I really enjoyed this conversation. It brought back my time as a nurse echocardiographer when my hospital was enrolled in early TAVR research. We did the studies that screened patients for enrollment in the TAVR program based on calculated valve area, LVOT diameters, etc. At the time only people at greater risk for complications or death from surgical AVR were enrolled. It was fascinating and extremely exciting to see patients before and after TAVR benefit immediately from the percutaneous procedure. I also wondered where the debris went that certainly was broken off of the brittle old stenotic valve, though I don't remember seeing many patients end up with stroke. The information that there's less debris than one might imagine is reassuring. Also, the finding that people with prior stroke or potentially debilitating stroke seem to have more benefit is intriguing.
One thing I do wonder about the use of hospitals as the instrument to pseudo randomize is the variability of skill that develops when a particular device or procedure is done more often in certain hospitals, especially teaching hospitals. Possibly Dr Cohen et al had a way to take that into account?
Anyway, thank you John for this delightful interview. I always enjoy your podcasts and welcome you at my breakfast table regularly.
Glad you enjoyed the discussion. Regarding your question, the instrumental variable analysis handles differences in skill with deploying embolic protection devices the same way as it is handled in any randomized trial. In other words, we are assessing the "average skill" across all the centers that used embolic protection. The question you have asked is definitely an interesting one, but would probably be better studied using a different design.
Great interview. Much learning was had. Thank you.
The last point dovetails with Dr. Prasad’s post yesterday, the part about how teaching of research methods is woefully inadequate during the course of training (I’d submit from med school through end of fellowship, at least in my era). I need to learn much more about instrumental variable analysis as a methodology, but it sounds promising to a newb like me.
I particularly appreciate how Dr. Cohen is obviously a proponent who is still acutely aware of, and checks, his blind spots. Interesting that his analysis almost replicated the protected TAVR results wrt ARR. This gives further confidence that there is “probably” a real benefit with this device, AND that benefit is probably very small. I would be interested in an ICER type analysis at this point, cuz the device isn’t cheap but neither is the downstream cost of disabling stroke.
As for the variable, I wonder whether “hospital” provides more quasi-randomization for urgent issues (eg MI) than for elective procedures like TAVR. OTOH, I think the presence of a falsification analysis is additionally compelling to further demonstrate quasi-randomization. The methods section of this paper provides value far beyond the subject matter at hand.
I'm glad you found the conversation interesting and eduational. I agree with your assessment that hospital center is probably even a better instrument (i.e., more random) for emergency hospitalizations like for acute MI or stroke. However, this is where having some clinical expertise comes in handy. Having spent about 15 years doing TAVR, it is clear to me that the vast majority of patients go to their "local center" for these procedures rather than shopping around making the site pretty darn close to a random variable.
Doctors place a valve up the aorta, across the diseased valve, and then place the new valve into the old valve. The verbs squishing or smooshing come to mind.
I don’t have a clear picture of how the valve is inserted from your description. Is the chest still cut open? Sewing involved? Would you mind describing the procedure a little more?
I have an article you may find of interest
How does salt restriction lead to heart dis-ease and fear based reactionary thinking?
I describe the link between dehydration or hyponatremia, same same, and the adrenals.
Hyponatremia is an emergency status. The adrenals run the show in emergencies. Deploying all the adrenocortical hormones not just aldosterone.
Chronic dehydration results in chronic adrenal control.
RAAS is switched off with salt.
Symptoms of low salt or dehydration need to be learnt so they can be remedied asap.
Eg a headache is not a signal to take a Panadol.
I assert chronic dehydration is the cause of dementia. Brains are extremely sensitive to dehydration. Women are taking up 70% of the dementia beds.
This is because women require more salt. Women are designed to carry and lose more fluid than men.
Hydration equals salt plus water. Water follows salt.
The salt restriction directives are responsible for the huge increase in chronic dis-ease.
Compare statistics from 1980 to 2023, many fold increases.
Think about chronic kidney dis-ease, aldosterone reverses the natural mode of kidney filtration, from removing excess salt to scavenger.
The salt sensitives have enlarged adrenals. Their hypertension without cause is easily explained by extra adrenal response to salt. Adrenals are not designed to be used chronically. A condition that salt restriction ensures. They have two choices: exhaustion or extra production via enlargement.
Infertility is also ensured with salt restriction. An emergency is no time for bringing children into being. The adrenals prevent conception.
The IVF industry has been built on salt restriction directives.
Food preservation prior to refrigeration used a lot of salt.
Salt aids digestion. HCl production requires salt. Low stomach acid causes heart burn. Food fermentation in the intestines causes gas to push open the valves as it ascends upwards, taking stomach acid with it.
And finally, I must update my article I recently learned
To restrict salt is an old colonial strategy used to induce dehydration, stress intolerance and compliance Eg harsh salt controls in India and the salt march of Gandhi.
I also have an article that logically dismisses the gaseous exchange of oxygen and carbon dioxide.
We breathe air not oxygen.
Mammalian physiology is based on hydration NOT oxygenation.
Oxygen toxicity is due to its power to dehydrate. Oxygen is primarily prescribed for the terminally ill NOT for breathlessness. Palliative care is not kind.
The lungs are rehydrating the RBCs as they pass through the alveoli capillaries with salt water. An IV saline infusion does the same.
The red light monitoring is checking hydration NOT oxygenation.
Reactive oxygen species ROS describes damage due to dehydration.
I assert dehydration is the insult that creates dis-ease.
I really enjoyed this conversation. It brought back my time as a nurse echocardiographer when my hospital was enrolled in early TAVR research. We did the studies that screened patients for enrollment in the TAVR program based on calculated valve area, LVOT diameters, etc. At the time only people at greater risk for complications or death from surgical AVR were enrolled. It was fascinating and extremely exciting to see patients before and after TAVR benefit immediately from the percutaneous procedure. I also wondered where the debris went that certainly was broken off of the brittle old stenotic valve, though I don't remember seeing many patients end up with stroke. The information that there's less debris than one might imagine is reassuring. Also, the finding that people with prior stroke or potentially debilitating stroke seem to have more benefit is intriguing.
One thing I do wonder about the use of hospitals as the instrument to pseudo randomize is the variability of skill that develops when a particular device or procedure is done more often in certain hospitals, especially teaching hospitals. Possibly Dr Cohen et al had a way to take that into account?
Anyway, thank you John for this delightful interview. I always enjoy your podcasts and welcome you at my breakfast table regularly.
Glad you enjoyed the discussion. Regarding your question, the instrumental variable analysis handles differences in skill with deploying embolic protection devices the same way as it is handled in any randomized trial. In other words, we are assessing the "average skill" across all the centers that used embolic protection. The question you have asked is definitely an interesting one, but would probably be better studied using a different design.
Great interview. Much learning was had. Thank you.
The last point dovetails with Dr. Prasad’s post yesterday, the part about how teaching of research methods is woefully inadequate during the course of training (I’d submit from med school through end of fellowship, at least in my era). I need to learn much more about instrumental variable analysis as a methodology, but it sounds promising to a newb like me.
I particularly appreciate how Dr. Cohen is obviously a proponent who is still acutely aware of, and checks, his blind spots. Interesting that his analysis almost replicated the protected TAVR results wrt ARR. This gives further confidence that there is “probably” a real benefit with this device, AND that benefit is probably very small. I would be interested in an ICER type analysis at this point, cuz the device isn’t cheap but neither is the downstream cost of disabling stroke.
As for the variable, I wonder whether “hospital” provides more quasi-randomization for urgent issues (eg MI) than for elective procedures like TAVR. OTOH, I think the presence of a falsification analysis is additionally compelling to further demonstrate quasi-randomization. The methods section of this paper provides value far beyond the subject matter at hand.
I'm glad you found the conversation interesting and eduational. I agree with your assessment that hospital center is probably even a better instrument (i.e., more random) for emergency hospitalizations like for acute MI or stroke. However, this is where having some clinical expertise comes in handy. Having spent about 15 years doing TAVR, it is clear to me that the vast majority of patients go to their "local center" for these procedures rather than shopping around making the site pretty darn close to a random variable.
Hi John
Doctors place a valve up the aorta, across the diseased valve, and then place the new valve into the old valve. The verbs squishing or smooshing come to mind.
I don’t have a clear picture of how the valve is inserted from your description. Is the chest still cut open? Sewing involved? Would you mind describing the procedure a little more?
I have an article you may find of interest
How does salt restriction lead to heart dis-ease and fear based reactionary thinking?
I describe the link between dehydration or hyponatremia, same same, and the adrenals.
Hyponatremia is an emergency status. The adrenals run the show in emergencies. Deploying all the adrenocortical hormones not just aldosterone.
Chronic dehydration results in chronic adrenal control.
RAAS is switched off with salt.
Symptoms of low salt or dehydration need to be learnt so they can be remedied asap.
Eg a headache is not a signal to take a Panadol.
I assert chronic dehydration is the cause of dementia. Brains are extremely sensitive to dehydration. Women are taking up 70% of the dementia beds.
This is because women require more salt. Women are designed to carry and lose more fluid than men.
Hydration equals salt plus water. Water follows salt.
The salt restriction directives are responsible for the huge increase in chronic dis-ease.
Compare statistics from 1980 to 2023, many fold increases.
Think about diabetes.
Salt restriction, adrenal cortical hormones, increased cortisol levels increases blood glucose.
Think about chronic kidney dis-ease, aldosterone reverses the natural mode of kidney filtration, from removing excess salt to scavenger.
The salt sensitives have enlarged adrenals. Their hypertension without cause is easily explained by extra adrenal response to salt. Adrenals are not designed to be used chronically. A condition that salt restriction ensures. They have two choices: exhaustion or extra production via enlargement.
Infertility is also ensured with salt restriction. An emergency is no time for bringing children into being. The adrenals prevent conception.
The IVF industry has been built on salt restriction directives.
Food preservation prior to refrigeration used a lot of salt.
Salt aids digestion. HCl production requires salt. Low stomach acid causes heart burn. Food fermentation in the intestines causes gas to push open the valves as it ascends upwards, taking stomach acid with it.
And finally, I must update my article I recently learned
To restrict salt is an old colonial strategy used to induce dehydration, stress intolerance and compliance Eg harsh salt controls in India and the salt march of Gandhi.
I also have an article that logically dismisses the gaseous exchange of oxygen and carbon dioxide.
We breathe air not oxygen.
Mammalian physiology is based on hydration NOT oxygenation.
Oxygen toxicity is due to its power to dehydrate. Oxygen is primarily prescribed for the terminally ill NOT for breathlessness. Palliative care is not kind.
The lungs are rehydrating the RBCs as they pass through the alveoli capillaries with salt water. An IV saline infusion does the same.
The red light monitoring is checking hydration NOT oxygenation.
Reactive oxygen species ROS describes damage due to dehydration.
I assert dehydration is the insult that creates dis-ease.
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