DrSclafani answers some questions

[drsclafani]

Sensitivity of 70% and specificity of 22% leave much to be desired. 30% of patients with positive US results will undergo unnecessary venography and 76% of patients who have a negative ultrasound will not get a venogram that can diagnose and treat their ccsvi

According to the Albany data's sensitivity and specificity results, ultrasound would not a very good screening test. it misses too much disease and adds too much cost by doing venography in too many patients without disease.

is that understandable? The conclusions are debatable but not based upon the data of their paper.

I understood this better today than the first time I read through it.
The use of IVUS might lower the false positive rate, with the false positives becoming accurate positives if ivus showed that venography is missing some stenoses that had been picked up by doppler ultrasound pre-imaging, but it's speculation because IVUS wasn't used.
I have to read the abstract again. http://www.sirmeeting.org/index.cfm?do= ... s&abs=2088

Cece, this is a very confusing but very important concept. I hope all the readers stay with this because this is going to be an important determinant of the quality of the service.

A false positive is a test that is called positive when it is actually negative. That should not be the problem with CCSVI. Most series are reporting at least two veins abnormal in CCSVI.

The use of IVUS generally lowers the false negative rate of venography. in other words, venograms that are interpreted as normal (or negative) (or absent abnormality) when IVUS shows an abnormal valve, web or septum are FALSE NEGATIVE VENOGRAMS. Thus IVUS lowers the false negative rate and increases the true positive rate. If the prevalence of the abnormality is high, like CCSVI in MS, then a group with a high negative rate should use IVUS to weed out the false negatives. THAT IS IIMPORTANT.

And it's not just the idea of detecting a stenosis or treating a vein. Some of the physicians are admitting they are performing angioplasty based upon flow disturbances and arbitrarily dilating lots of the vein, especially azygous, without LOCALIZING the abnormality.They are not seeing the cause of the flow disturbance.

keep asking questions. this is important in the evaluation of diagnoses and therapeutic technical outcomes.

[Cece]

And it's not just the idea of detecting a stenosis or treating a vein. Some of the physicians are admitting they are performing angioplasty based upon flow disturbances and arbitrarily dilating lots of the vein, especially azygous, without LOCALIZING the abnormality.They are not seeing the cause of the flow disturbance.

I have heard of this too. The benefit would be that the abnormality, if there is one, gets ballooned, so it does not go untreated. The drawback would be that healthy vein is ballooned as well, unnecessarily. This would carry a risk of complications such as clotting, intimal hyperplasia, scarring, etc. As techniques go, I've considered this not the best and not the worst. And I think the best is the goal.

The use of IVUS generally lowers the false negative rate of venography. in other words, venograms that are interpreted as normal (or negative) (or absent abnormality) when IVUS shows an abnormal valve, web or septum are FALSE NEGATIVE VENOGRAMS. Thus IVUS lowers the false negative rate and increases the true positive rate. If the prevalence of the abnormality is high, like CCSVI in MS, then a group with a high negative rate should use IVUS to weed out the false negatives. THAT IS IIMPORTANT.

Ok, we are now talking venograms, not doppler ultrasounds. A venogram shows no CCSVI. It is a negative, and no one knows it is a false negative, until IVUS is used and a hidden stenosis is revealed. Now the venogram can be identified as having been a false negative and the venogram+IVUS combination has revealed the true positive.

About a hundred more word problems of this nature are probably needed. It is complex with the layers of doppler ultrasound false or accurate positive or negative, venogram false or accurate positive or negative, and venogram+IVUS as the gold standard ('the buck stops here'). (And even then, will there be false negatives on IVUS that are shown to be positives when superIVUS that is like OCT is used?)

I remember another doctor asking in regards to IVUS, if indeed it increases the precision, how much precision is necessary?
It's possible that superIVUS is more precision than is necessary but I see many uses for the precision that can be obtained using IVUS.

[Robnl]

OK, when a bloodflow disturbance is seen....can stenosis/malformed valves appear at any 'moment' between 'switch' arterie-veins and 'switch' veins-arterie (a.k.a. the heart)??

What i mean f.e.; can a stenosis also be close to the heart??? or can a bunch of 'closed' capillaries result in bloodflow disturbance, can that be visualized??

[drsclafani]

OK, when a bloodflow disturbance is seen....can stenosis/malformed valves appear at any 'moment' between 'switch' arterie-veins and 'switch' veins-arterie (a.k.a. the heart)??

What i mean f.e.; can a stenosis also be close to the heart??? or can a bunch of 'closed' capillaries result in bloodflow disturbance, can that be visualized??

capillaries can be seen with a microscope. There is one called a nail fold videocapillaroscope, that looks at the capillaries in the nail fold. Normal dimensions of a capillary are 6-10 microns in diameter.

i am not sure of what you mean by switch arteries and veins

[drsclafani]

And it's not just the idea of detecting a stenosis or treating a vein. Some of the physicians are admitting they are performing angioplasty based upon flow disturbances and arbitrarily dilating lots of the vein, especially azygous, without LOCALIZING the abnormality.They are not seeing the cause of the flow disturbance.

I have heard of this too. The benefit would be that the abnormality, if there is one, gets ballooned, so it does not go untreated. The drawback would be that healthy vein is ballooned as well, unnecessarily. This would carry a risk of complications such as clotting, intimal hyperplasia, scarring, etc. As techniques go, I've considered this not the best and not the worst. And I think the best is the goal.

If you can't see what you are ballooning, how can you validate that you actually dilated it and seen that you did anything to improve it

[drsclafani]

The use of IVUS generally lowers the false negative rate of venography. in other words, venograms that are interpreted as normal (or negative) (or absent abnormality) when IVUS shows an abnormal valve, web or septum are FALSE NEGATIVE VENOGRAMS. Thus IVUS lowers the false negative rate and increases the true positive rate. If the prevalence of the abnormality is high, like CCSVI in MS, then a group with a high negative rate should use IVUS to weed out the false negatives. THAT IS IIMPORTANT.

Ok, we are now talking venograms, not doppler ultrasounds. A venogram shows no CCSVI. It is a negative, and no one knows it is a false negative, until IVUS is used and a hidden stenosis is revealed. Now the venogram can be identified as having been a false negative and the venogram+IVUS combination has revealed the true positive.

Yes, things are always compared against another standard thought to be a superior examination. In our situation, i think it safe to say the IVUS and venography provide a "golder" standard. Is it better than autopsy? possibly. How about surgery? impractical. How about against OCT? or "superIVUS" good question.

[Cece]

If you can't see what you are ballooning, how can you validate that you actually dilated it and seen that you did anything to improve it

Indirectly it is validated if the flow disturbance is resolved?

This reminds me of the ISNVD debate about, "It's all about the valve." Should the IRs focus on treating the structural abnormality or should they focus on treating the flow abnormality.

I am on the side of treating the structural abnormality, if that is what causes the flow abnormality. Treat the cause not the effect.

Hey, you're posting right now! Yes, venography + ivus may be better than autopsy because in autopsy, the process of fixing the veins may obscure whether the valves are fixed, stiff and immobile.

[Cece]

OK, when a bloodflow disturbance is seen....can stenosis/malformed valves appear at any 'moment' between 'switch' arterie-veins and 'switch' veins-arterie (a.k.a. the heart)??

What i mean f.e.; can a stenosis also be close to the heart??? or can a bunch of 'closed' capillaries result in bloodflow disturbance, can that be visualized??

Stenoses can be anywhere. Valvular stenoses typically appear in areas where valves are commonly found. We've seen images from Dr. Sclafani of innominate vein stenosis, which is closer to the heart than a jugular vein stenosis. But I think you are asking if valves typically appear at the junctions between veins and other veins? Such as the jugular valve is just before the junction between the jugular and the innominate vein? Or the vertebral valve just before the junction of the vertebral vein to the subclavian? I don't know if the innominate vein has a valve. After that it's the superior vena cava, and a stenosis there could cause superior vena cava syndrome and be treated without any of the controversy of CCSVI.

But I'm responding because of the last part you said fits with what Dr. Clive Beggs said awhile back. He was hypothesizing and it's nothing proven, but it made sense. He said that a possible explanation for patients who get no improvements is that the capillaries of the brain may have been thickened due to chronic reflux and all the negative conditions of CCSVI. These thickened capillaries could be causing resistance to blood flow within the brain itself. Restoring flow in the jugulars would not much help such a condition of thickened capillaries of the brain. I would imagine that such a condition, if it exists, can indeed be visualized and could help explain why some patients are nonresponders. I do not think this would be useful in patient selection because I think it would still benefit such patients to have their CCSVI treated.

Ok, back to Dr. Sclafani....

[drsclafani]

I remember another doctor asking in regards to IVUS, if indeed it increases the precision, how much precision is necessary?
It's possible that superIVUS is more precision than is necessary but I see many uses for the precision that can be obtained using IVUS.

Do you recall that short paper from Italy, that looked at CIS and ultrasound and did not find any correlation? Could it be that the valve abnormalities are not seen because the tissue is not thick enough or echogenic enough? I always ask myself why dont i see valves all the time and why not in patients w relatively early symptoms. While not a precise assessment, it is my impression that some patients with severe and prolonged ccsvi have thicker valves, more visible and more brightly echogenic . In other patients the degree of thickening and echogenicity is very mild. Indeed almost imperceptable. Do you remember the web in the vertebral vein that looked like a little dot? Perhaps a more refined and accurate IVUS will show such things all the time.

we certainly are not going to learn that without looking, are we? I do find it odd that there is so much resistance to IVUS. I know i was resistant to it throughout my career. I think it was a lot about unfmailiarity and resistance to change rather than any logic. But the question is also a valid one, How much precision is necessary? We will only find out after we have more precision.

[THEGREEKFROMTHED]

DR SCLAFANI...WERE YOU IN THIS AUDIENCE?

[Cece]

IVUS has a learning curve, you've said so yourself. Any doctor who has already mastered flouroscopy might not find IVUS as useful as flouroscopy until they've climbed the learning curve. And there's the expense, and time added on to the procedure, and the way they're doing it is the way they've always done it (which would be familiarity, which you said already). It's a lot to get past unless there is the research coming in showing that venogram+IVUS is superior.

I am on the edge of my seat waiting for images from new IVUS.

There is the notion that CCSVI begets more CCSVI. The reflux of CCSVI causes the valves at the heart of the flow abnormalities to be affected by those flow abnormalities and, over time, there would be that thickening and worsening. Yes, I remember the Italy paper, although I grouped it in with a bunch of papers finding no results, and did not think about it much. Very interesting.

[HappyPoet]

DrS, thank you for taking the time to explain to us the importance of understanding these definitions, concepts and how they apply to CCSVI and IVUS. I learned so much!

I'm saddened, though, for the many patients who might not realize they will have an incomplete procedure--a procedure without IVUS--and I'm maddened that many IRs still perform such incomplete procedures, especially when some have reaped great profits from this patient population; imo, these IRs can afford to invest in IVUS and training. The question is why aren't they??? DrS, do you know the percentage of patients you treated for CCSVI who turned down IVUS?

Edit: Cece, I didn't see your post until after I submitted mine. I agree that some IRs will cite the need for studies, but I believe, and think you'd agree, this reasoning is a weak argument, if not an outright cop-out, for IRs to spend time and money on IVUS now.

Edit: Drs, I forgot to say that you're "Leader of the pack... VROOOM, VROOOM." I see you driving the new one-thousand horsepower Shelby Cobra Mustang GT1000 which, unbelievably, is street-legal.

Edit: All readers, to clarify, my question, "The question is why aren't they???" is rhetorical and related to my prior sentence about money--I don't want anyone thinking I missed reading DrS's last post about why he thinks IVUS isn't used by more IRs.

No more edits, I promise!

[Robnl]

OK, when a bloodflow disturbance is seen....can stenosis/malformed valves appear at any 'moment' between 'switch' arterie-veins and 'switch' veins-arterie (a.k.a. the heart)??

What i mean f.e.; can a stenosis also be close to the heart??? or can a bunch of 'closed' capillaries result in bloodflow disturbance, can that be visualized??

capillaries can be seen with a microscope. There is one called a nail fold videocapillaroscope, that looks at the capillaries in the nail fold. Normal dimensions of a capillary are 6-10 microns in diameter.

i am not sure of what you mean by switch arteries and veins

I mean; blood with oxygen is going in organs etc, and than veins transport the blood back to the heart -> so, can stenosis occur in every part of the veinsystem; from the start to the heart (and than especally from the brain to the heart. Until now i've never read about a case with stenosis close to the heart

videocapillaroscope; that's a great hangman word, doc

[Robnl]

Cece wrote:

But I'm responding because of the last part you said fits with what Dr. Clive Beggs said awhile back. He was hypothesizing and it's nothing proven, but it made sense. He said that a possible explanation for patients who get no improvements is that the capillaries of the brain may have been thickened due to chronic reflux and all the negative conditions of CCSVI. These thickened capillaries could be causing resistance to blood flow within the brain itself. Restoring flow in the jugulars would not much help such a condition of thickened capillaries of the brain. I would imagine that such a condition, if it exists, can indeed be visualized and could help explain why some patients are nonresponders. I do not think this would be useful in patient selection because I think it would still benefit such patients to have their CCSVI treated.

Yes, that's what i mean; and a few problematic capillaries would cause no harm ( i think) but when a lot of them are problematic than it could slow down the bloodflow, right? And create pressure?

[drsclafani]

DR SCLAFANI...WERE YOU IN THIS AUDIENCE?

nah, i wuz liftin da tshirts