- Email: [email protected]
Factors Associated with Saphenous Vein Recanalization after Endothermal Ablation
Accepted Manuscript Factors associated with saphenous vein recanalization following endothermal ablation Avianne P. Bunnell , B.S., Shariq Zaidi , M.D., J. Leigh Eidson , III, M.D., W. Todd Bohannon , M.D., Marvin A. Atkins , M.D., Ruth L. Bush , M.D., J.D., M.P.H. PII:
S0890-5096(14)00613-X
DOI:
10.1016/j.avsg.2014.09.020
Reference:
AVSG 2171
To appear in:
Annals of Vascular Surgery
Received Date: 7 May 2014 Revised Date:
23 July 2014
Accepted Date: 10 September 2014
Please cite this article as: Bunnell AP, Zaidi S, Eidson JL III, Bohannon WT, Atkins MA, Bush RL, Factors associated with saphenous vein recanalization following endothermal ablation, Annals of Vascular Surgery (2014), doi: 10.1016/j.avsg.2014.09.020. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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FACTORS ASSOCIATED WITH SAPHENOUS VEIN RECANALIZATION FOLLOWING ENDOTHERMAL ABLATION
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Avianne P. Bunnell, B.S.1, Shariq Zaidi, M.D.2,3, J. Leigh Eidson, III, M.D.2, 3, W. Todd Bohannon, M.D. 3, Marvin A. Atkins, M.D.3, Ruth L. Bush, M.D., J.D., M.P.H.2,4
Corresponding Author
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University of Central Florida College of Medicine, Orlando FL1, Central Texas VA Healthcare System, Temple TX2, Baylor Scott and White Healthcare, Temple TX3, Texas A & M Health Science Center College of Medicine, Bryan, TX4
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Ruth L. Bush, M.D., J.D., M.P.H. Texas A&M Health Science Center MS 1359 8447 State Highway 47, HPEB 3064, Bryan, TX 77807-3260 phone: 979.436.0241 fax: 979.436.0092 [email protected]
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Abstract Purpose: Endovenous thermal ablation has emerged as an alternative therapy for the treatment of chronic superficial venous insufficiency (CVI) of the lower extremities. Recanalization, or
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anatomic failure, of a vein following endovenous radiofrequency ablation (RFA) has been
described, albeit an infrequent occurrence. This study was performed to demonstrate risk factors associated with the efficacy of RFA and recanalization in the treatment of CVI.
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Patients and Methods: Data were collected in an ongoing multicenter registry which was
retrospectively reveiwed. This study reviewed 249 limbs that underwent RFA of either the great
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(GSV) or small saphenous vein (SSV) over a three-year period, including only patients for which an intermediate (6 month) follow up venous duplex ultrasound was available. Patients in whom recanalization was demonstrated via duplex (N=17, 6.8%) were analyzed for patient-level characteristics. Logistic regression analysis was performed to determine the existence of any
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significant clinical risk factors associated with anatomical failure. The need for secondary interventions due to clinical symptoms associated with recanalization was analyzed as well. Results: In this cohort, the initial vein occlusion rate was 93.1%. Segmental (n=9, 53%) or
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complete (n=8, 47%) recanalization was seen in 17 limbs (6.8%) after initial successful GSV ablation. All SSV remained persistently ablated. Anatomic failure was associated with higher
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rate of clinical symptom recurrence (41% v 21%, RR 2.75, 95% CI, 0.99-7.6, p<0.05) as well as an increased need for secondary vein procedures in the affected limbs (35% v 12%, RR 3.96, 95% CI 1.3-11.7, p<0.05). Two recanalized GSVs required repeated endothermal ablation, in efforts to aid in the healing of ulcerations. Patient factors including diabetes, hypertension, hyperlipidemia, anticoagulation or antiplatelet agent usage, presence of deep venous reflux, or tobacco use did not increase the risk of RFA failure. Comparatively, patients with GSV
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recanalization had a longer mean follow up time (63.3 v. 41.6 weeks) but no difference in disease severity (C4, 35% v. 17%; C5, 18% v. 15%; C6, 6% v. 8%, NS). Conclusions: Endothermal ablation is an efficacious treatment for CVI with most patients
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remaining reflux-free. Recanalization of an isolated vein segment following RFA, while shown in recent literature to be effected by anatomical risk factors, appears to be a sporadic
phenomenon with respect to clinical risk factors. Nevertheless, in our cohort, anatomic failure
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was associated with a two-fold increase in symptom recurrence and the need for interval
secondary vein procedures. Ultrasound interrogation is recommended especially in patients with
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persistent or recurrent symptoms or non-healing ulcerations.
Keywords
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radiofrequency, recanalization, venous insufficiency, venous reflux
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Introduction Venous insufficiency, or reflux disease, is caused by the mechanical incompetence of venous valves allowing passage of blood from deep veins back into the superficial vasculature rather
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than toward the heart. Venous reflux affects more of the adult population than cardiovascular disease, which explains why the management and treatment of its complications occupy a large percentage of the healthcare budget.5 Left untreated, 20% of superficial venous reflux cases lead
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to venous varicosities6 progressing in severity to include symptoms of swelling, aching, skin
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discoloration, and venous ulceration.
Treatment options for venous reflux disease vary in approach, including conservative management with compression therapy, open surgery, sclerotherapy, and endovenous therapy. Endovenous treatment of symptomatic reflux disease has proven to be the current standard of
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treatment for chronic venous insufficiency (CVI) and symptomatic varicosities.12-14 Beginning with radiofrequency ablation (RFA) in 1999 and subsequently endovenous laser ablation (EVLA) in 2002, the use of these interventions has increased more than eightfold since 200515,
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effectively replacing traditional stripping and ligation.16 Functionally, laser or radiofrequency is used to precisely emit thermal energy directly to the vein wall, destructing the intima and leading
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to the breakdown of collagen in the media. Eventually this forms a fibroelastic seal of the lumen of the vein itself17 and leads to contraction (shrinkage) of the vessel wall.18 Studies prove these methods to be similarly or more effective than vein stripping while providing less postoperative morbidity.9,19,20
Recanalization, the anatomic failure of venous ablation, while infrequent is still seen in the use of RFA as demonstrated by Proebstle et al in 2011.23 Their cohort revealed a reflux rate of 4.3%
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(7.4% blood flow) detectable by duplex ultrasound at 3 year follow up. In 2008, we also learned that recanalization risk is greatly affected by anatomic risk factors, such as vein size at the saphenofemoral junction and entry sites for ablation.24 Contrary to the effects of anatomic
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factors, there has been shown to be no significant association between clinical risk factors, such as history of DVT, DVI, diabetes, smoking, or BMI25 on the presence of non-healing venous ulcers after intervention. This leaves to question the relationship between clinical risk factors and
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the rate of recanalization itself. For this reason, we aim to evaluate several of these theorized
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clinical risk factors and their association with RFA efficacy and the incidence of recanalization.
Methods Patients
All patient data were collected in an ongoing multicenter registry. In a review of 392 limbs
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consecutively treated over 3 years, all underwent endovenous ablation of either the GSV or small saphenous vein (SSV) via RFA. Our technique for endovenous ablation with RFA is consistent with other investigators and has been described elsewhere.15,26,27 In each case the intervention
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was selected based upon symptomology and duplex-documented pathophysiological reflux. Patients with a CEAP score of C3-6 were considered for possible treatment. After singling out
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for patients with available intermediate and six month follow up venous duplex ultrasounds 249 limbs remained for further stratification (see Figure I).
Recanalization was defined by duplex-documented evidence whether or not the patient was clinically symptomatic. Patients in whom recanalization was demonstrated were analyzed for
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patient-level clinical characteristics including disease severity, anticoagulant or antiplatelet use, tobacco use, diabetes, hypertension, congestive heart failure, and mean follow up time.
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Analyses
Binomial logistic regression was used to evaluate potential risk factors for anatomic failure. These risk factors included the presence of diabetes, hypertension, hyperlipidemia,
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anticoagulation or antiplatelet agent usage, deep venous reflux, and tobacco use, and were
entered into the equation as dichotomous indicator variables. Mean follow up time and disease
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severity were also evaluated, which were entered into the equation as continuous indicator variables. The results of these analyses indicate the likelihood of recanalization based on the presence/severity of these risk factors. The need for secondary interventions due to clinical
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symptoms associated with recanalization was analyzed as well.
Patient Evaluation and Intervention
Each patient received a preliminary evaluation consistent with current diagnostic and treatment
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guidelines. Upon suspicion of lower extremity venous insufficiency a focused duplex ultrasound was performed for examination of both deep and superficial venous systems, confirmation of
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reflux, determination of level of disease within the vessel, presence of perforator incompetence and classification by CEAP score. RFA was performed in clinic setting and solely for patients with symptomatic reflux. RFA treatment of the GSV and SSV were performed along with tumescence in accordance with recommended guidelines.26 Follow up duplex scans were taken at immediate post procedure to assess for thrombus extension and successful ablation. Repeat
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duplex US was performed at the 6 month follow up period for each participant assessing for recanalization whether or not symptoms were present at that time.
Central Texas Veterans Administration Healthcare System.
Results
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This study was approved by the institutional review boards of Scott & White Healthcare and the
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A total of 249 limbs were included for analysis, of which 69% were in women. The average age of patients with documented recanalization was 54.8 years; average BMI was 33.5 kg/m2 as
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compared to 30.3 kg/m2 in the limbs that remained closed. Patient demographics are presented in Table I. The overall incidence of recanalization in this study was 6.8% within 6 months postprocedure, defined by visible reflux on follow up duplex US. Of the recanalized population, 41% showed clinical symptom recurrence, compared to 21% in the group that retained ablation (RR
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2.75, 95% CI 0.99-7.6) (see Figure II).
Table II depicts the comorbidities and clinical factors of all included limbs and the rate of
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recanalization within each demographic. Patients with GSV recanalization had a mean follow up time of 63.3 versus 41.6 weeks in those that remained ablated (see Figure III). The disease
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severities of the limbs with documented recanalization versus persistently ablated limbs were C4: 35% v. 17%, C5: 18% v. 15%, and C6: 6% v. 8% respectfully (p= 0.57) (see Table II). The rate of secondary vein procedures in the affected limb was 35% in patients with demonstrated recanalization and 12% in those that remained ablated (RR 3.96, p=0.02) (see Figure IV). The decision to proceed with secondary intervention was based upon physician and patient preference.
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Discussion Our patient population showed a GSV recanalization rate of 6.8% over a six month follow up
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period. In this cohort of patients with recanalization, there wasno statistical evidence of disease severity, anticoagulant or antiplatelet use, tobacco use, diabetes, hypertension, or congestive heart failure behaving as clinical risk factors of recanalization itself. However, limbs that did
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undergo recanalization were shown to have a longer mean follow up time, were more likely to receive secondary intervention, and had significantly increased rates of symptom recurrence as
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compared to their successfully persistently ablated counterparts.
With the development of new treatment modalities, the course of CVI disease management has been refined throughout the years. While most clinicians initiate treatment with the least invasive
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method, compression therapy, studies show that approximately 68% of patients do not comply with this treatment regimen, mainly due to discomfort from the elastic compression stockings themselves.28 Also, the use of compression management alone still permits a large recurrence
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rate of venous ulcers, as high is 58% when compared to surgical options with rates up to 31%.29 Traditional open surgical ligation on the other hand comes with several risks due to its invasive
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nature. As some areas become difficult to target mechanically, sclerotherapy has often been used as a low cost means to augment treatment with minimal discomfort.30,31 While this would seem promising to certain patient demographics, recent studies have indicated the use of saphenofemoral ligation in combination with ultrasound guided foam sclerotherapy to be a more palliative rather than a curative management of chronic venous disease.32 These studies
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demonstrate how the aforementioned treatment modalities have not shown the same balance of efficacy and minimally invasive care offered by endovenous therapy.
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This research project was conceived in an effort to identify risk factors for saphenous
recanalization after successful radiofrequency ablation. A review of the available literature shows a significant body of work comparing the various endovenous treatment modalities.
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There are also many studies demonstrating the effectiveness of RFA in treating symptomatic venous reflux. Amongst that body of work, recanalization rates for RFA are reported and some
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studies do site specific risk factors that were identified.
Knipp et al in 2008 reported their outcomes following EVLA.24 In 364 patients, an occlusion rate of 91.4% at 30 months was reported. Vein diameter at the sapheno-femoral junction and the
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location of catheter entry site were both found to be statistically significant with regards to higher rates of recanalization. These factors were not specifically documented or studied in our
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cohort.
Gabriel et al looked at outcomes for patients undergoing endovenous closure while on long-term
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warfarin therapy.33 GSV and SSV closure rates were 100% on immediate follow up imaging. Perforator veins had a 77.3% closure rate in this unique study.33 Unfortunately there were no further follow up studies of this cohort. The idea that anticoagulation may hamper occlusion after ablation seems intuitive. However, the mechanism of RFA occlusion is from heat induced endothelial damage and not simply thrombosis of the vessel. In our study, anticoagulation did lead to an odds ratio of 2.1 for recanalization. However, anticoagulation itself did not have
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statistical significance as a predictive factor for recanalization.
Several studies over the past ten years have revealed not only age and female gender as risk
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factors, but also a history of varicosities, obesity, and standing vocations associated with the development of venous varicosities.34 At the 2011 VEITH Symposium, Dr. Dietzek presented multicenter data showing that the presence of multiple GSV and SSV varicosities increased the
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rate of recanalization.35 Body mass index was also found to be a statistically significant variable. Every 1-point increase in BMI resulted in an 8.9% increase in the hazard of developing recurrent
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flow. Our study did not look at the presence of multiple varicosities as a risk factor for recanalization and there was no significant difference in BMI found between groups. Over the course of six months, a 93.2% overall persistent occlusion rate was found in our study. Although the follow up time periods can vary drastically between studies, this outcome was
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comparable to findings in current literature that range from 90-100% occlusion rates. Notably, Dzieciuchowicz et al compared recanalization after RFA to recanalization after EVLA using various energies.36 At 1470 nm energy level, both RFA and EVLA had 0% recanalization. This
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was a small cohort of patients and the mean follow up time in the RFA group was shorter than the EVLA group. Also, Nordon et al found a 97% 3 month occlusion rate for RFA37, and in a
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randomized clinical trial comparing EVLT to RFA, Rasmussen et al found an RFA occlusion rate of 95.2% at 1 year follow up9. Dr. Dietzek's data presented at the VEITH Symposium demonstrates 91.8% occlusion rate at 4 years using the same radiofrequency catheter employed in this study.35
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Our cohort did not confirm any statistically significant clinical risk factors for recanalization. This and several previous studies, however, have agreeably disproved the suspicion that BMI and anticoagulation in particular would lead to higher recanalization rates. While the results here
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did not change our practice patterns, they do provide reassurance that particular comorbidities are not going to negatively affect the efficacy of treatment. Patients with recanalization were more likely to have symptom recurrence and need for secondary procedures. This finding is not
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surprising, however, it does again reassure that the pathology being treated is the true source of
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the patient's symptomatology, and by eliminating it, the treatment is clinically efficacious.
Limitations
We openly acknowledge the limitations of this study. Of the 392 limbs initially treated during the study period, only 294 limbs were subsequently included in the analysis as they contained data
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from intermediate period duplex US. Better follow up on all patients may or may not have skewed results. Limbs with saphenous recanalization were also studied later in time than those found not to have recanalization. A uniform time for follow up studies may have influenced
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results. It is not unreasonable to speculate that the recanalization rate overall may have been higher if all patients had been scanned at a later follow up. That being said the small amount of
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limbs with recanalization left for evaluation of patient level risk factors may have influenced the significance of the correlation analysis. Perhaps with a larger cohort, and larger number of recanalizations, several of the theorized clinical risk factors may prove to significantly affect the risk of recanalization after all. For this reason a more robust study or multi-center trial is needed to further pursue the validity of these results.
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Conclusion Endothermal ablation is an efficacious treatment for CVI with most patients remaining refluxfree. Outside of the anatomical risk factors confirmed in past literature, recanalization of an
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isolated vein segment following RFA appears to behave sporadically with respect to several clinical risk factors. Nevertheless, in our cohort, anatomic failure was associated with a two-fold increase in symptom recurrence and four-fold increased rate of interval secondary vein
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procedures. Ultrasound interrogation post-procedure, especially in patients with persistent or
recanalization.
Declaration of Conflicting Interests
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recurrent symptoms or non-healing ulcerations, is important for identifying late developing
Dr. Bush is proctor and consultant for Covidien (VNUS Medical) and LeMaitre Vascular, Inc.
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(Trivex)
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Table I: Patient Demographics No Recanalization
N=17
N=232
58.8%
69.8%
0.34
Average Age
54.8
57.4
0.47
BMI
33.5
30.3
0.07
Female Gender
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*BMI = body mass index
P Value
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Recanalization
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Variables
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Table II: Clinical Factors and Comorbidities Odds Ratio
P value
N=17
N=232
CEAP 5/6
23.5%
22.8%
1.0
0.57
Antiplatelet
0%
3.4%
--
Anticoagulation
11.7%
6%
2.1
Tobacco use
0%
9%
--
0.21
Diabetes
23.5%
11.6%
2.3
0.14
Hypertension
52.9%
44.8%
1.4
0.34
Congestive
5.8%
3%
2.0
0.43
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No Recanalization
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Recanalization
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Variables
heart failure
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*CEAP = Clinical Etiology Anatomy and Pathophysiology Classification
0.56 0.3
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References 1.
Carpentier PH, Maricq HR, Biro C, Poncot-Makinen CO, Franco A. Prevalence, risk
factors, and clinical patterns of chronic venous disorders of lower limbs: a population-based
2.
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study in France. J Vasc Surg 2004;40:650-9.
Sisto T, Reunanen A, Laurikka J, et al. Prevalence and risk factors of varicose veins in
lower extremities: mini-Finland health survey. The European journal of surgery = Acta
3.
SC
chirurgica 1995;161:405-14.
Evans CJ, Fowkes FG, Ruckley CV, Lee AJ. Prevalence of varicose veins and chronic
M AN U
venous insufficiency in men and women in the general population: Edinburgh Vein Study. Journal of epidemiology and community health 1999;53:149-53. 4.
Jawien A. The influence of environmental factors in chronic venous insufficiency.
Angiology 2003;54 Suppl 1:S19-31.
Carr SC. Diagnosis and management of venous ulcers. Perspectives in vascular surgery
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5.
and endovascular therapy 2008;20:82-5. 6.
Criqui MH, Jamosmos M, Fronek A, et al. Chronic venous disease in an ethnically
73. 8.
Callam MJ. Epidemiology of varicose veins. The British journal of surgery 1994;81:167-
AC C
7.
EP
diverse population: the San Diego Population Study. Am J Epidemiol 2003;158:448-56.
Kundu S, Lurie F, Millward SF, et al. Recommended reporting standards for endovenous
ablation for the treatment of venous insufficiency: joint statement of the american venous forum and the society of interventional radiology. J Vasc Interv Radiol 2007;18:1073-80.
ACCEPTED MANUSCRIPT 17
9.
Rasmussen LH, Bjoern L, Lawaetz M, Blemings A, Lawaetz B, Eklof B. Randomized
trial comparing endovenous laser ablation of the great saphenous vein with high ligation and stripping in patients with varicose veins: short-term results. J Vasc Surg 2007;46:308-15. Durkin MT, Turton EP, Wijesinghe LD, Scott DJ, Berridge DC. Long saphenous vein
RI PT
10.
stripping and quality of life--a randomised trial. Eur J Vasc Endovasc Surg 2001;21:545-9. 11.
Michaels JA, Brazier JE, Campbell WB, MacIntyre JB, Palfreyman SJ, Ratcliffe J.
SC
Randomized clinical trial comparing surgery with conservative treatment for uncomplicated varicose veins. The British journal of surgery 2006;93:175-81.
Bisang U, Meier TO, Enzler M, Thalhammer C, Husmann M, Amann-Vesti BR. Results
M AN U
12.
of endovenous ClosureFast treatment for varicose veins in an outpatient setting. Phlebology / Venous Forum of the Royal Society of Medicine 2012;27:118-23. 13.
McBride KD. Changing to endovenous treatment for varicose veins: how much more
Ireland 2011;9:150-9. 14.
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evidence is needed? The surgeon : journal of the Royal Colleges of Surgeons of Edinburgh and
Carradice D, Mekako AI, Mazari FA, Samuel N, Hatfield J, Chetter IC. Randomized
EP
clinical trial of endovenous laser ablation compared with conventional surgery for great saphenous varicose veins. The British journal of surgery 2011;98:501-10. Almeida JI, Kaufman J, Gockeritz O, et al. Radiofrequency endovenous ClosureFAST
AC C
15.
versus laser ablation for the treatment of great saphenous reflux: a multicenter, single-blinded, randomized study (RECOVERY study). J Vasc Interv Radiol 2009;20:752-9. 16.
Christenson JT, Gueddi S, Gemayel G, Bounameaux H. Prospective randomized trial
comparing endovenous laser ablation and surgery for treatment of primary great saphenous varicose veins with a 2-year follow-up. J Vasc Surg 2010;52:1234-41.
ACCEPTED MANUSCRIPT 18
17.
Roth SM. Endovenous radiofrequency ablation of superficial and perforator veins. The
Surgical clinics of North America 2007;87:1267-84, xii. Fan CM, Rox-Anderson R. Endovenous laser ablation: mechanism of action. Phlebology
/ Venous Forum of the Royal Society of Medicine 2008;23:206-13. 19.
RI PT
18.
Mekako AI, Hatfield J, Bryce J, Lee D, McCollum PT, Chetter I. A nonrandomised
Annals of vascular surgery 2006;20:451-7. 20.
SC
controlled trial of endovenous laser therapy and surgery in the treatment of varicose veins.
de Medeiros CA, Luccas GC. Comparison of endovenous treatment with an 810 nm laser
M AN U
versus conventional stripping of the great saphenous vein in patients with primary varicose veins. Dermatol Surg 2005;31:1685-94; discussion 94. 21.
Dexter D, Kabnick L, Berland T, et al. Complications of endovenous lasers. Phlebology /
Venous Forum of the Royal Society of Medicine 2012;27 Suppl 1:40-5. Harlander-Locke M, Jimenez JC, Lawrence PF, et al. Management of endovenous heat-
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22.
induced thrombus using a classification system and treatment algorithm following segmental thermal ablation of the small saphenous vein. J Vasc Surg;58:427-32. Proebstle TM, Moehler T, Herdemann S. Reduced recanalization rates of the great
EP
23.
saphenous vein after endovenous laser treatment with increased energy dosing: definition of a
24.
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threshold for the endovenous fluence equivalent. J Vasc Surg 2006;44:834-9. Knipp BS, Blackburn SA, Bloom JR, et al. Endovenous laser ablation: venous outcomes
and thrombotic complications are independent of the presence of deep venous insufficiency. J Vasc Surg 2008;48:1538-45.
ACCEPTED MANUSCRIPT 19
25.
Marrocco CJ, Atkins MD, Bohannon WT, Warren TR, Buckley CJ, Bush RL.
Endovenous ablation for the treatment of chronic venous insufficiency and venous ulcerations. World J Surg;34:2299-304. Bush RL, Ramone-Maxwell C. Endovenous and surgical extirpation of lower-extremity
RI PT
26.
varicose veins. Seminars in vascular surgery 2008;21:50-3. 27.
Perala J, Rautio T, Biancari F, et al. Radiofrequency endovenous obliteration versus
SC
stripping of the long saphenous vein in the management of primary varicose veins: 3-year outcome of a randomized study. Annals of vascular surgery 2005;19:669-72.
Maurins U, Hoffmann BH, Losch C, Jockel KH, Rabe E, Pannier F. Distribution and
M AN U
28.
prevalence of reflux in the superficial and deep venous system in the general population--results from the Bonn Vein Study, Germany. J Vasc Surg 2008;48:680-7. 29.
Howard DP, Howard A, Kothari A, Wales L, Guest M, Davies AH. The role of
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superficial venous surgery in the management of venous ulcers: a systematic review. Eur J Vasc Endovasc Surg 2008;36:458-65. 30.
Kalodiki E, Lattimer CR, Azzam M, Shawish E, Bountouroglou D, Geroulakos G. Long-
EP
term results of a randomized controlled trial on ultrasound-guided foam sclerotherapy combined with saphenofemoral ligation vs standard surgery for varicose veins. J Vasc Surg 2012;55:451-7. Bountouroglou DG, Azzam M, Kakkos SK, Pathmarajah M, Young P, Geroulakos G.
AC C
31.
Ultrasound-guided foam sclerotherapy combined with sapheno-femoral ligation compared to surgical treatment of varicose veins: early results of a randomised controlled trial. Eur J Vasc Endovasc Surg 2006;31:93-100.
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32.
Figueiredo M, de Araujo SP, Figueiredo MF. Late follow-up of saphenofemoral junction
ligation combined with ultrasound-guided foam sclerotherapy in patients with venous ulcers. Annals of vascular surgery 2012;26:977-81. Gabriel V, Jimenez JC, Alktaifi A, et al. Success of endovenous saphenous and perforator
RI PT
33.
ablation in patients with symptomatic venous insufficiency receiving long-term warfarin therapy. Annals of vascular surgery 2012;26:607-11.
Beebe-Dimmer JL, Pfeifer JR, Engle JS, Schottenfeld D. The epidemiology of chronic
SC
34.
venous insufficiency and varicose veins. Annals of epidemiology 2005;15:175-84. A D. Four-Year Follow-Up Data From a Perspective, Multicenter Study of the Efficacy
M AN U
35.
of the ClosureFast Catheter. 37th Annual Veith Symposium 2011. 36.
Dzieciuchowicz L, Krasinski Z, Gabriel M, Espinosa G. A prospective comparison of
four methods of endovenous thermal ablation. Polski przeglad chirurgiczny 2011;83:597-605. Nordon IM, Hinchliffe RJ, Brar R, et al. A prospective double-blind randomized
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37.
controlled trial of radiofrequency versus laser treatment of the great saphenous vein in patients
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with varicose veins. Ann Surg 2011;254:876-81.
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Figure Legend
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1. Patient selection for study cohort. During the time frame studied, 392 patients underwent RFA of the great saphenous vein (GSV). Of those who had a second ultrasound (beyond the initial 5-7 day ultrasound), 17 limbs demonstrated complete or partial GSV recanalization.
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2. Symptom Recurrence. Percentage of patients with recurrence of symptoms following RFA, with and without recanalization. Only 21% of patients who had recanalization had recurrent symptoms. 3. Average follow-up time.
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4. Need for secondary vein procedures. In the affected limb, secondary venin procedures were necessary for symptom recurrence in 35% in patients who had recanalization compared to 12% in those that remained ablated.
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Figures
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Figure I: Patient Selection
232 NEGATIVE FOLLOWUP US
392 LIMBS UNDERWENT SAPHENOUS ABLATION, NEGATIVE US
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143 EXCLUDED, NO INTERVAL DUPLEX US
17 LIMBS WITH INTERVAL RECANALIZATION
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249 WITH INTERMEDIATE FOLLOWUP DUPLEX US
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Figure II: Symptom Recurrence
Retained Ablation
21%
Recanalization
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41%
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Symptom Recurrence
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Figure III: Mean follow up time
41.6 63.3 Retained Ablation
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Recannalization
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Follow Up Time (weeks)
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Figure IV: Secondary Interventions Performed
No Additional Intervention
Recanalization Additional Intervention
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RFA - Secondary Interventions
Successful Ablation
Successful Ablation with Additional Intervention
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Successful Ablation, Secondary Procedures Recanalization, Observation
No Secondary Interventions
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Recanalization, Additional Procedure
S0890-5096(14)00613-X
DOI:
10.1016/j.avsg.2014.09.020
Reference:
AVSG 2171
To appear in:
Annals of Vascular Surgery
Received Date: 7 May 2014 Revised Date:
23 July 2014
Accepted Date: 10 September 2014
Please cite this article as: Bunnell AP, Zaidi S, Eidson JL III, Bohannon WT, Atkins MA, Bush RL, Factors associated with saphenous vein recanalization following endothermal ablation, Annals of Vascular Surgery (2014), doi: 10.1016/j.avsg.2014.09.020. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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FACTORS ASSOCIATED WITH SAPHENOUS VEIN RECANALIZATION FOLLOWING ENDOTHERMAL ABLATION
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Avianne P. Bunnell, B.S.1, Shariq Zaidi, M.D.2,3, J. Leigh Eidson, III, M.D.2, 3, W. Todd Bohannon, M.D. 3, Marvin A. Atkins, M.D.3, Ruth L. Bush, M.D., J.D., M.P.H.2,4
Corresponding Author
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University of Central Florida College of Medicine, Orlando FL1, Central Texas VA Healthcare System, Temple TX2, Baylor Scott and White Healthcare, Temple TX3, Texas A & M Health Science Center College of Medicine, Bryan, TX4
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Ruth L. Bush, M.D., J.D., M.P.H. Texas A&M Health Science Center MS 1359 8447 State Highway 47, HPEB 3064, Bryan, TX 77807-3260 phone: 979.436.0241 fax: 979.436.0092 [email protected]
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Abstract Purpose: Endovenous thermal ablation has emerged as an alternative therapy for the treatment of chronic superficial venous insufficiency (CVI) of the lower extremities. Recanalization, or
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anatomic failure, of a vein following endovenous radiofrequency ablation (RFA) has been
described, albeit an infrequent occurrence. This study was performed to demonstrate risk factors associated with the efficacy of RFA and recanalization in the treatment of CVI.
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Patients and Methods: Data were collected in an ongoing multicenter registry which was
retrospectively reveiwed. This study reviewed 249 limbs that underwent RFA of either the great
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(GSV) or small saphenous vein (SSV) over a three-year period, including only patients for which an intermediate (6 month) follow up venous duplex ultrasound was available. Patients in whom recanalization was demonstrated via duplex (N=17, 6.8%) were analyzed for patient-level characteristics. Logistic regression analysis was performed to determine the existence of any
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significant clinical risk factors associated with anatomical failure. The need for secondary interventions due to clinical symptoms associated with recanalization was analyzed as well. Results: In this cohort, the initial vein occlusion rate was 93.1%. Segmental (n=9, 53%) or
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complete (n=8, 47%) recanalization was seen in 17 limbs (6.8%) after initial successful GSV ablation. All SSV remained persistently ablated. Anatomic failure was associated with higher
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rate of clinical symptom recurrence (41% v 21%, RR 2.75, 95% CI, 0.99-7.6, p<0.05) as well as an increased need for secondary vein procedures in the affected limbs (35% v 12%, RR 3.96, 95% CI 1.3-11.7, p<0.05). Two recanalized GSVs required repeated endothermal ablation, in efforts to aid in the healing of ulcerations. Patient factors including diabetes, hypertension, hyperlipidemia, anticoagulation or antiplatelet agent usage, presence of deep venous reflux, or tobacco use did not increase the risk of RFA failure. Comparatively, patients with GSV
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recanalization had a longer mean follow up time (63.3 v. 41.6 weeks) but no difference in disease severity (C4, 35% v. 17%; C5, 18% v. 15%; C6, 6% v. 8%, NS). Conclusions: Endothermal ablation is an efficacious treatment for CVI with most patients
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remaining reflux-free. Recanalization of an isolated vein segment following RFA, while shown in recent literature to be effected by anatomical risk factors, appears to be a sporadic
phenomenon with respect to clinical risk factors. Nevertheless, in our cohort, anatomic failure
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was associated with a two-fold increase in symptom recurrence and the need for interval
secondary vein procedures. Ultrasound interrogation is recommended especially in patients with
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persistent or recurrent symptoms or non-healing ulcerations.
Keywords
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radiofrequency, recanalization, venous insufficiency, venous reflux
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Introduction Venous insufficiency, or reflux disease, is caused by the mechanical incompetence of venous valves allowing passage of blood from deep veins back into the superficial vasculature rather
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than toward the heart. Venous reflux affects more of the adult population than cardiovascular disease, which explains why the management and treatment of its complications occupy a large percentage of the healthcare budget.5 Left untreated, 20% of superficial venous reflux cases lead
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to venous varicosities6 progressing in severity to include symptoms of swelling, aching, skin
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discoloration, and venous ulceration.
Treatment options for venous reflux disease vary in approach, including conservative management with compression therapy, open surgery, sclerotherapy, and endovenous therapy. Endovenous treatment of symptomatic reflux disease has proven to be the current standard of
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treatment for chronic venous insufficiency (CVI) and symptomatic varicosities.12-14 Beginning with radiofrequency ablation (RFA) in 1999 and subsequently endovenous laser ablation (EVLA) in 2002, the use of these interventions has increased more than eightfold since 200515,
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effectively replacing traditional stripping and ligation.16 Functionally, laser or radiofrequency is used to precisely emit thermal energy directly to the vein wall, destructing the intima and leading
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to the breakdown of collagen in the media. Eventually this forms a fibroelastic seal of the lumen of the vein itself17 and leads to contraction (shrinkage) of the vessel wall.18 Studies prove these methods to be similarly or more effective than vein stripping while providing less postoperative morbidity.9,19,20
Recanalization, the anatomic failure of venous ablation, while infrequent is still seen in the use of RFA as demonstrated by Proebstle et al in 2011.23 Their cohort revealed a reflux rate of 4.3%
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(7.4% blood flow) detectable by duplex ultrasound at 3 year follow up. In 2008, we also learned that recanalization risk is greatly affected by anatomic risk factors, such as vein size at the saphenofemoral junction and entry sites for ablation.24 Contrary to the effects of anatomic
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factors, there has been shown to be no significant association between clinical risk factors, such as history of DVT, DVI, diabetes, smoking, or BMI25 on the presence of non-healing venous ulcers after intervention. This leaves to question the relationship between clinical risk factors and
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the rate of recanalization itself. For this reason, we aim to evaluate several of these theorized
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clinical risk factors and their association with RFA efficacy and the incidence of recanalization.
Methods Patients
All patient data were collected in an ongoing multicenter registry. In a review of 392 limbs
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consecutively treated over 3 years, all underwent endovenous ablation of either the GSV or small saphenous vein (SSV) via RFA. Our technique for endovenous ablation with RFA is consistent with other investigators and has been described elsewhere.15,26,27 In each case the intervention
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was selected based upon symptomology and duplex-documented pathophysiological reflux. Patients with a CEAP score of C3-6 were considered for possible treatment. After singling out
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for patients with available intermediate and six month follow up venous duplex ultrasounds 249 limbs remained for further stratification (see Figure I).
Recanalization was defined by duplex-documented evidence whether or not the patient was clinically symptomatic. Patients in whom recanalization was demonstrated were analyzed for
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patient-level clinical characteristics including disease severity, anticoagulant or antiplatelet use, tobacco use, diabetes, hypertension, congestive heart failure, and mean follow up time.
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Analyses
Binomial logistic regression was used to evaluate potential risk factors for anatomic failure. These risk factors included the presence of diabetes, hypertension, hyperlipidemia,
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anticoagulation or antiplatelet agent usage, deep venous reflux, and tobacco use, and were
entered into the equation as dichotomous indicator variables. Mean follow up time and disease
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severity were also evaluated, which were entered into the equation as continuous indicator variables. The results of these analyses indicate the likelihood of recanalization based on the presence/severity of these risk factors. The need for secondary interventions due to clinical
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symptoms associated with recanalization was analyzed as well.
Patient Evaluation and Intervention
Each patient received a preliminary evaluation consistent with current diagnostic and treatment
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guidelines. Upon suspicion of lower extremity venous insufficiency a focused duplex ultrasound was performed for examination of both deep and superficial venous systems, confirmation of
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reflux, determination of level of disease within the vessel, presence of perforator incompetence and classification by CEAP score. RFA was performed in clinic setting and solely for patients with symptomatic reflux. RFA treatment of the GSV and SSV were performed along with tumescence in accordance with recommended guidelines.26 Follow up duplex scans were taken at immediate post procedure to assess for thrombus extension and successful ablation. Repeat
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duplex US was performed at the 6 month follow up period for each participant assessing for recanalization whether or not symptoms were present at that time.
Central Texas Veterans Administration Healthcare System.
Results
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This study was approved by the institutional review boards of Scott & White Healthcare and the
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A total of 249 limbs were included for analysis, of which 69% were in women. The average age of patients with documented recanalization was 54.8 years; average BMI was 33.5 kg/m2 as
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compared to 30.3 kg/m2 in the limbs that remained closed. Patient demographics are presented in Table I. The overall incidence of recanalization in this study was 6.8% within 6 months postprocedure, defined by visible reflux on follow up duplex US. Of the recanalized population, 41% showed clinical symptom recurrence, compared to 21% in the group that retained ablation (RR
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2.75, 95% CI 0.99-7.6) (see Figure II).
Table II depicts the comorbidities and clinical factors of all included limbs and the rate of
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recanalization within each demographic. Patients with GSV recanalization had a mean follow up time of 63.3 versus 41.6 weeks in those that remained ablated (see Figure III). The disease
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severities of the limbs with documented recanalization versus persistently ablated limbs were C4: 35% v. 17%, C5: 18% v. 15%, and C6: 6% v. 8% respectfully (p= 0.57) (see Table II). The rate of secondary vein procedures in the affected limb was 35% in patients with demonstrated recanalization and 12% in those that remained ablated (RR 3.96, p=0.02) (see Figure IV). The decision to proceed with secondary intervention was based upon physician and patient preference.
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Discussion Our patient population showed a GSV recanalization rate of 6.8% over a six month follow up
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period. In this cohort of patients with recanalization, there wasno statistical evidence of disease severity, anticoagulant or antiplatelet use, tobacco use, diabetes, hypertension, or congestive heart failure behaving as clinical risk factors of recanalization itself. However, limbs that did
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undergo recanalization were shown to have a longer mean follow up time, were more likely to receive secondary intervention, and had significantly increased rates of symptom recurrence as
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compared to their successfully persistently ablated counterparts.
With the development of new treatment modalities, the course of CVI disease management has been refined throughout the years. While most clinicians initiate treatment with the least invasive
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method, compression therapy, studies show that approximately 68% of patients do not comply with this treatment regimen, mainly due to discomfort from the elastic compression stockings themselves.28 Also, the use of compression management alone still permits a large recurrence
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rate of venous ulcers, as high is 58% when compared to surgical options with rates up to 31%.29 Traditional open surgical ligation on the other hand comes with several risks due to its invasive
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nature. As some areas become difficult to target mechanically, sclerotherapy has often been used as a low cost means to augment treatment with minimal discomfort.30,31 While this would seem promising to certain patient demographics, recent studies have indicated the use of saphenofemoral ligation in combination with ultrasound guided foam sclerotherapy to be a more palliative rather than a curative management of chronic venous disease.32 These studies
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demonstrate how the aforementioned treatment modalities have not shown the same balance of efficacy and minimally invasive care offered by endovenous therapy.
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This research project was conceived in an effort to identify risk factors for saphenous
recanalization after successful radiofrequency ablation. A review of the available literature shows a significant body of work comparing the various endovenous treatment modalities.
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There are also many studies demonstrating the effectiveness of RFA in treating symptomatic venous reflux. Amongst that body of work, recanalization rates for RFA are reported and some
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studies do site specific risk factors that were identified.
Knipp et al in 2008 reported their outcomes following EVLA.24 In 364 patients, an occlusion rate of 91.4% at 30 months was reported. Vein diameter at the sapheno-femoral junction and the
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location of catheter entry site were both found to be statistically significant with regards to higher rates of recanalization. These factors were not specifically documented or studied in our
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cohort.
Gabriel et al looked at outcomes for patients undergoing endovenous closure while on long-term
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warfarin therapy.33 GSV and SSV closure rates were 100% on immediate follow up imaging. Perforator veins had a 77.3% closure rate in this unique study.33 Unfortunately there were no further follow up studies of this cohort. The idea that anticoagulation may hamper occlusion after ablation seems intuitive. However, the mechanism of RFA occlusion is from heat induced endothelial damage and not simply thrombosis of the vessel. In our study, anticoagulation did lead to an odds ratio of 2.1 for recanalization. However, anticoagulation itself did not have
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statistical significance as a predictive factor for recanalization.
Several studies over the past ten years have revealed not only age and female gender as risk
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factors, but also a history of varicosities, obesity, and standing vocations associated with the development of venous varicosities.34 At the 2011 VEITH Symposium, Dr. Dietzek presented multicenter data showing that the presence of multiple GSV and SSV varicosities increased the
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rate of recanalization.35 Body mass index was also found to be a statistically significant variable. Every 1-point increase in BMI resulted in an 8.9% increase in the hazard of developing recurrent
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flow. Our study did not look at the presence of multiple varicosities as a risk factor for recanalization and there was no significant difference in BMI found between groups. Over the course of six months, a 93.2% overall persistent occlusion rate was found in our study. Although the follow up time periods can vary drastically between studies, this outcome was
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comparable to findings in current literature that range from 90-100% occlusion rates. Notably, Dzieciuchowicz et al compared recanalization after RFA to recanalization after EVLA using various energies.36 At 1470 nm energy level, both RFA and EVLA had 0% recanalization. This
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was a small cohort of patients and the mean follow up time in the RFA group was shorter than the EVLA group. Also, Nordon et al found a 97% 3 month occlusion rate for RFA37, and in a
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randomized clinical trial comparing EVLT to RFA, Rasmussen et al found an RFA occlusion rate of 95.2% at 1 year follow up9. Dr. Dietzek's data presented at the VEITH Symposium demonstrates 91.8% occlusion rate at 4 years using the same radiofrequency catheter employed in this study.35
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Our cohort did not confirm any statistically significant clinical risk factors for recanalization. This and several previous studies, however, have agreeably disproved the suspicion that BMI and anticoagulation in particular would lead to higher recanalization rates. While the results here
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did not change our practice patterns, they do provide reassurance that particular comorbidities are not going to negatively affect the efficacy of treatment. Patients with recanalization were more likely to have symptom recurrence and need for secondary procedures. This finding is not
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surprising, however, it does again reassure that the pathology being treated is the true source of
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the patient's symptomatology, and by eliminating it, the treatment is clinically efficacious.
Limitations
We openly acknowledge the limitations of this study. Of the 392 limbs initially treated during the study period, only 294 limbs were subsequently included in the analysis as they contained data
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from intermediate period duplex US. Better follow up on all patients may or may not have skewed results. Limbs with saphenous recanalization were also studied later in time than those found not to have recanalization. A uniform time for follow up studies may have influenced
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results. It is not unreasonable to speculate that the recanalization rate overall may have been higher if all patients had been scanned at a later follow up. That being said the small amount of
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limbs with recanalization left for evaluation of patient level risk factors may have influenced the significance of the correlation analysis. Perhaps with a larger cohort, and larger number of recanalizations, several of the theorized clinical risk factors may prove to significantly affect the risk of recanalization after all. For this reason a more robust study or multi-center trial is needed to further pursue the validity of these results.
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Conclusion Endothermal ablation is an efficacious treatment for CVI with most patients remaining refluxfree. Outside of the anatomical risk factors confirmed in past literature, recanalization of an
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isolated vein segment following RFA appears to behave sporadically with respect to several clinical risk factors. Nevertheless, in our cohort, anatomic failure was associated with a two-fold increase in symptom recurrence and four-fold increased rate of interval secondary vein
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procedures. Ultrasound interrogation post-procedure, especially in patients with persistent or
recanalization.
Declaration of Conflicting Interests
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recurrent symptoms or non-healing ulcerations, is important for identifying late developing
Dr. Bush is proctor and consultant for Covidien (VNUS Medical) and LeMaitre Vascular, Inc.
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(Trivex)
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Table I: Patient Demographics No Recanalization
N=17
N=232
58.8%
69.8%
0.34
Average Age
54.8
57.4
0.47
BMI
33.5
30.3
0.07
Female Gender
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*BMI = body mass index
P Value
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Recanalization
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Variables
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Table II: Clinical Factors and Comorbidities Odds Ratio
P value
N=17
N=232
CEAP 5/6
23.5%
22.8%
1.0
0.57
Antiplatelet
0%
3.4%
--
Anticoagulation
11.7%
6%
2.1
Tobacco use
0%
9%
--
0.21
Diabetes
23.5%
11.6%
2.3
0.14
Hypertension
52.9%
44.8%
1.4
0.34
Congestive
5.8%
3%
2.0
0.43
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No Recanalization
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Recanalization
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Variables
heart failure
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*CEAP = Clinical Etiology Anatomy and Pathophysiology Classification
0.56 0.3
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References 1.
Carpentier PH, Maricq HR, Biro C, Poncot-Makinen CO, Franco A. Prevalence, risk
factors, and clinical patterns of chronic venous disorders of lower limbs: a population-based
2.
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study in France. J Vasc Surg 2004;40:650-9.
Sisto T, Reunanen A, Laurikka J, et al. Prevalence and risk factors of varicose veins in
lower extremities: mini-Finland health survey. The European journal of surgery = Acta
3.
SC
chirurgica 1995;161:405-14.
Evans CJ, Fowkes FG, Ruckley CV, Lee AJ. Prevalence of varicose veins and chronic
M AN U
venous insufficiency in men and women in the general population: Edinburgh Vein Study. Journal of epidemiology and community health 1999;53:149-53. 4.
Jawien A. The influence of environmental factors in chronic venous insufficiency.
Angiology 2003;54 Suppl 1:S19-31.
Carr SC. Diagnosis and management of venous ulcers. Perspectives in vascular surgery
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5.
and endovascular therapy 2008;20:82-5. 6.
Criqui MH, Jamosmos M, Fronek A, et al. Chronic venous disease in an ethnically
73. 8.
Callam MJ. Epidemiology of varicose veins. The British journal of surgery 1994;81:167-
AC C
7.
EP
diverse population: the San Diego Population Study. Am J Epidemiol 2003;158:448-56.
Kundu S, Lurie F, Millward SF, et al. Recommended reporting standards for endovenous
ablation for the treatment of venous insufficiency: joint statement of the american venous forum and the society of interventional radiology. J Vasc Interv Radiol 2007;18:1073-80.
ACCEPTED MANUSCRIPT 17
9.
Rasmussen LH, Bjoern L, Lawaetz M, Blemings A, Lawaetz B, Eklof B. Randomized
trial comparing endovenous laser ablation of the great saphenous vein with high ligation and stripping in patients with varicose veins: short-term results. J Vasc Surg 2007;46:308-15. Durkin MT, Turton EP, Wijesinghe LD, Scott DJ, Berridge DC. Long saphenous vein
RI PT
10.
stripping and quality of life--a randomised trial. Eur J Vasc Endovasc Surg 2001;21:545-9. 11.
Michaels JA, Brazier JE, Campbell WB, MacIntyre JB, Palfreyman SJ, Ratcliffe J.
SC
Randomized clinical trial comparing surgery with conservative treatment for uncomplicated varicose veins. The British journal of surgery 2006;93:175-81.
Bisang U, Meier TO, Enzler M, Thalhammer C, Husmann M, Amann-Vesti BR. Results
M AN U
12.
of endovenous ClosureFast treatment for varicose veins in an outpatient setting. Phlebology / Venous Forum of the Royal Society of Medicine 2012;27:118-23. 13.
McBride KD. Changing to endovenous treatment for varicose veins: how much more
Ireland 2011;9:150-9. 14.
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evidence is needed? The surgeon : journal of the Royal Colleges of Surgeons of Edinburgh and
Carradice D, Mekako AI, Mazari FA, Samuel N, Hatfield J, Chetter IC. Randomized
EP
clinical trial of endovenous laser ablation compared with conventional surgery for great saphenous varicose veins. The British journal of surgery 2011;98:501-10. Almeida JI, Kaufman J, Gockeritz O, et al. Radiofrequency endovenous ClosureFAST
AC C
15.
versus laser ablation for the treatment of great saphenous reflux: a multicenter, single-blinded, randomized study (RECOVERY study). J Vasc Interv Radiol 2009;20:752-9. 16.
Christenson JT, Gueddi S, Gemayel G, Bounameaux H. Prospective randomized trial
comparing endovenous laser ablation and surgery for treatment of primary great saphenous varicose veins with a 2-year follow-up. J Vasc Surg 2010;52:1234-41.
ACCEPTED MANUSCRIPT 18
17.
Roth SM. Endovenous radiofrequency ablation of superficial and perforator veins. The
Surgical clinics of North America 2007;87:1267-84, xii. Fan CM, Rox-Anderson R. Endovenous laser ablation: mechanism of action. Phlebology
/ Venous Forum of the Royal Society of Medicine 2008;23:206-13. 19.
RI PT
18.
Mekako AI, Hatfield J, Bryce J, Lee D, McCollum PT, Chetter I. A nonrandomised
Annals of vascular surgery 2006;20:451-7. 20.
SC
controlled trial of endovenous laser therapy and surgery in the treatment of varicose veins.
de Medeiros CA, Luccas GC. Comparison of endovenous treatment with an 810 nm laser
M AN U
versus conventional stripping of the great saphenous vein in patients with primary varicose veins. Dermatol Surg 2005;31:1685-94; discussion 94. 21.
Dexter D, Kabnick L, Berland T, et al. Complications of endovenous lasers. Phlebology /
Venous Forum of the Royal Society of Medicine 2012;27 Suppl 1:40-5. Harlander-Locke M, Jimenez JC, Lawrence PF, et al. Management of endovenous heat-
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22.
induced thrombus using a classification system and treatment algorithm following segmental thermal ablation of the small saphenous vein. J Vasc Surg;58:427-32. Proebstle TM, Moehler T, Herdemann S. Reduced recanalization rates of the great
EP
23.
saphenous vein after endovenous laser treatment with increased energy dosing: definition of a
24.
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threshold for the endovenous fluence equivalent. J Vasc Surg 2006;44:834-9. Knipp BS, Blackburn SA, Bloom JR, et al. Endovenous laser ablation: venous outcomes
and thrombotic complications are independent of the presence of deep venous insufficiency. J Vasc Surg 2008;48:1538-45.
ACCEPTED MANUSCRIPT 19
25.
Marrocco CJ, Atkins MD, Bohannon WT, Warren TR, Buckley CJ, Bush RL.
Endovenous ablation for the treatment of chronic venous insufficiency and venous ulcerations. World J Surg;34:2299-304. Bush RL, Ramone-Maxwell C. Endovenous and surgical extirpation of lower-extremity
RI PT
26.
varicose veins. Seminars in vascular surgery 2008;21:50-3. 27.
Perala J, Rautio T, Biancari F, et al. Radiofrequency endovenous obliteration versus
SC
stripping of the long saphenous vein in the management of primary varicose veins: 3-year outcome of a randomized study. Annals of vascular surgery 2005;19:669-72.
Maurins U, Hoffmann BH, Losch C, Jockel KH, Rabe E, Pannier F. Distribution and
M AN U
28.
prevalence of reflux in the superficial and deep venous system in the general population--results from the Bonn Vein Study, Germany. J Vasc Surg 2008;48:680-7. 29.
Howard DP, Howard A, Kothari A, Wales L, Guest M, Davies AH. The role of
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superficial venous surgery in the management of venous ulcers: a systematic review. Eur J Vasc Endovasc Surg 2008;36:458-65. 30.
Kalodiki E, Lattimer CR, Azzam M, Shawish E, Bountouroglou D, Geroulakos G. Long-
EP
term results of a randomized controlled trial on ultrasound-guided foam sclerotherapy combined with saphenofemoral ligation vs standard surgery for varicose veins. J Vasc Surg 2012;55:451-7. Bountouroglou DG, Azzam M, Kakkos SK, Pathmarajah M, Young P, Geroulakos G.
AC C
31.
Ultrasound-guided foam sclerotherapy combined with sapheno-femoral ligation compared to surgical treatment of varicose veins: early results of a randomised controlled trial. Eur J Vasc Endovasc Surg 2006;31:93-100.
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32.
Figueiredo M, de Araujo SP, Figueiredo MF. Late follow-up of saphenofemoral junction
ligation combined with ultrasound-guided foam sclerotherapy in patients with venous ulcers. Annals of vascular surgery 2012;26:977-81. Gabriel V, Jimenez JC, Alktaifi A, et al. Success of endovenous saphenous and perforator
RI PT
33.
ablation in patients with symptomatic venous insufficiency receiving long-term warfarin therapy. Annals of vascular surgery 2012;26:607-11.
Beebe-Dimmer JL, Pfeifer JR, Engle JS, Schottenfeld D. The epidemiology of chronic
SC
34.
venous insufficiency and varicose veins. Annals of epidemiology 2005;15:175-84. A D. Four-Year Follow-Up Data From a Perspective, Multicenter Study of the Efficacy
M AN U
35.
of the ClosureFast Catheter. 37th Annual Veith Symposium 2011. 36.
Dzieciuchowicz L, Krasinski Z, Gabriel M, Espinosa G. A prospective comparison of
four methods of endovenous thermal ablation. Polski przeglad chirurgiczny 2011;83:597-605. Nordon IM, Hinchliffe RJ, Brar R, et al. A prospective double-blind randomized
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37.
controlled trial of radiofrequency versus laser treatment of the great saphenous vein in patients
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with varicose veins. Ann Surg 2011;254:876-81.
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Figure Legend
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1. Patient selection for study cohort. During the time frame studied, 392 patients underwent RFA of the great saphenous vein (GSV). Of those who had a second ultrasound (beyond the initial 5-7 day ultrasound), 17 limbs demonstrated complete or partial GSV recanalization.
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2. Symptom Recurrence. Percentage of patients with recurrence of symptoms following RFA, with and without recanalization. Only 21% of patients who had recanalization had recurrent symptoms. 3. Average follow-up time.
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4. Need for secondary vein procedures. In the affected limb, secondary venin procedures were necessary for symptom recurrence in 35% in patients who had recanalization compared to 12% in those that remained ablated.
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Figures
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Figure I: Patient Selection
232 NEGATIVE FOLLOWUP US
392 LIMBS UNDERWENT SAPHENOUS ABLATION, NEGATIVE US
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143 EXCLUDED, NO INTERVAL DUPLEX US
17 LIMBS WITH INTERVAL RECANALIZATION
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249 WITH INTERMEDIATE FOLLOWUP DUPLEX US
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Figure II: Symptom Recurrence
Retained Ablation
21%
Recanalization
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41%
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Symptom Recurrence
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Figure III: Mean follow up time
41.6 63.3 Retained Ablation
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Recannalization
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Follow Up Time (weeks)
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Figure IV: Secondary Interventions Performed
No Additional Intervention
Recanalization Additional Intervention
RI PT
RFA - Secondary Interventions
Successful Ablation
Successful Ablation with Additional Intervention
SC
Successful Ablation, Secondary Procedures Recanalization, Observation
No Secondary Interventions
AC C
EP
TE D
M AN U
Recanalization, Additional Procedure