Notes: Market research indicates that over 2 million work days are lost annually in the US and $1.4 billion is spent each year on this common medical condition (Sources: American Heart Association, SIR,Brand et al. “The Epidemiology of Varicose Veins: The Framingham Study”)
Notes: Statistics show that of the 25 million people in the U.S. who suffer from symptomatic reflux, only about 5% seek treatment annually; 2/3 of patients who do seek treatment have saphenous reflux When left untreated, venous reflux can lead to significant clinical issues, like pain, swelling, varicose veins, skin changes, and ulcers With advancing age, especially with females, the prevalence of venous disease grows The typical female patient is in her 40’s and has had multiple pregnancies It is estimated that in America, 72% of women and 42% of men will experience varicose veins by the time they reach their 60s; prevalence is highly correlated to age and gender (Barron HC, Ross BA. Varicose Veins: A guide to prevention and treatment. NY, NY: Facts on File, Inc. [An Infobase Holdings Company]; 1995;vii.)
Notes: This diagram shows the interrelation between superficial and deep venous systems and the perforators that connect the two systems Deep venous system Superficial venous system Saphenous veins Lateral venous complex Perforating veins
Notes: Healthy leg veins contain valves that open and close to assist the return of blood back to the heart Venous insufficiency or venous reflux disease develops when the valves that keep blood flowing out of the legs and back to the heart become damaged or diseased Venous insufficiency is the result of over-dilation of the venous vessels in the legs. This dilation eventually prevents the valve cusps from closing properly, resulting in reflux. The pooling of blood results in ineffective flow back to the heart. In some cases the reflux is caused not only by the over-dilation of the vessel wall, but also by damaged or absent valves. In this case, the valves have been so badly damaged, or degenerated, that they are almost nonexistent and no longer function To assess if venous reflux is present, a duplex ultrasound scan is performed
Notes: Gender : Approximately four times as many women as men are affected by varicose veins, suggesting that female hormones may be a risk factor Age : Generally, most elderly individuals show some degree of varicose vein occurrence Heredity : Weak vein walls and valves, as well as shortage of vein valves, seem to be inherited characteristics, and may play a role in determining who develops varicose veins and at what age Pregnancy : is associated with an increase in blood volume. Also, added pressure on the veins in the legs by the weight of the growing uterus and the relaxation effects of the hormones estrogen and progesterone on the vein walls contribute to the development of varicose veins during pregnancy Standing occupation : causes a great amount of pressure to develop in the leg veins Obesity : the added weight causes a great amount of pressure on the veins in the legs Prior trauma or surgery to the leg could cause interruption of the normal blood flow channels Sedentary lifestyle/prolonged sitting : The calf muscles are inactive and therefore can’t help push venous blood back up to the heart. This causes blood to pool in the veins, thus resulting in increased pressure on the vein walls
Notes: Although often underestimated as a cosmetic problem, venous insufficiency can produce significant clinical problems for the patient An estimated 25 million people in the United States have varicose veins, 2 to 6 million have more advanced forms of chronic venous insufficiency (swelling, skin changes), and nearly 500,000 have painful venous ulcers. (White JV, Ryjewski C. Chronic venous insufficiency. Perspect Vasc Surg Endovasc Ther 2005;17:319-27) Overall, as the severity of the disease progresses, quality of life decreases
Notes: CEAP Classifications are used to determine the severity of venous disease. C= Clinical signs (grade 0-6) E= Etiologic Classification (congenital, primary, or secondary) A= Anatomic Distribution (superficial, deep, perforator; alone or in combination) P= Pathophysiologic Dysfunction (reflux of obstruction; alone or in combination) CEAP Class 0 - No visible or palpable signs of venous disease Patient is asymptomatic. CEAP Class 1 – Telangiectasias or reticular veins Patient presents with “spider veins” which are very small diameter vessels that appear as starburst-like lines. CEAP Class 2 - Varicose Veins Varicose veins are elongated, dilated, tortuous, pouched and thickened veins with incompetent valves. In addition to varicose veins, a high percentage of patients also have incompetence of one or more of the key “gatekeeper” valves, e.g., the terminal valves of the saphenofermoral junction or saphenopopliteal junction, and/or perforating veins. CEAP Class 3 - Edema This next progressive state of venous insufficiency occurs as the result of venous hypertension forcing fluid into the lymphatic and interstitial spaces resulting in extreme reflux and poor antegrade flow. This causes swelling of the limb. Pain and discomfort are typical of this classification, particularly in the lower leg (calf & ankle) where proximity of nerves exacerbates the situation. In addition to superficial involvement, these stages may include some portion of the deep system (including perforators). CEAP Class 4a and 4b - Skin Changes Including Pigmentation and Venous Ezcema or with Lipodermatosclerosis CEAP 5 and 6 – Healed and Active Venous Ulcer This is the most severe form of venous insufficiency and typically involve both the deep (including perforators) and superficial systems. Extreme reflux and venous hypertension result in changes in the microcirculation of the skin eventually leading to severe ulceration. It is believed that communication via the perforator veins between the deep and superficial systems is a primary component of these classes.
Notes: Collagen Contraction The application of heat to human tendon tissue causes collagen tissue to be shortened. (Vangsness, CT Jr. Et al:”Collagen Shortening: An Experimental Approach with Heat,” Clinical Orthopaedics and Related Research, No. 337, 267-271, 1997) VNUS animal research has demonstrated that the application of controlled heating to the vein wall causes the collagen fibrils to contract (shorten) and thicken, and the vein to significantly shrink in diameter. Effects of controlled heating of the vein wall Thermal energy is quickly transferred from the Closure FAST catheter’s heating element to the vein wall through conduction. Heating of the vein wall tissue causes endothelial destruction and collagen contraction that result in vein occlusion. Thermal energy causes collagen to undergo the following changes: Heat sensitive bonds break at 60ºC Crystalline extended structure begins to uncoil, causing the collagen fibrils to shorten and thicken. As the molecule contracts, its diameter increases, causing a reduction in vein lumen diameter Histological Effects of RF heating Controlled thermal injury to the vessel wall causes the following changes in the histology of the vessel resulting in vein contraction. When the vein wall is exposed to sufficient thermal energy it causes: Endothelial denudation, Collagen denaturation, Smooth muscle necrosis, Vein wall shrinkage and thickening, and Vessel lumen reduction. Following these immediate effects, the treated vessel undergoes an inflammatory response, fibroblast infiltration, new collagen deposition, and eventual fibrosis.
Notes: The procedure is performed under general and/or local anesthesia Using ultrasound, the Closure catheter is positioned into the diseased vein through a small opening in the skin The slender catheter is powered by radiofrequency (RF) energy which delivers heat to the vein wall As thermal energy is delivered, the vein wall shrinks and the vein is sealed closed Once the diseased vein is closed, blood is re-routed to other healthy veins Consider showing the VNUS ClosureFAST animation video to further detail the treatment
Notes: Source: Dietzek A, Two-Year Follow-Up Data From A Prospective, Multicenter Study Of The Efficacy Of The ClosureFAST Catheter, 35th Annual Veith Symposium. November 19, 2008. New York.
Notes: To play the Radiofrequency Ablation Procedure video, click on the graphic. Video file RF Ablation video for PPT slide 13.wmv needs to be in the same folder as the PowerPoint presentation for this video to play
Notes: Comparison between ClosureFAST and Endovenous laser ablation. (notice the speed and heating pattern between the two ablations) To play the video, click on the graphic. Video file Ablation Comparison video for PPT slide 14.wmv needs to be in the same folder as the PowerPoint presentation for this video to play
Notes: Following the VNUS Closure procedure, patients can resume normal activities within one to two days compared to the postoperative convalescence of two or more weeks commonly experienced following traditional vein stripping By addressing the underlying condition of venous reflux disease, the appearance of the legs may improve following the VNUS Closure procedure After the VNUS Closure procedure, patient symptoms can improve quickly and cosmetic issues become easier to address The Closure procedure is also widely covered by Medicare and most private insurance plans
Notes: From March 23, 2007 to December 14, 2007 a six-center single-blinded randomized trial was conducted evaluating the patient recovery experience of patients treated with the VNUS ClosureFAST RF Catheter and the 980nm endovenous laser. The study was sponsored by VNUS Medical Technologies. The data presented here has been independently reviewed for completeness and accuracy. Data is on file.
Notes: This slide looks at the average Maximum Pain Score from all participants in the trial. The patients were asked during their follow-up visits to rate their maximum pain level on a scale from zero to ten. This graph shows the average maximum score of all patients and all visits.
Notes: Ecchymosis was evaluated at each follow-up visit by visual evaluation by the practicing physician. They categorized their observations into 6 categories: no ecchymosis >0 but </=25% of treated surface area ecchymosed >25% but </= 50% >50% but </= 75% >75% but </=100% >100% (if the ecchymosis went beyond the treated area) This graph shows the “Moderate to Severe Ecchymosis” which is defined as >25% of the area ecchymosed. There were cases of ecchymosis in the lower 2 categories for CLF and laser, but this could be due to the infiltration of tumescent anesthesia. In order to compensate for tumescent, which is used in both CLF and laser procedures, we looked at those individuals who had >25% ecchymosis after the procedure.
Notes: ClosureFAST-treated limbs had significantly less bruising 4 weeks after treatment, compared to endovenous laser
Notes: Perforator veins serve as connections between the two networks of veins in the extremities, the superficial venous system and the deep venous system, somewhat like the rungs of a ladder connect the side rails, and normally drain blood from the superficial veins to the deep veins as part of the process of returning oxygen-depleted blood to the heart. Perforator veins have one-way valves designed to prevent backflow of blood down towards the superficial veins. When those valves no longer function properly and reflux occurs, the buildup of blood and pressure can cause not only the superficial veins but the perforators themselves to become incompetent. Incompetence can cause varicose veins by transmitting the deep system’s higher pressure into the lower pressure superficial veins Perforator veins in the lower leg and ankle are particularly vulnerable to distention and incompetence, and the resultant circulatory problems create an increased likelihood of edema, skin discoloration, dermatitis and skin ulcers in the immediate area.
Notes: Both Superficial and Perforator reflux are usually involved in venous ulceration. Valvular incompetence associated with venous ulceration can occur in the superficial, deep, or perforating systems. A duplex imaging was used to evaluate 95 extremities (78 patients) with current venous ulceration to determine the location of incompetence in each extremity. 63% of the 95 extremities in the study experienced incompetence in the perforating systems: 8.4% in perforating system only 19% in perforating system + superficial system 4.2% in perforating system + deep system 31.6% in perforating system + deep system + superficial system (Source: Hanrahn L. et al. Distribution of valvular incompetence in patients with venous stasis ulceration. JVS 13,6, 805-812 June 1991)
Notes: Minimally invasive outpatient procedure which can be performed under local anesthesia in the physician's office Quick patient recovery time - return to normal activities – usually within one day Minimal scarring at skin penetration points • Utilizes proven radiofrequency energy • Controlled, consistent thermal energy delivered to the vein wall To play the video, click on the graphic. Video file RFS Procedure video for PPT slide 24.avi needs to be in the same folder as the PowerPoint presentation for this video to play
Notes: Sources: Jamie R Barwell, Colin E Davies, Comparison of surgery and compression with compression alone in chronic venous ulceration (ESCHAR study): randomized controlled trial,THE LANCET, Vol 363, June 04 Nelzen O. Fransson I. True long-term healing and recurrence of venous leg ulcers following SEPS combined with superficial venous surgery: a prospective study. Eur J Vasc Endovasc Surg 34, 605-612 (2007)
Endovenous Radiofrequency Ablation of the Saphenous Vein The VNUS Closure ® Procedure VN20-86-E 4/09
<ul><li>25 Million people suffer from venous reflux disease, the underlying cause for most varicose veins </li></ul>VNUS Closure is the minimally invasive treatment for the medically indicated treatment of varicose veins Images courtesy of Paul McNeill, MD and Rajabrata Sarkar, MD
Prevalence and Etiology of Venous Insufficiency Millions Venous reflux disease is 2x more prevalent than coronary heart disease (CHD) and 5x more prevalent than peripheral arterial disease (PAD) 1 Annual U.S. Incidence U.S. Prevalence
Prevalence and Etiology of Venous Insufficiency Prevalence by Age and Gender 3,4 <ul><li>Of the estimated 25 million people with symptomatic superficial venous reflux 1 : </li></ul><ul><ul><ul><li>Only 1.7 million seek treatment annually 2 </li></ul></ul></ul><ul><ul><ul><li>Over 23 million go untreated </li></ul></ul></ul>43% 72% 60 - 69 24% 41% 40 - 49 1% 8% 20 - 29 Male Female Age
Venous System <ul><li>Venous blood flows from the capillaries to the heart </li></ul><ul><li>Flow occurs against gravity </li></ul><ul><ul><li>Muscular compression of the veins </li></ul></ul><ul><ul><li>Negative intrathoracic pressure </li></ul></ul><ul><ul><li>Calf muscle pump </li></ul></ul><ul><li>Low flow, low pressure system </li></ul>Image source: Fundamentals of Phlebology: Venous Disease for Clinicians. Illustration by Linda S. Nye. American College of Phlebology 2004. Deep femoral v. Femoral v. Popliteal v. Small saphenous v. Great saphenous v. Perforating v. Perforating v.
Risk Factors and Symptoms of Venous Insufficiency <ul><li>Gender </li></ul><ul><li>Age </li></ul><ul><li>Heredity </li></ul><ul><li>Pregnancy </li></ul><ul><li>Standing occupation </li></ul><ul><li>Obesity </li></ul><ul><li>Prior injury or surgery </li></ul><ul><li>Sedentary lifestyle </li></ul>Risk factors of venous insufficiency: <ul><li>Leg pain, aching, or cramping </li></ul><ul><li>Burning or itching of the skin </li></ul><ul><li>Leg or ankle swelling </li></ul><ul><li>“ Heavy” feeling in legs </li></ul><ul><li>Skin discoloration or texture changes </li></ul><ul><li>Open wounds or sores </li></ul><ul><li>Restless legs </li></ul><ul><li>Varicose Veins </li></ul>Symptoms of venous insufficiency:
20+ million 2 to 6 million Skin Ulcers 500,000 Manifestations of Venous Insufficiency Superficial venous reflux is progressive and if left untreated, may worsen over time. Below are manifestations of the disease. 5 Photos courtesy of Rajabrata Sarkar, MD, PhD. Swollen Legs Skin Changes Varicose Veins
CEAP Classifications <ul><li>Clinical Classifications of Venous Insufficiency (CEAP) </li></ul><ul><li>Class 0 - No visible or palpable signs of venous disease </li></ul><ul><li>Class 1 - Telangiectasias or reticular veins </li></ul><ul><li>Class 2 - Varicose veins </li></ul><ul><li>Class 3 - Edema </li></ul><ul><li>Class 4 - Skin changes </li></ul><ul><ul><ul><li>(4a) Skin changes including pigmentation or venous eczema </li></ul></ul></ul><ul><ul><ul><li>(4b) Skin changes with lipodermatosclerosis </li></ul></ul></ul><ul><li>Class 5 - Healed venous ulceration </li></ul><ul><li>Class 6 - Active venous ulceration </li></ul>
The VNUS Closure ® System <ul><li>The VNUS Closure System is a minimally invasive treatment alternative for patients with symptomatic superficial venous reflux and varicose veins </li></ul><ul><li>Using a catheter-based approach, the VNUS ClosureFAST™ catheter delivers radiofrequency (RF) energy to the vein wall </li></ul><ul><li>RF energy creates conductive heating that contracts the vein wall collagen, thereby occluding the vein </li></ul>
VNUS Closure® Procedure using the ClosureFAST™ Catheter
Efficacy of the ClosureFAST™ Catheter The ClosureFAST™ catheter ablates the vein in 7cm segments with 20-second treatment cycles, resulting in vein shrinkage and occlusion. Interim data from a multicenter prospective study have shown 97.4% vein occlusion 1 year post-treatment. 6
Ablation Comparison (simulation in beef liver)
VNUS Closure ® Visual Results One week post-treatment* Pre-treatment *Individual results may vary <ul><li>Ambulate frequently, a minimum of 30 minutes daily </li></ul><ul><li>Avoid heavy/strenuous exercise for a few days </li></ul><ul><li>Avoid prolonged sitting or standing </li></ul><ul><li>Wear compression stockings for up to 2 weeks </li></ul><ul><li>Patient should return for duplex scan within 72 hours </li></ul>Post-Procedure Instructions
RECOVERY Trial 7 A Prospective, Multi-Center, Randomized Study <ul><li>Purpose - Determine if patient recovery and other short term outcomes are different between radiofrequency and laser treatment </li></ul><ul><ul><li>Six center, single-blinded randomized trial of ClosureFAST vs. Endovenous Laser </li></ul></ul><ul><ul><li>69 patients; 87 limbs treated (46 CLF; 41 EVL) </li></ul></ul><ul><ul><li>Patient follow up at 2, 7, 14, and 30 days after treatment </li></ul></ul>
RECOVERY Trial 7 : Pain A Prospective, Multi-Center, Randomized Study Overall Maximum Pain Score (0 none to 10 max) ClosureFAST Laser p < 0.0001 2 4
RECOVERY Trial 7 : Ecchymosis A Prospective, Multi-Center, Randomized Study ClosureFAST Laser p < 0.0001 Moderate to Severe Ecchymosis (Bruising) After Treatment Moderate to severe ecchymosis is defined as bruising over greater than 25% of the treated surface area 2.2% 51.3%
RECOVERY Trial 7 : Ecchymosis A Prospective, Multi-Center, Randomized Study Presence of Any Ecchymosis (Post Procedure) 33.0% 80.5% 35.0% 74.3% 18.6% 66.7% 2.2% 22.5%
RECOVERY Trial 7 : Conclusion A Prospective, Multi-Center, Randomized Study <ul><li>Compared to laser, RF treatment with ClosureFAST produced significantly </li></ul><ul><ul><li>Less pain p < 0.0001 </li></ul></ul><ul><ul><li>Less tenderness p = 0.0008 </li></ul></ul><ul><ul><li>Less bruising p < 0.0001 </li></ul></ul><ul><ul><li>Fewer adverse events p = 0.021 </li></ul></ul>
ClosureFAST™ Catheter <ul><li>Indication: </li></ul><ul><li>The ClosureFAST Catheter is intended for endovascular coagulation of blood vessels in patients with superficial venous reflux </li></ul><ul><li>Contraindications: </li></ul><ul><li>Patients with thrombus in the vein segment to be treated </li></ul><ul><li>Potential Risks & Complications: </li></ul><ul><li>Potential complications include, but are not limited to, the following: vessel perforation, thrombosis, pulmonary embolism, phlebitis, hematoma, infection, adjacent nerve injury, skin burns, deep vein thrombosis </li></ul>
Perforating Veins and Reflux <ul><li>Perforator valves maintain one-way flow from superficial to deep veins </li></ul><ul><li>Perforator valve failure causes: </li></ul><ul><ul><li>Higher venous pressure and GSV/branch dilation </li></ul></ul><ul><ul><li>Increasing pressure results in GSV valve failure </li></ul></ul><ul><ul><li>Additional vein branches become varicose </li></ul></ul><ul><ul><li>Further GSV incompetence and dilation </li></ul></ul>
Systemic Reflux in Venous Ulceration Incompetent perforators found in 63% of venous ulcer patients Comprehensive care treats all sources of reflux Photos courtesy of Steven A. Kaufman, MD. 50% 63% 79% Deep Perforating Superficial Sources of Reflux in Venous Ulcer Patients 8
VNUS ClosureRFS™ <ul><li>VNUS ClosureRFS Benefits: </li></ul><ul><li>Minimally invasive </li></ul><ul><li>Outpatient procedure </li></ul><ul><li>Quick patient recovery </li></ul><ul><li>Only device cleared by the FDA for the endovenous ablation of incompetent perforator veins </li></ul>Click graphic to play video
Venous Ulcer Patient Outcomes <ul><li>Treating the underlying cause of venous ulceration results in improved clinical outcomes </li></ul><ul><li>Treating both the superficial and perforator hypertension results in: </li></ul><ul><ul><li>Faster ulcer healing time </li></ul></ul><ul><ul><li>Lower ulcer recurrence rate </li></ul></ul><ul><ul><li>than with compression therapy alone 9,10 </li></ul></ul>
References <ul><li>American Heart Association, SIR, Brand et al. “The Epidemiology of Varicose Veins: The Framingham Study” </li></ul><ul><li>US Markets for Varicose Vein Treatment Devices 2006, Millennium Research Group 2005. </li></ul><ul><li>Coon WW, Willis PW, Keller JB: Venous thromboembolism and other venous disease in the Tecumseh Community Health Study Circulation 1973; 48:839-846. </li></ul><ul><li>Barron HC, Ross BA. Varicose Veins: A guide to prevention and treatment. NY, NY: Facts on File, Inc. [An Infobase Holdings Company]; 1995;vii. </li></ul><ul><li>White JV, Ryjewski C. Chronic venous insufficiency. Perspect Vasc Surg Endovasc Ther 2005;17:319-27 </li></ul><ul><li>Dietzek A, Two-Year Follow-Up Data From A Prospective, Multicenter Study Of The Efficacy Of The ClosureFAST Catheter, 35th Annual Veith Symposium. November 19, 2008. New York. </li></ul><ul><li>Alameida JI. Lessons Learned After 2000 Endovenous Ablations. 34 th Veith Symposium. Nov 14-18, 2007. New York </li></ul><ul><li>Hanrahn L. et al. Distribution of valvular incompetence in patients with venous stasis ulceration. JVS 13,6, 805-812 June 1991 </li></ul><ul><li>Jamie R Barwell, Colin E Davies, Comparison of surgery and compression with compression alone in chronic venous ulceration (ESCHAR study): randomized controlled trial,THE LANCET, Vol 363, June 04 </li></ul><ul><li>Nelzen O. Fransson I. True long-term healing and recurrence of venous leg ulcers following SEPS combined with superficial venous surgery: a prospective study. Eur J Vasc Endovasc Surg 34, 605-612 (2007) </li></ul>