1. Cardiovascular Research Technology (CRT) 2011
Washington, DC, February 27 – March 1, 2011
……… min
Debate:
Venous Angioplasty for MS: Might Be Voodoo but Certainly Worth Investigating
Moderators: Richard F. Neville, MD Sean D. O’Donnell, MD & Mark H. Wholey, MD
Debate: Venous Angioplasty for MS
2:25 PM Sounds Like Voodoo and Not Worth Investigating Michael R. Jaff, DO
2:35 PM Might Be Voodoo but Certainly Worth Investigating Horst Sievert, MD
2:45 PM Venous Angioplasty for Multiple Sclerosis: A New Territory Richard F. Neville, MD .
Horst Sievert, Nina Wunderlich
CardioVascular Center Frankfurt
Frankfurt, Germany

2. 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 1

3. Debates can be more easy or more difficult
This is one of the easiest I ever had

4. Everything is worth investigating!
Why?
Everything is worth investigating!

5. It is common for all new discoveries that nobody could believe it or even think about it before it was discovered

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

7. 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

8. What is MS? An inflammatory demyelinating disease
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

9. 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

10. What does MS mean for the individual patient?
A progressive disease which leads to severe disability and/or death
No effective therapy available
Medical therapy has severe side effects including immune deficiency and cancer

11. Cerebral and central venous duplex
Zamboni et al: Chronic cerebrospinal venous unsufficiency 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. What supports the theory of CCSVI?
MS plaques have a perivascular 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

18. Current Status of Venoplasty
Almost 1000 patients have been treated worldwide
Very low risk
Only very few severe complications
After stent implantation
Patients do not have an alternative
Medical therapy is ineffective and has severe side effects
Cardiotoxicity
Bone marrow suppression
Neoplasms
immunosuppressive

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

20. -----Ursprüngliche Nachricht----- Von: Maureen Browne Gesendet: Sonntag, 11. Juli :04 An: S. Dancsecz Betreff: AW: Dr Sievert Dear Dr Sievert Thank you for the reply to my last . Firstly, may I report that I have noticed difinite cognitive improvements in the last week. I cannot begin to verbalize my appreciation for this. Cognitive function is the most dreaded loss in the ms scenario. At the onset of my ms, I always feared losing the function of my legs -but I have already spent time in a wheelchair and that is insignificant compared to loss of brain function. My headaches have virtually disappeared. Sincerely Maureen

21. -----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

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

23. The topic is how to develop science and medicine
However, the topic of this debate is not whether or not venoplasty is effective in MS
The topic is how to develop science and medicine

24. There is only one way To develop a new idea, concept, treatment
To test it first in case series and thereafter in randomized trials
To implement it into clinical practice
To validate the results in registries and clinical practice

25. Certainly Worth Investigating