Understanding venous disease and treatment options for your patients. Christopher Wulff, MD

Similar documents
Epidemiology: Prevalence

Management of Superficial Reflux: Which option, when? Kathleen Gibson, MD Lake Washington Vascular Surgeons Bellevue, WA

6/1/2017. Mechanico-Chemical Ablation MOCA? Disclaimer

Randomized trial comparing cyanoacrylate embolization and radiofrequency ablation for incompetent great saphenous vein

Chronic Venous Insufficiency Compression and Beyond

RECOGNITION AND ENDOVASCULAR TREATMENT OF CHRONIC VENOUS INSUFFICIENCY

Conflict of Interest. None

MOCA and GLUE: results and analyses of the RCTs

A treatment option for varicose veins. enefit" Targeted Endovenous Therapy. Formerly known as the VNUS Closure procedure E 3 COVIDIEN

Criteria For Medicare Members. Kaiser Foundation Health Plan of Washington

UNDERSTANDING VEIN DISEASE. UC EN - For use in the U.S. only

Why Tumescent-Free Therapy Will Replace RF and Laser

Thermal Techniques: Outcomes and Complications

Closurefast radiofrequency ablation for the treatment of GSV: Technique and outcome results

Additional Information S-55

TREATMENT OPTIONS FOR CHRONIC VENOUS INSUFFICIENCY

Endovenous Thermal vs. Endovenous Chemical Ablation What is the Best for the Patient

Venous Disease and Leg Ulcers. Edward G Mackay MD St. Petersburg, FL NCVH 2015 Orlando, FL

RADIOFREQUENCY ABLATION. Drs PIRET V, BERGERON P MEET CANNES 2009

Chronic Venous Insufficiency

Clinical case. Symptomatic anterior accessory great saphenous vein (AAGSV) reflux

VeClose trial Cyanoacylate closure vs. RF ablation 36-month results

Perforators: When to Treat and How Best to Do It? Eric Hager, MD September 10, 2015

How to choose which treatment method(s) to use for a particular varicose veins patient ESTABLISHING A TREATMENT PLAN.

Medical Policy. Description/Scope. Position Statement

Current Management of Varicose Veins

SAVE LIMBS SAVE LIVES! Endovenous Ablation for Chronic Wounds

VENOUS SYMPOSIUM: OVERVIEW

Medical Affairs Policy

Segmental GSV reflux

Are there differences in guidelines for management of CVD between Europe and the US? Bo Eklöf, MD, PhD Lund University Sweden

New Technologies in Superficial Vein Treatment

Endothermal Ablation for Venous Insufficiency. Dr. S. Kundu Medical Director The Vein Institute of Toronto

Recurrent Varicose Veins We All See Them

Clinical/Duplex Evaluation of Varicose Veins: Who to Treat?

The Vascular Disease Almost No One Teaches But Should!!! Chronic Venous Insufficiency

Le varici recidive Recurrent varices: how to manage them?

Non-Saphenous Vein Treatments. Jessica Ochs PA-C Albert Vein Institute Colorado Springs and Lone Tree, CO

OHTAC Recommendation. Endovascular Laser Treatment for Varicose Veins. Presented to the Ontario Health Technology Advisory Committee in November 2009

Priorities Forum Statement

SAFETY AND FEASIBILITY OF MECHANO-CHEMICAL ABLATION OF VARICOSE VEINS: INITIAL RESULTS

How varicose veins occur

Patient assessment and strategy making for endovenous treatment

AMERICAN PODIATRIC MEDICAL ASSOCIATION

CHRONIC VENOUS INSUFFICIENCY of the lower extremities

ORIGINAL ARTICLES. Masatoshi Jibiki 1, Tetsuro Miyata 1,2, Sachiko Futatsugi 3, Mitsumasa Iso 3 and Yasutaka Sakanushi 3.

Duplex Ultrasound Outcomes following Ultrasound-guided Foam Sclerotherapy of Symptomatic Recurrent Great Saphenous Varicose Veins

FIND RELIEF FROM VARICOSE VEINS. VenaSeal Closure System

Find From Varicose Veins. VenaSeal

Treatment of Varicose Veins/Venous Insufficiency

Medicare C/D Medical Coverage Policy

SURGICAL AND ABLATIVE PROCEDURES FOR VENOUS INSUFFICIENCY AND VARICOSE VEINS

Treatment of Varicose Veins

Laser and Radiofrequency Ablation Study (LARA study): A Randomised Study Comparing Radiofrequency Ablation and Endovenous Laser Ablation (810 nm)

Vein Disease Treatment

Treatment of the incompetent great saphenous vein by endovenous radiofrequency powered segmental thermal ablation: First clinical experience

The role of ultrasound duplex in endovenous procedures

Sadie Ahanchi, MD Sentara Vascular Specialists April 27,2018. Debate 1: Why Is Tumescent-Based Therapy The Gold Standard?

New Guideline in venous ulcer treatment: dressing, medication, intervention

Cyanoacrylate vs laser ablation. Turkish experience. A. Kursat Bozkurt MD University of Istanbul

chronic venous disorders, varicose vein, CEAP classification, lipodermatosclerosis, Klippel- Trenaunay syndrome DVT CVD

SURGICAL AND ABLATIVE PROCEDURES FOR VENOUS INSUFFICIENCY AND VARICOSE VEINS

LINC, Christine Teichert, MD University Medicine of Rostock, Dept. of diagnostic and interventional radiology, Germany

Treatment of Venous ulcers utilizing n-butyl Cyanoacrylate (Super Glue)

SURGICAL AND ABLATIVE PROCEDURES FOR VENOUS INSUFFICIENCY AND VARICOSE VEINS

MEDICAL POLICY SUBJECT: VARICOSITIES, TREATMENT ALTERNATIVES TO VEIN STRIPPING AND LIGATION. POLICY NUMBER: CATEGORY: Technology Assessment

Varicose veins. Natural history, assessment and management. Arteries and veins. Why do people get varicose veins? Classification of venous disease

o Self-Contained & Disposable: Fully self-contained, single-use device with no need for capital equipment purchase

Kathleen Gibson, MD. Lake Washington Vascular Surgeons Bellevue, WA

Long-term follow up for different varicose vein therapies: is surgery still. the best?

Endo-Thermal Heat Induced Thrombosis (E-HIT)

FIND RELIEF FROM VARICOSE VEINS. VenaSeal Sapheon Closure System

Srovnání 2 typů radiálních laserových vláken (1-ringových a 2-ringových) v nitrožilní léčbě křečových žil pomocí laseru o vlnové délce 1470 nm

Catheter-based treatments for varicose veins: evidence and practice.

Cardiology New Horizons in Cardiovascular Disease Management. Christopher Wulff, MD Cardiovascular Consultants Medical Group

SURGICAL AND ABLATIVE PROCEDURES FOR VENOUS INSUFFICIENCY AND VARICOSE VEINS

Treatment of Varicose Veins/Venous Insufficiency. Description

Subject: Treatments for Varicose Veins/Venous Insufficiency

PROVIDER POLICIES & PROCEDURES

2017 Florida Vascular Society

Surgery or combined endolaser ablation and sclerotherapy for varicose veins, a new trend in a developing country (Iraq); a cohort study

974 Kontothanassis et al JOURNAL OF VASCULAR SURGERY April 2009 release. The cutoff value for the superficial veins was 0.5 seconds. 6 However, our pa

The occlusion rate and patterns of saphenous vein after radiofrequency ablation

Which place for liquid sclerotherapy? Eberhard Rabe Department of Dermatology University of Bonn Germany

Influence of Warfarin on the Success of Endovenous Laser Ablation (EVLA) of the Great Saphenous Vein (GSV)

N.S. Theivacumar, R.J. Darwood, M.J. Gough*

POLICY PRODUCT VARIATIONS DESCRIPTION/BACKGROUND RATIONALE DEFINITIONS BENEFIT VARIATIONS DISCLAIMER CODING INFORMATION REFERENCES POLICY HISTORY

Endovenous Laser Ablation (EVLA) to Treat Recurrent Varicose Veins

Radiofrequency-Powered Segmental Thermal Obliteration Carried out with the ClosureFast Procedure: Results at 1 Year

Treatment of Varicose Veins/Venous Insufficiency

Original Policy Date

UPDATE: SAPHENOUS TREATMENTS. Pauline Raymond-Martimbeau Dallas Non Invasive Vascular Laboratory Vein Institute of Texas Dallas, Texas, USA

Determine the patients relative risk of thrombosis. Be confident that you have had a meaningful discussion with the patient.

Table XI. Reference Abstracts corresponding to references can be found using the listing RCTs by alphabetical order or RCTs by topic.

High Level Overview: Venous Anatomy of Lower Extremities. Anatomy of a Vein 5/11/2015. Barbara Deusterman, RN

Research Article Effects of Two Current Great Saphenous Vein Thermal Ablation Methods on Visual Analog Scale and Quality of Life

Treatment of Chronic Venous Insufficiency Including the Modern Treatment of Varicose Veins

Transcription:

Understanding venous disease and treatment options for your patients Christopher Wulff, MD

Understanding Chronic venous insufficiency (CVI)

Important Statistics About CVI Affects all age groups 1 Is ten times more prevalent then PAD 1 Direct cost of CVI in the US is estimated to be between $150 million and $1 billion per year 2 Mean incidence of hospital admission for CVI is 92/100,000 admissions 3 At least 20,556 patients receive a new diagnosis of venous ulcers each year 4 1 Gordon P, Treat-Jacobson D, Sossoman L.B. Society for Vascular Nursing Position Statement on Inclusion of Vascular Disease into Nursing Education. Soc for Vascular Nursing. 2012;Sept:10. 2 Heller J. Treatment of chronic venous insufficiency. Supplement to Endovascular Today. 2011;Oct:12-15. 3 Weiss R, Venous Insufficiency. Medscape. November 21, 2012. 4 Gloviczki P, Comerota A.J, Dalsing M.C et al. The care of patients with varicose veins and associated chronic venous diseases: Clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surg. 2011;53(suppl):2S-48S. 3

Prevalence of Chronic Venous Insufficiency More than 30 million Americans suffer from varicose veins or a more serious form of venous disease called Chronic Venous Insufficiency (CVI) 1 Of the over 30 million Americans affected: Only 1.9 million seek treatment annually. 1,2 The vast majority remain undiagnosed and untreated. CVI Prevalence 1,2* 30,000,000+ Seek Treatment *2 1,900,000 Treated 447,000 2 *Statistics based on individuals over the age of 40 1 Gloviczki P, et al. The care of patients with varicose veins and associated chronic diseases: clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. JVS; May 2011. 2 Lee, A. US markets for varicose vein treatment devices 2011. Millennium Research Group, Inc. (A Decision Resource, Inc. Company), www.mrg.net, May 2011. 4

Risk Factors for Varicose Veins and Chronic Venous Insufficiency Risk Factors Older age Family history DVT History of phlebitis Obesity Standing occupation Pregnancy Female gender Other Possible Risk Factors * Smoking Hypertension Oral contraceptives or hormone replacement therapy Physical activity Constipation *Not consistently supported by research Beebe-Dimmer Jl, Pfeifer JR, Engle, JS, et al. The Epidemiology of Chronic Venous Insufficiency and Varicose Veins. Ann Epidemiol. 2005;15(3):175-184. 5

VENOUS ANATOMY

Superficial Venous System - GSV Longest vein in body Areas of aplasia/hypoplasia common in lower thigh, knee and calf Often runs a superficial subcutaneous course from mid thigh-knee May enter and exit the saphenous sheath at various locations Closely associated with saphenous nerve below mid-calf Often duplicated (25% in the calf; 8% in thigh) Common Femoral Vein (CFV) Fossa Ovalis SFJ GSV Trunk Marginal Arch Image courtesy of Dr. Labropoulos Gloviczki P, ed. Handbook of Venous Disorders. 3rd ed. London, UK: Hodder Arnold; 2009 7

Cross Sectional View of the GSV in the Thigh Runs from dorsum of foot to medial malleolus to common femoral vein (CFV) Usually within saphenous sheath between saphenous and muscular fascial layers Image courtesy of Dr. Labropoulos Skin Subcutaneous fat Collagen Superficial fascia Perivenous fat Saphenous ligament Deep fascia 8

Accessory Veins of GSV Saphenous opening Common femoral vein Anterior accessory saphenous vein Superficial epigastric vein Posterior accessory saphenous vein Great saphenous vein Posterior accessory saphenous vein Great saphenous vein Small saphenous vein 9

Superficial Venous System SSV Within the fascial space (saphenous sheath) Begins posterior to the lateral malleolus Travels up calf between two heads of gastrocnemius muscle May have thigh extension Usually drains into the SPJ 10

Perforator Veins Pathologic 3.5 mm in size Outward flow >500 ms duration Located beneath chronic venous stasis skin changes / ulcer Gloviczki P, et al. The care of patients with varicose veins and associated chronic venous diseases: Clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surg. 2011;53:2S-48S. 11

Venous Pathophysiology Normal Vein Varicose Vein Normal functioning calf pumps are capable of emptying 40% to 60% of their volume with one muscle contraction 7 to 12 steps = decreased venous pressure from 100 mmhg to 22 mmhg Meissner MH, Gloviczki P, Bergan J, et al. J Vasc Surgery. 2007;46(suppl):4S-24S. 12

Reflux Development Image courtesy of Dr. Labropoulos Primary venous reflux can occur in any superficial or deep vein of the lower limbs but is more frequent in the former. Saphenous veins and tributaries are often involved in asymptomatic individuals and in those who have prominent or varicose veins. Labropoulos N, et al. J Vasc Surg. 2010;51:96-103 13

Pathophysiology of Venous Insufficiency

C in CEAP Clinical, Etiologic, Anatomic, Pathophysiologic C0 C1 C2 C3 C4a No visible or palpable signs of venous disease Telangiectasias or reticular veins Varicose veins Edema Pigmentation or eczema C4b Lipodermatosclerosis or atrophie blanche C5 C6 Healed venous ulcer Active venous ulcer 15

CEAP Classification for Chronic Venous Disorders (CVD) C1: Telangiectasia or Reticular Veins C2: Varicose Veins C3: Edema Images courtesy of Jennifer Heller, M.D. 16

CEAP Classification for Chronic Venous Disorders (CVD) C4a: Pigmentation or Eczema C4b: Lipodermatosclerosis or Atrophie Blanche C5: Healed Venous Ulcer C6: Active Venous Ulcer Images courtesy of Gordon Gibbs, M.D. and Jennifer Heller, M.D 17

Patient Assessment & Diagnosis Patient Assessment Current general health condition Past medical history Symptoms Physical exam Ultrasound Diagnostic Study Required in order to determine the source of reflux Evaluate for venous occlusion or thrombus Map the course of the incompetent superficial veins 18

TREATMENT MODALITIES

Current Treatment Modalities Conservative Therapies Exercise Leg elevation Compression stockings Unna boot Surgical Stripping Thermal Ablation Radiofrequency ablation Laser ablation Non-thermal, Non-tumescent Mechanochemical Foam Sclerotherapy Non-thermal, Non-tumescent, Non-sclerosant Cyanoacrylate adhesive 20

High Ligation & Surgical Stripping The term high ligation and division implies ligation and division of the Great Saphenous Vein (GSV) at its confluence with the common femoral vein, including ligation and division of all upper GSV tributaries. The term stripping means removal of a long vein segment, usually of the saphenous vein, by means of a stripping instrument. Performed for 100+ years. Typically requires general anaesthesia in O.R. Can be up to 4 weeks recovery time. 1 1 Gloviczki, P., MD., Comerota, A., MD., Dalsing, M., MD., Eklof, B., MD., Gillespie, D., MD., Gloviczki, M., MD., Wakefield, T., MD. The care of patients with varicose veins and associated chronic venous diseases: Clinical practice guidelines of the Society for Vascular Surgery and the American Venous Forum. J Vasc Surg. 2011 May; 53(5 Suppl): 2S-48S 21

Clinical Summary RFA VS. SURGICAL STRIPPING Study Type Rautio et al 1 Single center Randomized Lurie et al 2 Multi-center Randomized Stötter et al 3 Single center Randomized Study Size N=28 N=85 N=20 RFA N=20 SS RF Comparison ClosurePlus TM Catheter ClosurePlus TM Catheter ClosurePlus TM Catheter Hinchcliffe et al 4 Single-center Randomized Helmy et al 5 Single-center Randomized N=16 N=90 RFA N=90 SS ClosurePlus TM Catheter ClosureFast TM Catheter Rasmussen et al 6 Multi-center Randomized N=124 RFA N=123 SS ClosureFast TM Catheter Demonstrated Advantages of RFA over Surgical Stripping Pain & Bruising n/s n/s Recovery Time n/s n/s n/s Return to Work/ Normal Activity n/s Procedure Time n/s n/s n/s n/s Complications n/s n/s n/s n/s n/s QOL n/s n/s n/s n/s 1 Rautio T, Ohinmaa A, Perälä J, Ohtonen P, Heikkinen T, Wiik H, et al. Endovenous obliteration versus conventional stripping operation in the treatment of primary varicose veins: a randomized controlled trial with comparison of the costs. J Vasc Surg 2002;35:958-65. 2 Lurie F, Creton D, Eklof B, Kabnick LS, Kistner RL, Pichot O, et al. Prospective randomised study of endovenous radiofrequency obliteration (closure) versus ligation and vein stripping (EVOLVeS): two-year follow-up. Eur J Vasc Endovasc Surg 2005;29:67-73. 3 Stotter L, Schaaf I, Bockelbrink A, Baurecht HJ. Comparative outcomes of radiofrequency endoluminal ablation, invagination stripping, and cryostripping in the treatment of great saphenous vein insufficiency. Phlebology, 2006,21:60-54. 4 Hinchliffe RJ, Ubhi J, Beech A, Ellison J, Braithwaite BD. A prospective randomised controlled trial of VNUS closure versus surgery for the treatment of recurrent long saphenous varicose veins. Eur J Vasc Endovasc Surg 2006;31:212-8. 5 EK Helmy, et al. Great Saphenous Vein Radiofrequency Ablation vs Stripping in the Management of Primary Varicose Veins- A Randomized Study. Angiology. 2011 Jan;62(1):49-54 6 Rasmussen et al. Randomized clnical trial comparing endovenous laser ablation, radiofrequency ablation, foam sclerotherapy and surgical stripping for great saphenous varicose veins. BJS 2011;98:1079-1087 22

THERMAL ABLATION: LASER AND RFA

Endovenous Laser Ablation: Variable Inputs and Requires Continuous Pullback Variable Options Wavelengths Hemoglobin-targeted Water-targeted Fiber Tip Bare Radial Covered Power Setting 30w 15w Joules/sec Speed Pullback speed Continuous Pullback Mechanism of Action Energy source is on throughout treatment Energy delivery varies by pullback speed as well as other factors Small area treated at any given time 24

Radiofrequency Energy Delivered by the ClosureFast TM Catheter Mechanism of Action Segmental Ablation Delivered by the ClosureFast TM catheter Vein segment treated at one time No energy delivered during catheter pullback Energy delivery does not vary by pullback speed Controlled and consistent radiofrequency (RF) energy delivered through the ClosureFast catheter The catheter heats the vein wall and contracts the vein wall collagen, thereby occluding the vein. 25

ClosureFAST Segmental Ablation Stationary during treatment Shaft markings for repositioning Slight overlap between treatments Vein treated stepwise along the length 1 2 3 4 5 6 7

VNUS ClosureFAST Animation

Endovenous Radiofrequency Ablation Using the ClosureFast Catheter*: 5-Year Data Prospective, multicenter, singlearm study. Purpose: To evaluate long-term effects of RF segmental ablation of GSV using the CLF catheter 326 patients (396 limbs) were treated with the ClosureFast TM catheter at 13 sites (8 Europe, 5 US) Follow up: Patients were evaluated at 3, 6, 12, 24. 36, and 60 months post-procedure. 278 Limbs followed to 5 years Primary Endpoints Vein occlusion and absence of reflux in the treated vein as determined by duplex ultrasound (DUS) imaging. Vein occlusion was defined as absence of any blood flow along the entire length of the treated vein segment assessed by DUS imaging. Secondary Endpoints Presence of complications and side effects from the great saphenous vein (GSV) intervention. Status of clinical signs and symptoms of lower limb venous disease. Dietzek A. RF Segmental ablation: 5-year data. Annual Symposium on Vascular and Endovascular Issues, Techniques, Horizons (Veith Symposium) New York City; November 19, 2013 *Study funded by Covidien 28

Occlusion Rates Through 5 Years 96.6% 90.0% 1 Year 2 Years 3 Years 4 Years 5 Years Vein Occlusion 96.6% 94.3% 92.8% 91.1% 90.0% Dietzek A. RF Segmental ablation: 5-year data. Annual Symposium on Vascular and Endovascular Issues, Techniques, Horizons (Veith Symposium) New York City; November 19, 2013 29

CLF Reflux Free Rate at 5 Years KAPLAN-MEIER ANALYSIS 93.7% Reflux Free

Complication Rates Follow-Up Time Point 1 Week (N=395) 3 Months (N=371) 5 Years (N=350) Ecchymosis 23 (5.8%) 0 (0.0%) 0 (0.0%) Erythema 5 (1.3%) 0 (0.0%) 0 (0.0%) Hematoma 4 (1.0%) 1 (0.3%) 0 (0.0%) Paresthesia 6 (1.5%) 9 (2.4%) 1(0.3%) Phlebitis 5 (1.3%) 1 (0.3%) 0 (0.0%) Skin Pigmentation 0 (0.0%) 4 (1.1%) 0 (0.0%) Thermal Skin Injury 0 (0.0%) 0 (0.0%) 0 (0.0%) Thrombus Extension / DVT 6 (1.5%) 3 (0.8%) 0 (0.0%) Dietzek A. RF Segmental ablation: 5-year data. Annual Symposium on Vascular and Endovascular Issues, Techniques, Horizons (Veith Symposium) New York City; November 19, 2013 31

Summary CLOSUREFAST CATHETER STUDY Results showed durable closure clinical efficacy rates through 5-years: High occlusion rate of 90.0% at 5 years Overall reflux-free rate of 93.7% at 5 years Low complication rate Dietzek A. RF Segmental ablation: 5-year data. Annual Symposium on Vascular and Endovascular Issues, Techniques, Horizons (Veith Symposium) New York City; November 19, 2013 32

Trial Comparing EVLA, RFA, Foam Sclerotherapy and Surgical Stripping for GSV: Rasmussen Study 500 patients (580 limbs) with GSV reflux were randomized to receive one of the following: Stripping Ultrasoundguided foam sclerotherapy 124 125 124 125 EVLA* RFA Duplex ultrasound imaging was done before and after the procedure (3 days, 1 month, and 1 year) Primary Endpoints GSV closure expressed in vessel patency (treatment failure) one year post procedure. Secondary Endpoints Pain, absence from work and normal activity Scores of SF-36 TM * Aberdeen Varicose Vein Symptom Severity Score (AVVSS) Venous Clinical Severity Score (VCSS) Rasmussen et al. Randomized clinical trial comparing endovenous laser ablation, radiofrequency ablation, foam sclerotherapy and surgical stripping for great saphenous varicose veins. BJS 2011;98:1079-1087 *Trademark of its respective owner. * EVLA (17) 980 nm, (108) 1470 nm, bare fibre 33

Rasmussen Study Results Efficacy at 1 year (reflux-free rate) Post Intervention Pain Scores* (1 10) Time to return to normal activities (days) RF Ablation (n=124) Endovenous Laser Ablation (n=124) Vein Stripping (n=123) Ultrasound-Guided Foam Sclerotherapy (n=123) 95.2% 94.2% 95.2% 83.7% (p<0.001) 1.21 (p<0.001) 1 (p<0.001) 2.58 2.25 1.60 (p<0.001) 2 4 1 (p<0.001) Time to resume work (days) 2.9 (p<0.001) 3.6 4.3 2.9 (p<0.001) Indirect cost ( ) Lost work 560 840 1120 560 Total costs ( ) 1996 2200 2199 1559. Rasmussen et al. Randomized clinical trial comparing endovenous laser ablation, radiofrequency ablation, foam sclerotherapy and surgical stripping for great saphenous varicose veins. BJS 2011;98:1079-1087 34

Mechanochemical Tumescentless Endovenous Ablation (MOCA): Elias Study Prospective, single-center 30 GSVs in 29 patients Treated with ClariVein TM * catheter Avg. diameter was 8.1mm Avg. length of treated segment was 37.5cm Avg. total procedure time was 14 minutes Follow-ups were 1 week, 1 month, 3 months, and 6 months post-procedure Primary Endpoints Safety (measured through adverse events). Closure rate at 6 months. Secondary Endpoints Procedural pain, post procedural pain, pain medication use, and degree of ecchymosis. Elias and Raines Mechanochemical Tumescentless Endovenous Ablation: Final Results of the Initial Clinical Trial. Phlebology 2012;27:67-72 *Trademark of its respective owner. 35

Elias Study Results Closure Rate 96.7% Duration 260 days Elias and Raines Mechanochemical Tumescentless Endovenous Ablation: Final Results of the Initial Clinical Trial. Phlebology 2012;27:67-72 36

Polidocanol Endovenous Microfoam: VANISH 2 Study Randomized, multi-center Patients injected with polidocanol endovenous microfoam (PEM) 232 patients were randomized to: Primary Endpoints Patient-reported improvement in symptoms, as measured by the change from baseline to week 8 in the 7-day average VVSymQ TM * score. Placebo 57 125 PEM 0.125% PEM 0.5% 60 58 PEM 1.0% Secondary Endpoints Included the improvement in appearance of varicosities from baseline to week 8, as measured by patients (using PA-V) and by a physician review panel (IPR-V). Improvement in VCSS, VEINES-QOL and occlusion/reflux were also assessed at week 8 as tertiary endpoints. Todd KL 3rd, et. al. The VANISH-2 study: a randomized, blinded, multicenter study to evaluate the efficacy and safety of polidocanol endovenous microfoam 0.5% and 1.0% compared with placebo for the treatment of incompetence. Phlebology; 2013 Jul 17 37

VANISH 2 Study Results Duplex ultrasound response at 8 weeks: Placebo PEM 0.125% PEM 0.5% PEM 1.0% Duplex responders 1.8% 59.6% 83.3% 1 86.2% 2 The most commonly reported adverse events in %: Placebo PEM 0.125% PEM 0.5% PEM 1.0% Pain in extremity 10.5% 12.3% 5.0% 15.5% Retained coagulum 0 10.5% 11.7% 27.6% Thrombophlebitis superficial 1.8% 7.0% 13.3% 3.4% Deep vein thrombosis 0 0 0 8.6% CFVTE 3 0 3.5% 3.3% 6.9% Tenderness 0 0 1.7% 6.9% 1 P < 0.05 2 P < 0.001 compared to PEM 0.125% 3 CFVTE Common Femoral Vein Thrombus Extension. This is non-occlusive thrombi starting in the superficial vein and extending into the common femoral vein (similar to EHIT). Todd KL 3rd, et. al. The VANISH-2 study: a randomized, blinded, multicenter study to evaluate the efficacy and safety of polidocanol endovenous microfoam 0.5% and 1.0% compared with placebo for the treatment of incompetence. Phlebology; 2013 Jul 17 38

VANISH 2 Study Summary Percentage of patients treated with the 1.0% polidocanol solution experienced the following mild to moderate adverse events: Closure Rate Reported pain Experienced retained coagulum (blood trapped in varicosities) 15.5% 27.6% 86.20% Experienced a DVT 8.6% Duration 8 Weeks CFVTE 6.9% Todd KL 3rd, et. al. The VANISH-2 study: a randomized, blinded, multicenter study to evaluate the efficacy and safety of polidocanol endovenous microfoam 0.5% and 1.0% compared with placebo for the treatment of incompetence. Phlebology; 2013 Jul 17 39

Summary of Clinical Efficacy Percent Occlusion 102.0% 100.0% 98.0% 96.0% 94.0% 92.0% 90.0% 88.0% 86.0% 84.0% 99.7% 87.9% 2-8 Weeks 98.6% 96.7% 3-6 Months 95.2% 94.2% 83.7% 90.0% 1 Year 5 Years CLF EVLA MOCA UGFS Rasmussen et al. Randomized clinical trial comparing endovenous laser ablation, radiofrequency ablation, foam sclerotherapy and surgical stripping for great saphenous varicose veins. BJS 2011;98:1079-1087 Elias and Raines Mechanochemical Tumescentless Endovenous Ablation: Final Results of the Initial Clinical Trial. Phlebology 2012;27:67-72 Dietzek A. RF Segmental ablation: 5-year data. Annual Symposium on Vascular and Endovascular Issues, Techniques, Horizons (Veith Symposium) New York City; November 19, 2013 Todd KL 3rd, et. al. The VANISH-2 study: a randomized, blinded, multicenter study to evaluate the efficacy and safety of polidocanol endovenous microfoam 0.5% and 1.0% compared with placebo for the treatment of incompetence. Phlebology; 2013 Jul 17 40

Opportunities for Improvement Elimination of: Tumescent anesthesia Post-procedure compression stockings Post-procedure pain and bruising 41

Why Not Use Cyanoacrylate for Varicose Veins? If we can glue highflow cerebral AVMs, why can t we glue low-flow varicose veins? - Dr. R. Raabe, 2008 Large amount of adhesive/ thrombus is left in the AVM as seen on MRI. Courtesy of Dr. R. Raabe 42

Safety of Cyanoacrylate Adhesives Widely used medical tissue adhesive. 1 Antimicrobial effect against gram-positive organisms. 2 Used safely on millions of patients with no reported carcinogenicity in humans (1986 study). 2 1 Lawson et al. Sapheon: the solution? Phlebology 2013, 28 Suppl 1:2-9, p3 2 Quinn J., Tissue Adhesives in Clinical Medicine, 2nd ed.(2005) p 34-35 43

Properties of Ideal Cyanoacrylate for Venous Closure Ideal viscosity Polymerize quickly Soft and elastic Maintains a strong bond Eliminate need for compression stockings* *Some patients may benefit from compression stockings post procedure. 44

Cyanoacrylate in the Vessel When cyanoacrylate (CA) comes in contact with blood or plasma, it begins to polymerize. The body encapsulates the polymer as a foreign body. CA triggers inflammatory reaction in the vessel wall resulting in occlusion. Almeida J. et.al. Cyanoacrylate adhesive for the closure of truncal veins: 60 day swine model results. Vasc and Endovasc Surg (2011) 000(00) 1-5. DOI 10.1177/1538574411413938 http://ves.sagepub.com p.1 45

Features of the VenaSeal Procedure Procedure Features Eliminates need for tumescent anesthesia. No risk of thermal injury. No post treatment compression stockings needed. 1,2 * Rapid return to normal activities. 2 1 Almeida, J et al., Two-year follow-up of first human use of cyanoacrylate adhesive for treatment of saphenous vein incompetence. Phlebology / Venous Forum of the Royal Society of Medicine 2014. 2 Gibson, K. A Randomized, controlled study comparing cyanoacrylate adhesive embolization with radiofrequency ablation for treatment of incompetent great saphenous veins VeClose study. German Society of Phlebology, 2014. *Some patients may benefit from compression stockings post procedure. 46

Clinical Studies with the VenaSeal Closure System Feasibility Study 1 escope 2 (European multicenter study) VeClose 3 (U.S. pivotal trial) 38 Patients, enrollment completed Aug. 2011 1, 3, 6, 12, 24 and 36 month follow-ups Primary endpoints: safety and efficacy 70 patients, enrollment completed Sept. 2012 2 day, 1, 3, 6, 12, 24 and 36 month follow-ups Primary endpoint: closure w/o use of sedation, tumescent anesthesia or compression stockings 242 Patients, enrollment completed Sept. 2013 3 day,1,3,6,12, 24 and 36 month follow-ups Primary endpoint: non-inferior to RFA in GSV closure Secondary endpoint: superiority in reduction of post procedural pain and bruising 1 Almeida, J et al., Two-year follow-up of first human use of cyanoacrylate adhesive for treatment of saphenous vein incompetence. Phlebology / Venous Forum of the Royal Society of Medicine 2014. 2 Proebstle, T et al., The european multicenter cohort study on cyanoacrylate embolization of refluxing great saphenous veins. JVS: Venous and Lymphatic Disorders 2014; Accepted for publication. 3 Gibson, K. A Randomized, controlled study comparing cyanoacrylate adhesive embolization with radiofrequency ablation for treatment of incompetent great saphenous veins VeClose study. German Society of Phlebology, 2014. 47

Summary of Clinical Evidence with VenaSeal System The VenaSeal procedure is shown to be safe and effective, with consistent results across three studies. 1,2,3 High closure rate: 92% in Feasibility study through 3 year follow-up, 92.9% at 12 months in escope study and 98.9% in VeClose trial at 6 months. 4 Acceptable safety profile: Side effects are minor and infrequent. Use of the VenaSeal system does not require post procedure compression stockings as shown in Feasibility and escope studies.* The VenaSeal system does not require the use of tumescent anesthesia and eliminates the risk of thermal injury. The VenaSeal procedure allows a rapid return to normal activities. VenaSeal procedure is the only non-tumescent, non-thermal, non-sclerosant system for treatment of incompetent veins available in the United States. * Some patients may benefit from the use of compression stockings post procedure. 1 Almeida, J et al., Two-year follow-up of first human use of cyanoacrylate adhesive for treatment of saphenous vein incompetence. Phlebology / Venous Forum of the Royal Society of Medicine 2014. 2 Proebstle, T et al., The European Multicenter Cohort Study on Cyanoacrylate Embolization of Refluxing Great Saphenous Veins. JVS: Venous and Lymphatic Disorders 2014 3 Gibson, K. A Randomized, Controlled Study Comparing Cyanoacrylate Adhesive Embolization With Radiofrequency Ablation For Treatment Of Incompetent Great Saphenous Veins VeClose Study. German Society of Phlebology, 2014. 4 Almeida J. Three-year follow-up of first human us of cyanoacrylate adhesive for treatment of saphenous vein incompetence. AVF 2015. 50

Pretreatment Post Ablation Sclerotherapy Phlebectomy

Pre ablation Four days post ablation

Pre ablation post ablation and phlebectomy

Cardiology and OMT Vascular Case ALEXANDER WULFF, MS, OMS I OPSC CONFERENCE SAN DIEGO FEBRUARY 2018

Screening-Who Are These Patients? Vascular Patient Varicose Vein Leg pain not localized to a joint, heavy feeling Complain of swelling in the ankles Pain when sitting or standing for a long time

Autonomic Balance T1-5: Heart T10-L2: Lower Extremity Sub Occipital Release

Biomechanics Vascular Mechanics of pelvis (Adapted Mitchel Model) Mechanics of Gait Popliteal fossa Pre/Post-operative MFR

Circulation Cardiac Considerations Lymphatics lymphatic pump techniques Thoracic Inlet outlet/outlet Vascular Considerations Popliteal fossa and Pelvic Floor opening Hip Mechanics and Gait

Thank You Alesia Wagner, DO Jordan Keys, DO Christopher Wulff, MD John Glover, DO

References Kuchera ML. Osteopathic Considerations in Systemic Dysfunction. Greyden Press LLC, 1994 Williams A. An osteopathic cardiologist's review of hypertension: beyond the Fifth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. J Am Osteopath Assoc 1994;94(10):833. Osteopathic manipulation as a complementary treatment for the prevention of cardiac complications: 12-Months follow-up of intima media and blood pressure on a cohort affected by hypertension. Cerritelli, Francesco et al. Journal of Bodywork and Movement Therapies, Volume 15, Issue 1, 68 74 Nicholas, A. Osteopathic manipulative treatment for postoperative pain. JAOA September 2002; 102(9):S5-S8 Noll D. The effect of OMT on postoperative medical and functional recovery of coronary artery bypass graft patientsletter to the editor. JAOA August 2013; 113(8) 595-597