1. Lower Extremity Venous Disease: Peripheral Venous Insufficiency
Aman K Kakkar MD FACC
Heart and Vascular Care, Inc

2. 30 Million people suffer from venous reflux disease, the underlying cause for most varicose veins

3. Prevalence and Etiology of Venous Insufficiency
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
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”)
Millions

4. Prevalence of Venous Insufficiency
Of the estimated 30 million people with symptomatic superficial venous reflux1 :
Only 1.9 million seek treatment annually2
Only 500K Patients receive treatment
Over 28 million go untreated
Prevalence by Age and Gender3,4
Age
Female
Male 8% 1%
41%
24%
72%
43%
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.)

5. Venous System Venous blood flows from the capillaries to the heart
Deep femoral v.
Femoral v.
Popliteal v.
Small saphenous v.
Great saphenous v.
Perforating v.
Venous blood flows from the capillaries to the heart
Flow occurs against gravity
Muscular compression of the veins
Negative intrathoracic pressure
Calf muscle pump
Low flow, low pressure system
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
Image source: Fundamentals of Phlebology: Venous Disease for Clinicians. Illustration by Linda S. Nye. American College of Phlebology 2004.

6. Pathophysiology of Venous Insufficiency
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

8. Risk Factors and Symptoms of Venous Insufficiency
Risk factors of venous insufficiency:
Gender
Age
Heredity
Pregnancy
Standing occupation
Obesity
Prior injury or surgery
Sedentary lifestyle
Symptoms of venous insufficiency:
Leg pain, aching, or cramping
Burning or itching of the skin
Leg or ankle swelling
“Heavy” feeling in legs
Skin discoloration or texture changes
Open wounds or sores
Restless legs
Varicose Veins
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

9. Manifestations of Venous Insufficiency
Superficial venous reflux is progressive and if left untreated, may worsen over time.
Below are manifestations of the disease.5
Varicose Veins
Swollen Legs
Skin Changes
Skin Ulcers
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
20+ million
2 to 6 million
500,000
Photos courtesy of Rajabrata Sarkar, MD, PhD.

10. PATHOPHYSIOLOGY

11. CEAP Classifications
Clinical Classifications of Venous Insufficiency (CEAP)
Class 0 - No visible or palpable signs of venous disease
Class 1 - Telangiectasias or reticular veins
Class 2 - Varicose veins
Class 3 - Edema
Class 4 - Skin changes
(4a) Skin changes including pigmentation or venous eczema
(4b) Skin changes with lipodermatosclerosis
Class 5 - Healed venous ulceration
Class 6 - Active venous ulceration
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.

12. Great Saphenous Vein : The Culprit

13. American Venous Forum (AVF) Guidelines: Diagnosis

14. Great Saphenous Vein (GSV) : Reflux

15. Small Saphenous Vein (SSV): Reflux

16. TREATMENT ALGORITHM

17. AVF Guidelines: Treatment

18. AVF Guidelines: Treatment

19. Vein Closure: Indications, Risks
The Catheter ablation is intended for endovascular coagulation of blood vessels in patients with superficial venous reflux
Contraindications:
Patients with thrombus in the vein segment to be treated
Potential Risks & Complications:
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

20. Vein Closure: Options Stripping Foam Sclerotherapy
Radiofrequency Ablation
Laser Ablation

21. RECOVERY Trial7: Pain A Prospective, Multi-Center, Randomized Study
Overall Maximum Pain Score (0 none to 10 max)
p < 4
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. 2
ClosureFAST Laser

22. RECOVERY Trial7: Ecchymosis A Prospective, Multi-Center, Randomized Study
Moderate to Severe Ecchymosis (Bruising) After Treatment
Moderate to severe ecchymosis is defined as bruising over greater than 25% of the treated surface area
p <
51.3%
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.
2.2%
ClosureFAST Laser

23. RadioFrequency Ablation
The Radiofrequency Closure System is a minimally invasive treatment alternative for patients with symptomatic superficial venous reflux and varicose veins
Using a catheter-based approach, catheter delivers radiofrequency (RF) energy to the vein wall
RF energy creates conductive heating that contracts the vein wall collagen, thereby occluding the vein
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, , 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 ClosureFAST 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.

24. Procedure using the Radiofrequency Ablation Catheter
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

25. Procedure

26. Summary Easily Diagnosed but vastly untreated
Although many aspects of treatment have remained the same for over a century
Recent advances have provided new and better treatment options for patients with chronic venous disease.