Revista Médica del

Hospital General de México

REVIEW ARTICLE

Chronic venous disease: Literature review

Miguel A. Sierra-Juárez*, José E. Rejón-Cauich, Melvin G. Parada-Guzmán, and
Saira A. Castañeda-Morales
Service of Vascular Surgery, Hospital General de México “Dr. Eduardo Liceaga”, Mexico City, Mexico

Abstract
The venous system is responsible for bringing blood from the lower limbs to the heart. To achieve this, various mechanisms
are activated that work against gravitational force. A very important mechanism is the function of the venous valves. A family
history of venous disease is most commonly associated with valve dysfunction, which can lead to venous hypertension,
amongst several other risk factors, thus activating a cascade of events characterized by venous dilation and leukocyte mi-
gration. Chronic complications can be very expensive in relation to quality of life and the health system. At present, venous
disease studies include several diagnostic methods that, together with a wide range of therapeutic tools, have achieved
excellent results in the quality of life of patients.

Key words: Endovenous thermal ablation. Saphenous vein. Vascular surgery. Venous insufficiency.

Introduction According to the Framingham Heart Study, the 2-year

incidence of varicose veins in women and men was
Chronic venous disease (CVD) is a common disease 2.6% and 2.0%. CVI can occur as a result of primary
with an estimated worldwide prevalence of 83.6%. Var- and secondary causes (70% and 30% of cases,
icose veins of the lower extremities are the most com- respectively)4.
mon cause of chronic venous insufficiency (CVI) and Venous ulcers can affect at least 1-2% of the elderly
the most severe form of the disease is venous ulcer- population with a significant burden in terms of quality
ation. It is estimated that 30-40% of the adult popula- of life and health-care costs5.
tion has varicose veins and up to 6% of patients with
varicose veins develop ulcers at some time in their
lives. Up to 30% of varicose veins may progress to Pathophysiology and epidemiology of
more severe forms of CVI. Almost 1% of the general venous disease
population may develop venous ulceration at some time Thirty genetic loci strongly associated with varicose
and the prevalence of open venous ulceration is ap- veins have been identified, with the strongest associa-
proximately 0.1-0.3%1. The incidence of varicose veins tions occurring in the intron region CASZ1 (rs11121615;
is estimated to be about 2%/year2. Congenital venous p = 3.71 × 10-65), which has been implicated in blood
valve abnormalities are proposed to be the cause of pressure. In addition, mutations in the HFE gene have
varicose veins3. previously been associated with venous ulceration and

Correspondence: Date of reception: 08-07-2020 Available online: 19-04-2021

*Miguel A. Sierra-Juárez Date of acceptance: 19-11-2020 Rev Med Hosp Gen Mex. 2021;84(2):80-86
E-mail: [email protected] DOI: 10.24875/HGMX.20000072 www.hospitalgeneral.mx
0185-1063/© 2020 Sociedad Médica del Hospital General de Mexico. Published by Permanyer. This is an open access article under the CC BY-
NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

80
 M.A. Sierra-Juárez, et al.: Chronic venous disease

thromboembolism6. Studies seem to suggest an in- Table 1. The 2020 update of the CEAP classification
crease in varicose veins in type I collagen content and system and reporting standards
a decrease in type III collagen content, the latter being Summary of clinical © classifications
a factor in venous elasticity, both elastin, and laminin
C class description
content decreases in varicose veins. Laminins are a
group of glycoproteins of high molecular mass (140-400 C0 No visible or palpable signs
venous disease
kDa) that is part of the basal lamina associated with
other proteins such as collagen, entactin, proteogly- C1 Telangiectasia or reticular
veins
cans, and fibronectins7. The calf muscle pump is the
most important pump in providing venous return of the C2 Varicose veins
lower extremity, but the quadriceps and hamstring mus- C2r Recurrent varicose veins
cle pumps in the thigh are of importance in pumping
C3 Edema
blood to the heart8.
C4 Changes in skin and
Recently in a study by Rusinovich, the C6 CEAP
subcutaneous tissue
classification (Table 1) compared to C2 was associated secondary to CVD
with higher atrial contribution to right ventricular filling,
C4a Pigmentation or eczema
higher atrial contraction, and higher atrial ejection force.
Clinical class C6 CEAP was associated with impaired C4b Lipodermatosclerosis or
atrophie blanche
relaxation or diastolic dysfunction of the right heart9.
The Vein Consult program is an international, observa- C4c Corona phlebectatica

tional, prospective survey to collect global epidemiolog- C5 Healed

ical data. It reports on CVI; it estimates the global C6 Active venous ulcer
prevalence of CVI at 83.6% (C0-C6) with a global prev-
C6r Recurrent active venous ulcer
alence of C1 to C6 at 63.9%10. In a meta-analysis, it
was observed that 4677 (35.0%) of 13,361 women with Summary of etiologic (E) Summary of
parity > 1 developed varicose veins. In the control group classification pathophysiologic (P)

with 3746 women with no history of pregnancy, only 782 E class Description P class Description
(20.9%) cases of varicose veins were reported. Proges- Ep Primary Pr Reflux
terone inhibits smooth muscle contraction, while estro-
Es Secondary Po Obstruction
gen causes vasodilatation. Both mechanisms may result
in v­enous insufficiency caused by increased capacity Esi Secondary – intravenous Pr, Reflux and
o obstruction
and dilatation of the venous system, together with ve-
nous outflow obstruction by the pregnant uterus and Ese Secondary – extravenous Pn No pathophysiology
identified
increased weight gain during pregnancy. More research
is needed to explain the association between pregnan- Ec Congenital
cy and venous insufficiency. Pregnancy increases the En No cause identified
risk of developing varicose veins (odds ratio, 1.82; 95%
Summary of anatomic (A) classification
confidence intervals [CI], 1.43-2.33) 1.82-fold11. Venous
outflow obstruction affecting the iliocaval segment has A Class Description
been identified in 10%–30% and is therefore of para- As Superficial
mount importance in deep system analysis of CVI12. A
Old New* Description
prevalence of both deep (1.7%) and superficial (2.2%)
vein thrombosis of the venous systems was reported in 1. Tel Telangiectasia

patients with CVI undergoing ultrasound scans13. 1. Ret Reticular veins

2. GSVa Great saphenous vein above knee

Health costs involved in the care of 3. GSVb Great saphenous vein below knee
patients with venous disease
4. SSV Small saphenous vein
In the United States, it has been estimated that the
direct medical costs of CVD range between $150 (Continue)

81
 Revista Médica del Hospital General de México. 2021;84(2)

Table 1. The 2020 update of the CEAP classification Venous disease clinical diagnosis and
system and reporting standards laboratory study
Summary of anatomic (A) classification
In a study on biomarkers regarding CVI by Mosmiller,
A Class Description it was observed that the neutrophil count and neutro-
AASV Anterior accessory saphenous v phil/lymphocyte ratio were significantly higher in the
severe-to-mild CVI group. Moreover, the neutrophil/
5. NSV Non‑saphenous vein
lymphocyte ratio can serve as an independent predictor
Ad Deep of severity of CVI when it is > 2.91 with 74% sensitivity
Old New* Description and 77% specificity15.
6. IVC Inferior vena cava
Clinical assessment is found in CVD-related signs
and symptoms. Unfortunately, they are non-specific
7. CIV Common iliac vein
and difficult to associate with venous disease. Symp-
8. IIV Internal iliac vein toms associated with CVD include leg heaviness, ach-
9. EIV External iliac vein ing and throbbing, tiredness, fatigue, itching, tingling or
burning sensation, and nocturnal cramps16. At present,
10. PELV Pelvic veins
research in patients with superficial venous insufficien-
11. CFV Common femoral vein cy is invariably limited to assessment of the presence
12. DFV Deep femoral vein and sites of reflux. Flow volume measured by plethys-
mography may be more representative as indicated in
13. FV Femoral vein
a recent publication on venous reflux quantification.
14. POPV Popliteal vein However, the anterograde saphenous volume has been
15. TIBV Crural (tibial) vein shown to be a determinant of the resulting reflux vol-
15. PRV Peroneal vein
ume. Thus, the recirculation index may be an improve-
ment in venous reflux quantification17.
15. ATV Anterior tibial vein
The anatomical and functional assessment of the
15. PTV Posterior tibial vein venous system should be performed by Doppler ultra-
16. MUSV Muscular veins sound, the ideal method, as it is reproducible and
non-invasive. A Doppler flow duration of > 500 ms with
16. GAV Gastrocnemius vein
a diameter of > 3.5 mm was considered as pathological
16. SOV Soleal vein perforators. Color Doppler shows a sensitivity of 80%
Ap Perforator with an accuracy of 10% and the desired CI of 95%3.
Venous reflux has traditionally been managed first.
Old New* Description
However, advances in diagnostic and imaging tech-
17. TPV Thigh perforator vein niques, mainly intra-vascular ultrasound, have allowed
18. CPV Calf perforator vein us to understand better the obstructive physiology of
An No venous anatomic location identified
venous disease. In fact, venous outflow obstructions
affecting the iliocaval segment have been identified in
CVD: chronic venous disease
*New specific anatomic location (s) to be reported under each 10-30% of patients with severe venous insufficiency18.
P (pathophysiologic) class to identify anatomic location (s) corresponding to
P class.
By means of diagnostic equipment, v
enous disease analysis is more specific to differenti-
ate the affected segments to be treated.

million and $1 billion annually. In the United Kingdom,

Venous healthcare and medical treatment
2% of the national health budget per year (USD 1 bil-
of venous disease
lion) is spent on leg ulcer management. The cost of
caring for patients with CVI is estimated at EUR 600- The Society for Vascular Surgery (SVS) and the
900 million in Western Europe, representing 2% of American Venous Forum have developed clinical prac-
health-care expenditure. The estimated average direct tice guidelines for the care of patients with varicose
cost for treating each ulcer is EUR 9000, representing veins of the lower limbs. They follow compression ther-
90% of the total expenditure for CVI patients14. apy for patients with symptomatic varicose veins
82
 M.A. Sierra-Juárez, et al.: Chronic venous disease

(GRADE 2C) but recommend against compression increasing the risk of adverse effects. It is also likely to
therapy as primary treatment in patients who are can- exert a systemic effect on the course of CVD by inter-
didates for saphenous vein ablation (GRADE 1B). We fering with inflammatory chemokines26.
recommend compression therapy as primary treatment There are undoubtedly multiple pharmacological op-
to aid healing of venous ulceration (GRADE 1B). To tions, and every day new properties are discovered that
decrease the recurrence of venous ulceration, we rec- improve the consequences caused by venous hyper-
ommend ablation of incompetent superficial veins in tension in patients with CVD.
addition to compression therapy (GRADE 1A)19. In one
study, we observed the change in ankle joint range of
Surgical treatment of CVD
motion and muscle strength values measured with an
isokinetic dynamometer, pain scores, quality of life Surgical treatment of varicose veins has two objec-
scale, and venous return time in patients with CVI. In tives. On the one hand, it is aimed at correcting the
conclusion, it has been determined that increased mus- problem that caused the varicose veins. On the other
cle strength affects the venous pump and this improve- hand, the aim is to eliminate the visible veins that have
ment ensures venous function20. Compression is not become dilated. Nowadays, there are different tech-
recommended in patients with ABI < 0.521. niques for varicose vein surgery. High ligation with vein
Venoactive drugs are deemed an important compo- stripping (open surgery) involves the closure of the
nent of the medical (conservative) treatment of CVD. femoral saphenous junction and its branches through
According to available evidence, four drugs (MPFF, several incisions. Thermal ablation is a catheter-assist-
hydroxyethylrutosides, ruscus extract, and diosmin) are ed procedure that uses radiofrequency or laser energy
able to act in reducing edema. The first three showed causing the vein to collapse. Foam sclerotherapy for
significant reduction compared to placebo whereas di- large veins makes it possible to close and seal the vein.
osmin did not. MPFF was significantly superior to hy- Endoscopic surgery by means of camera-guided tro-
droxyethylrutosides and ruscus extract5,22. Several cars for perforator vein clamping and finally non-ther-
landmark studies have demonstrated the cascade of mal and non-tumescent methods (mechanochemical
interactions that correlate with increased venous pres- ablation and cyanoacrylate glue) (Fig. 1).
sure and capillary perfusion: white blood cell adhesion In response to less invasive treatment with endove-
and migration, endothelial leukocyte activation, capil- nous treatment, radiofrequency ablation (RFA) and en-
lary permeability, increased vascular proliferation and dovenous laser ablation (EVLA)27 have been developed.
altered lymph flow, leukocyte trapping, and skin pathol- Endovenous thermal ablation (EVTA) in a meta-analy-
ogy. Elevated L-selectin during venous hypertension sis review showed that technical success rates were
was considered an indication that leukocyte binding 84.8% for EVLA, 88.7% for RFA, and 32.8% for ultra-
occurred. A systematic literature review focused on the sound-guided foam sclerotherapy (UGFS). In conclu-
use of micronized purified flavonoid fraction (MPFF) in sion, both EVLA and RFA are effective in long-term
the treatment of CVD. An overall level of evidence sup- great saphenous vein occlusion28. EVTA with EVLA or
ports the recommendation of the therapeutic use of RFA is safe and effective for the treatment of recurrent
MPFF with beneficial outcomes without serious ad- varicose veins resulting from residual insufficiency of
verse events23. MPFF significantly improved nine de- greater saphenous vein surgical treatment. RFA is su-
fined leg symptoms, including pain, heaviness, swelling, perior to 980 nm EVLA in terms of post-procedure
cramps, paraesthesia, burning sensation, and pruritus ecchymosis29. Endothermal ablation is an effective
(itching). MPFF is highly effective in improving leg treatment for CVI and most patients remain free of re-
symptoms, edema, and quality of life in patients with flux. Recanalization of an isolated venous segment af-
CVD24. ter RFA, although shown in recent literature to be
Sulodexide protects the endothelium by restoring en- affected by anatomical risks, appears to be a sporadic
dothelial glycocalyx, preventing venous endothelial cell phenomenon with respect to clinical risk factors30. La-
apoptosis and inhibiting endothelial cell release of re- ser treatments must sometimes be accompanied by
active oxygen species and pro-inflammatory chemok- other therapeutic options, although obliteration of the
ines and interleukins (IL), such as monocyte chemotactic GSV above the knee improves symptoms independent-
protein and IL-625. Sulodexide has a venoactive effect ly of persistent below-knee reflux, the latter appears to
on the main signs and symptoms of venous disease, be responsible for residual symptoms and a greater
such as pain, cramps, heaviness, and edema without need for sclerotherapy for residual varicose veins31.
83
 Revista Médica del Hospital General de México. 2021;84(2)

Figure 1. Surgical ultrasound marking and endovenous 1470 nm laser ablation with radial fiber for chronic venous
disease.

Regarding the long-term effectiveness of thermal abla- diameter of five or less. Patients undergoing ultra-
tion of GSVs by radiofrequency (RPSA) or EVLA with sound-guided sclerotherapy (UGS) have better quality
less traumatic radial tip fibers (RTF), we have conclud- of life than surgical patients do, after 4 weeks of treat-
ed that both procedures have an equally high long-term ment due to less pain. In the literature, most studies
GSV obliteration rate and the treatments are equally show reduced evidence due to selection and random-
clinically effective32. Thermal ablation treatments have ization bias. Long-term results are still lacking and need
the highest incidence of endothermic heat-induced to be controlled by randomized trials1,37. We compared
thrombosis (EHIT) after EVTA with RFA than with EVLT. the effectiveness of EVLA, RFA, and UGFS versus
However, the overall incidence of EHIT is relatively conventional surgery in the treatment of varicose veins.
low33. The incidence of thrombotic complications after UGFS effectiveness compared to conventional surgery
EVTA of varicose veins is uncertain. Similar results in the treatment of small saphenous varicose veins
were found when the RFA and EVLA groups were an- (SSV) is uncertain38.
alyzed separately34. In a 20-centre trial, early endove- A third treatment option, first described by Hauer in
nous ablation resulted in faster healing of venous ulcers the 1980s, subfascial endoscopic perforator surgery
and more ulcer-free time than delayed endovenous (SEPS), has been performed to treat incompetent per-
ablation35. forator veins in cases with advanced skin changes39.
In conclusion, EVLA/RFA should be preferred to SEPS, which is performed for perforator ligation, re-
open surgery and foam sclerotherapy in the treatment quires endoscopic installation and expertise. The most
of venous incompetence36. commonly performed operation to address perforator
As for the surgical technique of foam sclerotherapy incompetence is still open subfascial ligation or punc-
for great saphenous vein treatment, the results are in- ture phlebotomy3.
ferior to surgery to eliminate venous reflux but the ad- Finally, there are cyanoacrylate adhesive devices (CAC)
vantage in some studies is that patients returned to for saphenous vein closure or devices that inject foam into
daily activities more quickly. Vein diameter greater than the saphenous vein while rotating at high speed inside it.
6 mm had worse closure results than those with a The combination of the chemical effect of the foam with
84
 M.A. Sierra-Juárez, et al.: Chronic venous disease

the mechanical effect of the catheter rotation maximizes Conclusions

its effect and makes it faster. The 36-month follow-up of
The treatment of CVD is now more specific, thanks
the first human use of cyanoacrylate adhesive for the
to diagnostic methods, as they help us to better identify
treatment of saphenous vein incompetence was 94.7%.
diseased segments, thus allowing for targeted surgery
Intravenous polidocanol foam (Varithena; sclerosing
with the construction of a surgical map. We can assess
agent) demonstrated a 1-year occlusion rate of 73%40. A
blood flow within the vein lumen and venous reflux
study comparing early and 2-year outcomes for N-butyl
analysis, measure vascular structures and detect com-
cyanoacrylate, EVLA in the treatment of varicose veins,
plications in the deep venous system, confirm that it is
concluded that no difference in occlusion rates was ob-
indeed a primary disease and rule out secondary caus-
served in the three modalities, but superior NBC ap-
es. They are a fundamental part of surgery and allow
peared with respect to pain during the procedure, return
for post-operative vigilance. This technology has been
to work, and decreased pre-operative venous clinical se-
extended to surgical tools that are now minimally inva-
verity scores41. In a 12-month follow-up with (CAC) and
sive with early recovery and are more accessible to
radiofrequency (RFA), almost identical occlusion rates
patients with higher risk conditions. In addition, they
were demonstrated in the target veins (96.8% in the CAC
ensure greater safety measures and provide better re-
group and 95.9% in the RFA group). However, the time
sults such as less postoperative pain as well as better
to complete occlusion was shorter and recanalization was
quality of life, with early recovery of the patient to their
greater with CAC than with RFA42. By month 24, closure
daily activities.
rates for CAC and RFA were also equivalent (95.3% and
94.0%, respectively) and the recanalization-free rate re-
mained higher in the CAC group, demonstrating the con- Conflicts of interest
tinued non-inferiority of CAC to RFA43. In the WAVES
The author declares have not any conflicts of
study, 1-year results demonstrated the safety and efficacy
interest.
of CAC for the treatment of GSVs up to 20 mm in diam-
eter, small saphenous veins (SSVs) and/or accessory sa-
phenous veins, with a 98% occlusion rate in all veins44. Ethical disclosures
CAC does not produce significant thrombosis because
Protection of human and animal subjects. The
the vein walls adhere to the adhesive immediately through
authors declare that no experiments were performed
the application of external compression resulting in an
on humans or animals for this study.
inflammatory and eventual fibrotic reaction rather than a
Confidentiality of data. The authors declare that
thrombotic one45. The VenaSeal system (non-thermal,
they have followed the protocols of their work center on
non-tumescent, and non-sclerosing technologies) is a
the publication of patient data.
promising therapeutic option for anatomic success at 6
Right to privacy and informed consent. The
months, with fewer adverse effects in patients with venous
authors have obtained the written informed consent of
insufficiency compared to other interventions46. Initial
the patients or subjects mentioned in the article. The
3-months results from the VeClose trial reported non-in-
corresponding author is in possession of this
feriority of cyanoacrylate endovenous closure (CAC) to
document.
RFA with saphenous vein closure rates greater than 99%
for the CAC group and 96% for the RFA group47. Regard-
ing mechanochemical modalities, initial data showed suc- References
cessful GSV occlusion rates with the ClariVein device 1. Rabe E, Guex JJ, Puskas A, Scuderi A, Quesada FF, VCP Coordinators.
(through a mechanochemical ablation catheter) at 94% Epidemiology of chronic venous disorders in geographically diverse popu-
lations: results from the vein consult program. Int Angiol. 2012;31:105-15.
comparable to RFA (thermal ablation)15,48. 2. Rabe E, Berboth G, Pannier F. Epidemiology of chronic venous diseases.
Wien Med Wochenschr. 2016;166:260-3.
This latest mechanochemical alternative seems very 3. Sureshkumar S, Vignesh N, Venkatachalam J, Vijayakumar C, Sudhar-
promising, but time is required to appreciate all its ad- sanan S. Clinical tests combined with color doppler versus color doppler
alone in identifying incompetent perforator veins of the lower limb: a
vantages, but its benefits are supported by the non-use prospective analytical study. Cures. 2018;1:e2026.
4. Erick U, Kartal A, Ferhatoglu M. Association between hemorrhoids and
of heat, which is associated with low pain rates, a quick lower extremity chronic venous insufficiency. Cureus. 2019;11:e4502.
return to normal activities and a better quality of life. 5. Attaran R, Chaar CI. Compression therapy for venous disease. Phlebo-
logy. 2017;32:81-8.
What is certain is that every day, there is more and 6. Fukaya E, Flores A, Lindholm D, Gustafsson S, Zanetti D, Ingelsson E, et al. Cli-
more technology available to treat patients that allow nical and genetic determinants of varicose veins. Circulation. 2018;138:2869-80.
7. Attaran R. Latest innovations in the treatment of venous disease. J Clin
them a quicker return to their daily activities. Med. 2018;7:77.

85
 Revista Médica del Hospital General de México. 2021;84(2)

8. Cetin C, Serbest M, Ercan S, Yavuz T, Erdogan A. An evaluation of the 30. Bunnell AP, Zaidi S, Eidson JL 3rd, Bohannon WT, Atkins MD Jr.,
lower extremity muscle strength of patients with chronic venous insuffi- Bush RL. Factors associated with saphenous vein recanalization after
ciency. Phlebology. 2016;31:203-8. endothermal ablation. Ann Vasc Surg. 2015;29:322-7.
9. Rusinovich Y, Rusinovich V. Association between right heart diastolic 31. Theivacumar NS, Darwood RJ, Dellagrammaticas D, Mavor AI,
function and clinical presentation of chronic venous disease and primary ­Gough MJ. The clinical significance of below-knee great saphenous vein
varicose veins of lower extremities. Phlebology. 2020;35:513-9. reflux following endovenous laser ablation of above-knee great saphe-
10. Javier J, Ortiz P. Treatment of chronic venous insufficiency in Latin nous vein. Phlebology. 2009;24:17-20.
America. J Vasc Surg Venous Lymphat Disord. 2020;8:667-75. 32. Lawson J, Gauw SA, Vlijmen CV, Pronk P, Gaastra MT, Tangelder MJ,
11. Ismail L, Normahani P, Standfield N. A systematic review and meta-analy- et al. Prospective comparative cohort study evaluating incompetent great
sis of the risk for development of varicose veins in women with a history saphenous vein closure using radiofrequency powered segmental abla-
of pregnancy. J Vasc Surg Venous and Lym Dis. 2016;4:518-24. tion or 1470 nm endovenous laser ablation with radial tip fibers (varico
12. Abou Ali AN, Avgerinos E, Chaer RA. Role of venous stenting for iliofe- 2 sutydy). J Vasc Surg Venous Lymphat Disord. 2018;6:31-40.
moral and vena cava venous obstruction. Surg Clin North Am. 2018; 33. Chait J, Kibrik P, Alsheekh A, Ostrozhynskyy Y, Marks N, Rajaee S, et al.
98:361-71. Radiofrequency ablation increases the incidence of endothermal heat-in-
13. Panpikoon T, Wedsart B, Treesit T. Duplex ultrasound findings and cli- duced thrombosis. J Vasc Surg. 2020;62:263-7.
nical classification of lower extremity chronic venous insufficiency in a 34. Healy DA, Kimura S, Power D, Elhaj A, Abdeldaim Y, Cross KS, et al. A
Thai population. J Vasc Surg Venous and Lym Dis. 2018;7:349-55. systematic review and meta-analysis of thrombotic events following en-
14. Gloviczki P, Comerota A, Dalsing M, Eklof BG, Gillespie DL, G ­ loviczki ML, dovenous thermal ablation of the great saphenous vein. Eur J Endovasc
et al. The care patients with varicose veins and associated chronic ve- Surg. 2018;56:410-24.
nous diseases: clinical practice guidelines of the society for vascular 35. Gohel M, Heatley F, Liu X, Bradbury A, Bulbulia R, Cullum N, et al. A
surgery and the American venous forum. J Vasc Surg. 2011;53:2S-48S. randomized trial of early endovenous ablation in venous ulceration. N
15. Mosmiller L, Steele K, Shrader C, Petrone AB. Evaluation of inflammatory Engl J Med. 2018;378:2105-14.
cell biomarkers in chronic venous insufficiency. Phlebology. 2017;32:634-40. 36. Boersma D, Kornmann VN, van Eekeren RR, Tromp E, Ünlü C, Reij-
16. Carman T, Omari AA. Evaluation and management of chronic venous nen MM, et al. Treatment modalities for small saphenous vein insufficiency:
disease using the foundation of CEAP. Curr Cardiol Rep. 2019;21:114. systematic review and meta-analysis. J Endovasc Ther. 2016;23:199-211.
17. Lattimer C, Rudolphi PB, Recke A, Geroulakos G, Kalodiki E, Kahle BK. 37. de-Abreu GC, de Camargo Júnior O, de-Abreu MF, Braga de-Aquino JL.
Comparison of four haemodynamic tests that quantify superficial venous Ultrasound-guided foam sclerotherapy for severe chronic venous insuffi-
insufficiency. Eur J Vasc Endovasc Surg. 2019;57:570-7. ciency. Rev Col Bras. 2017;44:511-20.
18. Abou Ali AN, Avgerinos E, Chaer R. Role of venous stenting for iliofe- 38. Vikram SC, Horne M, Dodd PD. Endovenous ablation therapy (laser or ra-
moral and vena cava venous obstruction. Surg Clin North Am. diofrequency) or foam sclerotherapy versus conventional surgical repair for
2018;98:361-71. short saphenous varicose veins. Cochrane Database Syst. 2016;29:1-28.
19. Wittens C, Davies AH, Baekgaard N, Broholm R, Cavezzi A, Chastanet S, 39. Kusagawa H, Haruta N, Shinhara R. Surgical methods and clinical results
et al. editor’s choice management of chronic venous disease: clinical of subfascial endoscopic perforator surgery in Japan. Phlebology.
practice guidelines of the european society for vascular surgery (ESVS). 2018;33:678-86.
Eur J Vasc Endovasc Surg. 2015;49:678-737. 40. Almeida JI, Javier JJ, Mackay EG, Bautista C, Cher DJ, Proebstle TM.
20. Ercan S, Cetin C, Yavuz T, Demir HM, Atalay YB. Effects of isokinetic Thirty-sixth-month follow-up of first-in-human use of cyanoacrylate adhe-
calf muscle exercise program on muscle strength and venous function in sive for treatment of saphenous vein incompetence. J Vasc Surg Venous
patients with chronic venous insufficiency. Phlebology. 2018;33:261-6. Lymphat Disord. 2017;5:658-66.
21. Dahm K, Myrhaug H, Strømme H, Fure B, Brurberg KG. Effects of pre- 41. Eroglu E, Yasmin A. A radomised clinical trial comparing N-Butyl cyanoa-
ventive use of compression stockings for elderly with chronic venous crylate. Radiofrequency ablation and endovenous laser ablation for the
insufficiency and swollen legs: a systematic review and meta-analysis. treatment of superficial venous incompetence: two year follow up results.
BMC Geriatr. 2019;19:76. Eur J Vasc Endovasc Surg. 2018;56:553-60.
22. Guo L, Huang R, Zhao D, Xu G, Liu H, Yang J, et al. Long-term efficacy 42. Morrison N, Gibson K, Vasquez M, Weiss R, Cher D, Madsen M, et al.
of different procedures for treatment of varicose veins. A network me- VeClose trial12-month outcomes of cyanoacrylate closure versus radio-
ta-analysis. Medicine. 2019;98:e14495. frequency ablation for incompetent great saphenous veins. J Vasc Surg
23. Bush R, Comerota A, Meissner M, Raffetto JD, Hahn SR, Freeman K. Venous Lymphat Disord. 2017;5:321-30.
Recommendations for the medical management of chronic venous disea- 43. Gibson K, Morrison N, Kolluri R, Vasquez M, Weiss R, Cher D, et al.
se: the role of micronized purified flavanoid fraction (MPFF). Phebology. Twenty-four results from a randomized trial of cyanoacrylate closure
2017;32:3-19. versus radiofrequency ablation for the treatment of incompetent great
24. Kakos K, Nicolaides N. Efficacy of micronized purified flavonoid fraction saphenous veins. J Vasc Surg Venous Lymphat Disord 2018;6:606-13.
(Daflon®) on improving individual symptoms, signs and quality of life in 44. Gibson K, Minjarez R, Gunderson K, Ferris B. Need for adjunctive pro-
patients with chronic venous disease: a systematic review and me- cedures following cyanoacrylate closure of incompetent great, small and
ta-analysis of randomized double-blind placebo-controlled trials. Int An- accessory saphenous veins without the use of postprocedure compres-
giol. 2018;37:143-54. sion: three-month data from a postmarket evaluation of the VenaSeal
25. Flota CL, Frati MA, Velázquez HA. Chronic venous disease treated with system (The WAVES study). Phlebology. 2019;34:231-7.
sulodexide: a survey among primary care physicians in Mexico. Int An- 45. Almeida JI, Min RJ, Raabe R, McLean DJ, Madsen M. Cyanoacrylate
giol. 2017;36:558-64. adhesive for the closure of truncal veins: 60-day swine model results.
26. Bignamini A, Matuska J. Sulodexide for the symptoms and signs of Vasc Endovasc Surg. 2011;45:631-5.
chronicvenous disease: a systematic review and meta-analysis. Adv 46. Kolluri R, Chung J, Kim S, Nath N, Bhalla BB, Jain T, et al. Network
Ther. 2020;37:1013-33. meta-analysis to compare VenaSeal with other superficial venous thera-
27. Berlramman A, Bootun R, Lane T, Davies AH. Endovenous management pies for chronic venous insufficiency. J Vasc Surg Venous and Lym Dis.
of varicose veins. Angiology. 2019;70:388-96. 2020;8:472-81.
28. Balint R, Farics A, Parti K, Vizsy L, Batorfi J, Menyhei G, et al. Which 47. Morrison N, Gibson K, McEnroe S, Goldman M, King T, Weiss R, et al.
endovenous ablation method does offer a better long-term technical Randomized trial comparing cyanoacrylate embolization and radiofre-
success in the treatment of the incompetent great saphenous vein? quency ablation for incompetent great saphenous veins (VeClose). J
Review. Vascular. 2016;24:649-57. Vasc Surg 2015;61:985-94.
29. Hwang J, Park S, Soo I. Endovenous thermal ablation of recurrent vari- 48. Kheirelseid E, Crowe G, Sehgal R. Systematic review and meta-analysis
cose veins due to residual great saphenous venous insufficiency after of randomized controlled trials evaluating long term outcomes of endo-
saphenous venous surgery: a comparative study. Dermatol Surg. venous management of lower extremity varicose veins. J Vasc Surg
2018;44:1287-94. Venous Lymphat Disord. 2018;6:256-70.

86