Five-year outcomes of mechano-chemical ablation of primary great saphenous vein incompetence

Abstract

Objective

The aim of the study is to report long-term results after mechano-chemical ablation for the treatment of great saphenous vein incompetence.

Methods

Mechano-chemical ablation was performed using the ClariVein device with polidocanol as the sclerosant. Clinical-Etiologic-Anatomic-Pathophysiologic (CEAP) classification, Venous-Clinical-Severity-Score (VCSS), anatomical-success, RAND-SF36 and the Aberdeen-Varicose-Vein-Questionnaire (AVVQ) were obtained by clinical examination, questionnaires and duplex ultrasonography through five years’ follow-up (Clinicaltrials.gov, NCT01459263).

Results

Ninety-four patients (113 great saphenous veins) were included in the study. Five-year follow-up data were available for 75 limbs (66.4%). Freedom from anatomical failure was 78.7% (N = 45) with 64.6% (N = 42) having an improvement in the VCSS ≥1. A total of five reinterventions were performed through five years with a median time to reintervention of 38 months. The VCSS at five years was 2 (IQR 1; 4) and was still significantly improved compared to baseline (p < 0.001). A deterioration of the VCSS was observed in 21.5%.

Conclusion

Through five-year follow-up, there are a significant number of anatomical and clinical failures in this series, mainly driven by partial recanalizations.

Keywords

Chronic venous insufficiency mechano-chemical ablation quality of life venous severity score patient-reported outcomes

Introduction

Chronic venous insufficiency is an endemic disease with the highest prevalence in the United States and Western Europe.¹ Where in the past, surgery was performed to remove the incompetent vein; nowadays, endovenous techniques are commonly used, including radiofrequency ablation (RFA) and endovenous laser ablation (EVLA). Endovenous techniques proved to be at least as effective as surgery and have been associated with fewer complications, less pain and shorter recovery time.^2–5 To reduce postoperative pain, newer techniques without the use of heat have been developed, such as ultrasound-guided foam sclerotherapy, cyanoacrylate vein ablation (CAVA) and mechano-chemical ablation (MOCA). Long-term results of foam sclerotherapy were rather disappointing, showing an anatomical success rate of 34% at five years.⁶ CAVA is related to a one-year success rate of 84.2%–93.9%,⁷ but so far, no long-term results have been published. MOCA combines mechanical damage to the endothelium caused by a rotating wire with simultaneous catheter-guided infusion of a liquid sclerosant that irreversibly damages the cellular membranes of the endothelium, causing fibrosis of the vein.⁸ Several studies have shown the efficacy of MOCA for the treatment of great saphenous vein (GSV) incompetency at one year with anatomical success rates of 87%–92%.⁹ The reported anatomic success rates at two- and three-year follow-up are 89% and 86.5%, respectively.^10,11 Different definitions of anatomical success are used in different studies. Furthermore, the technique is related to less pain and a quick return to daily activities with a median of one day.¹² However, a worsening of the clinical venous severity score, disease-specific health status and overall health status were reported through questionnaires at 36 months’ follow-up, which are likely related to the known recurrent nature of varicose veins.¹¹

This study is unique in that it is the first prospective study to report the longest follow-up (five years) after MOCA using polidocanol as the sclerosant.

Methods

Ethics

The study was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. The study was approved by the Medical Ethics committee of Nijmegen (NL26327.091.09) and the local Institutional Review Board of each participating center. Eligible patients who met the inclusion criteria were fully informed; those who signed informed consent were included. Data on the one- and three-year outcome have been previously published.^11,13 The trial design was registered at Clinicaltrials.gov (NCT01459263).

Treatment

MOCA was performed under local anesthesia with the ClariVein® catheter. Detailed descriptions of the ClariVein device and treatment have been previously described.¹³ Briefly, the catheter was inserted under ultrasound guidance. The tip of the device was positioned 1.5 cm distal of the saphenofemoral junction. First, a vasospasm was induced by activating the rotating wire. Subsequently, the catheter was withdrawn at a speed of ∼7 s/cm during the injection of liquid polidocanol (2% for the proximal part of the GSV and 1.5% for the remaining part). No concomitant phlebectomies were performed. After procedure, the patients were instructed to wear a compression thigh stocking for the next 24 h and during daytime for the following two weeks. No standard analgesics were prescribed. In the treatment sites, it was standard practice not to perform additional treatments during initial GSV treatment. After at least four weeks’ follow-up, additional treatments were offered if the results of GSV treatment were not satisfactory. Vascular surgeons perform endothermal ablation and MOCA, whereas phlebologists perform sclerotherapy, foam and Müller therapy.

Study design

Patients diagnosed with symptomatic incompetent GSV in the two study sites were asked to participate. Patients had to meet the following inclusion criteria: age >18 years, C2 to C5 varicose veins, GSV diameter of 3 to 12 mm and primary GSV insufficiency determined by duplex ultrasound examination. Exclusion criteria were: C6 varicose veins, comorbid small saphenous vein (SSV), anterior accessory great saphenous vein or posterior accessory saphenous vein incompetence; pregnancy and lactation; use of anticoagulants; coagulation disorders; previous surgical treatment of the target varicose vein; previous deep venous thrombosis; severe renal or liver insufficiency and allergy to polidocanol.

Pre-procedural physical examination was performed by a vascular surgeon, who determined the CEAP¹⁴ and VCSS.¹⁵ Patients were asked to complete the Dutch version of the RAND-SF36¹⁶ and the Aberdeen-Varicose-Vein-Questionnaire (AVVQ).¹⁷ A high score in RAND-SF36 and a low score in AVVQ indicates good health status. After treatment, the patients were instructed to complete a 14-day diary card to record the level of pain on the 100-mm visual analog scale (VAS) and the amount of analgesics used. On the diary card, the patients were also asked to provide information about returning to normal activities and work. The questionnaires (RAND-SF36 and AVVQ), examination by a vascular surgeon and duplex ultrasonography were repeated six weeks, six months and one, three, and five years after surgery.

Data were collected using case record forms and stored in a central online database with audit trail (“The research manager”, Deventer, The Netherlands).

Primary outcome measure was anatomic success (defined as occlusion of the treated venous segment). Secondary endpoints included technical success, defined as the ability to perform the procedure as planned without any technical problem; clinical success, defined as an improvement in VCSS ≥1; post procedural pain (VAS); time to return to daily activities and work; complications and general and disease-specific quality of life (RAND-SF36 and AVVQ). Anatomic failure was defined as the presence of flow and reflux in a recanalized segment of the treated GSV with a length ≥10 cm (partial recanalization) or the entire treated GSV segment (complete recanalization).

Statistical analysis

Normality was determined by visual inspection and tested using the Kolmogorov-Smirnov test. Continuous variables are presented as median and interquartile range (IQR). Categorical data are presented as number followed by percentage. Analyses of variance (ANOVA) with repeated measures design was used to analyze the changes over time in pain scores, VCSS, RAND-SF36 and AVVQ score. Anatomical and clinical success data were analyzed using Kaplan Meier analyses including censoring for patients lost to follow-up. Two-sided p value < 0.05 was considered significant. Statistical analyses were performed using IBM SPSS Statistics (SPSS version 25.0 for windows, IBM Corporation, Armonk, NY, USA).

Results

Between December 2010 and December 2011, 94 patients were included. Nineteen patients were treated bilateral, in two procedures at least four weeks apart, and 75 were treated unilateral (113 treated GSVs). During follow-up, one patient died because of an intracerebral hemorrhage. Another 15 patients withdrew informed consent. In one case, there was a leakage of sclerosant out of the device during treatment. Because of this technical failure, treatment was converted to RFA. In total, 60 patients (75 limbs) completed the study throughout all the follow-up visits. Baseline characteristics and procedural data have been previously described¹³ and summarized in Table 1.

Table 1.

Baseline characteristics of study population and procedural details.

	(n=113 legs, n=94 patients)
Age (years)	50.8 (41.9; 61.5)
Gender (female; %)	67
Previous ipsilateral venous treatment (n/%) per leg	12 (12.8)
Clinical classification (CEAP) (%)
C2	36.2
C3	34.0
C4a	22.3
C4b	3.2
C5	2.1
Diameter SFJ junction (mm)	5.5 (5.0; 7.0)
Diameter GSV at puncture site (mm)	4.7 (4.0; 5.5)
Length treated segment (cm)	45.0 (39.0; 50.0)

GSV: great saphenous vein; SFJ: saphenofemoral junction.

Outcome through three years

The outcome through three years has been previously published.^11,13 Briefly, three GSVs showed failure of treatment within 30 days. VCSS and AVVQ scores at 30 days significantly improved compared to baseline (Table 2, Figures 1 and 2).

Table 2.

Overview of the anatomical and clinical outcomes during five years’ follow-up.

	Early outcome (n=109 legs)	One year (n=101 legs)	Three years (n= 85 legs)	Five years (n=75 legs)
Anatomical failure (n/%)	3 (2.8)	16 (15.8)	22 (25.9)	28 (37.3)
Complete failure (n)	1(0.01)	8 (0.08)	6 (0.07)	10 (13.3)
Partial failure (n)	–	8 (0.08)	16 (18.8)	18 (24.0)
Proximal GSV recanalization	–	14 (13.9)	20 (23.5)	15 (20.0)
Difference in VCSS compared to baseline	2 (1; 4)	3 (2; 4)	2 (1;3)	1 (0; 2)
p compared to baseline	<0.001	<0.001	<0.001	<0.001
Change in VCSS compared to baseline
Improved	–	81 (80.2%)	63 (74.1%)	42 (64.6%)
Equal	–	4 (4.0%)	8 (9.4%)	9 (13.8%)
Deteriorated	–	4 (4.0%)	6 (7.1%)	14 (21.5%)

Note: Values expressed as number of legs with percentages in parentheses – n (%). Percentages calculated according to number of legs available at each year of follow-up.

GSV: great saphenous vein; VCSS: venous clinical severity score.

Figure 1.

(a) Median venous clinical severity score (VCSS) during baseline and all follow-up moments; p < 0.001 compared to baseline on all time points. (b) Percentage clinical improvement compared to baseline for all follow-up moments; p < 0.001 compared to baseline on all time points.

Figure 2.

Median Aberdeen Varicose Vein Questionnaire (AVVQ) score during baseline and all follow-up moments.

One- and three-year follow-up was available for 101 and 85 treated limbs, respectively. Freedom from anatomical failure at one and three years was 85.6% and 80.1%, respectively (Figure 3).

Figure 3.

Freedom from anatomical failure after MOCA during five years’ follow-up.

The VCSS was 1.0 (IQR 0.0; 1.0) and 1.0 (IQR 1.0; 3.0) after one and three years’ follow-up, respectively (Figure 1(a)). Clinical improvement was reported in 80% and 74% at one and three years, respectively (Figure 2). After one year, 92.1% of the patients showed an improved patient-reported disease-specific quality of life (AVVQ) compared to baseline. After three years, this percentage decreased to 86.1% (all p < 0.001; Figure 2).

Five-year outcomes

At five year, 75 treated limbs were available for follow-up (60 patients). Eighteen GSVs showed partial recanalization and 10 showed complete recanalization. Freedom from anatomical failure at five years was 78.7% (N = 45 from 58 at risk at five years’ follow-up; Figure 3). Median time to fail was 12 months (IQR: 7; 65 months) and time to reintervention was 38 months (IQR: 18; 71). Between three and five years’ follow-up, two patients had reintervention and after five years reinterventions were performed in three additional patients.

The VCSS at five years was 2 (IQR 1; 4) and remained significantly lower compared to baseline (p < 0.001). An improved VCSS was observed in 42 patients (64.6%; Figure 1), whereas a deterioration of the VCSS was observed in 14 patients (21.5%). No ulcers were reported at baseline or follow-up. AVVQ scores improved up to one-year follow-up, but worsened thereafter, although still significantly improved compared to baseline (p < 0.001; Figure 2). Besides the reinterventions for failure, in total 70 other venous additional treatments were performed during five-year follow-up in 40 patients (42.6%; data of eight patients unknown; Table 3). Some patients had multiple additional venous treatments. Thirty-five were ipsilateral, 29 contralateral and from six treatment side was not reported. Additional treatments included sclerotherapy, foam therapy, Müller, RFA, EVLA and MOCA of contralateral GSV, SSVs and side branches.

Table 3.

Overview of additional treatments during follow-up per treatment side.

	Additional treatments
	IPSI	CONTRA	Unknown
Sclerotherapy	16	11	6
Foam	9	2
Muller	4
VNUS GSV
VNUS SSV	2	2
EVT GSV		1
EVT side branch	2	1
MOCA GSV		10
MOCA SSV	1	1
MOCA side branch	1	1
Total	35	29	6

GSV: great saphenous vein; VCSS: venous clinical severity score; MOCA: mechanochemical-ablation; SSV: small saphenous vein.

Discussion

In the present study, the long-term freedom from anatomical failure of MOCA was 79%, whereas most failures occurred during the first year after treatment. This percentage is lower compared to the five-year anatomical success rate of 88% (95% CI: 82–92), as described for other endothermal techniques in a recent meta-analysis,⁶ but randomized trials with long-term follow-up are still lacking. It was recently shown that the two-year outcome of MOCA is comparable with RFA, both with regard to clinical and anatomical failures.¹⁸

The data from the present study reflect the early experience of a novel technique and as a consequence a learning curve effect is likely. It was the first study using polidocanol as the sclerosant. Since the inclusion period of the trial, the procedural practice has significantly evolved. In current practice, the proximal 10 cm of the GSV is now checked for vasospasm after initial treatment and when not collapsed treated again. Moreover, 3% polidocanol is currently used for the proximal part. In addition, at introduction of the technique, the device was first purged with saline. As the device retains about 1 mL of liquid, the first milliliter entering the vein was saline. Purgin with sclerosant is therefore advocated nowadays. These modifications, and also the increased operator experience, will likely reduce the failure rate, particularly of the partial recanalizations that occur in the proximal segment. In this trial, the choice for polidocanol was based on availability, as sotradecol is not registered in the Netherlands. The latter sclerosant is described to be more powerful when used as foam.¹⁹ Whether this is also true for MOCA remains to be shown. Eventually, randomized trials will need to prove the efficacy compared to the endothermal techniques.

The drop in anatomical success between one and five years was only 6%, indicating that most anatomical failures occur in the first postprocedural year. The opposite is true for the clinical success rate. In the current series, the clinical success rate at five years was only 65% and does not seem to correlate with the anatomical success rate. As such, this drop merely reflects the fact that superficial venous reflux is a chronic disease. When studying the long-term data on this pathology, consideration must be given to the fact that recurrence may not be technique related but simply results because of the nature of the disease and the inherited and general health condition of the patient. This is further supported by the high incidence of additional venous treatments that were performed through the five-year follow-up, also on the contralateral side (46.8% of patients).

In this trial, there were no concomitant phlebotomies performed during MOCA, which mimics the clinical situation in the Netherlands in most sites. Combined phlebectomies have been related to better short-term and better to equivalent long-term patient outcomes but is also related to a higher risk on heat-induced thrombosis.^20,21 In the current series, adjunctive phlebectomies were performed in only 34% of patients throughout follow-up, indicating that standard concomitant phlebotomies are not required with MOCA. Partial treatment of side branches might also already have occurred by diffusion of the sclerosant into the side branches, differentiating MOCA from heat-based techniques.

The current study has limitations; first of all, the data are derived for the early experience of the technique and may therefore not reflect the current outcomes. Second, five-year data were available for only 64% of patients (66.4% of legs), which may have induced a bias both positively and negatively. Third, the inclusion criteria of the study limit the patient applicability to those veins <12 mm in diameter, and it remains to be elucidated whether the technique is as effective in larger veins.

Conclusion

The current series was the first large prospective trial after the introduction of MOCA and has proven it to be safe and effective at the short term. Through five-year follow-up, there are a significant number of anatomical and clinical failures in this series. Adaptations in treatment protocol and increased experience may provide improved anatomical results in later series.

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) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This is an investigator-initiated study supported by Vascular Insights Ltd. Vascular Insights was not involved in study design, data collection, data analysis, article preparation or publication decision.

Ethical Approval

Guarantor

MMPJR.

Contributorship

All authors meet the criteria for authorship: 1. Made a substantial contribution to the concept or design of the work; or acquisition, analysis or interpretation of data, 2. Drafted the article or revised it critically for important intellectual content, 3. Approved the version to be published, 4. Each author should have participated sufficiently in the work to take public responsibility for appropriate portions of the content.

MMPJR and JPPMdV researched literature and conceived the study. MMPJR, JPPMdV, and SH were involved in protocol development and gaining ethical approval. DABW, JPPMdV, MMPJR, NDET, WHPMV and SH were involved in patient recruitment and follow-up. SH performed data analysis. NT wrote the first draft of the article. All authors reviewed and edited the article and approved the final version of the article.

Acknowledgements

The contribution of the patients is greatly acknowledged, as is the work from the research nurses and technicians of the department of Vascular Diagnostics. This study was presented at the international Veith Symposium, New York, 13–17 November 2018.

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