Advances in Vein Therapy

A Short Review of Catheter-Based Superficial Venous Disease Management: New Directions, New Paradigms

Julian J. Javier, MD

Julian J. Javier, MD

Cardiology has long ignored superficial venous disease, relegating it to a miscellaneous condition, then arterial disease; cardiology programs rarely offer vein training. Cardiologists had little grasp of the full scope of superficial venous disease apart from deep vein thrombosis (DVT). All of this changed with a confluence of several major evolutions in modern medicine: open surgical procedures increasingly transitioned to minimally invasive catheter-based procedures, cardiac reimbursements steadily declined, and risk factors for venous disease (advanced age, obesity) are on the rise. Cardiologists already adept with ultrasound imaging found their arterial practice could naturally expand into vein treatments. This review examines the current situation of catheter-based vein interventions with an emphasis on tumescentless versus thermal-injury techniques to treat superficial venous insufficiency.

Superficial Venous Disease

Venous disease is 2 times as prevalent as coronary disease and 5 times as prevalent as peripheral artery disease.1 Ambulatory catheter-based treatments, the substitute for surgical procedures to treat superficial venous disease, produce excellent results with 94% of limbs free of reflux at 1 year after thermal injury.2 Superficial venous disease occurs in 23% of adults and its main risk factors are female sex, advancing age, jobs that require standing for long periods, obesity, multiple pregnancies, and family history of venous disease.3 Symptoms of venous insufficiency include leg fatigue, burning sensations in the legs, skin changes, edema, and in severe cases, ulcers. Unlike arterial disease, superficial venous disease is more painful at rest and at the end of the day. Venous disease adversely affects patient quality of life,4 decreases productivity, can put stress on families, and costs the United States (US) healthcare system about $1 billion annually.5


Duplex ultrasound remains the most common tool for the diagnosis and management of superficial venous disease and should be considered the reference standard when evaluating vein physiology and hemodynamics.6 Since veins are a lower-pressure system, it is recommended that the patient be evaluated in an upright position, either standing or sitting at the edge of the exam table.6


Abnormal reflux occurs in the great saphenous vein (GSV) and the small saphenous vein (SSV) when the vessel diameter exceeds 5 mm and there is more than 0.5 seconds of reflux (Figure 1).

Goals of Vein Therapy

The primary goals of venous therapy are to eliminate the sources of reflux and, in that way, eliminate or reduce symptoms. For many patients, it is appropriate to begin with conservative treatments, such as compression stockings and elevating the legs often. Failure to respond to conservative therapy as well as the presence of an active ulcer indicate that invasive treatment should be considered.


For the past 12 years, the standard form of invasive treatment of venous disease in the US has been thermal injury. More recently, non-thermal treatments have been introduced.7 These new non-thermal treatments have generated considerable interest because non-thermal injury can be performed without the need for tumescent anesthesia (TA), which is required with thermal injury techniques and has been associated with patient pain and discomfort (Table 1).

Tumescentless Techniques

Tumescentless techniques might also be called chemical ablation in that they use chemical means rather than thermal injury to close veins.


Ultrasound-guided sclerotherapy (UGS). Although UGS is not a catheter-based treatment, its effectiveness has led to the development of catheter-based therapy using sclerosant. The goal of UGS is to cause endoluminal damage to the venous tissue of incompetent veins, which damages the endothelium and, to some extent, the media. UGS is simple, cost effective, and efficient, offering good short-term and mid-term results.8


UGS is performed by using ultrasound to identify the source of the reflux and then injecting sclerosant while maintaining visualization of the target incompetent vein. Two sclerosants are approved for use in the US: sodium tetradecyl sulfate and polidocanol. The newest of these, Varithema (formerly known as Varisol) is the latest of these drugs to be approved in the US (December 2013); it is a foam sclerosing agent that has been shown to be safe, effective, and associated with rapid recovery. Sclerosants are available in foam and liquid formulations in different concentrations. Damage to the vessel directly correlates with the concentration of the sclerosant at the time of contact with the vessel wall.


Catheter-assisted balloon sclerotherapy (CABS). CABS delivers a targeted application of a sclerosing agent to the incompetent GSV. Jens P. Bordersen designed a double-lumen catheter that is inserted into a refluxing GSV. Through one lumen, a balloon at the tip of the catheter can be inflated, stopping the blood flow. With the second lumen, the sclerosing agent can be injected and aspirated as needed. In one study, 27 out of 30 patients were closed at 6 months.9 In another study, a specially designed balloon was used to successfully treat 3 patients with GSV insufficiency, achieving complete occlusion at 12 months.10


CABs combines two well-established procedures (balloon catheterization and sclerotherapy) into a minimally invasive technique. CABS is a cost-effective form of endovenous therapy for incompetent veins and requires local anesthesia only at the puncture site. Due to its targeted delivery, it appears that CABS might reduce possible systemic side effects from the sclerosing agent. Catheter-directed sclerotherapy chemically injures the venous endothelium in a way that does not require perivenous anesthesia. However, it may be inferior to thermal ablation in terms of vein closure rates.11


Mechanical occlusion chemical ablation (MOCA). MOCA, approved in the US and Europe, combines mechanical and chemical injury to the vessel wall to achieve vein closure. The ClariVein catheter (Vascular Insights, LLC) provides simultaneous mechanical injury (from a rotating wire at the tip of the catheter) and delivery of sclerosant. The wire at the tip of the device rotates at speeds of up to 2000-3500 revolutions/minute.


Initial studies done by Elias on 30 patients demonstrated an average procedure time of 14 minutes with GSV sizes ranging from 5.5-12 mm in diameter and an average treatment length of 36 cm.12 At 1, 3, and 6 months, 29/30 veins treated (96%) were successfully closed. The only vein in this study that did not respond was in the first patient.12 Data from the trial patients and non-trial patients found 29/30 veins closed at 1 year and 27/28 veins (96%) closed at 2 years (1 patient died and 1 patient was lost to follow-up at 2 years).13 In a Dutch study, a total of 224 GSVs were treated; 182/185 (98%) were closed at 6 weeks and 40/42 (95%) were closed at 6 months, with no skin or nerve injuries.14
When MOCA was compared to radiofrequency (RF) ablation, MOCA allowed less pain and more rapid return to work and activities of everyday living, with equivalent quality of life (QoL).15 Compared to thermal approaches, MOCA eliminates the need for tumescent anesthesia, lowers the risk of potential nerve and surrounding tissue damage, and uses a relatively small catheter (4 Fr for MOCA vs 5-7 Fr catheter for RF ablation or endovenous laser therapy [EVLT]). Furthermore, with MOCA there is no need to purchase a generator (as with RF ablation) and the patient is at much less risk of pain and bruising.


While MOCA has been approved in US since March 20, 2008, some insurances do not cover it. United Healthcare quoted the Hayes report, concluding that the scope and quality of available clinical studies are insufficient to make an assessment as to the safety and efficacy of the ClariVein catheter, suggesting that larger randomized controlled trials are needed.16


Further data on long-term effectiveness will provide clinicians with better insight into this therapy, but MOCA appears to be positioning itself in the venous market as an attractive alternative to thermal injury in the field of tumescentless devices.


Cyanoacrylate (CA) closure devices. CA closure devices use a surgical glue (similar to SuperGlue) to close vessels. Approved in Europe and Canada, CA closure systems are under investigation in the US. The VenaSeal closure system (Sapheon) delivers an adhesive polymer into the saphenous vein using a proprietary catheter, designed to be inert to adhesive and suitable for saphenous vein use. The VenaSeal system does not require tumescent anesthesia. The Sapheon delivery system uses a 7 Fr introducer sheath/dilator, a 5 Fr delivery catheter, a 3 mL syringe, and a dispenser gun. The 5 Fr delivery catheter has a hydrophobic design using air-filled microchannels to enhance sonographic visibility and to help prevent CA-medicated adhesion to the vein. Engineers used mathematical volumetric calculations in cylindrical systems (to mimic venous tubes) to design the dispenser gun to deliver 0.08 or 0.16 mL of CA with each pull of the trigger.17


After endovenous administration, the CA polymerizes into a solid, leading to an inflammatory response in the vein wall (Figure 2). In a swine model, at 30 days following catheter-directed endovenous CA placement in superficial epigastric veins, a granulomatous foreign body reaction could be observed in the vein lumen.18 At 60 days, fibroblasts could be seen invading the contents of the vein lumen, resulting in 100% occlusion.


The first human studies using CA treated 38 incompetent GSVs with catheter-delivered CA and demonstrated that CA use was feasible, safe, and effective.19 In this first-in-man study, follow-up was conducted at 1, 3, and 6 months and showed an occlusion rate of 92% at 12 months. Adverse events were mild and self limited. The most frequent side effects were thread-like thrombus extensions into the common femoral vein, which occurred in 21% of patients and resolved spontaneously without anticoagulation, and phlebitis, which occurred in 15.8% of patients and could be treated with non-steroidal anti-inflammatory drugs. The Venous Clinical Severity Score (VCSS) improved in all patients from a mean value of 6.1 to 1.5 at 1 year. Edema improved in 89% of legs treated.19 In April of this year, Almeida et al reported that 26/38 patients reported to the clinic for 24-month follow-up, and found that 25/26 (96.2%) had durable closure and 1/26 had non-closure, defined as patency <5 cm.17 There was an improved VCSS in 73% of patients vs baseline, while 27% had no change in VCSS. Davies presented eSCOPE results at the American Venous Forum (AVF) meeting in 2013; eSCOPE was a prospective, single-arm, observational, multicenter study conducted in seven European vein centers between December 2011 and July 2012. Seventy patients were treated and showed 95.7% and 93.7% occlusion rates at 3-month and 6-month follow-up exams, respectively.


CA is currently being evaluated in an Investigational Drug Exemption (IDE) multicenter study in the US; a total of 220 patients are being randomized in a 1:1 ratio to evaluate CA treatment. Patients will be followed for a total of 36 months (8 visits/patient). The study commenced on March 11, 2013.


CA holds great promise as a safe, effective treatment for abnormal GSVs without the use of tumescent anesthesia.


Tumescent-Based Techniques

Thermal injury has a long track record of safety and efficacy and might even be considered the preferred form of therapy. Approved in the US in 1999, thermal injury replaced the previous method of GSV incision stripping. It has been estimated that in 1999, there were close to 155,000 GSV strippings performed in the US, but by 2007, there were 195,000 endovenous ablations a year.20 In the US, the two most commonly used thermal techniques are endovenous laser therapy (EVLT) and RF ablation.


Radiofrequency (RF) treatment. The first device available in the US to treat incompetent veins was an RF ablation system. Studies comparing RF to surgical vein stripping favor the RF approach. For instance, Rautio et al randomized 28 patients to RF therapy or vein stripping and demonstrated that RF therapy offered faster recovery, less pain, and less need for postoperative analgesia.21 The EVOLVeS study was a multicenter, prospective, randomized study that compared QoL with vein stripping vs RF therapy and found faster recovery, less pain, and fewer adverse events, with identical results at 2 years with over 90% of GSVs free of reflux.22 Further studies supported these findings.
The underlying mechanism of action of RF ablation is related to collagen contraction in response to thermal injury which, in turn, leads to a thickening of the vein wall and thus a reduction in the lumen diameter of the vein. An inflammatory response to thermal injury leads to fibrosis and vein occlusion.23


The first-generation RF devices were slow and cumbersome to use. The second-generation ClosureFAST device (VNUS Medical Technologies, Covidien), launched in May 2007, reduced procedure time to around 3 minutes vs the 20 minutes or more required by older systems.


RF treatment is performed via a 7 Fr sheath that is positioned under ultrasound guidance via the saphenofemoral junction (SFJ) about 2.5-3.0 cm from the epigastric vein. Tumescent anesthesia is administered throughout the length of the vein to be treated. It is recommended that pressure be applied to the skin to help aid contact of the catheter with the vein wall. RF can be used for GSV and SSV and is approved for perforator treatment with the VNUS ClosurePLEX catheter (VNUS Medical Technologies, Covidien).


The VNUS clinical registry was established in 1998, with over 30 centers worldwide contributing data. Ninety-four percent of limbs were free of reflux at 1 year. No reflux was observed on ultrasound in 91.4%, 90.1%, 86.3%, and 86.1% at 1, 2, 3, and 4 years, respectively.


The EVRF thermocoagulator system (F Care Systems) is an RF system used to treat GSV incompetence that has been approved in Europe but not in the US. The EVRF device is a monopolar, high-frequency thermocoagulation catheter capable of generating 4-12 mHz RF energy, which can cause vessel wall injury while sparing surrounding tissue.


The advantages of RF treatment are well known: safety, >90% success rate for GSV closure, and minimal postoperative pain. Drawbacks to RF treatments are the need for tumescent anesthesia, potential for nerve injury, and cost.
Endovascular laser therapy (EVLT). The mechanism of action with laser treatment differs from RF ablation. Lasers can be classified into hemoglobin-specific laser wavelengths (HSWLs) and water-specific laser wavelengths (WSLWs). The main form of action of an HSWL is a hemoglobin-mediated absorption of laser energy, generating steam bubbles. Available on the market in order of increasing affinity are the 810 nm, the 940 nm, and 980 nm systems. The thermal injury of the inner wall leads to a thrombotic occlusion of the treated vein.24 Regardless of the laser wavelength (810, 940, or 980 nm), all of these HSWL systems have similar capabilities in terms of generating steam bubbles; data show equivalent closure rates for all three of these wavelengths.24 This treatment is performed using a continuous pullback, which theoretically avoids perforation.


By contrast, the WSLW targets the water contained in the interstitial vein wall. Although 1319 nm and 1320 nm WSLW systems are available, they are rarely used today. The most recently introduced WSLW device is the 1470 nm VenaCure EVLT system (Angiodynamics). In a retrospective review of endovenous ablation, Proebstle et al demonstrated statistically significantly less pain and ecchymosis in patients treated with the 1320 nm laser system compared with conventional therapy.24 The newer 1470 nm WSLW system has an innovative design and a glass weld at the distal tip of a 600 µm fiber, which is designed for a homogenous ablation and may be associated with less charring of the vein wall. This new device has been found to offer atraumatic therapy and is safe, effective, and simple to operate.25 The 1470 nm laser allows effective vein ablation with targeted energy of 30-50 J/cm at a setting of 5-7 W.
Almeida and colleagues evaluated the 1470 nm WSLW system at different energy levels (20 J/cm at 5 W linear endovenous energy density [LEED] and 30 J/cm at 3 W LEED) and demonstrated that the 1470 nm WSLW laser could successfully close GSVs at lower energy.26


Several studies have shown the success rate of EVLT ranges from 95%-99%.27 The main drawbacks to EVLT are ecchymosis, postoperative pain, and bruising.


Steam ablation (SA). SA is another form of therapy based on thermal injury; SA has been approved in Europe but is under investigation in the US. The Ceram steam ablation system uses a continuous current to heat water, creating steam at the handle of the device; high pressure then sends this steam to the catheter tip, leading to vein wall injury. In a study of 164 SA-treated veins followed over 3 years, there was 1 case of deep vein thrombosis (DVT) and 3 skin burns at the introduction site.28


The VENI RF plus device (Veniti Medical), which is currently under investigation in the US, uses a catheter that heats normal saline solution, creating steam at the catheter tip. Reaching only temperatures close to 100 °F, this device avoids damage to the surrounding tissue. Animal studies using the Venire Plus device demonstrated circumferential transmural damage to the vein wall, no perforation, and no charring compared to EVLT.29 Like RF and EVLT approaches, SA requires the use of tumescent anesthesia.

Conclusion and Future Directions

Thermal injury for the treatment of incompetent SVGs has extensive data and a long track record showing it is safe and highly effective. However, the need to use tumescent anesthesia with these approaches has been shown to be a tedious, painful, and time-consuming procedure. This has encouraged the vein industry to search for alternative forms of therapies to avoid the need for tumescent anesthesia.


Indeed, tumescentless devices are showing great promise and resulting in patient satisfaction. Short-term data are good; however, long-term data are still needed to determine if tumescentless techniques are as effective as thermal injury. For example, MOCA in the US and cyanoacrylates in Europe and Canada show great promise as tumescentless options.


This is not to say that thermal techniques are not advancing. Angiodynamics is working on a device designed by our group that will deliver tumescent anesthesia from inside the lumen of the vein, which will avoid the multiple needle sticks required for the conventional administration of tumescent anesthesia. This is intended to make the thermal approach more comfortable for the patient.


Another promising technology is the water-specific laser waveform of 2000 nm, which might allow more absorption of the photon in the vein and thus require less energy. This could possibly evolve into a tumescentless system.
Today, vein specialists can count on many highly effective tools to assist with treating the large and growing population of patients with superficial venous disease. Venous insufficiency will continue to increase with our aging and increasingly obese population (age and obesity are risk factors for venous insufficiency). Patients will benefit from our ongoing search for safer, more effective, and more comfortable techniques to fight vein disease.

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___________________________________________________________________________

From the University of Miami School of Medicine, Miami, Florida and NOVA Southeastern University, Fort Lauderdale, Florida.

Disclosure: The author has completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Javier holds a patent through Angiodynamics.

Manuscript submitted March 18, 2014, provisional acceptance given May 30, 2014, final version accepted July 2, 2014.

Address for correspondence: Julian J. Javier, MD, FACC, FSCAI, 1168 Goodlette-Frank Rd, Naples, FL 34108. Email: julianjjaviermd@aol.com

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