A new non-tumescent endovenous ablation method for varicose vein treatment: Early results of N-butyl cyanoacrylate (VariClose®)

Abstract

Objective

This report aims to present the early results of a retrospective study of the use of N-butyl cyanoacrylate (VariClose®)-based non-tumescent endovenous ablation for the treatment of patients with varicose veins.

Method

One hundred and eighty patients with varicose veins due to incompetent saphenous veins were treated with the VariClose® endovenous ablation method between May 2014 and November 2014. The patient sample consisted of 86 men and 94 women, with a mean age of 47.7 ± 11.7 years. The patients had a great saphenous vein diameter greater than 5.5 mm and a small saphenous vein diameter greater than 4 mm in conjunction with reflux for more than 0.5 s. Patients with varicose veins were evaluated with venous duplex examination, Clinical, Etiological, Anatomical and Pathophysiological classification (CEAP), and their Venous Clinical Severity Scores were recorded.

Results

The median CEAP score of patients was three, and the saphenous vein diameters were between 5.5 and 14 mm (mean of 7.7 ± 2.1 mm). A percutaneous entry was made under local anesthesia to the great saphenous vein in 169 patients and to the small saphenous vein in 11 patients. Duplex examination immediately after the procedure showed closure of the treated vein in 100% of the treated segment. No complications were observed. The mean follow-up time was 5.5 months (ranging from three to seven months). Recanalization was not observed in any of the patients during follow-up. The average Venous Clinical Severity Scores was 10.2 before the procedure and decreased to 3.9 after three months (p < 0.001).

Conclusion

The application of N-butyl cyanoacrylate (VariClose®) is an effective method for treating varicose veins; it yielded a high endovenous closure rate, with no need for tumescent anesthesia. However, long-term results are currently unknown.

Keywords

Varicose vein N-butyl cyanoacrylate endovenous ablation

Introduction

Over the last two decades, minimally invasive methods have gained popularity for the treatment of varicose veins as an alternative to surgical treatments. First Bone and then Navarro and Min reported that they successfully applied thermal endovenous ablation using laser energy to treat varicose veins, which constituted a revolution in the treatment of this disease.^1,2 In 2002, Weiss and Weiss³ reported the use of radiofrequency energy for thermal ablation. Thermal ablation has since been performed using various laser catheters and wavelengths or various radiofrequency catheters, and these approaches have almost superseded classical surgery.

Today, thermal ablation performed using either laser or radiofrequency energy very effectively treats varicose veins. However, skin and tissue burns and nerve injuries due to thermal injury can occur during this procedure. Because temperatures can reach up to 700℃ during laser procedures and up to 120℃ during radiofrequency procedures, the use of tumescent anesthesia is obligatory during these procedures in order to minimize complications. However, tumescent anesthesia may be associated with complications due to the anesthetic agent, and hematoma and ecchymosis may be observed. Furthermore, the application of tumescent anesthesia requires that the patient’s leg be injected several times, which compromises the patient’s comfort. Complications observed during and after endovenous laser ablation and radiofrequency ablation (RFA) procedures have been reported by several different authors.^4–6

Therefore, we sought to perform endovenous ablation using methods other than thermal ablation. Foam sclerotherapy has been widely attempted as an alternative to thermal ablation. However, the success rate of this treatment method was low.⁷ Therefore, new treatment options, such as mechanochemical ablation, were developed.⁸ One of these new treatment options is endovenous ablation of the insufficient vein with cyanoacrylate, which is a tissue adhesive. To this end, the VariClose® vein sealing system was developed (Biolas, FG Grup, Ankara, Turkey). In this study, we present the short-time results of the use of endovenous ablation with the VariClose® vein sealing system for the treatment of patients with varicose veins.

Methods

Patients

One hundred and eighty patients were admitted to our unit with symptoms of venous insufficiency between May 2014 and November 2014. Patients with incompetent great and/or small saphenous veins diagnosed using colored Doppler ultrasonography (USG) were included in the study. The inclusion criteria were as follows: a great saphenous vein diameter greater than 5.5 mm and a small saphenous vein diameter greater than 4 mm in conjunction with reflux for more than 0.5 s. The exclusion criteria are given in Table 1. A maximum vein size was not imposed during patient selection. The patients were assessed again with colored Doppler USG immediately before the procedure. This assessment was conducted with a Mindray model M7 USG (Shenzen, China) by the surgeon who performed the cases. The patients were informed and their consent was obtained, and they were then taken to the operating room. The study protocol was approved by our local ethics committee.

Table 1.

Exclusion criteria.

1. Patients under the age of 18
2. Patients with obstruction in the deep venous system
3. Patients who have previously used another invasive treatment method (thermal and chemical ablation, surgery)
4. Patients with cardiac and renal failure
5. Immobile patients
6. Patients with secondary varicose vein
7. Hypercoagulability status
8. Local or systemic infection
9. Obesity (body mass index > 35)

After the ablation procedure, the ablation of the vein was immediately verified by the surgeon with duplex ultrasound to assess the success of the procedure. Elastic stockings were applied to the patients, and they were asked to return for a follow-up visit two days after the procedure. Additional follow-up visits were conducted at one month, three months, and six months after the procedure, during which the patients underwent clinical and duplex ultrasound examinations. Doppler USG assessment was performed by a radiologist. Additionally, patients were told to return to the hospital immediately in case of edema, rash, pain in the legs, or shortness of breath.

Procedure

All procedures were performed by experienced physicians for endovenous laser ablation and RFA. Endovenous ablation was performed on all patients using the VariClose Vein Sealing System. The catheterization and ablation were completed for all 180 patients without problems. The cyanoacrylate-based adhesive and delivery system were delivered in two separate vials of 1 cc, each in sterile conditions within the Disposable VariClose® kit, which consisted of the delivery system, a 6 F introducer, a 0.035 inch J guide wire, a 10 cc injector, an injection gun, a catheter with a 5F marker, and a 4F micro-catheter (delivery catheter) (Figure 1). The great saphenous vein was accessed with a 6F introducer set with the assistance of Doppler USG. A 0.035″ × 150 cm guidewire was sent through the 6F introducer sheath to the saphenofemoral junction (SFJ) or the saphenopopliteal junction (SPJ). Once the guidewire was confirmed to be in the SFJ or SPJ via Doppler USG, a 5F catheter was advanced to the SFJ or SPJ over the guidewire. After confirmation of the position of the 5F catheter at the beginning of the SFJ or SPJ, it was pulled back from the SFJ or SPJ by 6 cm. It was pulled back by 6 cm because the 4F delivery catheter’s tip comes out of the 5F marker catheter by 3 cm. Thus, the 4F delivery catheter had to be positioned 3 cm distal to the SFJ or SPJ. Once the position of the 4F delivery catheter was confirmed, the N-butyl cyanoacrylate (NBCA) injection groundwork was complete. A gun and adaptor were connected to each other, and two of the 3 cc of the NBCA were aspirated into the 2 cc injector. If more NBCA was required, the remaining 1 cc of NBCA was aspirated. The injector was connected to the gun adaptor and the end of the delivery catheter via a spin lock mechanism.

Figure 1.

The content of VariClose Vein Sealing System.

The procedure then began. First, pressure over the SFJ was applied with the Doppler USG, and the closure of the SFJ was confirmed. Prior to the injection of NBCA inside the vein lumen, the delivery catheter was primed. One trigger push was applied for one second to prime the delivery catheter. After priming, the trigger was pushed again for 5 s, and this time the delivery catheter was pulled back at 2 cm/s. The delivery catheter was set up for the injection of 0.03 cc of NBCA/cm. Continuous pressure was applied over the target vein segment simultaneously with the pulling back of the delivery catheter by the Doppler USG probe without releasing the pressure from the SFJ. Every 5 s or 10 cm, the trigger had to be pressed. This trigger-pressing and pressure application routine was performed continuously until the target vein segment was fully sealed. Once the entire vein segment was injected with NBCA with the continued application of pressure during the procedure, a final pressure was applied for 30 s over the entire target vein segment (Figure 2).

Figure 2.

The application of VariClose® Vein Sealing System.

Statistical method

Patient demographics, venous insufficiency characteristics, results and complications were described for all patients. Frequency and percentage values of categorical variables as well as median and range of continuous variables were determined. We compared data using the independent t tests for continuous variables. A probability value of less than 5% was considered significant.

Results

The patient sample consisted of 86 men and 94 women, with a mean age of 47.7 ± 11.7 years (range: 27–69 years).

The great saphenous vein was targeted in 169 patients, and the small saphenous vein was targeted in 11 patients. The median preoperative CEAP clinical classification was three (range: 2–5). The mean saphenous vein diameter was 7.7 ± 2.1 mm (range: 5.5–14 mm). The average length of the targeted saphenous veins was 26.2 cm (range: 9–43 cm). The average duration of the procedure was 15.2 min (range: 10–25 min). In all patients, 100% closure was observed in the saphenous veins based on the USG data collected immediately after the procedure. No adverse events—such as ecchymosis, hematoma, pulmonary embolus, or deep vein thrombosis—were observed in any of the patients. The average Venous Clinical Severity Scores was 10.2 before the procedure and 3.9 three months after the procedure (p < 0.001). The patient characteristics are shown in Table 2.

Table 2.

Patient characteristics.

Age	47.7 ± 11.7
Gender (M/F)	86/94
Targeted vein	Large saphenous vein: 169 patients (90 right, 79 left) Small saphenous vein: 11 patients (5 right, 6 left)
CEAP classification (min-med-max)	2-3-5
Diameter of saphenous vein	7.7 ± 2.1 mm (5.5–14 mm)
Distance of vein to skin at the point of intervention	15.7 ± 6.6 mm (3–40 mm)
Length of saphenous vein targeted for ablation	Was 26.2 ± 6.5 cm (9–43 cm)
Duration of procedure	15.2 ± 2.6 minutes (10–25 minutes)
VCSS (Pre-procedure)	10.2 ± 1.5 (7–15)
VCSS (Post-procedure)	3.9 ± 1.6 (2–9)

VCSS: Venous Clinical Severity Score.

Patients were followed up for an average of 5.5 months (range of three to seven months). Recanalization was not observed in any of the patients during follow-up, and the ablation rate in treated veins was 100%.

Discussion

Cyanoacrylate is the generic name for a family of strong and fast-acting adhesives with industrial, medical, and household uses. Cyanoacrylates include methyl 2-cyanoacrylate, ethyl-2-cyanoacrylate (commonly sold under the trade names “Super Glue” and “Crazy Glue”), NBCA, and 2-octyl cyanoacrylate (used in medical, veterinary, and first aid applications). NBCA, which is a type of glue, is a drug that has long been used for the treatment of brain aneurysms and arteriovenous malformations and has received FDA approval for this purpose.^9–11 Therefore, the intra-body use of NBCA is not a danger to human health. It is also successfully used to treat several other diseases, such as gastrointestinal hemorrhages, bone cysts, corneal perforations, and cecum resections. NBCA has also been used in the treatment of enlarged venous structures, such as varicoceles or mesenteric varices.^12,13

The experimental and subsequent clinical use of cyanoacrylate-based compounds for the treatment of varicose veins has recently gained popularity.

NBCA, which is a clear fluid, solidifies as a result of a polymerization reaction after intravascular injection and induces an inflammatory reaction in the vein wall.¹⁴ In a pig model, a granulomatous foreign body reaction was observed in the vein lumen 30 days after the catheter-directed endovenous placement of N-butyl polymer in the superficial epigastric veins.¹⁵ The invasion of fibroblasts into the contents of the vein lumen and 100% occlusion were observed after 60 days in the same model.¹⁶

Based on these experimental studies, Almeida et al.¹⁷ presented their endovenous ablation experiments that utilized NBCA in humans for the first time. They reported a cumulative occlusion rate of 92% after 12 and 24 months in 38 patients with saphenous vein insufficiency. This rate was acceptable compared with the thermal ablation rates. Toonder et al.¹⁸ achieved a success rate of 76% after three months when using the same chemical agent to perform perforating vein embolization. We observed a closure rate of 100% in 180 patients for an average follow-up period of 5.5 months. This ablation rate was better than that reported by Almeida et al. Our high closure rate may be due to changes in the chemical composition of the glue that result from faster bonding times. Furthermore, all patients wore compression stockings after treatment, which could have increased the success rate. In the same study, Almeida et al.¹⁷ reported the following incidences of side effects: 16% phlebitis and 21.1% thread-like thrombus or glue extensions across the SFJ, which ultimately dissolved within three months in all patients. In a recent study, Proebstle et al.¹⁹ published the results of 70 patients treated with NBCA, and occlusion rates were 98.6%, 95.7%, and 94.3% at the second day, third month, and sixth month after treatment, respectively. We did not observe thrombus or glue extensions across the SFJ on the post-procedural USG examinations. The aforementioned complications may be related to the chemical formulation of glue used in this system. They could also be related to the continuous pull-back procedure or other product-related factors. Compression stockings may help prevent these adverse events.

Morrison et al.²⁰ compared NBCA and RFA in a recent study and demonstrated a 99% closure rate for NBCA and a 96% closure rate for RFA at the third-month follow-up. They showed that complication rates were generally similar, but with the NBCA application, ecchymosis was observed significantly less often.

VariClose® is an NBCA-based polymer that has been modified via the addition of a monomer by the producing company. Small changes have been made in the chemical structure of this substance to enhance its adhesive effect. When in contact with biological tissue in humid environments, it rapidly polymerizes to form a thin, flexible membrane that exhibits high tension resistance and ensures firm adhesion to tissues. This membrane spontaneously adapts to the structures of tissues, it is watertight, and blood and organic fluids do not affect its structure. The polymerization time is a function of the contacting tissue type, fluid characteristics, and amount of product used. When applied at the proper conditions, VariClose® begins to polymerize after 1–2 s, and it completes the polymerization process within approximately 5 s. The polymerization reaction occurs at approximately 45℃.

This study has several limitations, including its nature as a retrospective analysis of one database, the small number of patients, and a heterogeneous study population in terms of inclusion of patients with varicose veins due to great and small saphenous vein insufficiency. We have failed to stratify the patients based on objective measures in reporting varicose veins or quality of life before and after the procedure. Besides these limitations, our follow-up period was too short, and data on the effectiveness of VariClose® during the late stages are currently lacking.

In conclusion, VariClose® seems to be an effective technique for managing varicose veins based on this observational study in the short-term period. Data on the effectiveness of VariClose® during the long-time period are currently lacking. However, similar results can also be expected for the late period given the high success rates in the short-time period. This agent has several advantages, such as short procedure duration, no need for tumescent anesthesia, improved patient comfort, and ease of application. Therefore, this agent may be preferable to laser and radiofrequency treatment.

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

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