman Battle Tanks (you have to be old enough to remember WW II)....they just "take a licking and keep on ticking".

BTW, the "INSPIRIS" tissue valve that started this thread is also manufactured by the same Edwards Lifesciences.....they have been a front runner in this industry from the beginning.

 

[ozsky]

Yes, it is quite different from the leaflet valves of today. It is "a little free floating plastic ball that moves up and down (opens and closes) within a metal cage". It is the same valve as the one introduced by Edwards Lifesciences iin 1960 and was manufactured by Edwards until 2007 without major redesign. It does require a slightly higher INR range (2.5-3.5).....not a big deal. My Cardio says these old Starr-Edwards ball valves are like the Sherman Battle Tanks (you have to be old enough to remember WW II)....they just "take a licking and keep on ticking".

BTW, the "INSPIRIS" tissue valve that started this thread is also manufactured by the same Edwards Lifesciences.....they have been a front runner in this industry from the beginning.

yes, Edwards Lifesciences is a brilliant company
specialized in heart valves. That's why I planned to choose Magna Ease tissue Valve at the first place. Although I changed to st Jude at the end.

I know some guys working in Edwards Lifesciences Chinese branch, they are good people and help me alot.

 

[carolinemc]

hx77, you mentioned that you are a smoker. Time to quit that bad habit. It had done a number on my aortic valve by the time I had my bypass and aortic valve replacement 16 years ago. Please get into a program and get rid of that smoking, you will feel better afterward.

 

[hx77]

hx77, you mentioned that you are a smoker. Time to quit that bad habit. It had done a number on my aortic valve by the time I had my bypass and aortic valve replacement 16 years ago. Please get into a program and get rid of that smoking, you will feel better afterward.

Hi Caroline, Thank you for your concerns. But I am not a smoker.

Hi Nocturne, I called and asked my family doctor to prescribe lp(a) test. I received test results for Lipoprotein fractionation. The results show I am not a high risk of CVD. I need to redo the test for lp(a).

As an update to my status, I did nor rush to an operating room. I am taking medical therapy for my CAD and I have less symptoms now. I have contacted a MIDCAB expert who said there is no urgency for me to do bypass for the LAD. He also questioned the angiogram conclusion that my LC is 70% blocked. He thought it's more likely 50%, consistent with my untrained eyes. I still prefer to do a bypass for LAD to improve quality of life. I am waiting to hear back from that surgeon.

I just took statin for three weeks and I have already further improved my lipoprotein profile. My recent blood test shows my LDL is only 58, HDL 65, Trig 61. I am keen to know my lp(a) reading.

Merry Christmas and Happy new year to everyone!

 

[Paleowoman]

Hi John,

I just remembered that you mentioned in an earlier post in this thread that you had developed some “micro-circulation”. I have just remembered reading about that on another forum and how some people totally avoid CABG because they develop sufficient “micro-circulation” - it’s called “collateral circulation”. No one seems to know why some people develop it, which saves them from heart attack and from surgery even, and why others don’t develop it. Here’s a couple of articles about it in case you’re interested: http://heart.bmj.com/content/89/11/1352 and https://www.ucl.ac.uk/news/news-articles/1109/30092011-heart-back-up-system

 

[hx77]

Hi Anne,

Thank you very much for the links! You are right it's called "collateral". My LAD is collateralized from RCA. I just do not know how sufficient it is. A few weeks ago, I still have the symptoms - chest pain, short of breath, angina etc. These symptoms are less common now after taking beta blockers. So I guess it's prudent to have a bypass (MIDCAB).

In a previous post several years ago, you mentioned you started vitamin K2 therapy to reduce chance of calcification in valves. K2 works against antiplatelet drugs like aspirin. I wonder how you seek a balance between the two. Thanks!

Merry Christmas and happy New Year!

John

 

[Paleowoman]

In a previous post several years ago, you mentioned you started vitamin K2 therapy to reduce chance of calcification in valves. K2 works against antiplatelet drugs like aspirin. I wonder how you seek a balance between the two. Thanks!

Hi John - I don't take aspirin or any antiplatelet drugs so it's not a problem. I'm not sure K2 helped the calcification on my bicuspid valve, although the valve was only moderately calcified when I had AVR so who knows ? Anyway, I have had three CT angiograms now over the past ten years and in none of them has any coronary plaque or coronary calcification be identified, calcium score 0, yet I always have very high cholesterol: total cholesterol around 320, LDL around 200, but HDL always around 135 and triglycerides around 45.

I started to take the K2 to help with osteoporosis but the added benefit is that it helps stop calcification in the coronary arteries. K2 puts calcium in the bones and keeps it away from the arteries, at least that's what I have read and understood.

 

[astle9]

i appreciate that this post appears to have slightly veered off of the original post but i will be having this valve fitted at New Cross Hospital Wolverhampton UK in the next 1 to 3 months, my surgeon seems to feel at 50 it has the potential to see me through the rest of my life and will enhance my active lifestyle, no guarantees of course.

 

[Warrick]

i appreciate that this post appears to have slightly veered off of the original post but i will be having this valve fitted at New Cross Hospital Wolverhampton UK in the next 1 to 3 months, my surgeon seems to feel at 50 it has the potential to see me through the rest of my life and will enhance my active lifestyle, no guarantees of course.

Thats great imo, hope it all goes well for you !

It certainly looks like it will change the landscape for AVR

 

[hx77]

Hi astle,

Good to hear you will get an Inspiris valve, first on this board. If you outlive the lifespan of the valve, you could get TAVR without OHS. What kind of symptoms you have now? What are your mean and peak gradients? What's the aortic valve area?

Best wishes,
John

 

[hx77]

yet I always have very high cholesterol: total cholesterol around 320, LDL around 200, but HDL always around 135 and triglycerides around 45.

Hi Anne, If statins don't work for you, there is new generation of PCSK9 inhibitors what lower cholesterol very effectively. Praluent and Repatha are two such drugs. You may also want to have your lp(a) tested.

 

[Paleowoman]

Hi Anne, If statins don't work for you, there is new generation of PCSK9 inhibitors what lower cholesterol very effectively. Praluent and Repatha are two such drugs.

Hi John - my cholesterol, though very high, is fine due to my lipid profile which is very protective: very high HDL, very low triglycerides, which means that the LDL is the large fluffy type which is benign, hence my CT angiograms over the past ten years have shown completely clear coronary arteries and calcium score of 0. That's why I mentioned my cholesterol lipid profile. Not everyone with high cholesterol gets heart disease, or rather high cholesterol may not be the cause of heart disease - some people with low cholesterol get heart disease - just think about it

 

[astle9]

Hi astle,

Good to hear you will get an Inspiris valve, first on this board. If you outlive the lifespan of the valve, you could get TAVR without OHS. What kind of symptoms you have now? What are your mean and peak gradients? What's the aortic valve area?

Best wishes,
John

Hello i have a heart murmur from childhood and i have only in the last year been bothered by it, i have had the echocardiogram and the other one through the groin, my surgeon explained that in the future if the valve becomes a problem any further surgery would be done as a TAVR, i admit to not understanding the technical jargon but i am happy to be guided by the team. My symptoms are shortness of breath and some dizziness.

 

[hx77]

Hi Noc,

Finally I got my lp(a) number. At my first lp(a) test, doctor ordered lp(farc). I went back to his office and took a second blood draw. I even told the lab the insurance code for the test as it's not in their system. Several weeks have passed and they never got back me with the results. Last week, when visiting a cardiac interventionist at a hospital, I asked the doctor to order lp(a) test for me. This morning I received the result.To my happiness, my lp(a) is 18! This is consistent with my being receptive to statins and it provides a better hope to treat my CAD.

Thank you for educating me lp(a). One less thing to worry about now.

John

 

[newarrior]

Ha ha! Doctor Nocturne! I'm the only adult of four living in this house who is NOT a doctor!

Calcium score of 777 at age 50? Well hot damn! That puts you right up in the 99th percentile for age -- just like me. You lucky dog, you!

Considering your otherwise great numbers (and assuming they have always been so), I'd say there is a very good chance that you have astronomically high Lp(a), like me. I'd get that looked into ASAP. Your docs probably never looked at it because they either didn't know anything about it or just don't like feeling impotent because there's really not much that can be done about high Lp(a) (Agian will disagree -- he is partly correct but his methods involve utilizing medication that is prohibitively expensive here in the USA and also niacin, which when I took it seems to have rocketed my fasting blood glucose into prediabetes).

The hopeful news is that there is a medication being developed by Ionis Pharmaceuticals (currently in stage 3 trials) that can lower Lp(a) by over 90%. We'll see how the situation in the States limits that med to the rich and famous, if it even passes through the FDA.

Are you absolutely sure that your valve is bicuspid? There is great and growing evidence that high Lp(a) increases one's odds of developing AVS. My own valve is noted as being tricuspid (normal) but "acting" bicuspid -- tricuspid morphology but functionally bicuspid or something like that.

If your Lp(a) is high, you might consider looking at your genetics (as Lp(a) is almost entirely determined by genetics -- it doesn't care what you eat or how much you exercise or how much you weigh). I have two copies of the faulty allele LPA rs 10455872, which results in sky high Lp(a) levels and about five times the normal chance of developing AVS. I learned this on my own by getting a 23andme genetics test done and from information gleaned at the Lp(a) Foundation website.

Here are a few things to look at:

Lp(a) Foundation Website:
http://www.lipoproteinafoundation.org/default.asp?

Lp(a) Foundation video about Lp(a) and AVS:


MESA risk score calculator, CAC inclusive:
https://www.mesa-nhlbi.org/MESACHDRisk/MesaRiskScore/RiskScore.aspx

pdf of a Nomogram predicting 5-15 year survival, CAC inclusive:
medicalxpress.com/pdf416763197.pdf

The most recent and most positive study regarding AVR and relative lifespan I have found to date:
j-atamis.org/icfj/index.php/icfj/article/download/138/pdf-2

The most positive study on long term survival with high CAC I have found to date:
https://www.sciencedirect.com/science/article/pii/S0735109707019328

If you want any help interpreting any of that, I'd be happy to. I will say that there are studies out there with less positive conclusions -- I'm just offering you the happy ones.

In a nutshell, if these studies are to be believed, your high CAC score shaves less than 5 years off of your life on average, and if you had AVR right now you'd have about a 75% chance of living at least another 20 years.

Get your Lp(a) checked, and if it's very high and you have kids, have them get theirs checked too. Mine is a monstrous 160+ (where 12 or so is average and 50 is "extremely high risk"), and my 4 kids are 50, 50, 100, and unknown. If Ionis' drug works, I want them on it before they start having to deal with this nonsense.

My LPA is 249 and my calcium scores are in the thousands. Hands tricuspid aortic stenosis with massive calcification beyond belief in my fifties

 

[newarrior]

Well, I'm no Pellicle, but I try.




Yeah, this stuff is scary as heck, and it's scarier because few people really know about it. Most cardio docs I talk to about it are either ignorant or lying to make me feel better; I'm never absolutely sure which. When a doc tells you that a statin will "freeze" your CAC growth, they are flat out wrong. When they tell you not to worry about sky-high Lp(a) because it "doesn't change your treatment", they are handing you a line. It's not out of malice, they just genuinely don't know much about the threat or do know and don't know what to do about it. Barring an Esselstyn type diet, which would leave you jealous of the dietary freedoms of diabetics who also have Celiac disease, and which may or may not work anyway, there isn't much you can do about Lp(a) or CAC growth.

There is a researcher named Budoff who I have gotten email responses from twice, who does research with CAC growth and Kyolic aged garlic extract. He claims it can slow CAC growth significantly, but the only person I have met who has taken it for an extended period of time (a fellow over on the Lp(a) Foundation forums) hasn't seen any reduction in CAC growth. I take the stuff anyway, because hey, my life is on the line, but the truth is there just isn't any established treatment for extremely high CAC score or Lp(a) other than the standard "eat a Mediterranean diet and get your exercise" routine that everyone else gets. Here's what I see: they know you're screwed, they just don't know what to do about it. And maybe they'd rather be dealing with patients that they actually know how to help.

That being said, it's not like you are doomed to die young. I have one grandfather, no doubt a carrier of the gene that raises my Lp(a), who had a stroke in his late 40s and died of a heart attack in his early 50s. I have another grandparent (not sure if it was my grandmother or grandfather, one had a stroke and the other suffered more than one heart attack) who had to have also been a carrier, and they both lived to be 89. What were their CAC scores like? I don't know.

Interesting that you have "mildly calcified leaflets". I have that on my first ECHO as well, along with a vague note about my leaflets being -- not bicuspid, but "odd". "Structurally tricuspid but functionally bicuspid" or some such. That, I do not understand.

I would be far less worried if I could see that I was unlikely to ever reach a CAC score that was beyond what other people have been known to get to, before reaching an unrealistically high age like 100. But I see the MESA and other studies top out around 10,000, and I know I'll be there before 85 with an average progression, and I am not sure for certain what that means but I know it can't be good.

Get your Lp(a) checked and maybe get a 23andme genetic test run and see what you can learn. I sort of feel like for me, the damage to my heart is already done, but it isn't too late for my kids or yet-to-be-born grandkids, so I'd better stay on top of it for their sake. I don't want any of them having to wake up at 41 to a knock on the door and a telegram announcing that their 40s are now effectively their 60s, like I got. Not for them.

Good luck and don't be a stranger!

I followed the esselstyn diet religiously in 2020 and then somewhere in 2021 when I got hospitalized for over 2 weeks with the Coronavirus and didn't have a choice as to what I could eat I felt like I started slipping. I'm now around 5 ft 8 or 9:00 I think I'm shrinking at 175 lb but I should be down closer to 155 160. When I was on his diet I was consistently at about 158. I'm afraid that I may have expedited my aortic stenosis but I'm not sure if it matters anyways because my lipoprotein is like 250 which I found out in 2021. I think the extreme diet that he recommends that I was on which is admittedly boring lowers my risk of arterial and heart disease but isn't going to do much for my valve disease.