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The Journal of Diabetic Foot ComplicationsOpen access publishingThe role of fluorescein angiography in the management of orphan heelsyndromeAuthors: Nicole Byerley, DPM*,Col (Ret) Charles A. Andersen, MD, FACS, FAPWCA1, Mario N.Ponticello, DPM, FACFAS, FAPWCA2, LTC, MC, Peter Kreishman, MD3The Journal of Diabetic Foot Complications, 2016; Volume 8, Issue 2, No. 3, Pages 38-44 All rights reserved.Abstract:Heel ulcers are common, and regardless of the etiology they may become ischemic because of the unique blood supplyto the heel (Orphan Heel Syndrome). Measurement of tissue perfusion in the assessment of heel ulcers is critical, andcommon non-invasive vascular testing can often be misleading. The following case report demonstrates the use ofFluorescein angiography to assess and monitor perfusion to a heel ulcer and surrounding soft tissues during treatment.We present an 81-year-old diabetic female with a right postero-lateral heel ulcer, non-palpable pulses, and an abnormaldoppler exam. She also had monophasic dorsalis pedis and perforating peroneal arteries with no signal in the posteriortibial artery. Initial Fluorescein angiography revealed no fluorescence in the wound base and little inflammatory reactionsurrounding the ulcer. She underwent placement of a popliteal stent, resulting in triphasic doppler signals in the dorsalispedis and perforating peroneal arteries with no audible posterior tibial artery. The immediate post-operative Fluoresceinstudy demonstrated improved perfusion to the ulcer and a peri-ulcerative area that was maintained at the 6-weekfollow-up period. With local wound care and off-loading, the patient healed in six weeks.All patients presenting with a heel ulcer should be assessed for coexisting arterial insufficiency. Because of thedistribution of arterial branches to the heel, and the possibility of regional ischemia, the clinician should be suspicious ofOrphan Heel Syndrome whenever a heel ulcer is present. Fluorescein angiography is a tool that can identify a regionalischemia, thus leading to appropriate treatment and avoidance of a major amputation.Key words: Flourescein Angiography, Heel Ulcer, Orphan Heel SyndromeCorresponding author* Nicole Byerley, DPMFellow, Complex Lower Extremity Surgery and Research FellowshipMadigan Army Medical CenterTacoma, WA 98431Email: nicole.byerley@gmail.comAffiliations1Chief, Vascular Surgery Service2Chief, Complex Lower Extremity Surgery and Research Fellowship3Deputy Chief, Department of SurgeryMadigan Army Medical CenterTacoma, WA 98431INTRODUCTIONHeel ulcers are common, occurringsecondary to 1) combined neuropathy andrepetitive trauma, 2) immobilization withprolonged skin pressure, or 3) direct trauma.1,2Heel ulcers heal slower than forefoot ulcerations,and unfortunately more amputations occur in thepresence of heel ulcers.3,4The likely explanation for slower healingrelates to a circulatory component to the diseaseprocess. The heel has a unique arterial supplyincluding contributions from the posterior tibialartery and the perforating peroneal artery withan increased potential for tissue ischemia.5 Thisassociated ischemia may lead to non-healingulcers and major complications such as infection,sepsis, amputation, and death. Therefore, allpatients with heel ulcers should be assessed forassociated ischemia.Due to the specific arterial supply of theheel, understanding and using the conceptof angiosomes in evaluating patients withheel ulcers is essential. No artery-to-arteryconnections between the posterior tibial arterialbranches and the branches of the peronealartery exist in the heel.5 Due to the distinctivevascularity and potential for the multi-vesseldistal disease, focal ischemia may be present.The presence of heel ulcers associated withfocal ischemia is referred to as Orphan HeelSyndrome.Revascularization plays an important role intreating Orphan Heel Syndrome. Ideally, whenrevascularizing ischemic heel ulcers the conceptof angiosome-guided revascularization shouldbe strongly considered. When possible, directrevascularization leads to increased rates of limb38
The Journal of Diabetic Foot Complications, 2016; Volume 8, Issue 2, No. 3, Pages 38-44salvage and complete wound healing. However, ifdirect revascularization is not possible, it remainsbeneficial to perform revascularization through anindirect method.6,7Due to the under appreciated presence ofregional heel ischemia, it is critical to measuretissue perfusion in patients with heel ulcers toproperly identify those with associated ischemia.Current methods used to evaluate tissueperfusion at the heel include ankle-brachialindex, toe pressures, skin perfusion pressure test(SPP), forefoot pulse volume recordings (PVR),and transcutaneous oximetry (tcpo2). Thesetests are often limited by medial calcinosis,scarring, previous amputations, or ulcer locationthat can lead to little clinically pertinent data andthe inability to dictate appropriate interventionmethods or monitor treatment efficacy.8Fluorescein angiography offers an additionalmethod to assess real-time tissue perfusion andassess the healing potential for ulcers.8 Thismodality is considered minimally invasive, safe,easy to perform, easily accessible, and low cost.9Fluorescein angiography is useful in identifyingheel ischemia and documenting improvedperfusion following revascularization and therapytreatments. Likewise, Fluoroscein angiographyallows for early recognition of arterialinsufficiency, which leads to modified treatmentand the potential to heal ulcers while preventingmajor amputations. If regional ischemia is notidentified, revascularization is not likely to beperformed, and the risk of limb loss increases.This case study demonstrates the utility ofFluorescene angiography in identifying regionalheel ischemia in a patient with a heel ulcer.In addition, this report documents increasedperfusion to the wound and surrounding tissueusing an indirect revascularization approach.Case ReportAn 81-year-old female with a medical historywith poorly-controlled insulin-dependent Type2 Diabetes Mellitus (DM) with neuropathy,nephropathy, hypertension, and hyperlipidemiapresented to the limb preservation clinic. Shehad a painful right postero-lateral heel ulcerationOpen access publishingthat had been present for three weeks (Figure1). Initial pulse examination revealed nonpalpable pedal pulses and an abnormal bedsidedoppler examination. The posterior tibial arterywas non-audible, while the dorsalis pedis andperforating peroneal arteries were monophasic.Non-invasive vascular testing revealed a rightlower extremity ankle-brachial index (ABI) of 0.51mmHg with waveforms suggestive of moderateto severe arterial disease. Outpatient Fluoresceinangiography showed a lack of perfusion to theulcer bed and minimal inflammatory response.Figure 1. Clinical appearance of wound at initial visit.Initial treatments included topical dressings(initially cadexomer iodine, later conversionto collagenase), heel offloading, instructionto remain non-weightbearing to the lowerextremity, and CT angiography. An arteriogramdemonstrated popliteal arterial occlusion andsingle vessel runoff through the perforatingperoneal artery (Figure 2). A popliteal stent wasplaced (Figure 3). Following the stent placement,arterial flow to the foot improved with a triphasicdorsalis pedis doppler signal, but no posteriortibial signal was appreciated.Twenty-four hours after revascularization,a repeat Fluorescene angiography study wasperformed to the right heel ulceration area. Itshowed improved perfusion to the ulcer andimproved surrounding inflammatory reaction.Following revascularization, the patient hadregular follow-up visits. Visits allowed for woundmonitoring, regular sharp debridement provision,and assurance of continued use of non-weight39
The Journal of Diabetic Foot Complications, 2016; Volume 8, Issue 2, No. 3, Pages 38-44bearing heel off-loading. Additionally, she wastreated on two different occasions with topicalapplication of amniotic biologics.Two weeks post popliteal artery stentplacement, she also had a monophasic posteriortibial arterial signal. At six weeks, the FluoresceinOpen access publishingangiography was repeated and showedsignificantly less peripheral inflammatory reactionwith much improved vascular perfusion to theentire wound bed. This showed increased healingpotential (Figure 4). Two weeks following the lastFluorescein angiography study, her ulcer wascompletely epithelialized (Figure 5). She wastransitioned to extra-depth diabetic shoes withappropriate accommodative orthotics.Figure 2. Appearance of artery prior to stenting.Figure 4. Images obtained during Fluorescein angiographyon three separate encounters: Encounter 1 is baseline;Encounter 2 is immediately post stenting; and Encounter 3is six weeks status post stenting.Figure 3. Appearance of artery following popliteal arterialstenting.Figure 5. Clinical appearance of healed wound.40
The Journal of Diabetic Foot Complications, 2016; Volume 8, Issue 2, No. 3, Pages 38-44DISCUSSIONThe etiology of heel ulcers occurs frombiomechanical or mechanically induced forceswith shearing/friction or increased pressuresleading to increased tissue hypoxia andchronic inflammation. Pressure to the heel isa cause of ischemia and is harmful either withlonger periods of time or increased force.2 Theonset and continuation of these forces can gounnoticed due to neuropathy and ischemia.However, for patients with peripheral arterialdisease, much less time or pressure is requiredto create an ulcer. Internationally, pressureulcers of the heel account for approximately 23%of all pressure ulcers.2 Limb salvage rates forpatients with heel ulcers have been estimatedto be between 65-89%. This is much lowerthan limb salvage rates for digits, forefoot, ormidfoot ulcers.10 One explanation for a decreasedsalvage rate would be the lack of vasculartesting. A study observing hospitalized patientsdemonstrated that up to 70% of the patients withheel ulcers did not receive thorough vasculartesting. Consequently, the one-year mortality ratefor the 65 and older patients in the study wasaround 70%.11Peripheral vascular disease affects between8 to 12 million patients over the age of 40 in theUnited States. Risk factors for the developmentof peripheral arterial disease (PAD) are DM,hypertension, hypercholesterolemia, andsmoking. Diabetes mellitus is a risk factor forPAD with prevalence rates cited between 10-40%of all diabetic patients. Diabetic patients are at afour-fold risk to develop PAD.12 Diabetic patientshave more distal arterial manifestations; theirdisease state progresses more rapidly; and theyhave a significantly higher mortality rate.12,13,14Due to their poor arterial flow these patientshave an increased risk of ulceration, which canlead to infection and, ultimately, amputation.Understanding the frequent presentation andrisk factors of diabetic patients is required whenconducting a thorough vascular examination. Inpatients with diabetic foot ulcers, up to 50% hadvarious degrees of PAD.13Open access publishingBesides arterial issues in the macroscopiclevel of the artery, there are matching eventsmicroscopically. Even at the molecular level,when a diabetic artery is directly compared toa non-diabetic artery, it has been found to havea decreased wall to lumen ratio, stiffer vessels,and issues with angiogenesis. Due to manyfactors associated with DM, the artery displaysderangement in the extracellular matrix anddisplays dysfunctionality of the smooth muscleand endothelium.14Patients with heel ulcers incur moreamputations and heal more slowly than thosewith forefoot ulcers.3 The arterial anatomy ofthe heel is variable. The heel has a uniquearterial supply with a potential for ischemia, andit requires an enhanced method to assess localheel tissue perfusion.The foot and ankle consist of six differentangiosomes. These derive from the posteriortibial artery, the anterior tibial artery, or theperoneal artery. However, the foot has severalarterial-to-arterial connections that allow forimmediate continued blood flow to an areaif the direct route is damaged or occluded.Understanding this can assist in the patient’sphysical exam and determining the predominateartery with a particular angiosome. Testing canbe performed with a doppler, and occlusion ofthe artery with pressure distal and proximal tothe placement of the probe. The choke vesselcan provide indirect vascular flow to an area thatis outside its normal angiosome distribution. Asimple doppler exam can determine if the flowis indirect from a choke vessel or from directpressure. If it is a manual occlusion, the arteryproximal to the doppler elicits a distal audiblesignal and there can be reasonable certainty thatthe flow is supplied by a different artery.5The heel is a unique angiosome becauseit receives blood supply from two sources, theposterior tibial artery and the peroneal artery. Nodirect artery-to-artery connections exist in thisarea.5 Due to the distinctive vascularity, whenconsidering angiosomes of the heel and multivessel diseases of diabetic patients, Orphan HeelSyndrome must be considered in patients that41
The Journal of Diabetic Foot Complications, 2016; Volume 8, Issue 2, No. 3, Pages 38-44present with ischemic ulcers of the heel. Thissituation is indicative of only one vessel partiallydistributing blood flow to the region, with little tono artery-to-artery reconstitution occurring to thearea.15Both the angiosome distribution of anulcer and a thorough patient evaluation todetermine any possible artery-to-arteryconnections supplying that area cannot beunderestimated. This is especially true forplanning revascularization. Due to multiple levelsof distal arterial occlusions, and the tendencyfor it to occur in multiple vessels, the reality ofrevascularization is more challenging. Severalstudies have evaluated limb salvage outcomesand ulcer healing rates of direct angiosomerevascularization. They have shown similar orimproved results when compared to indirectrevascularization.6,13 A recent systemic reviewhas found that reported rates of limb salvage atone year and three years were better for openrevascularization. At one year, diabetic patientsdisplayed increased limb salvage rates (between78-85%) when having a revascularizationprocedure performed than if treated withoutrevascularization (54%). At five years, theestimated average limb salvage rate was 77.5%.13By relying on and understanding dorsalispedis artery bypass, favorable results (86.5%)have been shown in the healing of heelulcerations.16 This connection is not a guarantee,which is an argument for direct revascularizationprocedures. Studies have shown results thatwere statistically significant for complete woundhealing in direct revascularization procedures(90.0% vs. 61.9%) than when not engagedwith direct revascularization procedures. Directrevascularization also showed an amputationrate four times less than in those having anindirect procedure.6 While many studies finddirect revascularization to be preferable for ulcerhealing, indirect revascularization should beconsidered in cases that do not allow for a directprocedure.7,17 This concept is extremely importantin understanding and predicting the healingpotential of a heel ulcer.18Open access publishingMeasurement of tissue perfusion is critical inassessing patients with heel ulceration. Currentmethods used to evaluate tissue perfusionto the foot include ABIs, toe pressures, SPP,forefoot PVR, and tcpo2. Following the physicalexam, the ABI and Toe-Brachial Index (TBI) arefrequently used as initial non-invasive vasculartests to determine disease status, location, andseverity.However, the ABI has shown to be ineffectivein measuring disease in diabetic patients. Oftenthe results are falsely elevated due to noncompressible arteries affected by medial arterycalcification. The ABI also has issues withdetecting any smaller vessel disease distal to theankle. A recent study found the ABIs specificityto be high (92.68%), but the sensitivities werelow (45.16%). The TBI can be useful when moredistal detection of arterial disease occurs and isless affected by arterial calcifications common inDM. The exact accuracy has been debated, andmore studies will be required. Recent sensitivitieswere found to be 63% with specificities around82% in patients with DM.12Toe pressures are difficult to obtain inpatients with skin ulcers, gangrene, pain, orprevious amputations.8 Both ABI and TBI havedecreased sensitivities as compared to non-DMpatients.12 Additionally, the ABI has beencalculated to be based off the anterior tibial arteryin 53.06% of feet and thus would not be directlyapplicable to the anticipated healing potentialof all foot ulcers.19 A study by Taylor includeda patient population with heel ulcers in which38% had normal ABI measurements but notablysevere perfusion decrease when angiographywas performed.15 Transcutaneous oxygenmonitoring is another tool that can be useful toevaluate wound healing. Testing is limited in theplantar foot due to the skin’s thickness.20CT angiography can only be used tovisualize the vessel’s lumen and cannot be usedto determine the end amount of tissue perfusion.The major complication rate of peripheralarteriogram is approximately 2.9%.21 Thearteriogram is far too invasive, with concern forcausing damage to the vessel, to be used as an42
The Journal of Diabetic Foot Complications, 2016; Volume 8, Issue 2, No. 3, Pages 38-44initial modality to determine location and severityof arterial disease status.Fluorescein angiography can assess tissueperfusion and identify the healing potential forheel ulcers. This modality is considered minimallyinvasive, safe, easy to perform, and inexpensive.9It consists of using indocyanine green (ICG)as an intravenous injectable and monitoringits dissemination into the tissues. Fluoresceinangiography/imaging has been found to providereliable qualitative and quantitative imagingto determine local tissue perfusion in mild tomoderate degrees of PAD.9 This has also shownto be useful in obtaining baselines and assessingefficacy during treatment.Though many clinicians use the modalityto see real time tissue perfusion qualitatively, astudy evaluated the quantitative data that can beobtained during the use of ICG imaging.22 Thisdata can be reliably derived from the images.The most reliable parameter is the time it takesthe ICG to reach maximum intensity. The casereport demonstrates the utility of Fluoresceinangiography in identifying ischemia in a patientwith a heel ulcer. The recognition of arterialinsufficiency in patients with heel ulcers leads toaltered treatment, lower potential heal ulceration,and prevention of major amputation.Open access publishingCONCLUSIONAll patients presenting with a heel ulcershould be assessed for coexisting arterialinsufficiency. Because of the distribution ofarterial branches to the heel, regional ischemiamay occur. This condition has been labeledOrphan Heel Syndrome. This condition mayoccur with normal ABIs and a palpable DPpulse. Understanding the concept of angiosomesand the unique blood supply to the heelleads to a high index of suspicion and furtherassessment of perfusion to the heel. Many ofthe initial non-invasive modalities are limited bymedial calcinosis, scarring, wounds, prior toeamputations, and infection. Current methodscan also be technically challenging, costly, andtime consuming, and they do not measure globalperfusion of the foot or regional perfusion ofthe heel. New and advanced modalities suchas Fluorescein angiography can be used toevaluate the healing potential of ulcers prior toand following surgical intervention. It has alsobeen shown to provide both qualitative andquantitative information in healing potentials, andcan assess the level of amputation and efficacyof treatments. Heel ischemia identification andtreatment may lead to improved heel ulcerhealing and a decreased amputation
* 1Nicole Byerley, DPM Fellow, Complex Lower Extremity Surgery and Research Fellowship Madigan Army Medical Center Tacoma, WA 98431 Email: nicole.byerley@gmail.com Affiliations Chief, Vascular Surgery Service 2 Chief, Complex Lower Extremity Surgery and Research Fellowship 3 Deputy
