Vascular Evaluation in Patients with Lower Extremity Ulceration

Written by
Michael Cumming, MD, MBA


Over 30% lower extremity ulcers and non-healing wounds arenot fully resolved at 6 months even though patients have received “best careavailable” and spending 10’s of billions of dollars in direct care costs.1–4 Nearly 15% of Medicare beneficiarieshave lower extremity ulcers with a conservative estimated annual cost of $32billion.5 Compounding this is therising prevalence (1-2%) of leg ulcers as people are living longer.6 Despite an abundance ofstudies and guidelines, there is significant variation in recommendations,which are often contradictory, causing confusion and raising barriers topatient’s receiving appropriate care.

Deficiencies in the management of leg ulcers are common andare due to incorrect diagnosis and treatment.7–9 Inappropriate treatment maycause deterioration of the wound, delay in wound healing and harm to the patient.Barriers to healing include lack of consensus, interprofessional rivalry, nostandardization,  care deliverystructure, limited resources and educational gaps.10,11 The delivery of health careservices is in a state of constant flux which is detrimental tointerdisciplinary teamwork, professional relationships, and a collaborativeenvironment.

This brief addresses the often misunderstood and underappreciatedrole of arterial and venous disease in patients with lower extremityulceration.

Knowledge Gaps

Nonhealing wounds are not a disease, but a symptom of anunderlying condition.12 Successful treatment dependson an accurate diagnosis of the underlying cause. The vast majority, over 85%,of lower extremity wounds have arterial, venous or mixed arterial and venousdisease as a primary cause.13–17

Much emphasis has been put on the making clinical diagnosisbased on ulcer anatomical location, characteristics, and morphology.14,18 While useful, this approachcan cause tunnel vision and result in patient’s not receiving appropriatetimely care. Old maxims such as all plantar wounds are neuropathic, or venouswounds only occur in the setting of varicose veins are wrong.

When faced with a lower extremity wound, the task at hand isto rule out an underlying correctable contributing etiology. This requires in-depthknowledge and understanding of the utility of clinical evaluation and diagnostictesting to include or exclude arterial and venous disease. 19–21 There are many physiologicand imaging tools to identify patients with arterial and venous disease. Mostof these tests are “good tests” but not “great tests”. They must be interpretedwith an understanding of the sensitivity, specificity, and disease prevalence. Inshort, the question is, “what is the chance that the clinical condition will bepresent or absent in the context of a positive or negative test?”.21

Arterial Disease

One of the first steps in evaluating a patient with a lowerextremity ulcer is to exclude ischemia as a potential contributor to the woundand to determine if revascularization required. Appallingly, in the UnitedStates, almost 50% of patients who undergo a major lower extremity amputation,do not have an appropriate arterial evaluation prior.22–24 An in-depth discussion of thenuances of evaluating lower extremity arterial perfusion in the setting ofcritical limb ischemia (CLI) is the subject another brief (“Evaluation of FootPerfusion”). The basics are covered here.

At the bedside, our primary tools include identifying riskfactors for peripheral arterial disease (PAD) and physical examination finding.Important risk factors include (but not limited to) smoking, diabetes, age, cardiovascularand cerebrovascular disease. Physical exam findings include pulses, capillary refill,trophic changes (loss of hair, dry scaly skin) and ulcer characteristics. Thesetools are useful for identifying patients with PAD – “rule in”.

However, these clinical tools are not useful to “rule out” significantPAD.25–27 More specifically, the clinicalexamination for ischemia has a “poor negative predictive value and should notbe used in isolation to triage patients with non-healing ulcers”.28

The presence or absence of PAD must be determined usingobjective testing. Objective tests for PAD are broadly classified into 2categories: physiologic and anatomical. Physiologic testing includes anklebrachial indices (ABI), toe brachial indices (TBI), segmental pressures, skinperfusion pressures, transcutaneous oxygen tension, pulse volume recordings, dopplerwaveforms and other newer modalities. Non-invasive anatomical imaging includesarterial ultrasound (US), CT angiography, and MR angiography. Physiologic testingshould always be utilized before anatomical imaging.29

Frustratingly, there are difficulties and limitations with physiologicevaluation. Surprisingly, the ABI, widely considered the gold standard fordetecting PAD, has limited negative predictive value in the setting of criticallimb ischemia, being falsely reassuring and falsely negative in over 30% of patients.30,31 An ABI should not be used inisolation when evaluating for CLI. The addition of a TBI improves the detectionof the presence of significant ischemia.32 Alternatively skin perfusionpressures (SPP), although not as well validated, are another option for vasculartesting in patients with CLI.

Diagnosing PAD is not always simple.33 A pragmatic approach, startingwith a detailed history and physical exam, followed by testing with ABI and TBIor SPP, is a cost effective strategy.34 Finally, prior to any amputation,referral to a critical limb expert for catheter angiography, should be mandatory.35

Venous Disease

Venous ulcerationis extremely distressing for patients, greatly affecting their quality of life,and causing about 40% more days of lost employment than any other disease.36,37 Our knowledge of the pathophysiology,hemodynamics, diagnostic imaging, and treatment of chronic venous insufficiency(CVI) has expanded greatly, particularly in the last decade. Venous pathology developsfrom valvular incompetence, obstruction, and/or muscle pump dysfunction causingvenous hypertension.38

Like PAD, theclinical findings (varicose veins, hyperpigmentation, statis dermatitis,atrophie blanch, lipodermatosclerosis) are useful to “rule in” CVI. There areno studies on the utility of these findings to “rule out” significant venousdisease. Unfortunately, there is the all-too-common misconception that the absenceof these clinical findings implies that there is no significant venous disease.The absence of varicose veins and/or leg swelling does not confer that apatient does not have significant venous disease.39 This can only be determined by objectivetesting.

Testing for CVI ispoorly understood by non-vascular specialists.40 This is due to limited education duringmedical training, rapidly evolving knowledge, and the variety of testsavailable.

Not all venous USstudies are the same. Most (all) clinicians are familiar with ordering a venousUS to evaluate for deep venous thrombosis (DVT). This examination has onepurpose - to determine if a patient has or does not have DVT. Unfortunately,even this widely used test, is inconsistently performed and can have higherfalse negative rate than expected.41 It is important for physicians to recognizethat a DVT US does not evaluate venous valvular function or venous obstruction.

Venous incompetenceUS is the primary diagnostic tool for evaluating venous valve function in boththe superficial and deep venous systems of the lower extremity.42,43 The adequate performance of a venous incompetenceUS requires specially trained and experienced US technologists. The supervisionand interpretation of these US studies must be done by a specialist with a deepunderstanding of the complexities of lower extremity venous disease.44

Venous obstructionis divided into inflow and outflow. Inflow disease is defined as obstruction inthe deep veins (common femoral, femoral, and popliteal veins) and outflow diseaseas obstruction of the iliac veins and/or the inferior vena cava.

The importance ofvenous outflow obstruction in the setting of CVI is becoming better understood.45–47 Physiologic testing, primarily with air plethysmography,is no longer reimbursed by Medicare. Non-invasive diagnostic imaging including venousUS, CT venography and MR venography while useful lack well validated parametersfor determining outflow disease. Invasive imaging with intravascular ultrasound(IVUS) is the best tool for identifying patients with significant venousoutflow compression.48

Inflow venous obstructionprimarily occurs after lower extremity DVT and is one of the main causes of postthrombotic syndrome (PTS).  Evaluation ofthe lower extremity deep venous system and potential therapies is an area ofintense research.49,50

Finally, all patientswith a suspected venous ulcer should have measurement of the ankle-brachialindex at the time of initial presentation.51


Lower extremitywounds are complex and challenging for patients, families, and healthcareproviders. Most lower extremity ulcers are secondary to either or both arterialand venous problems. A comprehensive history and physical assessment followedby appropriate imaging are essential to identify, diagnose and develop careplans. Dedicated vascular specialists should be involved in the care of alllower extremity ulcers and wounds to determine or exclude the presence ofsignificant arterial and/or venous disease.7,52 Rapid referral and treatment of theunderlying problem has been shown to improve wound healing, reducing patientmorbidity and improving quality of life.53–56


1.         Guest JF, Ayoub N, McIlwraith T,et al. Health economic burden that wounds impose on the National Health Servicein the UK. BMJ Open. 2015;5(12):e009283. doi:10.1136/bmjopen-2015-009283

2.         ChanB, Cadarette S, Wodchis W, Wong J, Mittmann N, Krahn M. Cost-of-illness studiesin chronic ulcers: a systematic review. J Wound Care.2017;26(sup4):S4-S14. doi:10.12968/jowc.2017.26.Sup4.S4

3.         Ma H,O’Donnell TF, Rosen NA, Iafrati MD. The real cost of treating venous ulcers ina contemporary vascular practice. J Vasc Surg Venous Lymphat Disord.2014;2(4):355-361. doi:10.1016/j.jvsv.2014.04.006

4.         DuffS, Mafilios MS, Bhounsule P, Hasegawa JT. The burden of critical limb ischemia:a review of recent literature. Vasc Health Risk Manag. 2019;15:187-208.doi:10.2147/VHRM.S209241

5.         NussbaumSR, Carter MJ, Fife CE, et al. An Economic Evaluation of the Impact, Cost, andMedicare Policy Implications of Chronic Nonhealing Wounds. Value Health.2018;21(1):27-32. doi:10.1016/j.jval.2017.07.007

6.         AlaviA, Sibbald RG, Phillips TJ, et al. What’s new: Management of venous leg ulcers:Treating venous leg ulcers. J Am Acad Dermatol. 2016;74(4):643-664; quiz665-666. doi:10.1016/j.jaad.2015.03.059

7.         MooijMC, Huisman LC. Chronic leg ulcer: does a patient always get a correctdiagnosis and adequate treatment? Phlebology. 2016;31(1 Suppl):68-73.doi:10.1177/0268355516632436

8.         GrayTA, Rhodes S, Atkinson RA, et al. Opportunities for better value wound care: amultiservice, cross-sectional survey of complex wounds and their care in a UKcommunity population. BMJ Open. 2018;8(3):e019440.doi:10.1136/bmjopen-2017-019440

9.         FrimanA, Wiegleb Edström D, Ebbeskog B, Edelbring S. General practitioners’ knowledgeof leg ulcer treatment in primary healthcare: an interview study. PrimHealth Care Res Dev. 2020;21:e34. doi:10.1017/S1463423620000274

10.        FLANAGANM. Barriers to the implementation of best practice in wound care. Wounds UK.2005;1:74-82.

11.         O’BrienML, Lawton JE, Conn CR, Ganley HE. Best practice wound care. Int Wound J.2011;8(2):145-154. doi:10.1111/j.1742-481X.2010.00761.x

12.        MoloneyMC, Grace P. Understanding the underlying causes of chronic leg ulceration. JWound Care. 2004;13(6):215-218. doi:10.12968/jowc.2004.13.6.26626

13.        NelzénO, Bergqvist D, Lindhagen A. Leg ulcer etiology--a cross sectional populationstudy. J Vasc Surg. 1991;14(4):557-564.

14.        KirsnerRS, Vivas AC. Lower-extremity ulcers: diagnosis and management. Br JDermatol. 2015;173(2):379-390. doi:10.1111/bjd.13953

15.        SpentzourisG, Labropoulos N. The Evaluation of Lower-Extremity Ulcers. Semin IntervRadiol. 2009;26(4):286-295. doi:10.1055/s-0029-1242204

16.        KörberA, Klode J, Al‐Benna S, et al. Etiology of chronic leg ulcers in31,619 patients in Germany analyzed by an expert survey. JDDG J DtschDermatol Ges. 2011;9(2):116-121.doi:

17.        VermaM, Singh AK, Kumar V, Mishra B. Role of Ankle Brachial Index (ABI) inManagement of Non-Healing Ulcers of Lower Limb. J Univers Surg.2018;6(1). doi:10.21767/2254-6758.100096

18.        ArmstrongDG, Boulton AJM, Bus SA. Diabetic Foot Ulcers and Their Recurrence. N Engl JMed. 2017;376(24):2367-2375. doi:10.1056/NEJMra1615439

19.        LeeWC. Selecting diagnostic tests for ruling out or ruling in disease: the use ofthe Kullback-Leibler distance. Int J Epidemiol. 1999;28(3):521-525.doi:10.1093/ije/28.3.521

20.       TrimbleM, Hamilton P. The thinking doctor: clinical decision making in contemporarymedicine. Clin Med. 2016;16(4):343-346.doi:10.7861/clinmedicine.16-4-343

21.        BaeyensJ-P, Serrien B, Goossens M, Clijsen R. Questioning the “SPIN and SNOUT” rule inclinical testing. Arch Physiother. 2019;9(1):4.doi:10.1186/s40945-019-0056-5

22.       VemulapalliSreekanth, Greiner Melissa A., Jones W. Schuyler, Patel Manesh R., HernandezAdrian F., Curtis Lesley H. Peripheral Arterial Testing Before Lower ExtremityAmputation Among Medicare Beneficiaries, 2000 to 2010. Circ Cardiovasc QualOutcomes. 2014;7(1):142-150. doi:10.1161/CIRCOUTCOMES.113.000376

23.       GoodneyPP, Travis LL, Nallamothu BK, et al. Variation in the use of lower extremityvascular procedures for critical limb ischemia. Circ Cardiovasc QualOutcomes. 2012;5(1):94-102. doi:10.1161/CIRCOUTCOMES.111.962233

24.       AllieDE, Hebert CJ, Lirtzman MD, et al. Critical limb ischemia: a global epidemic.Acritical analysis of current treatment unmasks the clinical and economic costsof CLI. EuroIntervention J Eur Collab Work Group Interv Cardiol Eur SocCardiol. 2005;1(1):75-84.

25.       KhanNA, Rahim SA, Anand SS, Simel DL, Panju A. Does the clinical examinationpredict lower extremity peripheral arterial disease? JAMA.2006;295(5):536-546. doi:10.1001/jama.295.5.536

26.       MoffattC, O’Hare L. Ankle pulses are not sufficient to detect impaired arterialcirculation in patients with leg ulcers. J Wound Care.1995;4(3):134-138. doi:10.12968/jowc.1995.4.3.134

27.       ArmstrongDW, Tobin C, Matangi MF. The accuracy of the physical examination for thedetection of lower extremity peripheral arterial disease. Can J Cardiol.2010;26(10):e346-e350.

28.       AzzopardiYM, Gatt A, Chockalingam N, Formosa C. Agreement of clinical tests for thediagnosis of peripheral arterial disease. Prim Care Diabetes.2019;13(1):82-86. doi:10.1016/j.pcd.2018.08.005

29.       MisraS, Shishehbor MH, Takahashi EA, et al. Perfusion Assessment in Critical LimbIschemia: Principles for Understanding and the Development of Evidence andEvaluation of Devices: A Scientific Statement From the American HeartAssociation. Circulation. 2019;140(12):e657-e672.doi:10.1161/CIR.0000000000000708

30.       RogersRK, Montero-Baker M, Biswas M, Morrison J, Braun J. Assessment of footperfusion: Overview of modalities, review of evidence, and identification ofevidence gaps. Vasc Med Lond Engl. 2020;25(3):235-245.doi:10.1177/1358863X20909433

31.        BrooksB, Dean R, Patel S, Wu B, Molyneaux L, Yue DK. TBI or not TBI: that is thequestion. Is it better to measure toe pressure than ankle pressure in diabeticpatients? Diabet Med J Br Diabet Assoc. 2001;18(7):528-532.doi:10.1046/j.1464-5491.2001.00493.x

32.       RandhawaMS, Reed GW, Grafmiller K, Gornik HL, Shishehbor MH. Prevalence of TibialArtery and Pedal Arch Patency by Angiography in Patients With Critical LimbIschemia and Noncompressible Ankle Brachial Index. Circ Cardiovasc Interv.2017;10(5). doi:10.1161/CIRCINTERVENTIONS.116.004605

33.       VriensB, D’Abate F, Ozdemir BA, et al. Clinical examination and non-invasivescreening tests in the diagnosis of peripheral artery disease in people withdiabetes-related foot ulceration. Diabet Med J Br Diabet Assoc. 2018;35(7):895-902.doi:10.1111/dme.13634

34.       BarshesNR, Flores E, Belkin M, Kougias P, Armstrong DG, Mills JL. The accuracy andcost-effectiveness of strategies used to identify peripheral artery diseaseamong patients with diabetic foot ulcers. J Vasc Surg. 2016;64(6):1682-1690.e3.doi:10.1016/j.jvs.2016.04.056

35.       MustaphaJA, Saab FA, Martinsen BJ, et al. Digital Subtraction Angiography Prior to anAmputation for Critical Limb Ischemia (CLI): An Expert Recommendation StatementFrom the CLI Global Society to Optimize Limb Salvage. J Endovasc Ther Off JInt Soc Endovasc Spec. 2020;27(4):540-546. doi:10.1177/1526602820928590

36.       RiceJB, Desai U, Cummings AKG, Birnbaum HG, Skornicki M, Parsons N. Burden ofvenous leg ulcers in the United States. J Med Econ. 2014;17(5):347-356.doi:10.3111/13696998.2014.903258

37.       HopmanWM, VanDenKerkhof EG, Carley ME, Kuhnke JL, Harrison MB. Factors associatedwith health-related quality of life in chronic leg ulceration. Qual Life ResInt J Qual Life Asp Treat Care Rehabil. 2014;23(6):1833-1840.doi:10.1007/s11136-014-0626-7

38.       BundensWP. Handbook of Venous Disorders, second edition. Ann Vasc Surg.2002;6(16):805. doi:10.1007/s10016-001-0319-x

39.       KumarH, Sharma PK, Garga UC. Role of Vascular Ultrasound in Cases of Lower LimbHyperpigmentation. Indian J Dermatol. 2019;64(6):456-460.doi:10.4103/ijd.IJD_393_18

40.       SPIRIDONM, CORDUNEANU D. Chronic Venous Insufficiency: a Frequently Underdiagnosed andUndertreated Pathology. Mædica. 2017;12(1):59-61.

41.        ZhangY, Xia H, Wang Y, et al. The rate of missed diagnosis of lower-limb DVT byultrasound amounts to 50% or so in patients without symptoms of DVT. Medicine(Baltimore). 2019;98(37). doi:10.1097/MD.0000000000017103

42.       KhilnaniNM, Min RJ. Imaging of Venous Insufficiency. Semin Interv Radiol.2005;22(3):178-184. doi:10.1055/s-2005-921950

43.       LeeD-K, Ahn K-S, Kang CH, Cho SB. Ultrasonography of the lower extremity veins:anatomy and basic approach. Ultrasonography. 2017;36(2):120-130.doi:10.14366/usg.17001

44.       Patel SK,Surowiec SM. Venous Insufficiency. In: StatPearls. StatPearlsPublishing; 2020. Accessed December 20, 2020.

45.       Raju S.Treatment of iliac-caval outflow obstruction. Semin Vasc Surg.2015;28(1):47-53. doi:10.1053/j.semvascsurg.2015.07.001

46.       KnuttinenM-G, Naidu S, Oklu R, et al. May-Thurner: diagnosis and endovascularmanagement. Cardiovasc Diagn Ther. 2017;7(Suppl 3):S159-S164.doi:10.21037/cdt.2017.10.14

47.       LabropoulosN, Volteas N, Leon M, et al. The role of venous outflow obstruction in patientswith chronic venous dysfunction. Arch Surg Chic Ill 1960.1997;132(1):46-51. doi:10.1001/archsurg.1997.01430250048011

48.       GagnePJ, Gasparis A, Black S, et al. Analysis of threshold stenosis by multiplanarvenogram and intravascular ultrasound examination for predicting clinicalimprovement after iliofemoral vein stenting in the VIDIO trial. J VascSurg Venous Lymphat Disord. 2018;6(1):48-56.e1. doi:10.1016/j.jvsv.2017.07.009

49.       VedanthamS, Goldhaber SZ, Julian JA, et al. Pharmacomechanical Catheter-DirectedThrombolysis for Deep-Vein Thrombosis. N Engl J Med.2017;377(23):2240-2252. doi:10.1056/NEJMoa1615066

50.       MD EE. PharmacomechanicalCatheter-Directed Thrombolysis (PCDT) Plus Anticoagulation Compared toAnticoagulation Alone for Acute Primary Iliofemoral Deep Venous; 2020. Accessed December 19, 2020.

51.        O’DonnellTF, Passman MA, Marston WA, et al. Management of venous leg ulcers: clinicalpractice guidelines of the Society for Vascular Surgery ® and the AmericanVenous Forum. J Vasc Surg. 2014;60(2 Suppl):3S-59S.doi:10.1016/j.jvs.2014.04.049

52.       ForssgrenA, Fransson I, Nelzén O. Leg ulcer point prevalence can be decreased bybroad-scale intervention: a follow-up cross-sectional study of a definedgeographical population. Acta Derm Venereol. 2008;88(3):252-256.doi:10.2340/00015555-0433

53.       GohelMS, Heatley F, Liu X, et al. Early versus deferred endovenous ablation ofsuperficial venous reflux in patients with venous ulceration: the EVRA RCT. HealthTechnol Assess Winch Engl. 2019;23(24):1-96. doi:10.3310/hta23240

54.       Liu X,Zheng G, Ye B, et al. A retrospective cohort study comparing two treatments foractive venous leg ulcers. Medicine (Baltimore). 2020;99(8):e19317.doi:10.1097/MD.0000000000019317

55.       Duff S,Mafilios MS, Bhounsule P, Hasegawa JT. The burden of critical limb ischemia: areview of recent literature. Vasc Health Risk Manag. 2019;15:187-208.doi:10.2147/VHRM.S209241

56.       BarnesJA, Eid MA, Creager MA, Goodney PP. Epidemiology and Risk of Amputation inPatients With Diabetes Mellitus and Peripheral Artery Disease. ArteriosclerThromb Vasc Biol. 2020;40(8):1808-1817. doi:10.1161/ATVBAHA.120.314595

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