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

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

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

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

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

Does it work? I really don't know!

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

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

"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!

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!

"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!"

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

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

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

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

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

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

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 http://ideas.repec.org/p/hhs/hastef/0594.html#provider www.medicalnewstoday.com/articles/130647.php

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

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

Duplex MS patients controls p 71% 0% < 0.0001 61% 37% 52% 3% 55% IJ or vertebral venous refux 71% 0% < 0.0001 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

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

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 0.5-40 yrs

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 87% IJ or vertebral occlusion 53% Abnormal IJ response to standing 40% Conclusion: Multiple sclerosis is highly correlated with chronic cerebrospinal venous insufficiency

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

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

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

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

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

-----Message d'origine-----> De : Lucie Godbout [mailto:lucie -----Message d'origine-----> De : Lucie Godbout [mailto:lucie.jacques@videotron.ca] Envoyé : 7 décembre 2010 20:49> À : 'info@cvcfrankfurt.de'> 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

Could it still be placebo? Yes, of course

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

"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!"

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

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

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