1. CCSVI: Can We Justify this Procedure at this Time? - Pro -
CRT 2012
Washington, DC, USA, Feb 4-7, 2012
10min
CCSVI: Can We Justify this Procedure at this Time?
- Pro -
Horst Sievert, Ilona Hofmann
CardioVascular Center Frankfurt,
Frankfurt, Germany .
CCSVI: Can We Justify this Procedure at this Time? - Pro
4:40PM
4:50PM
Horst Sievert, MD
Diplomat Ballroom
CCSVI: Can We Justify this Procedure at this Time? - Con
5:00PM
Richard F. Neville, MD

2. Horst Sievert, MD Consulting Fees: CSI Epitek Gore HLT Lifetech NDC
Recor

3. Consulting Fees:
Trireme
Veryan
Trivascular
My presentation will include off label discussions:
Not yet decided

4. Conflict of Interest Statement
Physician name
Company
Relationship
Horst Sievert
Access Closure, AGA, Ardian, Arstasis, Atritech, Atrium, Avinger, Bard, Boston Scientific, Bridgepoint, CardioKinetix, CardioMEMS, Coherex, Contego, CSI, EndoCross, Epitek, Evalve, ev3, FlowCardia, Gore, Guidant, Lumen Biomedical, HLT, Kyoto Medical, Lifetech, Lutonix, Medinol, Medtronic, NDC, NMT, Occlutech, Osprey, Ovalis, pfm Medical Mepro GmbH, ReCor, Rox Medical, Sorin, Spectranetics, SquareOne, TriReme Medical, Trivascular, Veryan Medical, Viacor
Consulting fees,
Travel expenses,
Study honoraria
Cardiokinetix, Access Closure, CoAptus, Lumen Biomedical, Coherex
Stock options,
Stocks 4

5. Jugular Vein Angioplasty for Treatment of Multiple Sclerosis
... is certainly one of the most controversial interventional treatments
Interventionalists are eager to do it
Neurologists are eager to fight against it
Patients travel around the world to get it

6. Does it work?
I really don't know!

7. Can We Justify this Procedure at this Time?
Yes, we can!

8. Yes, we can – but ... ... only under certain circumstances!
Patient should not have other options
Which always seems to be the case
Patient should understand
that we do not really know
whether the procedure helps
whether the effect – if any – is long lasting
the potential risks of the procedure

9. "But there is no evidence at all"
That is true and not true!
There are no randomized trials
not even well controlled non-randomized trials
But there are thousands of patients who have experienced substantial benefit!
You can not just ignore!

10. There are many other treatments without very good evidence!
Appendectomy
PCI
Safety belts
Hip replacement
Drinking water
Aspirin against headache
Vascular surgery for PAD
Could all be placebo!

11. "I have operated on thousands of patients with PAD!
Dr. Richard F. Neville:
"I have operated on thousands of patients with PAD!
And I know very well that it is not placebo – even without randomized trial!"

12. I believe you!
But the colleagues in Poland, India and Slovenia have told me the same about venoplasty!

13. I know you do not believe them ...
... and I am also not 100% convinced

14. But it is very common for all new discoveries that nobody could believe it or even think about it before it was discovered

15. Nobody could think about it before it was done
Antibiotic treatment for gastric ulcer
Bypass surgery
PCI
TAVI
Driving a car
Flying to the moon
The wheel
Pizza
America

16. What is the concept of venous angioplasty for MS?
MS is the result of venous obstructions of cerebral and spinal cord veins
or these obstructions aggravate MS
Treatment of these obstructions can
improve symptoms and/or
slow down or even reverse progression of MS

17. What is MS? An inflammatory disease Wide range of symptoms
currently considered to be an autoimmune disease
Wide range of symptoms
Paresthesia, ataxia, dysarthria, pain, fatigue,….
Incidence 1 : 1,000
Associated with
Past Ebstein-Barr virus exposure
History of smoking
Living far away from the equator
Living close to high altitudes
Some genetic factors

18. What does MS mean for the economy and the health care system?
In hospital treatment or one single relapse costs > 12,000 US $
Annual costs are > 47,000 US $ per patient
Total annual costs in the UK: 1.4 billion GBP
O'Brien et al, BMC Health Serv Res 2003, 3:17

19. What does MS mean for the individual patient?
A progressive disease which leads to severe disability and/or death
Medical therapy
has severe side effects
Cardiotoxicity
Bone marrow suppression
Neoplasms
Immunosuppression
and it is ineffective!
Patients do not have an alternative

20. Cerebral and central venous duplex
Zamboni et al: Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2009, 80:358
65 patients with MS
235 controls
Cerebral and central venous duplex
Blinded analysis
Venography in patients with flow abnormalities

21. Duplex MS patients controls p 71% 0% < 0.0001 61% 37% 52% 3% 55%
IJ or vertebral venous refux
71% 0%
<
Deep cerebral venous reflux
61%
B-mode demonstration of venous stenosis
37%
IV or vertebral occlusion
52% 3%
Failure of IV to dilate in recumbency and/or collapse when erect
55%
11%
Zamboni et al: J Neurol Neurosurg Psychiatry 2009, 80:358

22. Venography
Patients with at least 2 duplex findings had significant extracranial venous stenosis
Jugular stenosis: 91 %
Azygos vein stenosis 86 %
Zamboni et al: J Neurol Neurosurg Psychiatry 2009, 80:358

23. 70 patients with MS Age 15-58 Symptoms 0.5-40 yrs
Simka et al: Extracranial doppler sonographic criteria of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. Int Angiology 2010, 29:109
70 patients with MS
49 relapsing-remitting
5 primary progressive
16 secondary progressive
Age 15-58
Symptoms yrs

24. IJ or vertebral reflux 43% IJ stenoses 87%
Simka et al: Extracranial doppler sonographic criteria of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. Int Angiology 2010, 29:109
≥ 2 Zamboni criteria 90%
IJ or vertebral reflux 43%
IJ stenoses %
IJ or vertebral occlusion 53%
Abnormal IJ response to standing %
Conclusion: Multiple sclerosis is highly correlated with chronic cerebrospinal venous insufficiency

25. Venous angioplasty in 65 patients with MS Mean FU 18 mo Results
Zamboni et al: Prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J Vasc Surg 2009, 50:1348
Venous angioplasty in 65 patients with MS
Mean FU 18 mo
Results
50% relapse free
Pts with active MS lesions 50%12%
Significant symptomatic improvement in the majority of patients

26. What supports the theory of CCSVI?
MS plaques have a perivenous distribution
MS Lesions have an increased parenchymal iron deposition (like in venous stasis)
Venous abnormalities in MS had been described by others decades before Zamboni
Leriche et al, Acta radiol Suppl 1976
Aboulker et al, Acta Radiol Suppl 1976
Brunereau et al, Am J Beuroradiol 1996

27. The CCSVI theory impaired venous flow ↓
leakage of red blood cells from vessels
red blood cell degradation and accumulation of iron
iron stimulates an inflammatory response
2006 Zamboni P. The big idea: Iron dependent inflammation in venous disease and proposed parallels in multiple sclerosis, J of the Royal Society of Medicine

28. Current Status of Venoplasty
>> 10,000 patients have been treated worldwide
Very low risk
Only very few severe complications
Mostly after stent implantation
Several single center series have shown impressive results regarding symptoms
Randomized trials are planned but have not yet really taking off

29. The clinical benefit of the procedure is amazing
I would wish that all our procedures would have such a clinical benefit

30. -----Message d'origine-----> De : Lucie Godbout [mailto:lucie
-----Message d'origine-----> De : Lucie Godbout Envoyé : 7 décembre :49> À : Objet : RE: CCSVI diagnostic and treatment Hi, News from Canada: Before the intervention Jacques didn't feel his right leg and his right arm, he had extreme fatigue and had a speech problem at the end of the day. He also had problems of bladder. He couldn't work all week long and not long hours. As you saw the day after the intervention, Jacques was feeling much better. It's been almost 1 month since Jacques had the intervention. He has never felt better.  He doesn't have any symptoms anymore.  Everything is back to normal.  He restarted to work 5 days a week until 6:00PM.  He started to take some long walks, even a little bit of jogging, even if I told him it was too early to do so. Thanks again for everything! I will write to you in a month. Have a very Merry Christmas! Lucie and Jacques

31. Could it still be placebo?
Yes, of course

32. You know what one of my patients said when I told him about the placebo effect?

33. "I have talked to other patients who had this procedure
"I have talked to other patients who had this procedure! Some of them had MS for more than 20 yrs. They have gone through all kind of therapies – and had experienced nothing than side effects. After this venoplasty, they for the first time had a benefit. And this benefit was striking!"

34. "I am looking forward to have this placebo effect!"
"You know what?"
"I am looking forward to have this placebo effect!"

35. Yes, of course it is "justified"!
If we can not offer another option
If we inform the patient that we do not know whether it helps
If the patient knows and accepts the risks

36. At least in a free country
That's how it should be!
At least in a free country