commentary: myths and proofs of angiosome applications in cli: where do we stand?

^COMMENTARY ——————————————————————————————— ^

Myths and Proofs of Angiosome Applications in CLI:Where Do We Stand?

Vlad-Adrian Alexandrescu, MD

General, Thoracic, and Vascular Surgery Department, Princess Paola Hospital,Marche-en-Famenne, Belgium.

Since its first formulation by Taylor andPalmer1 in 1987, the angiosome conceptcontinues to inspire researchers to add newapplications in various therapeutic fields.1,2

Particularly in critical limb ischemia (CLI)treatment, there is mounting contemporaryevidence that novel AC applications producebetter ischemic tissue regeneration and limbpreservation.2–8 Parallel to unremitting pro-gress in vascular technology, new insightsconcerning either bypass or endovasculartherapy are now available based on theconcept of ‘‘wound-directed’’ revasculariza-tion.3–9 The article by Iida et al.10 in this issueof the JEVT represents one of these gradualsteps toward wider comprehension of themechanisms and related treatments that haveevolved for CLI in recent years.8,9

DIRECT VS. INDIRECTREVASCULARIZATION

There is a question as to whether we achievebetter wound healing and limb preservationwith the direct or indirect approach. Tissuepreservation seems better sustained by topo-graphic or direct revascularization (followingspecific arterial bundles).1,2 This observationis supported by contemporary studies inreconstructive plastic surgery,1,2 intervention-al cardiology,1,11 neurosurgery,1,12 and inter-ventional radiology13 domains. Other

publications over the last decade have ex-panded the application of angiosome-basedtreatment in CLI.2–9,11–14 Despite being pre-dominantly retrospective3–8,14–18 studies rath-er than prospective19 trials (although there are3 recent meta-analyses9,20,21), these articlesoffer somewhat encouraging results of ische-mic wound healing for direct (angiosome- orwound-oriented) vs. indirect (wound-indiffer-ent) arterial reconstruction whenever theformer is feasible.2–9,18–21 While most authorsfind the angiosome concept appropriate indistal bypass,2,4,5,18 endovascular below-the-knee (BTK) reperfusion,3,6–8,16 and even ex-treme deep vein arterialization,22–24 othershave reservations about acknowledging thebenefits of surgical25 or transcatheter26 angio-some-guided distal leg revascularization.

Nevertheless, over the last few years, therehas been progress in angiosome interpreta-tion derived from complementing initial limbsalvage or patency endpoints2,3,5,6 with morespecific regional perfusion13,16 and tissueregeneration8,16,21 measures. More refinedinformation is now available regarding the‘‘choke vessels’’1,2 that connect the footangiosomes1,2,4,16 in specific populations,such as diabetic3,7,8,18,27 or renal16,24,25 pa-tients with scarce collateral reserve.7,16 Iden-tification of the importance of the footarches,2,14 the large (.0.5 mm) arterial-arterialcollaterals,2,4,16,28 and the key role of metatar-

Invited commentaries published in the Journal of Endovascular Therapy reflect the opinions of the author(s) and do notnecessarily represent the views of the Journal or the INTERNATIONAL SOCIETY OF ENDOVASCULAR SPECIALISTS.

The author declares no association with any individual, company, or organization having a vested interest in the subjectmatter/products mentioned in this article.

Corresponding author: Vlad-Adrian Alexandrescu, MD, Department of Vascular Surgery, Princess Paola Hospital,Marche-en-Famenne, Belgium. E-mail: [email protected]

616 J ENDOVASC THER2014;21:616–624

Q 2014 INTERNATIONAL SOCIETY OF ENDOVASCULAR SPECIALISTS doi:10.1583/14-4692C.1 Available at www.jevt.org

sal perforators2,8,15–17 has also occurred sincewound-oriented vs. blind revascularizationwas conceived.2,4,14–16

In keeping with this advance in knowledgeabout the angiosome concept, the article byIida et al.10 offers the reader new insights intoapplying the angiosome strategy in currentBTK practice. Based on a robust but retro-spective CLI database,6,29 Iida and colleaguesalready documented encouraging long-termresults for direct vs. indirect revascularizationfollowing the angiosome methodology.29

More recently (yet using similar retrospectiveanalysis), they focused on major amputationand global reintervention consequences re-flected by MALE (major adverse limb events)for CLI foot wounds in patients with infectionand hyperglycemic disorders.30 The authorsdescribed worse outcomes in this selectedgroup of patients treated by indirect BTKangioplasty.

Following parallel clinical reasoning, thepresent article from Iida et al.10 tries toenlarge our comprehension of angiosomedirected revascularization, this time focusingon CLI ulcers without concurrent local sepsisor diabetes mellitus (a logical continuation oftheir previous work30). The statistical sectionof this methodology adds the advantages ofpropensity score matching to the same retro-spective multicenter database.29,30 The mainclinical outcome of this new study is that thewound healing rate is still statistically better inthe direct rather than the indirect revascular-ization group, whereas MALE and amputa-tion-free survival (AFS) appear unaffected inthe above subset of patients.

Beyond the undeniable merits of this quitewell structured study, some questions mayarise from a vascular practitioner’s point ofview. For one, does the propensity scorematching analysis and risk factor stratification(even in their finest statistical variant) com-pensate for the group heterogeneity seen inprevious retrospective works? Is the lack ofsignificant difference in the AFS and MALEendpoints in the two cohorts convincingwithout uniform sepsis diagnosis and footwound–related classification beyond the ge-neric Rutherford scale? This lack in populationhomogeneity is fairly discussed by the au-

thors as a disadvantage of their retrospectiveanalysis.

Regardless, the originality of this angio-some-dedicated article should not be under-rated. Among the plethora of retrospectivedata2–8,17,18 and only scarce prospectivereferences9,19 available in the contemporaryliterature, the new study from Iida et al.10

addresses specific challenges that any vas-cular interventionist may encounter in his orher daily BTK practice. As other researchershave noted,7–9 the authors also stressed theapparent paradox that even after successfuldirect revascularization, different pathologi-cal patterns react in a dissimilar mannerinside the same hemodynamic CLI globalcontext.2–5,7–9,17–19 Moreover, it becomesclearer that not all categories of CLI footulcers are able to share comparable tissueregeneration reserves31 after successful an-giosome reperfusion!3,7–9,16,25,27 Despiteprobably better healing results from directrevascularization (for bypass and endovas-cular therapy),2–9,19–21 why do all thesediscrepancies25,26,32 still exist in roughlysimilar direct vs. indirect revascularizationanalyses?9,20,21 It is obvious that more large,prospective, randomized data are required toassess the usefulness of the angiosomeconcept9,20,21; yet, will all this statisticalinformation clarify the detailed mechanismsassociated with the healing process?16,28

It has been shown that unlike ischemicconditions in other organs,1,12 critically ische-mic limbs add puzzling complementary factorswith substantial roles in tissue regenerationindependent of successful direct revasculari-zation!3,7,27,31 Apropos the study protocol fromIida’s present article,10 the MALE and AFSendpoints can still can be considered contro-versial as long as dissimilar ulcer selectionand local wound treatment persist.9,21 Accord-ing to contemporary observations, correctwound-directed revascularization promotesgradual tissue changes3,4,7,18 in nonlinearand ‘‘pathology-dependent’’31 curves of recov-ery.3,25 Not surprisingly, tissue regenerationafter CLI rescue often needs synchronousmultidisciplinary control,3,16,31,33 as Iida andcolleagues point out in their article.

The newly regained foot perfusion mayfollow a few sequential and time-related

J ENDOVASC THER COMMENTARY 6172014;21:616–624 Alexandrescu

physiological phases of reperfusion16,34 thatneed their own specific hemodynamic evalu-ation16 in tissue recovery follow-up.16,31 Moreprecise interpretation of this specific ‘‘phase-related’’ reperfusion after direct/indirect re-vascularization may disclose new insights indecoding the global and sometimes blurred‘‘healing’’ endpoint in the contemporary an-giosome literature.8,9,20,21

It is also true that indirect revascularizationcan equally induce (to some degree) tissueregeneration25,26 and may temporarily saveCLI limbs from the threat of amputa-tion,4,14,16,31 which the angiosome opponentschampioned in the last decade.9,21 It is alsotrue that the more controversial the evidencefor this very young concept, the more fear-some the debate in CLI applications.28 Thequestions to ask for future analysis probablyremain how (by which macro- and microcir-culatory evaluation)16,35 and when (in whichphase of reperfusion)16,29 does direct revas-cularization provide consistent tissue regen-eration to prove superiority over indirectrevascularization.

The article of Iida et al.10 touches anotherenthralling issue for discussion concerningthe relative vagueness in the methodologiesand clinical appraisal of the new direct/indirect revascularization strategy in currentreferences.16,27–30,32 If one takes a closer lookspecifically at methods, there is a relative lackof consensus as to how the direct/indirectrevascularization strategy is explained in theprotocol.2–9,14–20,32 A majority of authors em-ploy the principal foot angiosome arteries asthe standard method in topographical directrevascularization applications.1–3,5–8,18,29,30

Yet, following the same wound-directed re-vascularization meaning (often but not alwaysassociated with direct revascularization),16,21

other researchers reveal comparable results,acknowledging either correct foot archesreperfusion,14 the reconstitution of large be-low-the-ankle collaterals2,4 and optimal footrunoff scores,17 or both.2,16,17,28 These obser-vations probably do not contradict the intrin-sic concept of true angiosome-orientedreperfusion because undivided foot arches14

or medium-to-large (0.5–1 mm)16 arterial-arterial collaterals (part of the choke ves-sels)1,2,4,15 are likely to represent intentional

and effective flow prolongation toward thewound territory.2,4,16

The designated angiosome chart1,2 associ-ates patent foot arches (.1 mm diameter)14,16

and competent arterial-arterial connections(.0.5 mm diameter).4,15,16 In many authors’view, it stands as a logical guide to accurateanatomical and hemodynamic wound-direct-ed reperfusion.2,16 However, at the currentlevel of knowledge regarding CLI mecha-nisms, even with better definitions of aneffective direct revascularization proce-dure,9,19–21,30 do we really control all smallmicrocirculatory changes15,16,29 inside themacrovascular perfusion system that containsthe angiosome level?16

WOUND-DIRECTEDREVASCULARIZATION FROM A

MACRO- AND MICROCIRCULATORYPERSPECTIVE

Modern clinical and diagnostic informationprovides clinicians with valuable clues aboutmacro- and microcirculatory patterns in eachfoot ulcer presentation.1–4,16,28 Still, somecomplex CLI wounds, particularly in diabet-ic27,33,36 or renal24,25 patients, may involvetwo or three distal leg or forefoot angiosomesin about 35% to 55% of global presenta-tions.15–18 Explicit angiosome orientation by‘‘routine’’ examination may be more challeng-ing or even misleading in some situations.32,33

Nevertheless, this observation is reasonablyvalid for every new clinical situation. Accord-ing to concurrent reports, simultaneous mac-ro- and microcirculatory assessment canprovide real benefit in extensive or multiplefoot tissue defects that are more difficult to‘‘decode.’’6,8,16 This is particularly true for CLIwounds combining inflammatory, septic, orlocal foot compartmental high-pressure fea-tures.16,36 Deep tissue hyperemic changes canenhance notable microcirculatory distor-tions3,31,36 that may trigger remote macro-vascular septic thrombosis31 with subcuta-neous and tegumental ulcerations31,36 in‘‘apparently’’ angiosome-unrelated loca-tions.32,33,36,37 The synchronous presence ofancient scars, chronic dermosclerosis,8,16 se-vere neuropathy,3,7,8,36 or fresh digital collat-eral septic thrombosis (the end-artery

618 COMMENTARY J ENDOVASC THERAlexandrescu 2014;21:616–624

occlusive disease concept)31 may renderclinical observation even more trouble-some.33 In such situations, isolated superficialtissue estimation based on the ulcer’s area33

and depth (up to 10 mm)32 can bring only littlehelp and may outwardly conflict with thegenuine angiosome orientation.28,32

Trying to provide a more accurate anatom-ical perspective, foot perfusion was contem-porarily analyzed as an orderly subdividedanatomical system that scaffolds a few mainbifurcation levels.16 Briefly, the angiosomemain arterial branches and large collaterals(0.5–1 mm diameter), including the footarches and most of the metatarsal perfora-tors, were integrated in level III of the arterialdivision, while level IV holds the medium andsmall size (,0.5 mm) collaterals.16

Macrocirculation features can be usefullyassessed in levels I–IV (including the angio-some division stage) by a series of exams (i.e.,duplex, computed tomography, or magneticresonance angiography),38 although digitalsubtraction angiography39 and intraoperativeangiography (up to 500 micrometers detec-tion for small vessel diameter) are the mostprecise.16,32 With equal distinction in angio-some usage, intraoperative wound blush39

and indocyanine green angiography40 wererecently described as having good reliabilityfor indicating topographic CLI reperfu-sion.16,35

The microcirculation is further involved inlevels V and VI and includes the arterioles andthe capillary tear.16 Specific microcirculatoryevaluation can provide serviceable informa-tion about subcutaneous and tegumental footperfusion (often misshaped by local woundcharacteristics)18,27,31,36 and complete themacrocirculatory appraisal.16,35 Miscella-neous methods,35,41–43 such as the transcuta-neous oxygen pressure,8,41 skin perfusionpressure30,41 (also performed by Iida et al.10),tissue oxygen saturation mapping,32 and thenew group of molecular scintigraphic imagingtechniques,43,44 are available currently; theseexams can provide valuable noninvasivemicrovascular (up to the molecular level)evaluation,43,44 eventually by adding the an-giosome orientation.8,16,30,44

Interestingly, only a few publications re-garding the importance of macro- and micro-

circulation assessment in CLI are available inthe literature35 and even scarcer are observa-tions about their specific investigation.16,35

Although macrocirculatory arterial pathwaysgenerally respect the 6 foot and ankle angio-somes1,2 (with 9%–12% described anatomicalvariations37,46), independent microcirculatoryevaluation (particularly in collateral-deprivedpatients)8,16–18,31,45 can be crucial while per-forming direct revascularization (Figs. 1 and2).4,9,17,28,35,45

THE NEXT STEP

Complementary clinical evidence is certainlyneeded to enlarge our understanding of thepotential usefulness of the angiosome con-cept. In the near future, more large prospec-tive and randomized analyses will probablyadvance our knowledge of the angiosomeconcept so as to support or refute its efficacyin CLI. Beyond the solid statistical frameworkthat the vascular community eagerly awaits, afew purely clinical questions need to beasked:

^ How can we better assess the collateralthreshold between macro- and microcir-culation in each patient so that directrevascularization wound-oriented reperfu-sion becomes clinically indispensable?

^ Does this threshold depend on the samerisk factors (specific pathologies)8,31 thatinfluence both the collateral mass16,31,35

and foot arterio- and angiogenesis pro-cesses?34,36

^ Do we actually have accurate diagnostictools to explore both the angiosomemacro- and also the microcirculation16

before and after direct/indirect revascular-ization? If so, can this evaluation eventu-ally influence indications for CLI treat-ment?16,35

^ What changes in wound microcirculationmay appear after bypass direct revascu-larization compared to endovascular directrevascularization and how will MALE, AFS,healing, and ambulation accordingly varyin comparable wound-oriented vesselsand patients?

By integrating available contemporary clini-cal2–8,15–19,27,28,30,45 and meta-analysis da-


Figure 1 ^ A diabetic CLI foot undergoing direct macro- and microcirculatory revascularization. (A) A complexCLI wound, with gangrene of the toes and dorsal and forefoot abscesses. Beyond extensive deep tissueinfection, potential septic thrombosis of interdigital collaterals can be assumed. Although the case ischallenging, preliminary clinical interpretation points to tripartite angiosome involvement [the dorsalis pedis(DP) from the anterior tibial artery (ATA) and both plantar arteries from the posterior tibial artery]. In the firstpart of the intervention, (B) intraoperative angiography for macrovascular assessment reveals completeocclusion of all the distal tibial trunks, imperceptible foot arches, and a few remaining diagonal large-to-medium collaterals that bridge the dorsum of the foot to the remnant lateral plantar network. (C) Afterdebridement and local pus evacuation, the early microcirculatory status of the forefoot is shown by real-timeintraoperative laser speckle Doppler (PeriCam PSI System, Perimed, Sweden). The capillary microcirculationseems totally compromised on the toes and distal metatarsal region (dark zones on the Doppler). (D) The firststage of the planned wound-directed revascularization is specifically opening the ATA and DP. In the samesetting, the loop technique is attempted, trying to restore the plantar circulation (the two adjacent plantarangiosomes are likely involved in the same ischemic presentation). This maneuver proves to be unsuccessfuldue to heavy calcifications at the great metatarsal perforator level. (E) The angiographic macrocirculatorycontrol shows reconstituted perfusion in the DP angiosome and the dorsal arch. A few permeable diagonalcollaterals are also visible, which indirectly fill the lateral plantar territory. At this point of the planned directrevascularization procedure, is this enough to achieve correct wound-targeted reperfusion? Should theintervention be stopped? (F) The real-time microcirculatory evaluation unfortunately demonstrates littlecapillary irrigation on the plantar side of the toes despite conceptually appropriate direct revascularization onthe dorsum of the foot. An improved blood supply can, however, be seen in the lateral plantar angiosometerritory via some mediotarsal collaterals. These discrete changes in the plantar microcirculation seeminsufficient to serve the whole metatarsal zone. Remember, there is no communication between the twoarches (infeasible ‘‘loop technique’’) in a diabetic patient with global collateral deprivation.


ta,9,20,21 a few recommendations can be made

concerning the implication of the angiosome

concept in current BTK practice.

Direct revascularization: If technically feasi-

ble, this should be encouraged in CLI wounds

for appropriate healing. It probably enhances

optimal macro- and microcirculatory condi-

tions for tissue regeneration,2–9,15–21,29,45 par-

ticularly in collateral-deprived renal or diabetic

patients.3,7–9,16,27,45 Successful direct revascu-

larization can be documented by macrocircu-

latory evaluation16,35 if targeted angiosomes

are successfully reopened or neighboring

angiosome(s) assisted by complete foot arch-

es14,17 or permeable large collaterals2,4,45 are

optimally reperfused.2–8,14–16,45 Microcirculato-

Figure 2 ^ The second part of this intervention. (A) Following synchronous microcirculatory observation (thePSI system in this case), the posterior tibial artery was additionally targeted and recanalized in antegradefashion. (B) After specific ostial angioplasty of the plantar arteries, the same difficulties are encounteredwhen attempting to loop into the dorsal foot circulation. Staged dilations are further performed in the maincourses of the medial and lateral plantar arteries. (C) In the macrocirculatory completion angiogram, bothterritories joining the dorsal and the plantar forefoot show appropriate reperfusion despite a lack of directcommunication between the arches. The newly reperfused plantar angiosomes seem to properly supplylarge and medium plantar and forefoot collaterals by angiographic and local ‘‘blush’’ estimation. (D) The finalmicrocirculatory appearance after complementary plantar direct revascularization (the first phase of flowredistribution). In this case, real-time microcirculatory assessment (laser Doppler) complements themacrocirculation evaluation (on-table angiography) of the complete topographic direct revascularization ina difficult 3 angiosome ischemic presentation. (E,F) Clinical evolution after transmetatarsal amputation withintentional preservation of both arches at 3 and 26 weeks; the patient regained her ability to ambulate.


ry assessment can be complementary inspecific presentations having complex ormultiple foot lesions (Fig. 1 and 2), relying onthe operator’s best judgment.16,28,35

Indirect revascularization: If direct revascu-larization or adjacent angiosomes sustainedby effective collaterals16,28 are impossible toreconstitute (obviated by perioperative mac-rocirculatory exams),2–8,35,39,40 rescue indirectrevascularization via the best remnant collat-eral choke vessels could be attempted.2,4,16 Inthis alternative, the microcirculation evalua-tion has a pivotal role in detecting the lastingperfusion around the wound zone.16,35,45

Since competent foot arches or large (.0.5mm diameter) arterial-arterial connectionsare lacking, either real-time periproceduralmicrocirculatory analysis30,32,35,41 or earlypostoperative capillary assessment may bebeneficial.16,35,42,44

In sum, it becomes clear that macro- andmicrocirculatory oxygenated flow16,35 inten-tionally oriented toward specific ischemic footwounds may enhance tissue healing.9,20,21,35

Finally, however the direct revascularizationconcept is described in the literature, acorrectly reconstituted blood supply remainscrucial, whether it is carried by pre-designatedangiosome bundles2–9,15–21 or distributed bywound-oriented arterial axes in accordancewith local competent arches or large arterial-arterial foot perforators.2,4,14–16,45

Parallel revascularization outcomes, suchas MALE and AFS, although clearly evaluatedusing propensity score matching and multi-variate Cox proportional analysis in the articleby Iida et al.,10 can be refined by furtherprospective work. Larger analysis addingspecific macro- and microcirculation appraisalin distinct groups of CLI pathologies mayapproach the very essence of this theory inthe future.

REFERENCES

1. Taylor GI, Palmer JH. The vascular territories(angiosomes) of the body: experimental stud-ies and clinical applications. Br J Plast Surg.1987;40:113–141.

2. Attinger CE, Evans KK, Bulan E, et al. Angio-somes of the foot and ankle and clinicalimplications for limb salvage: reconstruction,

incisions and revascularization. Plast ReconstrSurg. 2006;117(7 Suppl):261S–293S.

3. Alexandrescu V, Hubermont G, Philips Y, et al.Selective angioplasty following an angiosomemodel of reperfusion in the treatment ofWagner 1–4 diabetic foot lesions: practice in amultidisciplinary diabetic limb service. J Endo-vasc Ther. 2008;15:580–593.

4. Varela C, Acin NF, Haro JD, et al. The role offoot collateral vessels on ulcer healing and limbsalvage after successful endovascular andsurgical distal procedures according to anangiosome model. Vasc Endovasc Surg. 2010;44:654–660.

5. Neville RF, Attinger CE, Bulan EJ, et al.Revascularization of a specific angiosome forlimb salvage: does the target artery matter?Ann Vasc Surg. 2009;23:367–373.

6. Iida O, Nanto S, Uematsu M, et al. Importanceof the angiosome concept for endovasculartherapy in patients with critical limb ischemia.Catheter Cardiovasc Interv. 2010;75:830–836.

7. Soderstrom M, Alback A, Biancari F, et al.Angiosome-targeted infrapopliteal endovascu-lar revascularization for treatment of diabeticfoot ulcers. J Vasc Surg. 2013;57:427–435.

8. Alexandrescu V, Vincent G, Azdad K, et al. Areliable approach to diabetic neuroischemicfoot wounds: below-the-knee angiosome-ori-ented angioplasty. J Endovasc Ther. 2011;18:376–387.

9. Biancari F, Juvonen T. Angiosome-targetedlower limb revascularization for ischemic footwounds: systematic review and meta-analysis.Eur J Vasc Endovasc Surg. 2014;47:517–522.

10. Iida O, Takahara M, Soga Y, et al. Impact ofangiosome-oriented revascularization on clini-cal outcomes in patients with critical limbischemia without concurrent wound infectionand diabetes mellitus. J Endovasc Ther. 2014;21:607–615.

11. Young PM, Gerber TC, Williamson EE, et al.Cardiac I\imaging : part 2, normal, variant andanomalous configurations of the coronaryvasculature. AJR Am J Roentgenol. 2011;4:816–826.

12. Hong MK, Pan WR, Wallace D, et al. Theangiosome territories of the spinal cord: ex-ploring the issue of preoperative spinal angi-ography. Laboratory investigation. J Neuro-surg Spine. 2008;4:352–364.

13. Yin ZX, Peng TH, Ding HM, et al. Three-dimensional visualization of the cutaneousangiosome by using angiography. Clin Anat.2013;26:282–287.


14. Rashid H, Slim H, Zayed H, et al. The impact ofarterial pedal arch quality and angiosomerevascularization on foot tissue loss healingand infrapopliteal bypass outcome. J VascSurg. 2013;57:1219–1226.

15. Osawa S, Terashi H, Tsuji Y, et al. Importanceof the six angiosome concept through arterial-arterial connections in CLI. Int Angiol. 2013;32:375–385.

16. Alexandrescu V. The angiosome concept: ana-tomical background and physiopathologicallandmarks in CLI. In: Angiosomes Applicationsin Critical Limb Ischemia: In Search for Rele-vance. Torino, Italy: Edizioni Minerva Medica.2012;1–30,71–88.

17. Kret MR, Cheng D, Azarbal AF, et al. Utility ofdirect angiosome revascularization and run-offscores in predicting outcomes in patientsundergoing revascularization for critical limbischemia. J Vasc Surg. 2013;13:1260–1263.

18. Lejay A, Georg Y, Tartaglia E, et al. Long-termoutcomes of direct and indirect below-the-kneeopen revascularization based on the angio-some concept in diabetic patients with criticallimb ischemia. Ann Vasc Surg. 2014;28:983–989.

19. Kabra A, Suresh KR, Vivekanand V, et al.Outcomes of angiosome and non-angiosometargeted revascularization in critical lower limbischemia. J Vasc Surg. 2013;57:44–49.

20. Sumpio BE, Forsythe RO, Ziegler KR, et al.Clinical implications of the angiosome model inperipheral vascular disease. J Vasc Surg. 2013;58:814–826.

21. Bosanquet DC, Glasbey JC, Williams IM, et al.Systematic review and meta-analysis of directversus indirect angiosomal revascularization ofinfrapopliteal arteries. Eur J Vasc EndovascSurg. 2014;48:88–97.

22. Houlind K, Christensen J, Hallenberg C, et al.Early results from an angiosome-directed opensurgical technique for venous arterialization inpatients with critical lower limb ischemia.Diabet Foot Ankle. 2013;17:1–5.

23. Alexandrescu V, Ngongang C, Vincent G, et al.Deep calf veins arterialization for inferior limbpreservation in diabetic patients with extendedischaemic wounds, unfit for direct arterialreconstruction: preliminary results accordingto an angiosome model of perfusion. Cardio-vasc Revasc Med. 2011;12:10–19.

24. Alexandrescu V. Is limb loss always inevitablefor critical neuro-ischemic foot wounds indiabetic patients with end stage renal diseaseand unfit for vascular reconstructions? In:Diseases of Renal Parenchyma. Sahay M, ed.

Rijeka, Croatia: InTech Open Science; 2012:228–246.

25. Azuma N, Uchida H, Kokubo T, et al. Factorsinfluencing wound healing of critical ischaemicfoot after bypass surgery: is the angiosomeimportant in selecting bypass target artery? EurJ Vasc Endovasc Surg. 2012;43:322–328.

26. Blanes O, Riera V, Puigmacia L, et al. Percuta-neous revascularization of specific angiosomein critical limb ischemia. Angeologia. 2011;63:11–17.

27. Fossaceca R, Guzzardi G, Cerini P, et al.Endovascular treatment of diabetic foot in aselected population of patients with below-the-knee disease: is the angiosome model effec-tive? Cardiovasc Intervent Radiol. 2013;36:637–644.

28. Alexandrescu VA. Is the angiosome conceptuseful ? Vascular and Endovascular Controver-sies Update. 2012; London: Biba Publ. Ltd;2012:469–482.

29. Iida O, Soga Y, Hirano K, et al. Long-termresults of direct and indirect endovascularrevascularization based on the angiosomeconcept in patients with critical limb ischemiapresenting below-the-knee lesions. J VascSurg. 2012;55:363–370.

30. Iida O, Takahara M, Soga Y, et al. Worse limbprognosis for indirect versus direct endovas-cular revascularization only in patients withcritical limb ischemia complicated with woundinfection and diabetes mellitus. Eur J VascEndovasc Surg. 2013;46:575–582.

31. O’Neal LW. Surgical pathology of the foot andclinicopathologic correlations. In: Levin andO’Neal’s The Diabetic Foot. Philadelphia: Mos-by Elsevier; 2008:367–401.

32. Kagaya Y, Ohura H, Suga H, et al. Realangiosome assessment from peripheral tissueperfusion using tissue oxygen saturation foot-mapping in patients with critical limb ischemia.Eur J Vasc Endovasc Surg. 2014;47:433–441.

33. Aerden D, Denecker N, Gallala S, et al. Woundmorphology and topography in the diabeticfoot: hurdles in implementing angiosome-guided revascularization. Int J Vasc Med.2014;2:1–5.

34. Ziegler MA, Distasi MR, Bills RG, et al. Marvels,mysteries and misconceptions of vascularcompensation to peripheral artery occlusion.Microcirculation 2010;17:3–20.

35. Kawarada O, Yokoi Y, Higashimori A, et al.Assessment of macro- and microcirculation incontemporary critical limb ischemia. CatheterCardiovasc Interv. 2011;78:1051–1058.


36. Jorneskog G. Why critical limb ischemia crite-ria are not applicable to diabetic foot and whatthe consequences are. Scand J Surg. 2012;101:

114–118.

37. Yamada T, Gloviczki P, Bower, et al. Variationsof the arterial anatomy of the foot. Am J Surg.

1993;166:130–135.

38. Jens S, Koelemay MJ, Reekers J, et al.Diagnostic performance of computed tomog-

raphy angiography and contrast-enhancedmagnetic resonance angiography in patients

with critical limb ischaemia and intermittentclaudication: systematic review and meta-anal-ysis. Eur Radiol. 2013;3:3104–3114.

39. Utsunomiya M, Nakamura M, Nakanishi M, etal. Impact of wound blush as an angiographicend point of endovascular therapy for patients

with critical limb ischemia. J Vasc Surg. 2012;55:113–121.

40. Yamamoto M, Orihashi K, Nishimori H, et al.

Indocyanine green angiography for intra-oper-ative assessment in vascular surgery. Eur J

Vasc Endovasc Surg. 2012;43:426–432.

41. Yang C, Weng H, Chen L, et al. Transcutaneousoxygen pressure measurement in diabetic footulcers: mean values and cut-point for woundhealing. J Wound Ostomy Continence Nurs.2013;40:585–589.

42. Palestro CJ, Love C. Nuclear medicine anddiabetic foot infections. Semin Nucl Med. 2009;39:52–65.

43. Orbay H, Hong H, Zhang Y, et al. PET/SPECTimaging of hindlimb ischemia: focusing onangiogenesis and blood flow. Angiogenesis.2013;16:279–287.

44. Marre F, Sibille L, Nalda E, et al. (18)F-FDG PET/CT imaging of critical ischemia in the diabeticfoot. Clin Nucl Med. 2013;38:269–271.

45. Acin F, Varela C, de Maturana IL, et al. Resultsof infrapopliteal endovascular procedures per-formed in diabetic patients with critical limbischemia and tissue loss from the perspectiveof an angiosome-oriented revascularizationstrategy. Intern J Vasc Med. 2014;10:2–15.

46. Bouchet A, Cuilleret J. Topographic anatomy ofthe inferior limb. 3rd ed Simep Publ. Masson;1995:69–107.


commentary: myths and proofs of angiosome applications in cli: where do we stand?

Documents