High Volume Endurance Training and Tissue/Mechanical Valves...

[pellicle]

Hi
so, allow me to get back to this

but I haven’t found a good chart that is more recent ( let’s say 2018+)

here's the thing; we don't do studies on things which are

1. well established
2. nothing has changed
3. there is no funding for

Human metabolism has not undergone any observable evolution in genetics in the last few decades, and Warfarin has been studied since the 1950's (coming up for a century). Now there could be a case made for "mixed racial" studies but somehow I don't think you'll find much funding for that (unless you're tapping into something for "first nations budgets" and even then

• how many people will benefit from that
• how stable is their anticoagulation therapy drug adherence anyway
• what other compunding factors are there (booze is a big one for increasing INR)

its like water; we no longer study how many kcal is required to raise 1 L of water by x degrees C because that's well established and doesn't change. The same can not be said about Dark Matter and MOND ... or the search for that big particle and the next bigger hadron collider ¯\_(ツ)_/¯

So

and more importantly one that shows the trade off of bleeding vs thrombo just for aortic mech valves.

this is pretty clear and obvious ... high INR exacerbates bleeds, and the threshold is "patient dependent" due to factors like differences (and age degredation of the tunica intima (this is the inner layer of the artery wall, and is supported by the internal elastic lamina).

My dad as he aged bled easily and bruised easily, but he was never on warfarin or any "blood thinners". I blame the degredation over time of the above elastic systems.

High INR therefore simply allows a bleed to go longer and thus may unmask any small bleeds that were happening but not noticed before.

Now the threshold of thrombogenesis is a different matter altogether, its the interplay between the time taken for activated thrombin to bind to either a platelet and form a "raft" or to thrombomodulin. This is a receptor protein on the endothelial membrane of blood vessels. By changing the amount of activated thrombin (which is what warfarin does and by (perhaps also) changing the amount of platelets which can be activated (the role that aspirin performs) we then know our clotting tendency. There are of course a "5hitT0n" of genetic variations around this so we can't know it to within a high specificity for a particular person. Thus its a gamble to skirt too close to the lower bounds (and no doubt why the lower bound found in the well known (infamous?) study by On-X. (good reading here)

So rather than just look at "That Graph" I usually post lets as a single thing, lets look at another very similar graph which is discussed well here, that shows two things in one graph too...

We see a reasonably clear situation where early death rates are higher than "mid term" death rates and then death rates again go up over time ... "wear out failures" is probably intended to be applied to machines, but you know our bodies are just big clusters of very tiny molecular machines. This guy does fantastic visualisations of our molecular biology (and I'm pretty sure that if we put in death rates it would be very steep around the 70 year mark).







HTH

 

[Windfinder]

Hi
so, allow me to get back to this

here's the thing; we don't do studies on things which are

1. well established
2. nothing has changed
3. there is no funding for

Human metabolism has not undergone any observable evolution in genetics in the last few decades, and Warfarin has been studied since the 1950's (coming up for a century). Now there could be a case made for "mixed racial" studies but somehow I don't think you'll find much funding for that (unless you're tapping into something for "first nations budgets" and even then

• how many people will benefit from that
• how stable is their anticoagulation therapy drug adherence anyway
• what other compunding factors are there (booze is a big one for increasing INR)

its like water; we no longer study how many kcal is required to raise 1 L of water by x degrees C because that's well established and doesn't change. The same can not be said about Dark Matter and MOND ... or the search for that big particle and the next bigger hadron collider ¯\_(ツ)_/¯

So



this is pretty clear and obvious ... high INR exacerbates bleeds, and the threshold is "patient dependent" due to factors like differences (and age degredation of the tunica intima (this is the inner layer of the artery wall, and is supported by the internal elastic lamina).

My dad as he aged bled easily and bruised easily, but he was never on warfarin or any "blood thinners". I blame the degredation over time of the above elastic systems.

High INR therefore simply allows a bleed to go longer and thus may unmask any small bleeds that were happening but not noticed before.

Now the threshold of thrombogenesis is a different matter altogether, its the interplay between the time taken for activated thrombin to bind to either a platelet and form a "raft" or to thrombomodulin. This is a receptor protein on the endothelial membrane of blood vessels. By changing the amount of activated thrombin (which is what warfarin does and by (perhaps also) changing the amount of platelets which can be activated (the role that aspirin performs) we then know our clotting tendency. There are of course a "5hitT0n" of genetic variations around this so we can't know it to within a high specificity for a particular person. Thus its a gamble to skirt too close to the lower bounds (and no doubt why the lower bound found in the well known (infamous?) study by On-X. (good reading here)

So rather than just look at "That Graph" I usually post lets as a single thing, lets look at another very similar graph which is discussed well here, that shows two things in one graph too...

View attachment 890731

We see a reasonably clear situation where early death rates are higher than "mid term" death rates and then death rates again go up over time ... "wear out failures" is probably intended to be applied to machines, but you know our bodies are just big clusters of very tiny molecular machines. This guy does fantastic visualisations of our molecular biology (and I'm pretty sure that if we put in death rates it would be very steep around the 70 year mark).







HTH

 

[Windfinder]

Yes, the problem is the funding in this case, each brand only pays for their own study for their own product and that always has less credibility. I have read many of the articles, I just sent the graphs to compare to yours because I couldn’t get both using the phone. I had seen the LivaNova one that you share, it reminds me of the On-X…but there seems to be more and more consensus about a lower INR range for isolated AVR with newer aortic valves and manufacturers feel pretty confident about it ( not just On-X) and many reputable surgeons too but for some reason, an an individual level, most people are scared (including me) to go under INR 2…even more after reading some cases in here but of course these are always going to happen in any INR range.

 

[tjay]

Yes, the problem is the funding in this case, each brand only pays for their own study for their own product and that always has less credibility. I have read many of the articles, I just sent the graphs to compare to yours because I couldn’t get both using the phone. I had seen the LivaNova one that you share, it reminds me of the On-X…but there seems to be more and more consensus about a lower INR range for isolated AVR with newer aortic valves and manufacturers feel pretty confident about it ( not just On-X) and many reputable surgeons too but for some reason, an an individual level, most people are scared (including me) to go under INR 2…even more after reading some cases in here but of course these are always going to happen in any INR range.

You're correct. Getting scared of numbers is human nature, but it varies from one individual to another. For example, some people get scared of aorta being ruptured at 4.5 cm while others carry on thru 5 cm (or 5.5 cm). But then everyone's genetics or biology is different, and lack of such personalized biomarkers will continue to dog us (including in the case of INR management at a given level).

There are some folks here who're very confident about lower INR numbers as advertised (e.g. with On-X valve), and are sticking to those. You can search this website for their opinions. I'm too new to this post-op phase and watching, but lean on optimizing it, and not higher the better bandwagon.

For normal population who don't have valve issues or take coumadin for any reason, people have different probability of stroke. Why would (some of) that not continue to be a factor afterwards.

 

[pellicle]

but lean on optimizing it, and not higher the better bandwagon.

Do we have such a group?

 

[pellicle]

most people are scared (including me) to go under INR 2…

You may have noticed me saying that depending on your stroke risk (have you had one, have you had one at INR > 2) the preoperative management (for things like colonoscopies, biopsies and minor surgeries) can be done more subtly than the usual calls for you going off warfarin for a week beforehand, commencing heparin bridging no then resuming post procedure is overkill.

I usually suggest that it's all statistical risk analysis, and if your only issue is mechanical valve that managing INR down to under 1.5 (in consultation with the surgeon / clinician) is entirely adequate.

Eg
https://cjeastwd.blogspot.com/2017/12/perioperative-management-of-inr.html

https://cjeastwd.blogspot.com/2022/05/rapid-dust-off-inr-management.html

As to one's regular INR range I avoid recommending anything and recommend you and your surgeon and or cardiologist be followed because they (should) know your specific particulars.

Best wishes

 

[Windfinder]

You may have noticed me saying that depending on your stroke risk (have you had one, have you had one at INR > 2) the preoperative management (for things like colonoscopies, biopsies and minor surgeries) can be done more subtly than the usual calls for you going off warfarin for a week beforehand, commencing heparin bridging no then resuming post procedure is overkill.

I usually suggest that it's all statistical risk analysis, and if your only issue is mechanical valve that managing INR down to under 1.5 (in consultation with the surgeon / clinician) is entirely adequate.

Eg
https://cjeastwd.blogspot.com/2017/12/perioperative-management-of-inr.html

https://cjeastwd.blogspot.com/2022/05/rapid-dust-off-inr-management.html

As to one's regular INR range I avoid recommending anything and recommend you and your surgeon and or cardiologist be followed because they (should) know your specific particulars.

Best wishes

Yes I have noticed you say that and I totally agree with it from what I’ve read and what I have been told.
In regards to particular INR range, my cardio agrees with the reduced AC but he agrees that the 1.5 to 2 INR is too narrow even with frequent home monitoring. He told me to stay around 2 and not worry about it since at that level he says bleeding risk it’s so low that it’s irrelevant and/or difficult to quantify for a single individual.

 

[tjay]

Do we have such a group?

It seems that the consensus here (based on certain studies) seems to go higher INR (say 2.5, 3 or even higher) even if someone's cardiologist suggested a particular number (e.g. 2). Everyone's situation and biology is different. Then, we also have to listen to our body e.g. i used to bleed very easily even before surgery, low platelets etc. My blood is also very thin, perhaps because of decades of living a certain lifestyle and herbs etc. No family history of strokes. So I've to factor all that in as well. Some members here may get swayed, or left confused, if they feel they may be maintaining INR too low, even if their prescribed range is personalized for them.

I'm too early in tracking but I feel I've to listen to everyone: On-X marketing range (FDA approved), consensus here, my cardiologist's opinion, and my own inner voice That's all I meant.

 

[tjay]

It seems that the consensus here (based on certain studies) seems to go higher INR (say 2.5, 3 or even higher) even if someone's cardiologist suggested a particular number (e.g. 2). Everyone's situation and biology is different. Then, we also have to listen to our body e.g. i used to bleed very easily even before surgery, low platelets etc. My blood is also very thin, perhaps because of decades of living a certain lifestyle and herbs etc. No family history of strokes. So I've to factor all that in as well. Some members here may get swayed, or left confused, if they feel they may be maintaining INR too low, even if their prescribed range is personalized for them.

I'm too early in tracking but I feel I've to listen to everyone: On-X marketing range, consensus here, my cardiologist's opinion, and my own inner voice That's all I meant.

Then I wonder what patients in the developing and underdeveloped world do in terms of INR management. They probably get mechanical valve (mostly), and I wonder if they are assigned INR management teams, home-meters or readily access to lab testing etc. If they are given proper training, or monitoring, or if patients stick to guidelines and recommendations themselves (e.g. limiting leafy greens, liquor etc to name a few).

Their mechanical valves "probably" go thru more abuse or sub-optimal handling (not all fault of their own), and I wonder if any studies are done there, or any data available otherwise.

Again, we don't have to revert in that direction, rather make good use of our access to healthcare and training, but I can't help but wonder what their bleeding and stroke risk is, as we watch the same like a hawk here in the west.

May all live healthy and happy thereafter, everywhere.

 

[pellicle]

Hi

It seems that the consensus here (based on certain studies) seems to go higher INR (say 2.5, 3 or even higher) even if someone's cardiologist suggested a particular number (e.g. 2).

ahh ... I see now what you mean. I guess it depends on what you mean by "optimising" ... as you said:

I'm too new to this post-op phase and watching, but lean on optimizing it,

so, given that you're new and don't have much experience could you explain what you mean by optimising? Is it:

1. making it the lowest it can be before you get a stroke?
2. making it the easiest to enable you to maintain a single dose without having to constantly make changes chasing an INR that you can't quite sit on (such as 2) because it drifts a bit?
3. is it to make stroke less likely in the face of increased bleed risks (not many bleeds are even dangerous, but most strokes are)

Please define your view on "optimising"

I'm already on warfarin now for over 13 years; I've had no thrombo events (but I have cut myself and had one impromptu bleed which turned out to be something more common than I thought (or so the dr's surgery informed me) and something which I took no actions on and it started dissipating by itself over the next 3 or so days.

Apparently these happen more with age (I was 58 then) and are not rare. I've not since had another.

Now, in contrast you may prefer to optimise your INR below that level I do (my INR is set to a target of 2.5, and I take no action on changing dose until its over 3.0 or below 2.0), in which case how do you know you are not risking a stroke over a longer period until you've had one?

I'm keen to know.

Lets examine the usual graph I post (still haven't read those other studies nor been able to find them to have any sort of faith). We understand that if you are maintaining an INR between 1.5 and 1.9 that you'll have something like a 0.266 percent risk of stroke per year. As the odds are usually calculated the other way (what are the chances you'll be OK) that is 1 - 0.266 = 0.734 (where 1 is a certainty and 0 is no chance). The formula to determine the "odds" is risk R to the power of the number of years n you are interested in so that's R^n

Sadly this gives me only a 4% chance that I will not have had a stroke by this time

However if we were to use the On-X approach

https://pmc.ncbi.nlm.nih.gov/articles/PMC6472691/

The mean follow-up was 3.8 years and was 98% complete. The mean age was 55 years. ... The mean INR was 1.89 in the test group and 2.5 in the control group (p < 0.001).​

which is quite interesting because if we take "that graph" and run that out to n = 4 we get about 31% chance that nobody has had a stroke, so they made a bit of a safe bet in choosing that duration of follow up (and they did have a higher stroke incidence but down played that).


So when "optimising" one needs to be clear on what you are calling optimal and why.

Again, taking "that graph" data in the table:

and electing to be above 2.2 but under 3.0 we can most likely expect to not hit the "fifty fifty" point until about 33 years.

I'll make my own optimisation towards safety; because blood cells are more easily replaced than brain cells; and I'll trust the literature (and as it happens my cardiologist and surgeon totally agree with all of the above) more than one persons cardiologist. Indeed, its not just "me and my cardio and my surgeon" its this whole organisation



Click image or here for text.

Lastly on the penalty for getting it wrong; from a member here with a bio prosthesis (you don't apparently need warfarin for them anyway right?)

https://www.valvereplacement.org/threads/different-strokes.889520/

​

An MRI of my head a few days later showed tiny cerebellar infarcts, which the consultant said might explain my symptoms. It thankfully wasn’t a bigger and more debilitating cerebellar infarction. These tiny infarcts were new and not showing on my previous August MRI following the double vision episode. I’ve noticed distinct short-term memory issues since this “minor stroke”.​

Best Wishes

 

[tjay]

I actually have no INR related concerns at this time. I was just responding to someone else's concerns/questions. I was trying to say that we may overthink INR at times, and tend to doubt our own prescribed or well researched numbers

I'm cool with my own INR situation for now, and will seek advice as necessary. I know we've experts like you here, Pellicle. I appreciate your detailed response and calculations. You are always here to help I know.

Thanks

 

[pellicle]

I was trying to say that we may overthink INR at times, and tend to doubt our own prescribed or well researched numbers

indeed ... and I've never deviated from my surgeons recommendation
Last years data; a couple of points approaching 3, one below it and a bit of dose dancing to keep it under control there

presently I'm dosing 7mg again (LHS vertical is INR RHS vertical is daily mg)

 

[nobog]

Their mechanical valves "probably" go thru more abuse or sub-optimal handling (not all fault of their own), and I wonder if any studies are done there, or any data available otherwise.

I don't know where you came up with that .....

 

[pellicle]

I don't know where you came up with that .....

I suspect that he means "improper anticoagulation" ... not handling associated with implantation.
¯\_(ツ)_/¯
dunno
Younger generations seem woefully unskilled at framing a statement or even just using the English language in any sort of manner that allows a listener (who isn't them) to get it. Reddit is perhaps the prime offender (although Facebook is a close second)

 

[tjay]

I don't know where you came up with that .....

The paragraph above the one you tagged provided the context:

Then I wonder what patients in the developing and underdeveloped world do in terms of INR management. They probably get mechanical valve (mostly), and I wonder if they are assigned INR management teams, home-meters or readily access to lab testing etc. If they are given proper training, or monitoring, or if patients stick to guidelines and recommendations themselves (e.g. limiting leafy greens, liquor etc to name a few).

 

[pellicle]

Then I wonder what patients in the developing and underdeveloped world do in terms of INR management.

I'm sure that it depends on financial capacity. I know some people here from India have used Coaguchek, I guess (because I know some do) many just go to a clinic at some interval ... perhaps monthly.

Many are on Sinthrome and INR variability is different there.

I'd say by and large most people everywhere just bumble through

I've had conversations with many Indians over the years here

 

[tjay]

I'm sure that it depends on financial capacity. I know some people here from India have used Coaguchek, I guess (because I know some do) many just go to a clinic at some interval ... perhaps monthly.

Many are on Sinthrome and INR variability is different there.

I'd say by and large most people everywhere just bumble through

I've had conversations with many Indians over the years here

Point was that modern mechanical valves may have more tolerance than we probably assume.
In any case, it wasn't too important to discuss here.

 

[pellicle]

Point was that modern mechanical valves may have more tolerance than we probably assume.

what do you mean by tolerance? Only INR range? Because I'm pretty sure that the valves are made to highly exacting tolerance. They are very durable (but this isn't tolerance) and not demonstrated to be significantly more or less tolerant to endocarditis.

If its the INR, then what do you think I'm usually arguing when I share evidence that anywhere between 2.4 and 4.5 isn't dangerous?

https://www.valvereplacement.org/th...d-tissue-mechanical-valves.889793/post-938023

Its pretty important to be clear about what one means to not give the wrong idea to readers.

If you are actually arguing that dose can remain fairly constant and the amount of INR variation found will not effect health then I would agree with you and again point to the data I point to above.

 

[d333gs]

I’m 72 yo and almost two years out from getting an Inspiris Resilia tissue valve. I have 3,700 road cycling miles so far this year and often ride in the 65–85% of MHR zone. My last echo was normal. In discussing with my cardiologist the issue of wearing out my valve with hard aerobic efforts, his view was that the relatively small percentage of time I’m in those training zones compared with the time at a low heart rate during daily normal activities isn’t of concern. Of course, I realize two years isn’t a good test of potential longevity of my valves.

Good stuff! How many times a week are you biking? What are you getting your heart rate up to?