CHRONICVENOUSINSUFFICEINCYSukritaSamphao,M.D.Supervisors:BoonprasitKritpracha,M.D.DhanakomPremprabha,M.D.DepartmentofSurgery,SongklanagarindHospital.FacultyofMedicine,PrinceofSongklaUniversity.

INTRODUCTIONChronic venous disease (CVD) refers to a wide spectrum of morphologic and/or functional abnormalities of the

venous system of long duration. It varies in presentations, initially, it is asymptomatic. The most common presentations of CVD are telangiectases, reticular veins, and varicose veins (1).

Chronicvenousinsufficiency(CVI)describesaconditionthataffectsthevenoussystemofthelowerextremities(1).Itgenerallyreferstoanadvancedformofchronicvenousdisease(2),bydefinition,isassociatedwithclinicalsymptoms,soclassC3andabove(accordingtoCEAPclassification)aredesignatedasCVI(3).

CVI isoneof themostcommonconditionsaffectinghumankind(4,5). It isassociatedwithavarietyof

symptomsandalsothecomplicationssuchasvenous legulcer.Thishassubstantialsocioeconomiceffectsandsignificantlyimpactspatients’qualityoflife(3).

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VENOUSANATOMY

§ Vein– Venousanatomyismuchmorecomplexthanarterialanatomy.– Anofficialanatomicnomenclatureofvenoussystemwasupdatein

2001.Thechangeswereshowedintable1.– Theextremityvenoussystemscomposeoftreecomponents;

superficial,deepandperforatorveins(Figure1andFigure2).1. Superficialveins

– Superficialveinsconsistofgreatsaphenousvein,smallsaphenousvein,accessorysaphenoustributaries(anteriorandposterior),thecommunicatingveins,reticularvenousplexusandsubpapillaryvenousplexus.

– Theyarelocatedinthecompartmentabovemusclefasciacalled‘superficialcompartment’.Intheleg,thereisasaphenousfascia(previouslycalledsuperficialfascia,theCollesorScarpafascia,orthesubcutaneouspseudofascia)liesabovemusclefasciacontributestosubcompartmentcalled‘saphenouscompartment’whichcontainsthemainsaphenoustrunk.Theremainingsuperficialveinsarelocatedinthesuperficialcompartmentabovesaphenouscompartment.

2. Deepveins

– Deepveinsarelocatedinthefascialmusclecompartments.

– Deepveinsoflowerextremityconsistofaxialvein,whichfollowthecourseofmajorarteries,andintramuscularveins,includingvenoussinusoidsandplexi.

– Mostofthemhavethesamenamesasarteries.3. Perforatorveins

– Theytransversesthemuscularfascia,connectingbetweenthedeepandsuperficialveins.

– Theydirectflowfromthesuperficialtodeepsystemstoreturndeoxygenatedbloodtotheheart.

– Theyarelocatedat6-cmintervalfromthebaseoftheheeltotheupperpartofthethigh.

Table 1 Changes in Nomenclature for the Superficial and Deep Veins of the Leg Based on the 2001 Conference

Old term New term

superficial

Greater/long saphenous vein Great saphenous vein

Lesser/short saphenous vein Small saphenous vein

Saphenofemoral junction (SFJ)

Confluence of the superficial inguinal veins

Giacomini’s vein Intersaphenous vein

Posterior arch/Leonardo’s vein Posterior accessory great saphenous vein

Deep

Superficial femoral vein (SFV) Femoral vein (FV)

Perforators

Cockett perforators (I, II, III) Posterior tibial perforators (lower, middle, upper)

Boyd’s perforator Paratibial perforator (proximal)

Sherman’s perforator Paratibial perforator

24 cm perforator Paratibial perforator

Hunter’s and Dodd’s Perforators of the

femoral canal

May’s or Kuster’s Ankle perforators

Figure 1. Relationship between the fascia and veins of the lower extremity. The fascia covers the muscle and separates the deep compartment from the superficial compartment. Superficial veins (a) drain the subpapillary and reticular venous plexuses and they are connected to deep veins through perforating veins (b). The saphenous fascia invests the saphenous vein. The saphenous

compartment is a subcompartment of the superficial compartment. (From Pounds Lori L., Killewich Lois A. Venous Physiology. In: Cronenwett, Jack L., Johnston K. Wayne, editors. Rutherford’s Vascular Surgery. 8th ed. Philadelphia: Elsevier; 2014)

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§ Venousvalves

– Venousvalvescanbefoundthroughoutthebody,buthighestconcentrationinlowerextremities.Theycanbefoundinbothdeepandsuperficialveinsandinallsizeofveinsdowntothelevelofvenules(6).

– Thevalvesare1-waybicuspid,functioningtopreventtheretrogradeflowofthebloodfromproximaltodistaldirection(6).

– Thefrequencyofthevalvesincreasesfromproximaltodistallegtopreventanincreasepressurewithinthedistalveinsbecauseofgravitationaleffects(1).

– Venousvalvedistribution(6)o IVC:novalvewasfoundo Iliofemoral system: a mean of 1.2 valves on the Right and 0.97

valvesonthelefto Femoralvein:1-4valves,90%ofpopulationhaveatleast2valveso Poplitealvein:2valveso Greatsaphenousvein:rangebetween2-9valves(7),2.26valveson

theleftsideand2.07valvesontherightside(8).– Venousvalvesareconsistentlylocatedinspecificsitesinthecommon

femoral,femoralandpoplitealveinsoftheleg.ValvesintheCFV,neartheinguinalligament,intheFVjustdistaltotheDFVtributaryandinthePVneartheadductorhiatuswerethemostconsistentlyreportedsites(Figure3)(9).

§ VenouswallVeinwallarecomposedof3layers.

1. Intima– Intimaisasinglecelllayerrestingonconnectivetissue.– Thevalveisalayerofintima.Venousvalvesarelinedonbothsidesofthevein.

2. Media– Themediacomposesofsmoothmuscleandconnectivetissuesuchascollagen.– Inthelargevein,ithasthickmediawhichhasagreatcapacityofmusclecontractionandinpreventingdilatation

andvaricosityformation.Incontrast,thetributariesofthegreatsaphenousveinhavelittlemediaandarepronetoformvaricosity.

3. Adventitia– Thislayercontainslooseconnectivetissue,vasavasorumandadrenergicnervefibers.

Figure 2. anatomy of deep and superficial venin of lower extremities. (adapted from Pounds LL, Killewich LA. Venous Physiology. In: Cronenwett JL, Johnston KW, editors. Rutherford’s Vascular Surgery. 8th ed. Elsevier; p. 150–62.e2.)

Figure 3. The most constant locations of valves within the femoral and popliteal veins. (From Moore HM, Gohel M, Davies AH. Number and location of venous valves within the popliteal and femoral veins – a review of the literature. J Anat. 2011 Oct;219(4):439–43.)

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VENOUSPHYSIOLOGY

§ Functions:Thevenoussystemhastwoimportantfunctions.1. Returnsthebloodfromperipheralbacktotheheart.2. Maintainsthecardiovascularhemostasisbychangingincapacities.

§ HemodynamicsNormally,insupineposition,bloodpressureatcapillarybedisabout12-18mmHgwhichishigherthanthe

pressureinrightatriumwhichisabout4-7mmHg,sothebloodfromthecapillarybedcanflowbacktotheheartalongthisgradientinnormalcondition.Inuprightposition,venousflowinthelowerextremitiesisdominatedbytheeffectsofhydrostaticpressure,whichisderivedfromtheweightofthecolumnofbloodbelowtherightatrium.Thishydrostaticpressureneededtobeovercomeandthecalfmusclepumpplaysanimportantroleingeneratinghighpressure,workingtogetherwithvenousvalvestoreturnthebloodbacktotherightatrium.

§ MusclepumpMusclepumpfacilitatesthereturnofvenousbloodtotheheart.It

takes place in the thigh, in the calf and in the conjunctionwith thevenousplexusontheplantaraspectofthefoot.Thecalfmusclepump,whichincludesthesolealandgastrocnemiusmuscles(figure4),theirintramuscular venous sinusoids, and the superficial anddeep veins,appears to be more important than the thigh pump. It generatespressureupto200mmHgduringmusclecontractionandexpels40-60%ofthevenousbloodofthecalf(100-150mL)(6).

Musclecontractionproduceshigherpressureinthedeepvenoussystemthaninthesuperficialvenoussystem.However,therefluxofthebloodfromthedeeptothesuperficialvenoussystemispreventedby theone-wayvalve in theperforatingveinswhichdirect the flowfromthesuperficialveinstothedeepveins.Whenthemusclesrelax,the intramuscularvenoussinusoidsarerefilled fromthedistaldeepveinstoproximaldeepveins,andfromthesuperficialvenoussystemtothedeepvenoussystem.

§ VenouscomplianceandCapacitanceTheveinsalsoplayanimportantroleinmaintainingcardiovascularhemostasisbystoringlargevolumesof

blood,about60-80%ofsystemicbloodvolumeatatime.Theyhaveanabilitytomaintainthepressure,eventhereisamassivechangeinbloodvolume,bychangingintheirshapeswhichisregulatedbyreflexchangeinvasomotortone,togetherwithpassivedistentionorrecoilofveins(6,10).

Venouscomplianceisthechangeinbloodvolumethatoccursforeachunitofchangeintransmuralpressureinthesegmentofvein.(transmuralpressureisthedifferencebetweenintraluminalpressureactingtoexpandavein and tissue pressure acting to collapse the vein: Transmural pressure = intraluminal pressure – tissuepressure)(6).Whentransmuralpressureisabove30mmHg,thevenouscomplianceisdecreasedwhichmeansthehigherpressureisrequiredtostretchthevenouswall(figure5).Atthearterialpressure,veinsbecomeasstiffasarteries.

Figure 4. anatomy of gastrocnemius and soleus muscle

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VENOUSPATHOPHYSIOLOGY

Dysfunctionor incompetenceof thevalves in the superficial venous systemallows retrograde flowofblood,whichiscalled“reflux”andservestoincreasehydrostaticpressures(1).Saphenousveinsvalverefluxisassociatedwithvarices.Varicesarecausedbysystemicweaknessintheveinwall.Varicosechangesmayinvolvethegreatandsmallsaphenousveins(“truncalvarices”),theirtributaries(“branchvaricosities”),orboth(11).

Thecausesofsuperficialveinvalvefailurecanbedividedinto

1. Primarycausewhichcausebypre-existingweaknessinthevesselwallorvalveleaflets.2. Secondarycausessuchasdirectinjury,superficialphlebitis,orexcessivevenousdistentionresultingfrom

hormonaleffectsorhighpressure.Pathogenesisofchronicvenousinsufficiency(CVI)iscomplexandnotyetwellunderstood(3,10).Venous

hypertensionplays an important role in developingCVI. Thismay result fromvenous valvular incompetence,venous obstruction, or a combination of these mechanisms, which is common (1,3,11). These factors areexacerbated by muscle pump dysfunction, most notably of the calf muscles. Venous hypertension activatesleukocytes (10) and other inflammatory cytokines (3,11) point to adaptive responses to injury and abnormalhealingcausingtheveinwallfibrosis.Theveinwallfibrosiscontributestovalvulardamage,whichthenworsensthehydrostaticpressure regulationandconsequentlypromotesgreatervenoushypertensionwith theuprightposition(10).

Therefluxbetweenthesuperficialanddeepsystem,eitherattheperforatorveinsorthroughthejunctions

of the deep and superficial systems, at the saphenofemoral and saphenopopliteal junctions, accounts for anincreaseinvenoushydrostaticpressuretransmittedtothesuperficialveinsandtissuesandleadingtoCVI.Thisprocessisworsenedbyvenousobstruction(10).Dysfunctionofthedeepveinvalveshasbeenshowntoincreasetherateofprogressionofvenousdiseasewithahigherrateofvenousulcerationformation(1).

Venousoutflowobstructionplaysasignificantrole in thepathogenesisofCVI(1),especially iliacvein

obstruction(11).Suchlesionsarepresentinabout60%oftheasymptomaticgeneralpopulationbutarefoundinmorethan90%ofsymptomaticpatients(11).Obstructionofiliacveincanbecausedbybothpost-thromboticandnon-thromboticobstruction.Non-thromboticobstructionsoccurintheiliacveinwhereitiscrossedbytheiliacorhypogastricartery,andtheyarethoughttobecausedbythetraumaofarterialpulsations(11).

Deepveinsobstructioncausesanincreaseinvenouspressurewithmusclecontraction,leadstosecondary

musclepumpdysfunction.Musclepumpdysfunctionoftenoccurswithsevererefluxorobstruction.Dysfunctionofthemusclepumpsmayleadtoineffectiveemptyingofvenousbloodfromthedistallowerextremityandappearstobeasignificantmechanismforthedevelopmentofcomplicationssuchasvenousulcers(1).

Figure 5. A, Cross-section of a venous lumen at various transmural pressures. At lower pressures the vein is elliptical, whereas at high pressures it is circular. B, Relationship of venous volume to transmural pressure. At low pressures, veins are compliant and change shape easily to accommodate large increases in volume. At high pressures, they become stiff and cannot accommodate large changes in volume. (From Pounds Lori L., Killewich Lois A. Venous Physiology. In: Cronenwett, Jack L., Johnston K. Wayne, editors. Rutherford’s Vascular Surgery. 8th ed. Philadelphia: Elsevier; 2014)

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EPIDEMIOLOGYANDRISKFACTORS

§ PrevalencePrevalence estimates varywidely by geographic location,with the highest reported rates inWestern

countries.Reportsofprevalenceofchronicvenousinsufficiencyvaryfrom<1%to40%infemalesandfrom<1%to17%inmales.Prevalenceestimatesforvaricoseveinsarehigher,<1%to73%infemalesand2%to56%inmales (5). Its prevalence is very low in African and Asian or Australasian aborigine populations althoughimmigrantsubjectsfromtheseregionshavethesameriskasthepopulationoftheirhostcountry(12).

§ Riskfactors

TherearemultiplerelatedriskfactorsofCVI,includingpregnancy(1),advanceage,obesity,prolongedstanding(2),femalegender(1,13),genetics,(1,2),andrarely,congenitalabsenceofvalves,priorDVTortrauma.

Kanchanabatetal.studiedtheriskfactorsofCVIinThaipopulationandfoundstatisticallysignificantriskfactorswereBMI,physicalevidenceofvaricoseveins,historyofipsilaterallegtraumaandproportionofuprightpostureduringworkinghours(2).

CLASSIFICATIONCVIisoneofthemostdifficultpathologiestoclassifyonaccountofthecomplexityofitsexpression.

Severalclassificationshavebeenproposed tobetterdefineCVIandassigndegreesofseverity(4). In1994,aninternationalgroupofexperts,meetingatMaui,workedoutanewclassificationthatwouldbeaspreciseandcompleteaspossible(4).Thisclassificationiscalled“CEAP”.TheCEAPclassificationsystemwasdevelopedinaneffort not only to incorporate use of Duplex scanning in diagnosis, but also to standardize evaluation forcomparisonofoutcomesacrossclinicalstudies(5).TheuseoftheCEAPclassificationintheevaluationofCVDhasastrongrecommendationintheCPG(1,15).Eachletterstandsforaparticulardimension(table2) (1,4).C: Clinical, divided into 7 categories (0-6)according to objective clinical signs of chronicvenous disease. The presence of symptoms ortheir absence is identified by the letters S(symptomatic)orA (asymptomatic)positionedaftertheletterC.E: Etiology, divided into Congenital (Ec),Primary (Ep), Secondary (Es) and no venouscauseidentified(En).A: Anatomy, based on class is based on thevenous systems; Superficial veins (As), Deepveins(Ad),Perforatingveins(Ap)andnovenouslocationidentified(An).P: Pathophysiology, divided into Reflux (r),Obstruction (o), Both (r,o) and no venouspathophysiologyidentified(Pn).

Table 2 CEAP CLASSIFICATION Clinical Etiology Anatomy Pathophysiology

C0 = no visible or palpable signs of venous disease Congenital

(Ec) Superficial veins (As) Reflux (r)

C1 = Telangiectasia or reticular veins

C2 = Varicose veins Primary

(Ep)

Deep veins (Ad)

Obstruction, thrombosis (o) C3 = Edema

C4 = Changes in skin and subcutaneous tissue; A: pigmentation, venous eczema, B: lipodermatosclerosis, atrophic blanches

Secondary (Es)

Perforating

veins (Ap) Both (r,o)

C5 = Skin changes with healed ulcer

No venous cause

identified (En)

No venous location

identified (An)

No venous pathophysiology

identified (Pn)

C6 = Skin changes with active ulcer

Telangiectases: <1 mm, reticular veins: 1-3 mm, varicose veins: >3 mm *measured in the upright position C4 is subdivided into A and B, B indicating higher severity of disease and having a higher risk for ulcer development.

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Mostrecently,theVenousSeverityScoring(VSS)systemwasintroducedasausefulandreliablemethodforassessmentofanindividualpatient’sresponsetotreatmentaswellastoallowimprovedoutcomeassessment(15,16).TheVSSsystemconsistsofthreecomponentsasthefollowings(5,16);

1. VCSS(venousclinicalseverityscore)whichisamodificationtoreplaceCEAPclinicalscore.2. VSDS(venoussegmentaldiseasescore)whichisacombinationoftheanatomicandpathophysio-

logiccomponentsofCEAP.3. VDS(venousdisabilityscore)amodificationoftheoriginalCEAPdisabilityscore.

Fromthestudy,Kakkosetal.foundthatVSShascorrelationwithseverityoftheCVI.VCSS,andVDShasalinearassociationwithCEAPclinical class (16).However,Passmanetal. suggested thatVCSShasmoreglobalapplicationindeterminingoverallseverityofvenousdisease,whileatthesametimehighlightingthestrengthsoftheothervenousassessmenttools(17).Therevisedvenousclinicalseverityscoreprovidesclarificationof thetermsandbetterdefinitionofthedescriptorsandhasfurtherclinicalapplicability(table3)(1).

CLINICALMANIFESTATIONS

PatientwithCVIfrequentlycomplainof‘heavyleg’aswellaseveningedema,dilatedveins,legpain,skinirritation,pruritus,tingling,musclecrampsandcutaneouschangesintheleg(1,3,15).

Telangiectases,reticularveinsandvaricoseveinsaredilatedsuperficialveins,whicharetheinitialstage

(C1-C2) of chronic venous disease (CVD) and are not associatedwith any specific clinical symptom.They areprimarilyacosmeticproblemforthepatients.

ThenextstageofCVD(C3)referstothedevelopmentofvaricoseveinwithlegedema,definedasanonset

ofCVI(3).Edemabeginsintheperimalleolarregionandascendsupthelegwithdependentfluidaccumulation.Legdiscomfortisdescribedasheavylegorachingafterprolongedstandingandisrelievedbylegelevation.Itisthoughttobeproducedbyincreasedintracompartmentalandsubcutaneousvolumeandpressure.Chronicedemamayleadtostasisdermatitis,characterizedbyerythematous,scaly,andsometimespruriticlesionsonthelowerlegs(Figure7).Itisoccasionallymistakenforerysipelas/cellulitis.

Obstructionofthedeepvenoussystemmayleadtovenousclaudication(orintenselegdiscomfortwithambulation)(1).

ContinueprogressioninCVIresultsincutaneouschanges(C4)includeskinhyperpigmentationbecause

ofhemosiderindepositionandeczematousdermatitis.Lipodermatosclerosis,afibroticprocessinthedermisand

Table 3 (Copy from Eberhardt RT, Raffetto JD. Chronic Venous Insufficiency. Circulation. 2014 Jul 22;130(4):333–46.)

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subcutaneousfat,andatrophicblanchesareanotherformofcutaneouschange.Theyareassociatedwithhigherseverityofdiseaseandhavehigherriskofcellulitis,legulceration,anddelayedwoundhealing.

Avenousulcer(C5,C6)isthemostseveremanifestationofCVI(10),themedialmalleolusmost

commonlyaffected;completehealingoflegulcersfrequentlyrequiresprolongedwoundtreatment(3).

DIAGNOSISOFCVI ThediagnosisofCVIisbasedonhistory,clinicalpresentation,andnoninvasivediagnostictest.Invasivetestingmayalsobeusedtoestablishthediagnosisbut is typicallyreservedforassessingdiseaseseverityor ifsurgicalinterventionisbeingcontemplated(1,3).

§ History

Asdescribeabove,thecommonpresentingsymptomsofCVIarevary.Thepatientsmaycomplainofheavyleg, evening leg edema, dilated veins, leg pain, skin irritation, pruritus, tingling,muscle cramps or cutaneouschangesintheleg(1,3,14).

Specificfeaturesofthepainshouldbenoted,including,degreeofpainthatinterfereswiththepatient’soccupationorlifestyleandamountoftimethatthepatientcanstandbeforetheonsetofpainorswelling.Ageofonset also shouldbeasked, as anearlyonsetmay suggest a congenital abnormality suchasKlippel-Trenunaysyndrome.Familyhistoryofvaricoseveinsispresentinonethirdofthepatient.Finally,pasttreatmentsofvaricoseveinorvenousdiseaseshouldberecorded(15).

§ Physicalexamination

Physical examination of the patient should include a general examination in addition to a detailedexaminationofthelowerextremities.Thepatientshouldbeexaminedinthestandingpositionwithundressedfromthegroinstothetoestopermitcompleteexaminationofentireextremity.

Visualinspectionandpalpationmayrevealevidenceofvenousdisorders.Thelocationanddistributionofallmajorsubcutaneousvaricositiesshouldberecorded.Theskinisexaminedforvenousabnormalitiessuchastelangiectases, reticular veins or varicose veins. Skin changes, such as hyperpigmentation, stasis dermatitis,atrophie blanche (or white scarring with a paucity of capillaries), or lipodermatosclerosis, also should beconcerned.

Theedemaand its severityalso shouldbeassessed.Theedemaseen inCVI isdependentandusuallypittingandoftenrelativesparingoftheforefoot,thismighthelptodistinguishtheothercauseofedema.Prominentswellingisnotacommonfeatureofsuperficialvenousdisease,althoughepisodicankleedemaiscommon.Edemaextendingbeyondtheanklesuggestsdeepvenousthrombosis(11).Sincetheearlysignsofvenouscongestionarecalffullnessorincreasedlimbgirth,calfmuscleconsistencyshouldbeassessed,andmeasurementofthelimbgirthshouldbeperformed(1).However,it’snotinformativeunlessit’sperformedatthesametimeoftheday(11).

Thepresenceofactiveorhealedulcers,typicallyinadistributionnearthemedialaspectoftheanklewithGSV refluxor lateral aspectsof theanklewith small saphenousvein reflux,maybe seenwithmoreadvanceddisease.

A B

Figure 7. A: Hyperpigmentation and severe lipodermatosclerosis with leg edema. Notice healed ulcers in the gaiter region of the medial leg. B: Venous leg ulcer on the right ankle with lipodermatosclerosis and asteatotic eczema of the surrounding skin (A: from Eberhardt RT, Raffetto JD. Chronic Venous Insufficiency. Circulation. 2014 Jul 22;130(4):333–46.,

B: from Santler B, Goerge T. Chronic venous insufficiency – a review of pathophysiology, diagnosis, and treatment. JDDG J Dtsch Dermatol Ges. 2017 May 1;15(5):538–56.)

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Carefulpalpitationofthethighandlegmayrevealsaphenoustrunkvaricositiesthatmaybemissedbyvisualinspectionandpalpationofthelegshouldalsobeperformedtodetecttemperaturedifferencesbetweenthelegs(15).

§ Brodie-Trendelenburgtest(1,18)

Brodie-Trendelenburgtestisusedtodetermineifthereisanyexistingretrogradeflowofbloodthroughthesaphenofemoral junction(SFJ)orperforatorveins,however, itdoesnotindicatetheleveloftheperforatorveinsincompetent.Therefore,thismaydeterminewhetherornothighligationofthesaphenousanditsbranchesisindicated,and,secondly,whetherornotanadditionalligationatalowerlevelisnecessary.

Procedures:

1. Thepatientispositionedtoliedownwithlegelevationtoemptybloodfromthevein.2. Applya tourniquetormanual compression toocclude the superficial vein justbelowsaphenofemoral

junction.3. Thevaricoseveinsareobservedwithresumptionofanuprightposturefor30seconds.4. Removetourniquetorthemanualcompressionandobservetherefillingofvaricoseveinsagain.

Interpretations:

1. 1stphase,whichthepressureisstillapplied,indicatesthestatusofperforatorveinsbelowtheoccludedpoint.

2. 2ndphase, thevaricoseveinsareobservedafter tourniquetormanualpressure removal, indicates thestatusofsaphenofemoraljunction.

Afterstandingwithoutremovingtourniquet,ifthebloodisfilledwithin30secondsfrombelow,suggests

the incompetent of perforator veins, but if the vein is gradually filled over 30 seconds suggests competent ofperforatorveins.

After removing the tourniquet or manual pressure, if the vein is refilled rapidly, incompetent ofsaphenofemoraljunctionvalveissuspected.Intheotherhand,afterreleasingthepressure,ifthesaphenousveinsareslowlyrefilled,incompetentofsaphenofemoralvalveisunlikely.

Thetestisnegativewhenthereisrefillingofvaricoseveinsfrombelowwithintheperiodof30secondswithtourniquetison.Andafterremovingthetourniquet,thereisnoincreasedrateoffillingisobserved. ThismeansthereisacompetentofperforatorveinsbelowSFJ,butnoSFJvalveincompetent(Figure8A).

Thetestispositivewhenthereisnovaricoseveinfillingby30secondsafterthepatientisstandingandtourniquetisinplace,butrapidfillingofthevaricoseveinsfromaboveisobservedafterthetourniquetisremoved.Here,thevalveofSFJisincompetent,whilethevalvesofperforatorveinsareintact(Figure8B).

The test isdoublypositivewhen the tourniquet on and there is a filling of varicose veinswithin 30seconds,andalsoarapidfillingofvaricoseveinstakesplaceafterremovingthetourniquet.ThismeansthereareincompetentofperforatorveinsandSFJvalves(Figure8C).

Thetestisnil,whentourniquetinplaceandagainwiththetourniquetremoved,thereisonlyslowfillingoftheveinsfrombelow.Thiswouldindicatecompetencyofthevalvesofboththesaphenousandperforatorveins(Figure8D).

TheBrodie-Trendelenburgtestishighlysensitivefortheidentificationofsuperficialandperforatorreflux(91%),althoughpoorlyspecific(15%)(19).

Figure 8: Brodie-Trendelenburgtest

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§ Differentialdiagnosis

ThecommonpresentingsymptomsofCVIarelimbswellingandlimbdiscomfort,so,initially,acutevenous

problem such as acute deep vein thrombosis must be exclude. Then, systemic causes of edema need to beconsidered,suchasheartfailure,nephrosis,liverdisease,orendocrinedisorders,andalsotheadverseeffectsofmedication,suchcalciumchannelblockers,nonsteroidalanti-inflammatoryagents,ororalhypoglycemicagents.

Criticaldisorderstoconsiderarelymphedema,lipedema,andthecombineddisorderoflipolymphedema.Lymphedemacausesbytheobstructionoflymphaticdrainagewhichleadstofluidaccumulationthatextendsintothefootandtoes, incontrastwithCVI,whichrelativelysparesthefoot.Theedemamaybepittingearly inthecourseofthediseasebutasthediseaseprogressesbecomesnonpitting.Incontrast,lipedemaischaracterizedbyfattytissueaccumulationratherthanfluid,thus,itisnotpitting.Itusuallysparesinvolvementofthefeet,oftenwithacuffoftissueattheankle.

Finally, other regional considerations should be made, such as ruptured popliteal cyst, soft tissuehematomaormass,exertionalcompartmentsyndrome,orgastrocnemiustear.Theuseofexaminationfindingsandnoninvasivetestingshouldallowfortheproperdiagnosistobeestablished.

INVESTIGATION

Noninvasivetesting

§ VenousdupleximagingVenousdupleximagingisthemostcommontechniqueusedtoconfirmthediagnosisofCVI.Itsadvantages

includethatitisnoninvasive,canberepeatedasoftenasnecessary,givesreproducibleresult,andallowsanatomic,physiologicandhemodynamicevaluationofvenoussystem(15).ThestudyisperformedwithB-modeimagingandspectralDoppleranalysisassessmentofflowdirectionwithprovocativemaneuvers(1,14).

Duplexexaminationoftheveinsmustbesystematicandorderly.Thedeepvenoussystemisevaluatedfirst.Thepresenceofvenousobstructionbecauseof chronicdeepvein thrombosisorvenousstenosismaybedirectlyvisualizedorinferredfromalterationinspontaneousflowcharacteristics.

Venous valvular competence is evaluated with Valsava maneuver for upper thigh segment and limbcompressionforthelowerlimbsegment(15).Thepreferredmethodtoassessforrefluxinvolvestheuseofacuffinflation-deflationtechniquewithrapidcuffdeflationinthestandingposition(1).Thisprovidesinformationabouttheanatomicdistributionofrefluxdiseaseinvolvingthedeepandsuperficialvenoussystems,aswellasperforatorveins.

Thepresenceofrefluxisdeterminedbytheretrogradeflowtowardthefeet(Figure9).Thedurationofrefluxisknownastherefluxtime.Arefluxtimeof>0.5secondsforsuperficialveinsand1.0secondfordeepveinsistypicallyusedtodiagnosethepresenceofreflux.Alongerdurationofrefluximpliesmoreseverediseasebutdoesnotcorrelatewellwithclinicalmanifestations.

Venousdupleximagingprovidesinformationaboutlocalvalvefunctiontoconstructananatomicmapofdiseaseintermsofthesystemsandlevelsofinvolvement.Thisisoftensufficientdatatohelpguidetherapy,butifthecontributionoftherefluxtoglobalhemodynamicsisrequired,thenfurthertesting,suchasplethysmographictechniques,shouldbeconsidered.

Figure 9: Venous duplex ultrasound demonstrating reflux in the great saphenous vein. Blood flow direction is determined after increasing central venous return with rapid cuff inflation then deflation. Flow in the direction of the feet is because of incompetent valves, as shown in red in the color image and above the baseline in the pulse Doppler. The Doppler spectrum quantifies the duration of reflux, and in the example above it is ≈4 seconds. (copy from Eberhardt RT, Raffetto JD. Chronic Venous Insufficiency. Circulation. 2014 Jul 22;130(4):333–46.)

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§ AirPlethysmography

Plethysmograph isan instrument fordeterminingandregisteringvariations in thesizeofanorganorlimbresultingfromchangesintheamountofbloodpresentorpassingthroughit.

Air plethysmography (APG) is anoninvasive test used to assesspathophysiologicmechanismsofCVI,includingreflux,obstruction,andmusclepumpdysfunction(1,5).

Venousocclusionplethysmographyinvolvestheinterruptionofvenousdrainagebyplacingacuffaroundtheupperleg.Lower-legcircumferenceisthenassessedusingastraingauge,thusprovidinginformationaboutvenous capacity and venous drainage. In air plethysmography, a cuffwith air chambers is placed around thepatient’slowerleg,whichenablesthemeasurementofvolumechanges.

§ ComputedTomographicorMagneticResonanceVenography

These techniques are useful to evaluatemore proximal veins and their surrounding structure to

assessforintrinsicobstructionorextrinsiccompression.Propertechniqueallowingforbettervisualizationto assess obstructive disease, varicose veins, perforating veins, and other venous malformations. Bothcomputedtomographyandmagneticresonancevenographymaybeusedtodefinecomplexvenousanatomy,suchasileofemoralvenousobstructionbeforeintervention(1).

Invasivetesting§ ContrastVenography

Venography allows directly visualized of the venous system by either an ascending or descendingapproach(1).Ascendingvenographyprovidesanobjectiveanatomicandhemodynamicevaluationofthevenoussystemthatmaybeusefulwithsurgicalinterventions.Itinvolvesinjectionofcontrastinthedorsumofthefootwithvisualizationofcontrast-travelingcephaladinthedeepvenoussystemofthelimb(1).Descendingvenographyisusedtoidentifyvalvularincompetence,involvesproximalinjectionofcontrastinasemiverticalpostureonatilttablewiththe use of theValsalvamaneuver.However, venography is expensive, invasive, uncomfortable for patients, andassociatedwithasmallincidenceofphlebitisandothercomplicationsrelatedtocontrastadministration.

§ IntravascularUltrasound

Intravascularultrasoundisusedinthemanagementofvenousdiseaseandisincreasinglybeingusedtohelpguideinterventions.Thetechniqueusesacatheter-basedultrasoundprobetovisualizeperiluminalvascularanatomy to assess for obstructive or stenotic disease of the venous system. It is superior to venography inestimatingthemorphologyandseverityofcentralvenousstenosisandinvisualizingthedetailsofintraluminalanatomy.

§ AmbulatoryVenousPressure

AmbulatoryvenouspressuremonitoringisthegoldstandardinassessingthehemodynamicsofCVI.Thistechniqueprovidesinformationonglobalcompetenceofthevenoussystem.Itisperformedbyintroducingintoadorsal foot vein a 21-gauge needle,which is then connected to a pressure transducer. Themean ambulatoryvenouspressureandrefilltimearethemostusefulparameters.AmbulatoryvenouspressurehasbeenshowntobevaluableinassessingtheseverityandclinicaloutcomesinCVI.Thistechniqueisseldomusedinclinicalpracticebecauseofitsinvasivenature,potentiallimitations,andalternativediagnosticmodalities(1,14).

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TREATMENTOFCVI

ConservativeManagement InitialtreatmentofCVIinvolvesconservativetreatmenttoreducesymptomsandpreventdevelopmentofsecondarycomplicationsandprogressionofdisease.Iftheconservativeisfailorprovideunsatisfactoryresponse,futuretreatmentshouldbeconsideredonthebasisofanatomicandpathophysiologicfeature. AreferraltovascularspecialistshouldbemadeforpatientswithCEAPclassesC4toC6(orprobablyclassC3),whichusuallyneedaspecificandinvasivetreatment.ThesepatientswithuncorrectedadvanceCVIareatriskforulceration,recurrentulceration,andnonhealingulcerswithprogressiveinfection.

§ CompressiveLegGarments

Compressiontherapyprovidesgradedexternalcompressiontothelegandopposethehydrostaticforceof venous hypertension. It also helps to improve the calf muscle pump function and reduces reflux in veinsegments. There are several types of compression garments available such as graded elastic compressivestockings,pastegauzeboots, layerbandage,adjustablelayeredcompressiongarment.Thestudiesshowedthatcompressivegarmentimprovewoundhealingandpreventrecurrentofulcer.

Compressiontherapyisconsideredfirst-linetherapyforthosewith symptomatic varicose veins or greater but not a candidate forgreatsaphenousablation.Compressiontherapyisalsorecommendedasanadjuncttosuperficialvenousablationtoreducetheriskofulcerrecurrence.

The pressures used for CVI are range between 20 and 50mmHg,basedontheCEAPclinicalseverity(Table4).

Themostcommonlengthiskneelength.Thestockingsneededtobechangedevery6-9monthsifworndailytomaintaintheadequatetension.

§ WoundandSkinCare

InadvanceCVI,thepatient’sskinmayloseitsintegrity.Theskinisneededtokeepmoisttomaintainskinhealthandpreventinfection.Ifthepatientsdevelopstasisdermatitis,topicalsteroidmaybeapplied.Incaseofinfection,aggressivewoundcareisrequiredtominimizeinfectiouscomplication.

§ PharmacologicTherapy

FourgroupsofdrugshavebeenevaluatedinthetreatmentofCVI,includingcoumarins(α-benzopyrenes),flavonoids (γ-benzopyrenes), saponosides (horse chestnut extracts), and other plant extracts such as horsechestnutseedextract,whichiseffectiveascompressionstockingsintheshorttermatreducinglegedemaandpainfromCVI,butthelong-termsafetyandefficacyhavenotbeenestablished.Thesedrugshavevenoactiveproperties.

Theprinciple forusing thesevenoactiveagents is to improvevenous toneandcapillarypermeability,howevermechanismofactionforthesedrugsisnotyetfullyunderstood.Thesevenoactiveagentsprovidereliefofpainandswellingoracceleratevenousulcerhealingwhenusedinconjunctionwithcompression.

Theuseofotheragents,suchasaspirinandplatelet-derivedgrowthfactor,hasbeenreportedtopromotehealingorpreventtherecurrenceofvenousulceration,butnolargerandomizedstudieshavebeenconducted.

§ ExerciseTherapy

AbnormalitiesincalfmusclepumpfunctionsplayasignificantroleinthepathophysiologyofCVI.After6months,patientsreceivingacalfmuscleexerciseregimennormalizedcalfmusclepumpfunctionparametersbuthadnochange in theamountofrefluxorseverityscores.Calfmuscleexercisemaybeneficialassupplementaltherapytomedicalandsurgicaltreatmentinadvanceddisease.

Table 4 Level of compression based on clinical menifestation

Clinical manifestation Tension (mmHg) Varicose veins with or without edema (C2-C3)

20-30

Advanced venous skin changes, or ulcers (C4-C6)

30-40

Recurrent ulcers 40-50

Copy from Eberhardt RT, Raffetto JD. Chronic Venous Insufficiency. Circulation. 2014 Jul 22;130(4):333–46.,

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InterventionalManagement§ Sclerotherapy

Venous sclerotherapy is a treatment modality for obliterating telangiectases, varicose veins, and venoussegmentswithreflux.

Indicationsforvenoussclerotherapy

o Facialtelangiectasiaso Vascularmalformationso Congenitalmalformationo Unsightlyveinsofthehandsandfeeto Failedsegmentsofendothermalablationo Recurrentvaricositieso Telangiectasiaso Reticularveinso varicoseveins<8mmdiametero perforatorveinincompetenceof4-to7-mmdiameter

There are a number of sclerosing agents, including hypertonic solution of sodium chloride (23.4%);detergents such as sodium tetradecyl sulfate, polidocanol, and sodiummorrhuate; andothers such as sodiumiodideandchromatedglycerin.Sclerosingagentssuchaspolidocanolhavebeenshowntobesuperiortonormalsalineinbothobliteratingincompetentvaricoseveinsandimprovingvenoushemodynamicsat12weeks.Foamsclerotherapyinvolvestheinjectionofasclerosantfoamintothesaphenousveins.

Acommoncomplicationofsclerotherapyishyperpigmentationofthesurroundingskinfromhemosiderindegradation.

§ EndovenousAblativeTherapy

Ablative therapyuses the thermal injury in the formof radiofrequencyor laser toablate incompetentveins,frequentlyusedforGSVrefluxasanalternativetostripping.Theheatgeneratedcausesalocalthermalinjurytotheveinwallleadingtothrombosisandfibrosis.90%ofpatientstreatedwithradiofrequencyablationarefreefromsaphenousveinrefluxat24-monthfollowup,and95%ofpatientsreportsatisfactionandimprovementofsymptoms(regardlessofthetechnicalsuccess)(20).

§ EndovenousDeepSystemTherapy

Abnormalitiesinvenousoutflow,involvingiliacveinsstenosisandobstruction,contributetosymptomsin10%to30%ofpatientswithsevereCVI.Previously,theyweretreatedwithsurgicalprocedures.However,theuseofstentsisbecomingincreasinglycommonandprovidessatisfiedoutcomeswithcompletepainreliefin≈50%,completeresolutionofedemain≈30%,andcompletehealingofulcersin≈50%(1).thecumulativeratesofstentpatency at 5 years were 86% in cases of post-thrombotic disease and 100% in nonthrombotic cases (11).Complications included deep venous thrombosis (occurring in 1.5% of patients within 30 days after theprocedure)andtransientpostoperativebackpain(in25%ofthepatients)(11).

Figure 10: Recanalization of an Occluded Iliac Vein with Stent Placement. Picture on the left shows collateral veins around the occluded iliac vein. Picture on the right showed the collateral vessels disappear with stent placement.

(copy from Raju S, Neglen P. Chronic Venous Insufficiency and Varicose Veins. N Engl J Med. 2009 May 28;360:2319–27.)

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§ Mechanochemicalendovenousablation(MOCA)

ThenewlydevelopedMechanochemicalEndovenousAblation(MOCA)deviceusesatechniquethatcombinesmechanicalendothelialdamageusingarotatingwirewiththeinfusionofaliquidsclerosant.Itisanontheramalablation,soheatingoftheveinandtumescentanesthesiaarenotrequired;onlylocalanesthesiaisutilizedattheinsertionsite.

MechanochemicalendovenousablationusingtheClariVeinincombinationwithliquidsclerosantisassociatedwiththeanatomicalsuccessrateof92%(95%CI88–95%)91%(95%CI86–94%)andAfter6and12months.Thelong-termanatomicalsuccessratesat2and3yearswere91%(95%CI85–95%)and87%(95%CI75–94%),respectively.Majorcomplicationsandespeciallynerveinjurywereveryrare(21).

§ EndovenousCyanoacrylateGlue

Cyanoacrylateglue,aliquidadhesive,deliveredendovenouslyisanewnon-ablativeprocedureusedintreatmentofvenousincompetence.Itdoesnotrequiretumescenceanesthesia.Uponintravascularinjection,Cyanoacrylategluerapidlysolidifiesviaapolymerizationreactionandproducesaninflammatoryveinwallreaction.Granulomatousforeignbodyreactionisobservedat30daysaftertreatmentandfibroblastscanbeseeninvadingthecontentsofthetunicaintimaandtunicamediaat60days(22).

In2016,Chanetal.conductedthestudyfortheevaluationofefficacyofendovenouscyanoacrylate(sapheonvenasealclosuresystem)forthetreatmentofprimarygreatsaphenousreflux.ThestudyshowedthattheGSVclosurerateswere98.2%,94.3%,89.7%,and78.5%atpost-op1week,1month,6months,and1year,respectively.AndthemeanofGSVdiametergreaterthan8mmwasasignificantpredictorforrecanalization(hazardratio6.92,95%CI1.34–35.67,p.0.021)(23).

SurgicalManagement

Surgical management of CVI may be considered to complement the compressive stocking in those

refractorytomedicalandendovenoustherapy.Thechoiceofsurgeryisconsideredbasedonthevenousterritoriesandunderlyingpathophysiologicmechanisms.

§ SurgeryforTruncalVeinorVenousTributaries

Interruptionandremovaloftruncalveinspreventstheconsequencesofrefluxinthesuperficialvenoussystem,whereassurgeryonveintributariesisdirectedtowardremovaloftheresultingvaricosedveins.ExcisionoftheGSVwithhighligationofthesaphenofemoraljunction(SFJ)canbeappliedtoalloftheCEAPclinicalclasses(C2–C6)withGSVreflux.RecurrenceratesaremarkedlyreducedwhentheGSVistrippedcompareswithhighligationalone.Ligationandstrippinghavebeenshowntoimprovevenoushemodynamics,toprovidesymptomaticrelief,andpossiblytoassistinulcerhealing,howeverendovenousablationisprefertovenousstrippinginulcerrecurrentprevention.

Rasmussenetal.studiedtheshorttermoutcomeofendovenouslaserablationofthegreatsaphenousveincomparedwith high ligation and stripping in patientswith varicose veins and found no statistical significantdifferent of improvement in quality-of-life scores and VCSS score at 3months,mean time to resume normalphysicalactivityandwork,butinfectionandPostoperativepainandbruisingwashigherinthehighligationandstrippinggroup,butnodifferenceintheuseofanalgesicswasrecorded(24).Rasmussenetal.alsostudiedtheclinicalandduplexoutcomeafter5-yearfollow-upofvenousstrippingcomparedwithendovenousablationandfound no statistical significant different between in open reflux (10.1 vs 17.9%, P =0.2145) and in clinicalrecurrence(37.7%vs38.6%,P=0.7209)(25).

§ PerforatorVeinSurgery

Incompetent perforator veins may contribute to the pathophysiology of CVI and its advancedmanifestations, primarily ulceration. The interruption of perforator veins which contributed to focal venoushypertensionwithligationisperformed.Thecurrentpreferredtechniqueforcorrectionofperforatorveinsrefluxisendoscopicresection(subfascialendoscopicperforatorsurgery,orSEPS).Thechoiceoftechniquestodisrupt

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pathologicperforatorveinsremainsanareaofinvestigationbuthasbeenfavoringlessinvasivemethods,suchasendovenousablationandfoamsclerotherapy(1).

§ ValveReconstruction

Deep venous valves with reflux due to either a nonthrombotic or post-thrombotic cause can bereconstructedbymeansofopensurgery,butthisproceduremaynotbeavailableoutsideofspecializedcenters(11).VenousvalvereconstructionofthedeepveinvalveshasbeenperformedselectivelyinadvancedCVIwithrecurrentulcerationanddisablingsymptoms(1).

Complicationsfromvalvuloplastyincludebleeding,deepvenousthrombosis,pulmonaryembolism,ulcerrecurrence,andwoundinfections(1).

CONCLUSION

Chronicvenousdiseaseisoneofthemostcommondiseaseaffectinghumankind.Itaffectspatient’squalityoflifeandalsohealthcaresystem.Normalfunctionofvenousvalvesandmusclepumparerequiredfornormalvenousfunction.Disturbanceofthesefunctionsleadingtovenoushypertensionandeventuallychronicvenousinsufficiency(CVI).Evaluationofthesepatientsbeginswithacarefulhistoryandphysicalexamination.Theduplexultrasonographyusedtoconfirmdiagnosis.Anadditionaltestmaybeaddedinsomepatients.Patient’sdiseasecanbeclassifiedaccordingtoCEAPsystemandvenousseverityscoringsystemwhichservesasabasisforpropertreatmentandintervention.Sclerotherapyandphlebectomyareprimarilyusedforisolatedtributaryorperforatorincompetence,recurrentvaricoseveins,aswellasincombinationwithotherprocedures.Inthecaseoftrunkincompetence,classicsurgicalmethodssuchassaphenofemoralligationandstrippingorthenewerendovenousmethodsshouldbeemployed.Combinationofsurgicalorendovenousprocedureswithadequatecompressiontherapyisatherapeuticmainstay.

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