One-year duplex ultrasound–assessed closure outcomes of percutaneous endovenous microwave ablation for the treatment of varicose veins of the lower limbs

Abstract

Purpose

This study aims to investigate the safety and efficacy of a new device using microwave technology for the endovenous ablation of the great saphenous vein (GSV) causing symptomatic lower limb varicose veins (LLVV).

Materials and Methods

This prospective, single-arm, single-center, cohort study investigated the safety and effectiveness of endovenous microwave ablation for the treatment of symptomatic LLVV. Enrollment period was set between January and December 2020. Primary safety endpoint was the occurrence of procedure-related complications and primary efficacy endpoint was anatomical success defined as the duplex ultrasound (DUS)–proven GSV occlusion at 1 year follow-up. Secondary endpoints included 1-year clinical success (CEAP classification improvement), repeat procedures rate due to GSV recanalization, and pain assessment at 24 h post treatment.

Results

In total, 50 patients (42 female; mean age: 62 ± 12 years) with 64 limbs were treated. No procedure-related complications were noted. Technical success was 95.3% (61/64 GSVs), as three cases of GSV recanalization were detected. Clinical success was 100%, as in all cases symptoms improvement by at least one grade according to CEAP classification, was achieved. Mean CEAP grade significantly improved from 3.3 ± 0.72 (median: 3) at baseline to 1.8 ± 0.85 (median: 2) at 1-year (p < 0.0001). There were no repeat procedures due to GSC recanalization. The median 24-h VAS value was 2 (mean: 1.9 ± 1.4).

Conclusions

Endovenous microwave ablation was safe and effective for the treatment of varicose veins, achieving high 1-year GSV occlusion rates.

Keywords

Endovenous ablation microwave varicose veins lower limbs

Introduction

Percutaneous endovenous ablation is currently an established first-line treatment method for lower limb varicose veins (LLVV).^1,2 Ablative modalities include endovenous thermal ablation (EVTA), mostly using laser (EVLA) and radiofrequency (RFA), and non-thermal ablation techniques such as mechanochemical ablation (MOCA) and cyanoacrylate glue injection.^3-7 Evidence on the safety and efficacy of the above treatment options have been extensively published, with similarly satisfactory clinical outcomes, while each modality presents specific advantages and disadvantages mainly regarding procedure-related pain, minor complications, technical details, and the use of tumescence.²

As the number of endovenous ablation procedures continuously grows, new technologies have been developed to optimize the technique and minimize the disadvantages of the previously available devices.^8,9 Microwave ablation technology is well-established in the field of interventional oncology and has been widely used for the percutaneous treatment of malignancies.¹⁰ Only recently, endovenous microwave ablation (EMWA) has been proposed, as a novel thermal ablation method, using molecular vibrations to induce tissue inner heating, and initial mid-term results seem promising, indicating similar success rates with fewer complications compared to surgical and other ablative modalities.^11-13 However, data for EMWA remain scarce, and confined to the Asian population. The purpose of this study was to investigate the mid-term safety and efficacy of EMWA in a cohort of European patients suffering from symptomatic LLVV.

Materials and methods

This was a prospective, single-arm, single-center, cohort study, designed to investigate the safety and effectiveness of EMWA using the ECO endovenous microwave ablation system (Nanjing; China) for the treatment of LLVV, attributed to great saphenous vein incompetence according to duplex ultrasound (DUS) criteria. The study was approved by the Hospital’s Scientific and Ethics Committee. Prior to enrollment, patients were informed about the details of the study and signed the relative informed consent form. Enrollment period was set between January and December 2020. The study’s inclusion criteria were DUS-documented ≥ 0.5 s saphenofemoral junction or GSV reflux, correlated with symptomatic GSV insufficiency (swelling, throbbing, heaviness, pruritus, skin changes, healed or active ulceration, edema, etc.) and LLVV. Exclusion criteria were LLVV attributed to small saphenous and/or perforators insufficiency, LSG vein diameter over 15 mm, pregnancy, nursing, deep venous obstruction, coagulopathy or hypercoagulability syndromes, contraindication to lidocaine, inability to cooperate, wear compression stockings, and ambulate.

The study’s endpoints were defined according to international reporting standards.¹⁴ Primary safety endpoint was the occurrence of procedure- and/or device-related complication rate, and primary efficacy endpoint was anatomic success at 1 year defined as DUS-proven occlusion of the treated GSV. Patency detected by DUS within a GSV segment measuring > 5 cm was considered an anatomic failure. Secondary endpoints included 1-year clinical success defined as clinical status improvement according to Clinical, Etiologic, Anatomical and Pathophysiologic (CEAP) classification by at least one grade, repeat procedures rate due to GSV recanalization, peri-procedural (30-day) analgesic use, and pain assessment at 24 h, using a 0–10 visual-analogue score (VAS). A standard t-test was performed to compare continuous variables in cases of normal data distribution. The Mann–Whitney non-parametric test was used in cases in which data did not assume a normal distribution. Statistical analysis was performed with the SPSS software (version 25, IBM, USA). Statistical significance was set at a p value < 0.05.

Device and procedure

The ECO endovenous microwave ablation system (Model ECO-100E2; Nanjing, China) consists of a microwave 2450 MHz generator, a 6Fr microwave antenna, control, and display system. Endovenous ablation is achieved by low temperature, instantaneous coagulation from inside to outside, producing a uniformly heated, clear-edge ablation area, with concomitant hemostatic effect.^12,15 Technical characteristics of the system, according to the company, are presented in Table 1. The procedure was performed according to previously published studies and international guidelines.^12-16 In brief, the GSV was accessed at the lowest point of reflux, but not below mid-calf, with a 4-Fr micro-puncture kit under ultrasound guidance using a linear 10 MHz probe. A standard 6-Fr arterial sheath was used to secure venous access, and the microwave probe was advanced 2 cm below the saphenofemoral junction. Ultrasound-guided injection of tumescent anesthesia was performed using a solution of 1-Lt saline 0.9% and lidocaine 2%. Ablation was subsequently performed in pulse mode with 60 W, using a probe withdrawal rate of 2–4 mm/s, (2-s pulse and 1-s interval). After completion of the procedure, puncture sites were covered with a self-adhering dressing, and compression stockings (25–35mmHg) were applied to the treated limb. The patient was immediately mobilized and advised to remove the compression stockings for the first time after 48 h. Compression stockings were recommended for 2 weeks, day and night, while for the following 2 weeks, only daywear was advised. Ibuprofen was recommended only in cases of post-procedural pain.¹⁶ Pre-scheduled clinical and DUS follow-up was set at 1 and 12 months, and was performed by a radiologist who did not participate in the procedure and was blinded to the ablation method used.

Table 1.

Technical characteristics of the device.

Working frequency	2450 ± 20 MHz
Output power	Continuously adjustable; 0–150W in one channel, 0–125W in multiple channels; (deviation: ±20%)
Voltage standing wave ratio (VSWR)	≤ 1.5
Output mode	Continuous and intermittent pulse
Cooling temperature	0 ∼ 50°C, deviation ≤ ±1°C)
Input power	≤ 900 VA + 10%
Microwave leakage	≤ 2 mW/cm²
Cold circulation system	1. Pipe connections no leakage
Cold circulation system	2. Cooling liquid flow: 25 mL/min ∼60 mL/min

Results

In total, 50 patients (42 female; 84%), with 64 limbs and a mean age of 62 ± 12 years, were enrolled in the study. The mean pre-procedural CEAP class was 3.3 ± 0.72 (median: 3; range: 2–6). Baseline severity of the disease according to CEAP classification was C2S: 7.8% (5/64), C3: 64.0% (41/64), C4 (a–b): 23.5% (15/64), C5: 3.1% (2/64), and C6: 1.6% (1/64) (Figure 1). In the single C6 case, an active ulcer was present for 9 months. The study’s primary safety endpoint was met as there were only two (3.1%; 2/64 ablations) minor complications noted (two puncture-site scars auto resolved at 1 and 3 months, respectively). There were no cases of deep venous thrombosis, superficial thrombophlebitis, paresthesia, or skin burn. The mean diameter of the treated GSV was 10 ± 2.5 mm (range: 6–15 mm). Anatomic success was 95.3% (61/64 GSVs), as three cases of GSV recanalization were detected at 1-year DUS follow-up. Clinical success was 100%, as in all cases, symptoms improvement by at least one grade, according to CEAP classification, was achieved at 1-year clinical follow-up. Mean CEAP grade significantly improved from 3.3 ± 0.72 (median: 3) at baseline to 1.8 ± 0.85 (median: 2; range: 0–5) at 1-year (p < 0.0001; Figure 1). Specifically, the clinical severity of the disease according to CEAP classification at 1 year follow-up was C0: 3.1% (2/64), C1 34.4% (22/64), C2: 50% (32/64), C3: 9.4% (6/64), C4 (a): 1.6% (1/64), and C5: 1.6% (1/64). There were no repeat procedures due to GSC recanalization. The mean VAS pain value at 24 h was 1.9 ± 1.4 (median: 2; interquartile range (IQR): 0–2) (Figure 2). Peri-procedural analgesic use (ibuprofen) recorded within the first month was 16.0% (8/50 patients), for a mean period of 3 ± 2 days (range: 1–7 days). The median time to return to normal activities or work was 1 day (IQR: 1–1 days), with an average value of 1.22 ± 0.9 days (range: 1–7 days). Patients’ baseline characteristics and main procedural outcoms are reported in Table 2.

Figure 1.

Histograms depicting CEAP classification at (a) baseline and (b) one-year follow-up.

Figure 2.

Histogram of visual-analogue scale results for the assessment of pain 24 h after the procedure.

Table 2.

Patients’ baseline characteristics and outcomes.

Patients	50
Limbs	64
Mean GSV vein diameter (mm)	10 ± 2.5
Mean baseline CEAP	3.3 ± 0.72
Anatomic success at 1 year	61 (95.3)
Clinical success at 1 year	70 (94.6)
GSV revascularization	3 (4.7)
Complete/partial	2/1
Adjunctive GSV ablation procedures	0 (0)
Major complications	0 (0)
Minor complications	2 (3.1%)
Use of analgesics	8 (16.0)
24 h median VAS score*	2 (0–2)
Time to return to normal activities (days)^a	1 (1–1)

Data are reported on a limb basis. Categorical data are presented as counts and percentages in the parentheses.

^aMedian and interquartile range in parenthesis

Note: GSV: great saphenous vein

Discussion

In this prospective, single-center study of European patients with symptomatic LLVV, EMWA achieved a 95.3% DUS-assessed GSV occlusion rate at 1-year, which was also translated in a high clinical success rate of 100% documented by CEAP improvement. According to the literature, similar GSV occlusion rates have been noted using the established thermal ablation modalities. Specifically, the 1-year primary obliteration rates using RFA or new-generation EVLA have been reported to be around 95%, while cyanoacrylate glue has also achieved similarly high occlusion rates of approximately at 2 years’ follow-up.^2,14,17,18 On the other hand, according to the results of a multicenter randomized controlled trial, the 1-year anatomic success using MOCA was reported to be lower (83.5%) and significantly inferior compared to RFA (94.2%).¹⁸ Interestingly, despite the difference in anatomic success, similar clinical success rates were reported indicating that symptoms’ relapse is not always directly correlated with GSV revascularization. Similarly, in this study, re-interventions were not required for the three cases of GSV recanalization, and symptoms regression persisted at up to 1 year follow-up, even after GSV reperfusion. Nevertheless, long-term follow-up beyond 1 year was not available, and therefore, long-term symptom relapse following reperfusion cannot be excluded. Moreover, in two out of three cases of GSV recanalization, anatomical failure could be correlated to the fact that these patients initiated intense physical activity within the first 48h following the procedure, though they were advised to avoid strenuous activity for at least 7 days.

Notably, no severe complications were noted, and minimal minor complications occurred (two small puncture-site scars), which auto resolved within 3 months, demonstrating the safety of the device. According to the literature, complications such as temporary or even permanent paresthesia following EMWA have been previously reported in series in which EMWA was applied even at the distal infrapopliteal GSV.^11-13 The authors speculate that there were no cases of paresthesia noted in this specific cohort due to the combination of device safety, correct tumescence/ablation technique, and the decision not to perform ablation of the GSV below the mid-calf.

The low pain intensity recorded 24 h post-procedure (median VAS value: 2; mild pain), as well as the infrequent and transient use of analgesic therapy, probably contributed to the short time required for most of the patients to return to their everyday activities following treatment. Specifically, 45 out of 50 patients (90%), returned to their normal activities the following day. The maximum time to return to normal activities was 7 days (noted in only one patient) and was attributed to pain treated with ibuprofen twice daily. These outcomes are deemed extremely satisfactory and comparable to those previously reported following RFA treatment, which has been correlated with similar TR but decreased postoperative pain and bruising compared to EVLA.^16,19 Additionally, in a prospective comparative study recently published by Yang L, et al., EMWA demonstrated similar occlusion and clinical success rates compared with EVLA, but significantly shorter procedural time, lower complication, and local recurrence rates. TR and 24 h VAS were similar to those achieved in the herein presented study.¹²

Theoretically, EMWA presents some advantages over RFA and EVLA due to the mechanism used to produce heat. Compared to RFA technology, the main advantage is that tissue inner heating (both blood and venous wall) is induced due to molecular vibrations, and therefore, the microwave antenna does not have to be in direct contact with the venous wall to solidify it.¹³ Compared to EVLA technology, EMWA presents the same advantages such as water heating, ablation without direct contact, and radial ablation, but without the need for any laser precautions (specific license and room for laser use, eye protection, etc.), and perhaps a less aggressive, more controllable ablation.¹³ On the other hand, a limitation of the device remains its larger profile compared to laser fibers and some RF catheters, which could represent a factor for increased access—site complications and/or complications correlated with the ablation of small-diameter veins. In this study, the mean size of the treated GSVs was relatively large (approx. 10 mm), so conclusions regarding EMWA safety in small veins cannot be drawn. Nevertheless, no complications were noted in cases in which the maximum GSV diameter measured ≤ 7 mm.

The limitations of this study include the single-center design that limits the external validity of the study and the relatively small number of patients included that limit the statistical validity of the outcomes. Moreover, comparable data are not provided due to the absence of a control group. As a result, the level of evidence provided by this study is low.

Conclusively, according to this single-center, single-arm, prospective study, endovenous microwave ablation of the great saphenous vein, for the treatment of symptomatic lower limb varicose veins, was safe and effective, resulting in very low complication rates, without any incidences of DVT or paresthesia, low levels of post-procedural pain, and extremely satisfactory radiological and clinical mid-term outcomes. Larger, comparative studies are required to verify these results.

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.

ORCID iD

Stavros Spiliopoulos

References

National Institute for Health and Care Excellence . Varicose veins: diagnosis and management (NICE guideline 168). https://www.nice.org.uk/guidance/cg168 (2013, accessed 10 January 2022).

Wittens

Davies

Bækgaard

, et al. Editor’s choice - management of chronic venous disease: clinical practice guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg 2015; 49(6): 678–737.

Lurie

Creton

Eklof

, 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.

Pronk

Gauw

Mooij

, et al. Randomised controlled trial comparing sapheno-femoral ligation and stripping of the great saphenous vein with endovenous laser ablation (980 nm) using local tumescent anaesthesia: one year results. Eur J Vasc Endovasc Surg 2010; 40(5): 649–656.

Elias

Raines

. Mechanochemical tumescentless endovenous ablation: final results of the initial clinical trial. Phlebology 2012; 27: 67–72.

Morrison

Gibson

McEnroe

, et al. Randomized trial comparing cyanoacrylate embolization and radiofrequency ablation for incompetent great saphenous veins (VeClose). J Vasc Surg 2015; 61(4): 985–994.

Gibson

Morrison

Kolluri

, et al. Twenty-four month results from a randomized trial of cyanoacrylate closure versus radiofrequency ablation for the treatment of incompetent great saphenous veins. J Vasc Surg Venous Lymph Disord 2018; 6(5): 606–613.

Crawford

Gasparis

Almeida

, et al. A review of United States endovenous ablation practice trends from the medicare data utilization and payment database. J Vasc Surg Venous Lymph Disord 2019; 7(4): 471–479.

Milleret

Huot

Nicolini

, et al. Great saphenous vein ablation with steam injection: results of a multicentre study. Eur J Vasc Endovasc Surg 2013; 45: 391–396.

10.

Vietti Violi

Duran

Guiu

, et al. Efficacy of microwave ablation versus radiofrequency ablation for the treatment of hepatocellular carcinoma in patients with chronic liver disease: a randomised controlled phase 2 trial. Lancet Gastroenterol Hepatol 2018; 3(5): 317–325.

11.

Yang

Wang

, et al. Randomized clinical trial of endovenous microwave ablation combined with high ligation versus conventional surgery for varicose veins. Eur J Vasc Endovasc Surg 2013; 46(4): 473–479.

12.

Yang

Wang

Wei

, et al. The clinical outcomes of endovenous microwave and laser ablation for varicose veins: a prospective study. Surgery 2020; 168(5): 909–914.

13.

Mao

Zhang

Wang

, et al. A retrospective study comparing endovenous laser ablation and microwave ablation for great saphenous varicose veins. Eur Rev Med Pharmacol Sci 2012; 16(7): 873–877.

14.

Khilnani

Grassi

Kundu

, et al. Multi-society consensus quality improvement guidelines for the treatment of lower-extremity superficial venous insufficiency with endovenous thermal ablation from the society of interventional radiology, cardiovascular interventional radiological society of Europe, American college of phlebology, and Canadian interventional radiology association. J Vasc Interv Radiol 2010; 21: 14–31.

15.

Subwongcharoen

Praditphol

Chitwiset

. Endovenous microwave ablation of varicose veins. Surg Laparosc Endosc Percut Tech 2009; 19(2): 170–174.

16.

Spiliopoulos

Theodosiadou

Sotiriadi

, et al. Endovenous ablation of incompetent truncal veins and their perforators with a new radiofrequency system. Mid-term outcomes. Vascular 2015; 23(6): 592–598.

17.

Lawson

Gauw

van Vlijmen

, et al. Prospective comparative cohort study evaluating incompetent great saphenous vein closure using radiofrequency-powered segmental ablation or 1470-nm endovenous laser ablation with radial-tip fibers (Varico 2 study). J Vasc Surg Venous Lymph Disord 2018; 6(1): 31–40.

18.

HolewijnRRJP

van Eekeren

RRJP

Vahl

MARADONA study group , et al. Two-year results of a multicenter randomized controlled trial comparing Mechanochemical endovenous Ablation to RADiOfrequeNcy Ablation in the treatment of primary great saphenous vein incompetence (MARADONA trial). J Vasc Surg Venous LymphDisord 2019; 7(3): 364–374.

19.

Rasmussen

Lawaetz

Bjoern

, et al. Randomized clinical trial comparing endovenous laser ablation, radiofrequency ablation, foam sclerotherapy and surgical stripping for great saphenous varicose veins. Br J Surg 2011; 98(8): 1079–1087.