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Editor's Choice – Direct vs. Indirect Angiosomal Revascularisation of Infrapopliteal Arteries, an Updated Systematic Review and Meta-analysis

Open ArchivePublished:August 24, 2018DOI:https://doi.org/10.1016/j.ejvs.2018.07.017

      Background

      The importance of the angiosome concept in tibial artery revascularisation remains controversial. The aim of this review was to assess the outcomes of direct revascularisation (revascularisation to the angiosome of tissue loss; DR) versus indirect revascularisation (IR) in infrapopliteal arteries.

      Methods

      A previously conducted systematic review was updated according to PRISMA guidelines. Studies comparing DR with IR by both endovascular and surgical means for patients with localised tissue loss were included. Meta-analyses were performed to assess the effect of DR versus IR on wound healing (total and time to healing), limb salvage, mortality, and re-intervention rates, with multiple sensitivity analyses. Outcome data quality was determined using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool.

      Results

      Seven studies (2278 limbs) were identified in the updated search, which when combined with the previous search resulted in 22 studies, comprising 4146 limbs, being included. Wound healing rates (odds ratio [OR] 0.51; 95% CI 0.39–0.68, p < 0.001), time to wound healing (standard mean difference [SMD] −1.70; 95% CI –3.34 to −0.07, p = .04) and limb salvage (OR 0.37; 95% CI 0.24–0.58, p < .0001) were significantly better with DR compared with IR. Sensitivity analyses were concordant with the primary analysis for these outcomes, with the exception of the effect of wound healing rates between DR and IR, which was lost on sensitivity analysis for bypass surgery. Mode of revascularisation had no effect on mortality or on re-intervention rates. GRADE outcomes were very low.

      Conclusion

      DR of the tibial vessels appears to result in improved wound healing and limb salvage rates compared with IR, with no effect on mortality or re-intervention rates. For surgical revascularisation the importance of DR appears to be lost for wound healing. When possible, these low quality data suggests DR should be undertaken in preference to IR.

      Keywords

      When performing revascularisation to the tibial or pedal vessels for tissue loss, the importance of considering the angiosome concept during planning is uncertain. Relatively small meta-analyses have previously shown an improvement in wound healing and limb salvage when limbs undergo direct (rather than indirect) angiosomal revascularisation. This updated review has identified a number of recent studies (all observational), and shown that limbs undergoing direct revascularisation appear to do better in terms of wound healing, time to healing, and limb salvage. When surgical bypasses were considered separately, the importance of angiosomal revascularisation was lost, with a non-significant trend towards direct revascularisation only. These results comprise the strongest evidence to date for the importance of the angiosomal model, although these conclusions are only based on observational data and require cautious interpretation and application into clinical practice.

      Introduction

      The angiosome concept, first described in 1987, defines an angiosome as an area of tissue comprising skin, subcutaneous tissue, fascia, muscle, and bone supplied by a specific artery and drained by a specific vein.
      • Taylor G.I.
      • Palmer J.H.
      The vascular territories (angiosomes) of the body: experimental study and clinical applications.
      The foot consists of six angiosomes: three arising from the posterior tibial artery, two from the peroneal artery, and one from the anterior tibial artery
      • Taylor G.
      • Pan W.
      Angiosomes of the leg: anatomic study and clinical implications.
      • Attinger C.E.
      • Evans K.K.
      • Bulan E.
      • Blume P.
      • Cooper P.
      Angiosomes of the foot and ankle and clinical implications for limb salvage: reconstruction, incisions, and revascularization.
      (Fig. 1). Patients with critical limb ischaemia (CLI) who develop tissue loss in a specific angiosome(s) and undergo tibial artery revascularisation are considered to have a “direct revascularisation” (DR) when the artery of interest supplies the area of tissue loss, and “indirect revascularisation” (IR) when it does not.
      Figure 1
      Figure 1Angiosomes of the foot and ankle. There are six angiosomes of the foot and ankle which are supplied by three main arteries. The anterior tibial (ATA) and the dorsalis pedis artery supply the dorsum side of the foot and toes (left image). The posterior tibial artery (PTA) supplies the plantar aspect of the foot which comprises of three angiosomes, a calcaneal branch to the heel, the medial and lateral foot are supplied by the medial and lateral plantar artery respectively (middle image). The heel and lateral border of the ankle are supplied by the peroneal artery (PA) (right image). Figure reproduced with permission from Iida et al.
      • Iida O.
      • Soga Y.
      • Hirano K.
      • Kawasaki D.
      • Suzuki K.
      • Miyashita Y.
      • et al.
      Long-term results of direct and indirect endovascular revascularization based on the angiosome concept in patients with critical limb ischemia presenting with isolated below-the-knee lesions.
      There is some debate as to the importance of the angiosome concept when undertaking tibial artery revascularisation.
      • Taylor G.I.
      • Palmer J.H.
      The vascular territories (angiosomes) of the body: experimental study and clinical applications.
      • Setacci C.
      • De Donato G.
      • Setacci F.
      • Chisci E.
      Ischemic foot: definition, etiology and angiosome concept.
      Initial small observational studies suggested that DR was superior to IR for both open bypass surgery
      • Kabra A.
      • Suresh K.R.
      • Vivekanand V.
      • Vishnu M.
      • Sumanth R.
      • Nekkanti M.
      Outcomes of angiosome and non-angiosome targeted revascularization in critical lower limb ischemia.
      and endovascular revascularisation.
      • Attinger C.E.
      • Evans K.K.
      • Bulan E.
      • Blume P.
      • Cooper P.
      Angiosomes of the foot and ankle and clinical implications for limb salvage: reconstruction, incisions, and revascularization.
      • Alexandrescu V.
      • Söderström M.
      • Venermo M.
      Angiosome theory: fact or fiction?.
      • Attinger C.
      • Cooper P.
      • Blume P.
      • Bulan E.
      The safest surgical incisions and amputations applying the angiosome principles and using the Doppler to assess the arterial-arterial connections of the foot and ankle.
      More recent studies have tended to highlight the importance of DR over IR, but have also stressed the importance of adequate collaterals, with some suggesting IR in the presence of adequate collaterals has equivalent outcomes to DR.
      • Alexandrescu V.
      • Söderström M.
      • Venermo M.
      Angiosome theory: fact or fiction?.
      • Attinger C.
      • Cooper P.
      • Blume P.
      • Bulan E.
      The safest surgical incisions and amputations applying the angiosome principles and using the Doppler to assess the arterial-arterial connections of the foot and ankle.
      Meta-analysis of these earlier studies showed a trend towards superior wound healing and limb salvage rates with DR with no difference in mortality or re-intervention rates between the two types of revascularisation, although the quality of evidence was low and total number of included papers was few.
      • Bosanquet D.C.
      • Glasbey J.C.D.
      • Williams I.M.
      • Twine C.P.
      Systematic review and meta-analysis of direct versus indirect angiosomal revascularisation of infrapopliteal arteries.
      There was also a suggestion on certain sensitivity analyses that the value of DR over IR was less pronounced for open bypass than endovascular revascularisation.
      • Jongsma H.
      • Bekken J.A.
      • Akkersdijk G.P.
      • Hoeks S.E.
      • Verhagen H.J.
      • Fioole B.
      Angiosome-directed revascularization in patients with critical limb ischemia.
      Since this initial meta-analysis, a number of further studies have been published. The results from these generally small observational studies vary, and as a result uncertainty as to the importance of the angiosome concept remains.
      • Aboyans V.
      • Ricco J.-B.
      • Bartelink M.-L.E.L.
      • Björck M.
      • Brodmann M.
      • Cohnert T.
      • et al.
      2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European society for vascular surgery (ESVS).
      The aim of this updated systematic review and meta-analysis was to collate all studies of DR and IR of infrapopliteal vessels during both open and endovascular revascularisation, and to provide pooled data for key clinical outcomes.

      Methods

      Search strategy

      This systematic review and meta-analysis was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for interventional studies.
      • Liberati A.
      • Altman D.G.
      • Tetzlaff J.
      • Mulrow C.
      • Gøtzsche P.C.
      • Ioannidis J.P.A.
      • et al.
      The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration.
      • Moher D.
      • Shamseer L.
      • Clarke M.
      • Ghersi D.
      • Liberati A.
      • Petticrew M.
      • et al.
      Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement.
      The Cochrane collaboration specified protocol was utilised.
      • Higgins J.
      • Green S.
      Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011].
      Medline (via PubMed), Embase, the Cochrane Library Database, and the Cochrane Collaboration Central Register of Controlled Clinical Trials were searched without date or language restrictions. A previous search was updated,
      • Bosanquet D.C.
      • Glasbey J.C.D.
      • Williams I.M.
      • Twine C.P.
      Systematic review and meta-analysis of direct versus indirect angiosomal revascularisation of infrapopliteal arteries.
      with the last search date on 31 December 2017. The term “angioso*” was used as the search word, which searches numerous terms including angiosomal, angiosome and angiosomes. A further search for other articles was undertaken by firstly performing a comprehensive review of the bibliography of key articles, and also by exploring the “related articles” list of key papers in PubMed. The European Journal of Vascular and Endovascular Surgery, the British Journal of Surgery, and the Journal of Vascular Surgery websites were also searched. Results were restricted to human research published in English, with review articles excluded.

      Inclusion and exclusion criteria

      All studies that reported outcomes (as given below) between DR and IR of the infrapopliteal vessels either by endovascular or open surgery (or both) in patients with CLI were included. Cohorts with patients undergoing concomitant “inflow” procedures were included. The following studies were excluded: non-English language papers; papers arising or suspected of arising from the same patient cohort; papers with non-extractable data; papers with no clinical outcomes reported.

      Data extraction and assessment of study quality

      Two authors (N.D. and D.C.B.) independently extracted data and assessed the methodological quality of the studies. If any disagreements arose a consensus was reached with reference to the third author (C.P.T.). The following data were extracted from each study: first author; year of publication; study design and type (retrospective or prospective, single or multiple centres, whether consecutive patients were enrolled, if the angiosome concept was considered when performing revascularisation), number of patients and individual limbs undergoing revascularisation, follow up time, revascularisation modality (endovascular or surgical bypass, vein or prosthetic conduit, or both), and the target vessel(s) revascularised. Study quality was assessed using the Newcastle–Ottawa (NO) score.
      • Wells G.A.
      • Shea B.
      • O'Connell D.
      • Peterson J.
      • Welch V.
      • Losos M.
      • et al.
      The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses.
      The NO score assigns points which are based on three parameters: (1) the quality of patient selection (maximum 4 points); (2) the comparability of the cohort (maximum 2 points); and (3) outcome assessment (maximum 3 points). Studies which scored ≥6 were considered to be of higher quality.
      Where studies presented propensity score matched data (presented because of significant baseline differences between patient groups), these were extracted preferentially. Data were extracted at one year follow up when given, and at maximum follow up time.

      Outcome measures

      Outcome measures were collected and analysed for individual limbs rather than patients, except for mortality. The outcome measures were defined as
      • (1)
        wound healing: complete epithelialisation of the targeted lesion with or without secondary interventions such as debridement, skin grafting, etc. Analysed as dichotomous (healed vs. not at time points) and continuous (time to healing) depending on data given.
      • (2)
        limb salvage: the absence of major amputation (any amputation proximal to the tarsometatarsal joint)
      • (3)
        mortality
      • (4)
        re-intervention.
      All outcomes were analysed for the quality of evidence and strength of recommendation using the Cochrane collaboration's recommended tool the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.
      Details of parameters used in the GRADE system are given in Appendix I. The resultant evidence strength can be “high”, “medium”, “low”, or “very low”.

      Statistical analysis and evidence rating

      Data analysis was performed using Review Manager version 5.3 (Cochrane Collaboration, Software Update, Oxford, UK). Statistical analyses of dichotomous variables were performed using odds ratios (ORs) as the summary statistic. The OR for each study was weighted based on sample size and reported with 95% confidence intervals (CIs). Continuous data were analysed using an inverse variance random effects model, and the standard mean difference used as the summary statistic, and reported with 95% CIs. The methodology described by Hozo et al.
      • Hozo S.P.
      • Djulbegovic B.
      • Hozo I.
      Estimating the mean and variance from the median, range, and the size of a sample.
      was used to transform continuous data presented as a median and range to a mean and standard deviation (SD). When SDs were missing, they were imputed as per Cochrane recommendations.
      • Higgins J.
      • Green S.
      Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011].
      Wound healing, limb salvage, mortality, and re-intervention rates were evaluated in a meta-analysis comparing DR and IR. In order to account for clinical heterogeneity, a random effects model using the Mantel–Haenszel method was utilised. Heterogeneity was assessed by means of the I2 test and was considered statistically significant when p < .05. I2 values range from 0 to 100% (0–24%, no heterogeneity; 25–49%, moderate heterogeneity; 50–74%, high level of heterogeneity; 75–100%, extreme heterogeneity).
      • Lau J.
      • Ioannidis J.P.
      • Schmid C.H.
      Quantitative synthesis in systematic reviews.
      • Higgins J.P.T.
      • Thompson S.G.
      • Deeks J.J.
      • Altman D.G.
      Measuring inconsistency in meta-analyses.
      When two or more studies were included for an outcome measure sensitivity analyses were performed, except for “time to wound healing” where certain data were based on imputations. The following sensitivity analyses were undertaken: endovascular treatment alone, surgical bypass alone, larger studies (n > 100), studies with propensity score matched groups, studies with a NO score of ≥6, studies with a follow up given at one year, and studies enrolling diabetic patients only.

      Results

      Search and selection process of papers

      Paper selection involved the inclusion of papers from a previous meta-analysis,
      • Bosanquet D.C.
      • Glasbey J.C.D.
      • Williams I.M.
      • Twine C.P.
      Systematic review and meta-analysis of direct versus indirect angiosomal revascularisation of infrapopliteal arteries.
      combined with the findings of an updated systematic review of which the methodology is given above. A total of 1881 articles were identified from the current literature search, of which 15 were retrieved for full evaluation. Seven studies (2278 limbs) were identified in this current search. The prior meta-analysis included 15 studies,
      • Bosanquet D.C.
      • Glasbey J.C.D.
      • Williams I.M.
      • Twine C.P.
      Systematic review and meta-analysis of direct versus indirect angiosomal revascularisation of infrapopliteal arteries.
      resulting in a total of 22 studies (of which two were conference proceedings), comprising 4146 limbs, which matched the inclusion criteria and were suitable for data extraction and meta-analysis (Fig. 2).
      • Kabra A.
      • Suresh K.R.
      • Vivekanand V.
      • Vishnu M.
      • Sumanth R.
      • Nekkanti M.
      Outcomes of angiosome and non-angiosome targeted revascularization in critical lower limb ischemia.
      • Acín F.
      • Varela C.
      • López De Maturana I.
      • De Haro J.
      • Bleda S.
      • Rodriguez-Padilla J.
      Results of infrapopliteal endovascular procedures performed in diabetic patients with critical limb ischemia and tissue loss from the perspective of an angiosome-oriented revascularization strategy.
      • Neville R.F.
      • Attinger C.E.
      • Bulan E.J.
      • Ducic I.
      • Thomassen M.
      • Sidawy A.N.
      Revascularization of a specific angiosome for limb salvage: does the target artery matter?.
      • Osawa S.
      • Terashi H.
      • Tsuji Y.
      • Kitano I.
      • Sugimoto K.
      Importance of the six angiosomes concept through arterial-arterial connections in CLI.
      • Oshima S.
      • Noda K.
      • Sumida H.
      • Fukushima H.
      • Nishijima T.
      • Morihisa K.
      • et al.
      Impact of the angiosome concept for endovascular therapy in patients with critical limb ischemia due to isolated below-the knee lesions.
      • Rashid H.
      • Slim H.
      • Zayed H.
      • Huang D.Y.
      • Wilkins C.J.
      • Evans D.R.
      • et al.
      The impact of arterial pedal arch quality and angiosome revascularization on foot tissue loss healing and infrapopliteal bypass outcome.
      • Ricco J.B.
      • Gargiulo M.
      • Stella A.
      • Abualhin M.
      • Gallitto E.
      • Desvergnes M.
      • et al.
      Impact of angiosome- and nonangiosome-targeted peroneal bypass on limb salvage and healing in patients with chronic limb-threatening ischemia.
      • De Athayde Soares R.
      • Brochado Neto F.C.
      • Matielo M.F.
      • Lehn C.N.
      • Nakamura E.T.
      • Godoy M.R.
      • et al.
      Concept of angiosome does not affect limb salvage in infrapopliteal angioplasty.
      • Söderström M.
      • Albäck A.
      • Biancari F.
      • Lappalainen K.
      • Lepäntalo M.
      • Venermo M.
      Angiosome-targeted infrapopliteal endovascular revascularization for treatment of diabetic foot ulcers.
      • Soon C.
      • Tay K.
      • Taneja M.
      • Teo T.
      • Lo R.
      • Burgmans M.C.
      • et al.
      Angiosome directed angioplasty for limb salvage in critical limb ischemia.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      • Troisi N.
      • Turini F.
      • Chisci E.
      • Ercolini L.
      • Frosini P.
      • Lombardi R.
      • et al.
      Pedal arch patency and not direct-angiosome revascularization predicts outcomes of endovascular interventions in diabetic patients with critical limb ischemia.
      • Alexandrescu V.-A.
      • Hubermont G.
      • Philips Y.
      • Guillaumie B.
      • Ngongang C.
      • Vandenbossche P.
      • et al.
      Selective primary angioplasty following an angiosome model of reperfusion in the treatment of Wagner 1–4 diabetic foot lesions: practice in a multidisciplinary diabetic limb service.
      • Varela C.
      • Acín F.
      • de Haro J.
      • Bleda S.
      • Esparza L.
      • March J.R.
      The role of foot collateral vessels on ulcer healing and limb salvage after successful endovascular and surgical distal procedures according to an angiosome model.
      • Zheng X.T.
      • Zeng R.C.
      • Huang J.Y.
      • Pan L.M.
      • Su X.
      • Wu Z.H.
      • et al.
      The use of the angiosome concept for treating infrapopliteal critical limb ischemia through interventional therapy and determining the clinical significance of collateral vessels.
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      • Azuma N.
      • Uchida H.
      • Kokubo T.
      • Koya A.
      • Akasaka N.
      • Sasajima T.
      Factors influencing wound healing of critical ischaemic foot after bypass surgery: is the angiosome important in selecting bypass target artery?.
      • Fossaceca R.
      • Guzzardi G.
      • Cerini P.
      • Cusaro C.
      • Stecco A.
      • Parziale G.
      • et al.
      Endovascular treatment of diabetic foot in a selected population of patients with below-the-knee disease: is the angiosome model effective?.
      • Jeon E.Y.
      • Cho Y.K.
      • Yoon D.Y.
      • Kim D.J.
      • Woo J.J.
      Clinical outcome of angiosome-oriented infrapopliteal percutaneous transluminal angioplasty for isolated infrapopliteal lesions in patients with critical limb ischemia.
      • Iida O.
      • Takahara M.
      • Soga Y.
      • Yamauchi Y.
      • Hirano K.
      • Tazaki J.
      • et al.
      Impact of angiosome-oriented revascularization on clinical outcomes in critical limb ischemia patients without concurrent wound infection and diabetes.
      • Kret M.R.
      • Cheng D.
      • Azarbal A.F.
      • Mitchell E.L.
      • Liem T.K.
      • Moneta G.L.
      • et al.
      Utility of direct angiosome revascularization and runoff scores in predicting outcomes in patients undergoing revascularization for critical limb ischemia.
      • Lejay A.
      • Georg Y.
      • Tartaglia E.
      • Gaertner S.
      • Geny B.
      • Thaveau F.
      • et al.
      Long-term outcomes of direct and indirect below-the-knee open revascularization based on the angiosome concept in diabetic patients with critical limb ischemia.
      All included studies were cohort studies in which DR outcomes were compared with IR outcomes. One paper included a group of “combined revascularisation” (CR) when both DR and IR was performed,
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      otherwise CR was reported as DR in other papers. Only 22 patients were available for CR data specifically, and because of low numbers were not extracted for separate analysis. Excluded papers of note included seven duplicate publications,
      • Alexandrescu V.
      • Vincent G.
      • Azdad K.
      • Hubermont G.
      • Ledent G.
      • Ngongang C.
      • et al.
      A reliable approach to diabetic neuroischemic foot wounds: below-the-knee angiosome-oriented angioplasty.
      • Iida O.
      • Nanto S.
      • Uematsu M.
      • Ikeoka K.
      • Okamoto S.
      • Dohi T.
      • et al.
      Importance of the angiosome concept for endovascular therapy in patients with critical limb ischemia.
      • Iida O.
      • Soga Y.
      • Hirano K.
      • Kawasaki D.
      • Suzuki K.
      • Miyashita Y.
      • et al.
      Long-term results of direct and indirect endovascular revascularization based on the angiosome concept in patients with critical limb ischemia presenting with isolated below-the-knee lesions.
      • Iida O.
      • Takahara M.
      • Soga Y.
      • Yamauchi Y.
      • Hirano K.
      • Tazaki J.
      • et al.
      Worse limb prognosis for indirect versus direct endovascular revascularization only in patients with critical limb ischemia complicated with wound infection and diabetes mellitus.
      • Nishijima T.
      • Ono T.
      • Morihisa K.
      • Kugimiya F.
      • Fukushima H.
      • Sumida H.
      • et al.
      Direct flow utilizing the angiosome concept is valuable for salvaging limbs in critical limb ischemia patients.
      • Špillerová K.
      • Sörderström M.
      • Albäck A.
      • Venermo M.
      The feasibility of angiosome-targeted endovascular treatment in patients with critical limb ischemia and foot ulcer.
      • Špillerová K.
      • Settembre N.
      • Biancari F.
      • Albäck A.
      • Venermo M.
      Angiosome targeted PTA is more important in endovascular revascularisation than in surgical revascularisation: analysis of 545 patients with ischaemic tissue lesions.
      two with un-extractable data,
      • Pavé M.
      • Benadiba L.
      • Berger L.
      • Gouicem D.
      • Hendricks M.
      • Plissonnier D.
      Below-the-knee angioplasty for critical limb ischemia: results of a series of 157 procedures and impact of the angiosome concept.
      • Kawarada O.
      • Fujihara M.
      • Higashimori A.
      • Yokoi Y.
      • Honda Y.
      • Fitzgerald P.J.
      Predictors of adverse clinical outcomes after successful infrapopliteal intervention.
      and one with non-clinical outcome measures only.
      • Rother U.
      • Krenz K.
      • Lang W.
      • Horch R.E.
      • Schmid A.
      • Heinz M.
      • et al.
      Immediate changes of angiosome perfusion during tibial angioplasty.
      Two groups presented different outcome data in a similar clinical group.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      • Iida O.
      • Takahara M.
      • Soga Y.
      • Yamauchi Y.
      • Hirano K.
      • Tazaki J.
      • et al.
      Impact of angiosome-oriented revascularization on clinical outcomes in critical limb ischemia patients without concurrent wound infection and diabetes.
      • Iida O.
      • Soga Y.
      • Hirano K.
      • Kawasaki D.
      • Suzuki K.
      • Miyashita Y.
      • et al.
      Long-term results of direct and indirect endovascular revascularization based on the angiosome concept in patients with critical limb ischemia presenting with isolated below-the-knee lesions.
      • Špillerová K.
      • Settembre N.
      • Biancari F.
      • Albäck A.
      • Venermo M.
      Angiosome targeted PTA is more important in endovascular revascularisation than in surgical revascularisation: analysis of 545 patients with ischaemic tissue lesions.
      Data extraction used both publications outcome data to maximise data available for sensitivity analyses.
      Figure 2
      Figure 2Flow chart demonstrating the literature search strategy for Systematic Reviews and Meta-Analysis (PRISMA) detailing the process of identification for eligible studies.

      Baseline characteristics and the study design

      Study demographics are provided in Table 1. All studies were retrospective except for one prospective study,
      • Kabra A.
      • Suresh K.R.
      • Vivekanand V.
      • Vishnu M.
      • Sumanth R.
      • Nekkanti M.
      Outcomes of angiosome and non-angiosome targeted revascularization in critical lower limb ischemia.
      and one without information.
      • Oshima S.
      • Noda K.
      • Sumida H.
      • Fukushima H.
      • Nishijima T.
      • Morihisa K.
      • et al.
      Impact of the angiosome concept for endovascular therapy in patients with critical limb ischemia due to isolated below-the knee lesions.
      Thirteen were single centre studies
      • Kabra A.
      • Suresh K.R.
      • Vivekanand V.
      • Vishnu M.
      • Sumanth R.
      • Nekkanti M.
      Outcomes of angiosome and non-angiosome targeted revascularization in critical lower limb ischemia.
      • Acín F.
      • Varela C.
      • López De Maturana I.
      • De Haro J.
      • Bleda S.
      • Rodriguez-Padilla J.
      Results of infrapopliteal endovascular procedures performed in diabetic patients with critical limb ischemia and tissue loss from the perspective of an angiosome-oriented revascularization strategy.
      • Neville R.F.
      • Attinger C.E.
      • Bulan E.J.
      • Ducic I.
      • Thomassen M.
      • Sidawy A.N.
      Revascularization of a specific angiosome for limb salvage: does the target artery matter?.
      • Osawa S.
      • Terashi H.
      • Tsuji Y.
      • Kitano I.
      • Sugimoto K.
      Importance of the six angiosomes concept through arterial-arterial connections in CLI.
      • Rashid H.
      • Slim H.
      • Zayed H.
      • Huang D.Y.
      • Wilkins C.J.
      • Evans D.R.
      • et al.
      The impact of arterial pedal arch quality and angiosome revascularization on foot tissue loss healing and infrapopliteal bypass outcome.
      • De Athayde Soares R.
      • Brochado Neto F.C.
      • Matielo M.F.
      • Lehn C.N.
      • Nakamura E.T.
      • Godoy M.R.
      • et al.
      Concept of angiosome does not affect limb salvage in infrapopliteal angioplasty.
      • Söderström M.
      • Albäck A.
      • Biancari F.
      • Lappalainen K.
      • Lepäntalo M.
      • Venermo M.
      Angiosome-targeted infrapopliteal endovascular revascularization for treatment of diabetic foot ulcers.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      • Troisi N.
      • Turini F.
      • Chisci E.
      • Ercolini L.
      • Frosini P.
      • Lombardi R.
      • et al.
      Pedal arch patency and not direct-angiosome revascularization predicts outcomes of endovascular interventions in diabetic patients with critical limb ischemia.
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      • Azuma N.
      • Uchida H.
      • Kokubo T.
      • Koya A.
      • Akasaka N.
      • Sasajima T.
      Factors influencing wound healing of critical ischaemic foot after bypass surgery: is the angiosome important in selecting bypass target artery?.
      • Fossaceca R.
      • Guzzardi G.
      • Cerini P.
      • Cusaro C.
      • Stecco A.
      • Parziale G.
      • et al.
      Endovascular treatment of diabetic foot in a selected population of patients with below-the-knee disease: is the angiosome model effective?.
      • Lejay A.
      • Georg Y.
      • Tartaglia E.
      • Gaertner S.
      • Geny B.
      • Thaveau F.
      • et al.
      Long-term outcomes of direct and indirect below-the-knee open revascularization based on the angiosome concept in diabetic patients with critical limb ischemia.
      and four were multiple centre studies
      • Ricco J.B.
      • Gargiulo M.
      • Stella A.
      • Abualhin M.
      • Gallitto E.
      • Desvergnes M.
      • et al.
      Impact of angiosome- and nonangiosome-targeted peroneal bypass on limb salvage and healing in patients with chronic limb-threatening ischemia.
      • Alexandrescu V.-A.
      • Hubermont G.
      • Philips Y.
      • Guillaumie B.
      • Ngongang C.
      • Vandenbossche P.
      • et al.
      Selective primary angioplasty following an angiosome model of reperfusion in the treatment of Wagner 1–4 diabetic foot lesions: practice in a multidisciplinary diabetic limb service.
      • Zheng X.T.
      • Zeng R.C.
      • Huang J.Y.
      • Pan L.M.
      • Su X.
      • Wu Z.H.
      • et al.
      The use of the angiosome concept for treating infrapopliteal critical limb ischemia through interventional therapy and determining the clinical significance of collateral vessels.
      • Iida O.
      • Takahara M.
      • Soga Y.
      • Yamauchi Y.
      • Hirano K.
      • Tazaki J.
      • et al.
      Impact of angiosome-oriented revascularization on clinical outcomes in critical limb ischemia patients without concurrent wound infection and diabetes.
      (no data for 5
      • Oshima S.
      • Noda K.
      • Sumida H.
      • Fukushima H.
      • Nishijima T.
      • Morihisa K.
      • et al.
      Impact of the angiosome concept for endovascular therapy in patients with critical limb ischemia due to isolated below-the knee lesions.
      • Soon C.
      • Tay K.
      • Taneja M.
      • Teo T.
      • Lo R.
      • Burgmans M.C.
      • et al.
      Angiosome directed angioplasty for limb salvage in critical limb ischemia.
      • Varela C.
      • Acín F.
      • de Haro J.
      • Bleda S.
      • Esparza L.
      • March J.R.
      The role of foot collateral vessels on ulcer healing and limb salvage after successful endovascular and surgical distal procedures according to an angiosome model.
      • Jeon E.Y.
      • Cho Y.K.
      • Yoon D.Y.
      • Kim D.J.
      • Woo J.J.
      Clinical outcome of angiosome-oriented infrapopliteal percutaneous transluminal angioplasty for isolated infrapopliteal lesions in patients with critical limb ischemia.
      • Kret M.R.
      • Cheng D.
      • Azarbal A.F.
      • Mitchell E.L.
      • Liem T.K.
      • Moneta G.L.
      • et al.
      Utility of direct angiosome revascularization and runoff scores in predicting outcomes in patients undergoing revascularization for critical limb ischemia.
      ). Thirteen studies enrolled consecutive patients.
      • Acín F.
      • Varela C.
      • López De Maturana I.
      • De Haro J.
      • Bleda S.
      • Rodriguez-Padilla J.
      Results of infrapopliteal endovascular procedures performed in diabetic patients with critical limb ischemia and tissue loss from the perspective of an angiosome-oriented revascularization strategy.
      • Neville R.F.
      • Attinger C.E.
      • Bulan E.J.
      • Ducic I.
      • Thomassen M.
      • Sidawy A.N.
      Revascularization of a specific angiosome for limb salvage: does the target artery matter?.
      • Oshima S.
      • Noda K.
      • Sumida H.
      • Fukushima H.
      • Nishijima T.
      • Morihisa K.
      • et al.
      Impact of the angiosome concept for endovascular therapy in patients with critical limb ischemia due to isolated below-the knee lesions.
      • Rashid H.
      • Slim H.
      • Zayed H.
      • Huang D.Y.
      • Wilkins C.J.
      • Evans D.R.
      • et al.
      The impact of arterial pedal arch quality and angiosome revascularization on foot tissue loss healing and infrapopliteal bypass outcome.
      • Ricco J.B.
      • Gargiulo M.
      • Stella A.
      • Abualhin M.
      • Gallitto E.
      • Desvergnes M.
      • et al.
      Impact of angiosome- and nonangiosome-targeted peroneal bypass on limb salvage and healing in patients with chronic limb-threatening ischemia.
      • De Athayde Soares R.
      • Brochado Neto F.C.
      • Matielo M.F.
      • Lehn C.N.
      • Nakamura E.T.
      • Godoy M.R.
      • et al.
      Concept of angiosome does not affect limb salvage in infrapopliteal angioplasty.
      • Söderström M.
      • Albäck A.
      • Biancari F.
      • Lappalainen K.
      • Lepäntalo M.
      • Venermo M.
      Angiosome-targeted infrapopliteal endovascular revascularization for treatment of diabetic foot ulcers.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      • Varela C.
      • Acín F.
      • de Haro J.
      • Bleda S.
      • Esparza L.
      • March J.R.
      The role of foot collateral vessels on ulcer healing and limb salvage after successful endovascular and surgical distal procedures according to an angiosome model.
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      • Iida O.
      • Takahara M.
      • Soga Y.
      • Yamauchi Y.
      • Hirano K.
      • Tazaki J.
      • et al.
      Impact of angiosome-oriented revascularization on clinical outcomes in critical limb ischemia patients without concurrent wound infection and diabetes.
      • Kret M.R.
      • Cheng D.
      • Azarbal A.F.
      • Mitchell E.L.
      • Liem T.K.
      • Moneta G.L.
      • et al.
      Utility of direct angiosome revascularization and runoff scores in predicting outcomes in patients undergoing revascularization for critical limb ischemia.
      • Lejay A.
      • Georg Y.
      • Tartaglia E.
      • Gaertner S.
      • Geny B.
      • Thaveau F.
      • et al.
      Long-term outcomes of direct and indirect below-the-knee open revascularization based on the angiosome concept in diabetic patients with critical limb ischemia.
      Twelve studies (2182 limbs) performed endovascular revascularisation alone,
      • Acín F.
      • Varela C.
      • López De Maturana I.
      • De Haro J.
      • Bleda S.
      • Rodriguez-Padilla J.
      Results of infrapopliteal endovascular procedures performed in diabetic patients with critical limb ischemia and tissue loss from the perspective of an angiosome-oriented revascularization strategy.
      • Osawa S.
      • Terashi H.
      • Tsuji Y.
      • Kitano I.
      • Sugimoto K.
      Importance of the six angiosomes concept through arterial-arterial connections in CLI.
      • Oshima S.
      • Noda K.
      • Sumida H.
      • Fukushima H.
      • Nishijima T.
      • Morihisa K.
      • et al.
      Impact of the angiosome concept for endovascular therapy in patients with critical limb ischemia due to isolated below-the knee lesions.
      • De Athayde Soares R.
      • Brochado Neto F.C.
      • Matielo M.F.
      • Lehn C.N.
      • Nakamura E.T.
      • Godoy M.R.
      • et al.
      Concept of angiosome does not affect limb salvage in infrapopliteal angioplasty.
      • Söderström M.
      • Albäck A.
      • Biancari F.
      • Lappalainen K.
      • Lepäntalo M.
      • Venermo M.
      Angiosome-targeted infrapopliteal endovascular revascularization for treatment of diabetic foot ulcers.
      • Soon C.
      • Tay K.
      • Taneja M.
      • Teo T.
      • Lo R.
      • Burgmans M.C.
      • et al.
      Angiosome directed angioplasty for limb salvage in critical limb ischemia.
      • Troisi N.
      • Turini F.
      • Chisci E.
      • Ercolini L.
      • Frosini P.
      • Lombardi R.
      • et al.
      Pedal arch patency and not direct-angiosome revascularization predicts outcomes of endovascular interventions in diabetic patients with critical limb ischemia.
      • Alexandrescu V.-A.
      • Hubermont G.
      • Philips Y.
      • Guillaumie B.
      • Ngongang C.
      • Vandenbossche P.
      • et al.
      Selective primary angioplasty following an angiosome model of reperfusion in the treatment of Wagner 1–4 diabetic foot lesions: practice in a multidisciplinary diabetic limb service.
      • Zheng X.T.
      • Zeng R.C.
      • Huang J.Y.
      • Pan L.M.
      • Su X.
      • Wu Z.H.
      • et al.
      The use of the angiosome concept for treating infrapopliteal critical limb ischemia through interventional therapy and determining the clinical significance of collateral vessels.
      • Fossaceca R.
      • Guzzardi G.
      • Cerini P.
      • Cusaro C.
      • Stecco A.
      • Parziale G.
      • et al.
      Endovascular treatment of diabetic foot in a selected population of patients with below-the-knee disease: is the angiosome model effective?.
      • Jeon E.Y.
      • Cho Y.K.
      • Yoon D.Y.
      • Kim D.J.
      • Woo J.J.
      Clinical outcome of angiosome-oriented infrapopliteal percutaneous transluminal angioplasty for isolated infrapopliteal lesions in patients with critical limb ischemia.
      • Iida O.
      • Takahara M.
      • Soga Y.
      • Yamauchi Y.
      • Hirano K.
      • Tazaki J.
      • et al.
      Impact of angiosome-oriented revascularization on clinical outcomes in critical limb ischemia patients without concurrent wound infection and diabetes.
      seven studies (628 limbs) used bypass surgery,
      • Kabra A.
      • Suresh K.R.
      • Vivekanand V.
      • Vishnu M.
      • Sumanth R.
      • Nekkanti M.
      Outcomes of angiosome and non-angiosome targeted revascularization in critical lower limb ischemia.
      • Neville R.F.
      • Attinger C.E.
      • Bulan E.J.
      • Ducic I.
      • Thomassen M.
      • Sidawy A.N.
      Revascularization of a specific angiosome for limb salvage: does the target artery matter?.
      • Rashid H.
      • Slim H.
      • Zayed H.
      • Huang D.Y.
      • Wilkins C.J.
      • Evans D.R.
      • et al.
      The impact of arterial pedal arch quality and angiosome revascularization on foot tissue loss healing and infrapopliteal bypass outcome.
      • Ricco J.B.
      • Gargiulo M.
      • Stella A.
      • Abualhin M.
      • Gallitto E.
      • Desvergnes M.
      • et al.
      Impact of angiosome- and nonangiosome-targeted peroneal bypass on limb salvage and healing in patients with chronic limb-threatening ischemia.
      • Azuma N.
      • Uchida H.
      • Kokubo T.
      • Koya A.
      • Akasaka N.
      • Sasajima T.
      Factors influencing wound healing of critical ischaemic foot after bypass surgery: is the angiosome important in selecting bypass target artery?.
      • Kret M.R.
      • Cheng D.
      • Azarbal A.F.
      • Mitchell E.L.
      • Liem T.K.
      • Moneta G.L.
      • et al.
      Utility of direct angiosome revascularization and runoff scores in predicting outcomes in patients undergoing revascularization for critical limb ischemia.
      • Lejay A.
      • Georg Y.
      • Tartaglia E.
      • Gaertner S.
      • Geny B.
      • Thaveau F.
      • et al.
      Long-term outcomes of direct and indirect below-the-knee open revascularization based on the angiosome concept in diabetic patients with critical limb ischemia.
      and three (830 limbs) performed both.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      • Varela C.
      • Acín F.
      • de Haro J.
      • Bleda S.
      • Esparza L.
      • March J.R.
      The role of foot collateral vessels on ulcer healing and limb salvage after successful endovascular and surgical distal procedures according to an angiosome model.
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      Decisions on target vessel revascularisation were based on local policy/protocol in five studies (873 limbs),
      • Neville R.F.
      • Attinger C.E.
      • Bulan E.J.
      • Ducic I.
      • Thomassen M.
      • Sidawy A.N.
      Revascularization of a specific angiosome for limb salvage: does the target artery matter?.
      • Rashid H.
      • Slim H.
      • Zayed H.
      • Huang D.Y.
      • Wilkins C.J.
      • Evans D.R.
      • et al.
      The impact of arterial pedal arch quality and angiosome revascularization on foot tissue loss healing and infrapopliteal bypass outcome.
      • De Athayde Soares R.
      • Brochado Neto F.C.
      • Matielo M.F.
      • Lehn C.N.
      • Nakamura E.T.
      • Godoy M.R.
      • et al.
      Concept of angiosome does not affect limb salvage in infrapopliteal angioplasty.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      • Troisi N.
      • Turini F.
      • Chisci E.
      • Ercolini L.
      • Frosini P.
      • Lombardi R.
      • et al.
      Pedal arch patency and not direct-angiosome revascularization predicts outcomes of endovascular interventions in diabetic patients with critical limb ischemia.
      four studies (814 limbs) based this decision on input from the multidisciplinary team,
      • Ricco J.B.
      • Gargiulo M.
      • Stella A.
      • Abualhin M.
      • Gallitto E.
      • Desvergnes M.
      • et al.
      Impact of angiosome- and nonangiosome-targeted peroneal bypass on limb salvage and healing in patients with chronic limb-threatening ischemia.
      • Alexandrescu V.-A.
      • Hubermont G.
      • Philips Y.
      • Guillaumie B.
      • Ngongang C.
      • Vandenbossche P.
      • et al.
      Selective primary angioplasty following an angiosome model of reperfusion in the treatment of Wagner 1–4 diabetic foot lesions: practice in a multidisciplinary diabetic limb service.
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      • Iida O.
      • Takahara M.
      • Soga Y.
      • Yamauchi Y.
      • Hirano K.
      • Tazaki J.
      • et al.
      Impact of angiosome-oriented revascularization on clinical outcomes in critical limb ischemia patients without concurrent wound infection and diabetes.
      and in two studies (170 limbs) the decision was at the discretion of the individual surgeon.
      • Kabra A.
      • Suresh K.R.
      • Vivekanand V.
      • Vishnu M.
      • Sumanth R.
      • Nekkanti M.
      Outcomes of angiosome and non-angiosome targeted revascularization in critical lower limb ischemia.
      • Kret M.R.
      • Cheng D.
      • Azarbal A.F.
      • Mitchell E.L.
      • Liem T.K.
      • Moneta G.L.
      • et al.
      Utility of direct angiosome revascularization and runoff scores in predicting outcomes in patients undergoing revascularization for critical limb ischemia.
      Endovascular revascularisation was considered first line over bypass surgery in six studies (748 limbs).
      • De Athayde Soares R.
      • Brochado Neto F.C.
      • Matielo M.F.
      • Lehn C.N.
      • Nakamura E.T.
      • Godoy M.R.
      • et al.
      Concept of angiosome does not affect limb salvage in infrapopliteal angioplasty.
      • Söderström M.
      • Albäck A.
      • Biancari F.
      • Lappalainen K.
      • Lepäntalo M.
      • Venermo M.
      Angiosome-targeted infrapopliteal endovascular revascularization for treatment of diabetic foot ulcers.
      • Alexandrescu V.-A.
      • Hubermont G.
      • Philips Y.
      • Guillaumie B.
      • Ngongang C.
      • Vandenbossche P.
      • et al.
      Selective primary angioplasty following an angiosome model of reperfusion in the treatment of Wagner 1–4 diabetic foot lesions: practice in a multidisciplinary diabetic limb service.
      • Varela C.
      • Acín F.
      • de Haro J.
      • Bleda S.
      • Esparza L.
      • March J.R.
      The role of foot collateral vessels on ulcer healing and limb salvage after successful endovascular and surgical distal procedures according to an angiosome model.
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      • Jeon E.Y.
      • Cho Y.K.
      • Yoon D.Y.
      • Kim D.J.
      • Woo J.J.
      Clinical outcome of angiosome-oriented infrapopliteal percutaneous transluminal angioplasty for isolated infrapopliteal lesions in patients with critical limb ischemia.
      For bypass surgery, four studies (336 limbs) used a venous conduit alone,
      • Varela C.
      • Acín F.
      • de Haro J.
      • Bleda S.
      • Esparza L.
      • March J.R.
      The role of foot collateral vessels on ulcer healing and limb salvage after successful endovascular and surgical distal procedures according to an angiosome model.
      • Azuma N.
      • Uchida H.
      • Kokubo T.
      • Koya A.
      • Akasaka N.
      • Sasajima T.
      Factors influencing wound healing of critical ischaemic foot after bypass surgery: is the angiosome important in selecting bypass target artery?.
      • Kret M.R.
      • Cheng D.
      • Azarbal A.F.
      • Mitchell E.L.
      • Liem T.K.
      • Moneta G.L.
      • et al.
      Utility of direct angiosome revascularization and runoff scores in predicting outcomes in patients undergoing revascularization for critical limb ischemia.
      • Lejay A.
      • Georg Y.
      • Tartaglia E.
      • Gaertner S.
      • Geny B.
      • Thaveau F.
      • et al.
      Long-term outcomes of direct and indirect below-the-knee open revascularization based on the angiosome concept in diabetic patients with critical limb ischemia.
      and five studies (872 limbs) used both venous and prosthetic material as conduits.
      • Kabra A.
      • Suresh K.R.
      • Vivekanand V.
      • Vishnu M.
      • Sumanth R.
      • Nekkanti M.
      Outcomes of angiosome and non-angiosome targeted revascularization in critical lower limb ischemia.
      • Neville R.F.
      • Attinger C.E.
      • Bulan E.J.
      • Ducic I.
      • Thomassen M.
      • Sidawy A.N.
      Revascularization of a specific angiosome for limb salvage: does the target artery matter?.
      • Rashid H.
      • Slim H.
      • Zayed H.
      • Huang D.Y.
      • Wilkins C.J.
      • Evans D.R.
      • et al.
      The impact of arterial pedal arch quality and angiosome revascularization on foot tissue loss healing and infrapopliteal bypass outcome.
      • Ricco J.B.
      • Gargiulo M.
      • Stella A.
      • Abualhin M.
      • Gallitto E.
      • Desvergnes M.
      • et al.
      Impact of angiosome- and nonangiosome-targeted peroneal bypass on limb salvage and healing in patients with chronic limb-threatening ischemia.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      Six studies (1885 limbs) revascularised preferentially to the angiosome containing the target tissue loss,
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      • Alexandrescu V.-A.
      • Hubermont G.
      • Philips Y.
      • Guillaumie B.
      • Ngongang C.
      • Vandenbossche P.
      • et al.
      Selective primary angioplasty following an angiosome model of reperfusion in the treatment of Wagner 1–4 diabetic foot lesions: practice in a multidisciplinary diabetic limb service.
      • Zheng X.T.
      • Zeng R.C.
      • Huang J.Y.
      • Pan L.M.
      • Su X.
      • Wu Z.H.
      • et al.
      The use of the angiosome concept for treating infrapopliteal critical limb ischemia through interventional therapy and determining the clinical significance of collateral vessels.
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      • Fossaceca R.
      • Guzzardi G.
      • Cerini P.
      • Cusaro C.
      • Stecco A.
      • Parziale G.
      • et al.
      Endovascular treatment of diabetic foot in a selected population of patients with below-the-knee disease: is the angiosome model effective?.
      • Iida O.
      • Takahara M.
      • Soga Y.
      • Yamauchi Y.
      • Hirano K.
      • Tazaki J.
      • et al.
      Impact of angiosome-oriented revascularization on clinical outcomes in critical limb ischemia patients without concurrent wound infection and diabetes.
      and four (376 limbs) did not consider the angiosome containing tissue loss
      • De Athayde Soares R.
      • Brochado Neto F.C.
      • Matielo M.F.
      • Lehn C.N.
      • Nakamura E.T.
      • Godoy M.R.
      • et al.
      Concept of angiosome does not affect limb salvage in infrapopliteal angioplasty.
      • Azuma N.
      • Uchida H.
      • Kokubo T.
      • Koya A.
      • Akasaka N.
      • Sasajima T.
      Factors influencing wound healing of critical ischaemic foot after bypass surgery: is the angiosome important in selecting bypass target artery?.
      • Jeon E.Y.
      • Cho Y.K.
      • Yoon D.Y.
      • Kim D.J.
      • Woo J.J.
      Clinical outcome of angiosome-oriented infrapopliteal percutaneous transluminal angioplasty for isolated infrapopliteal lesions in patients with critical limb ischemia.
      • Kret M.R.
      • Cheng D.
      • Azarbal A.F.
      • Mitchell E.L.
      • Liem T.K.
      • Moneta G.L.
      • et al.
      Utility of direct angiosome revascularization and runoff scores in predicting outcomes in patients undergoing revascularization for critical limb ischemia.
      (no data for 12). Details of the target vessel revascularised were given in five papers (519 limbs)
      • Neville R.F.
      • Attinger C.E.
      • Bulan E.J.
      • Ducic I.
      • Thomassen M.
      • Sidawy A.N.
      Revascularization of a specific angiosome for limb salvage: does the target artery matter?.
      • Varela C.
      • Acín F.
      • de Haro J.
      • Bleda S.
      • Esparza L.
      • March J.R.
      The role of foot collateral vessels on ulcer healing and limb salvage after successful endovascular and surgical distal procedures according to an angiosome model.
      • Kret M.R.
      • Cheng D.
      • Azarbal A.F.
      • Mitchell E.L.
      • Liem T.K.
      • Moneta G.L.
      • et al.
      Utility of direct angiosome revascularization and runoff scores in predicting outcomes in patients undergoing revascularization for critical limb ischemia.
      • Lejay A.
      • Georg Y.
      • Tartaglia E.
      • Gaertner S.
      • Geny B.
      • Thaveau F.
      • et al.
      Long-term outcomes of direct and indirect below-the-knee open revascularization based on the angiosome concept in diabetic patients with critical limb ischemia.
      • Iida O.
      • Soga Y.
      • Hirano K.
      • Kawasaki D.
      • Suzuki K.
      • Miyashita Y.
      • et al.
      Long-term results of direct and indirect endovascular revascularization based on the angiosome concept in patients with critical limb ischemia presenting with isolated below-the-knee lesions.
      (Table 2), which demonstrated that a significantly greater number of limbs were revascularised via the anterior tibial/dorsalis pedis artery in the DR group than the IR group (p < .0001, chi-square test, Table 2). Additionally, significantly fewer limbs were revascularised via the peroneal artery in the DR group than the IR group (p < .0001, chi-square test, Table 2). Tibial revascularisation alone was reported in three papers (549 limbs),
      • De Athayde Soares R.
      • Brochado Neto F.C.
      • Matielo M.F.
      • Lehn C.N.
      • Nakamura E.T.
      • Godoy M.R.
      • et al.
      Concept of angiosome does not affect limb salvage in infrapopliteal angioplasty.
      • Troisi N.
      • Turini F.
      • Chisci E.
      • Ercolini L.
      • Frosini P.
      • Lombardi R.
      • et al.
      Pedal arch patency and not direct-angiosome revascularization predicts outcomes of endovascular interventions in diabetic patients with critical limb ischemia.
      • Iida O.
      • Takahara M.
      • Soga Y.
      • Yamauchi Y.
      • Hirano K.
      • Tazaki J.
      • et al.
      Impact of angiosome-oriented revascularization on clinical outcomes in critical limb ischemia patients without concurrent wound infection and diabetes.
      and four papers (518 limbs) included patients undergoing concomitant inflow revascularisation (Appendix II).
      • Kabra A.
      • Suresh K.R.
      • Vivekanand V.
      • Vishnu M.
      • Sumanth R.
      • Nekkanti M.
      Outcomes of angiosome and non-angiosome targeted revascularization in critical lower limb ischemia.
      • Acín F.
      • Varela C.
      • López De Maturana I.
      • De Haro J.
      • Bleda S.
      • Rodriguez-Padilla J.
      Results of infrapopliteal endovascular procedures performed in diabetic patients with critical limb ischemia and tissue loss from the perspective of an angiosome-oriented revascularization strategy.
      • Rashid H.
      • Slim H.
      • Zayed H.
      • Huang D.Y.
      • Wilkins C.J.
      • Evans D.R.
      • et al.
      The impact of arterial pedal arch quality and angiosome revascularization on foot tissue loss healing and infrapopliteal bypass outcome.
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      Revascularisation was to the tibial vessels only in 17 papers (2712 limbs)
      • Kabra A.
      • Suresh K.R.
      • Vivekanand V.
      • Vishnu M.
      • Sumanth R.
      • Nekkanti M.
      Outcomes of angiosome and non-angiosome targeted revascularization in critical lower limb ischemia.
      • Acín F.
      • Varela C.
      • López De Maturana I.
      • De Haro J.
      • Bleda S.
      • Rodriguez-Padilla J.
      Results of infrapopliteal endovascular procedures performed in diabetic patients with critical limb ischemia and tissue loss from the perspective of an angiosome-oriented revascularization strategy.
      • Neville R.F.
      • Attinger C.E.
      • Bulan E.J.
      • Ducic I.
      • Thomassen M.
      • Sidawy A.N.
      Revascularization of a specific angiosome for limb salvage: does the target artery matter?.
      • Osawa S.
      • Terashi H.
      • Tsuji Y.
      • Kitano I.
      • Sugimoto K.
      Importance of the six angiosomes concept through arterial-arterial connections in CLI.
      • Ricco J.B.
      • Gargiulo M.
      • Stella A.
      • Abualhin M.
      • Gallitto E.
      • Desvergnes M.
      • et al.
      Impact of angiosome- and nonangiosome-targeted peroneal bypass on limb salvage and healing in patients with chronic limb-threatening ischemia.
      • De Athayde Soares R.
      • Brochado Neto F.C.
      • Matielo M.F.
      • Lehn C.N.
      • Nakamura E.T.
      • Godoy M.R.
      • et al.
      Concept of angiosome does not affect limb salvage in infrapopliteal angioplasty.
      • Söderström M.
      • Albäck A.
      • Biancari F.
      • Lappalainen K.
      • Lepäntalo M.
      • Venermo M.
      Angiosome-targeted infrapopliteal endovascular revascularization for treatment of diabetic foot ulcers.
      • Soon C.
      • Tay K.
      • Taneja M.
      • Teo T.
      • Lo R.
      • Burgmans M.C.
      • et al.
      Angiosome directed angioplasty for limb salvage in critical limb ischemia.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      • Troisi N.
      • Turini F.
      • Chisci E.
      • Ercolini L.
      • Frosini P.
      • Lombardi R.
      • et al.
      Pedal arch patency and not direct-angiosome revascularization predicts outcomes of endovascular interventions in diabetic patients with critical limb ischemia.
      • Alexandrescu V.-A.
      • Hubermont G.
      • Philips Y.
      • Guillaumie B.
      • Ngongang C.
      • Vandenbossche P.
      • et al.
      Selective primary angioplasty following an angiosome model of reperfusion in the treatment of Wagner 1–4 diabetic foot lesions: practice in a multidisciplinary diabetic limb service.
      • Varela C.
      • Acín F.
      • de Haro J.
      • Bleda S.
      • Esparza L.
      • March J.R.
      The role of foot collateral vessels on ulcer healing and limb salvage after successful endovascular and surgical distal procedures according to an angiosome model.
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      • Fossaceca R.
      • Guzzardi G.
      • Cerini P.
      • Cusaro C.
      • Stecco A.
      • Parziale G.
      • et al.
      Endovascular treatment of diabetic foot in a selected population of patients with below-the-knee disease: is the angiosome model effective?.
      • Jeon E.Y.
      • Cho Y.K.
      • Yoon D.Y.
      • Kim D.J.
      • Woo J.J.
      Clinical outcome of angiosome-oriented infrapopliteal percutaneous transluminal angioplasty for isolated infrapopliteal lesions in patients with critical limb ischemia.
      • Iida O.
      • Takahara M.
      • Soga Y.
      • Yamauchi Y.
      • Hirano K.
      • Tazaki J.
      • et al.
      Impact of angiosome-oriented revascularization on clinical outcomes in critical limb ischemia patients without concurrent wound infection and diabetes.
      • Lejay A.
      • Georg Y.
      • Tartaglia E.
      • Gaertner S.
      • Geny B.
      • Thaveau F.
      • et al.
      Long-term outcomes of direct and indirect below-the-knee open revascularization based on the angiosome concept in diabetic patients with critical limb ischemia.
      and both tibial and pedal vessels in four papers (829 limbs).
      • Rashid H.
      • Slim H.
      • Zayed H.
      • Huang D.Y.
      • Wilkins C.J.
      • Evans D.R.
      • et al.
      The impact of arterial pedal arch quality and angiosome revascularization on foot tissue loss healing and infrapopliteal bypass outcome.
      • Zheng X.T.
      • Zeng R.C.
      • Huang J.Y.
      • Pan L.M.
      • Su X.
      • Wu Z.H.
      • et al.
      The use of the angiosome concept for treating infrapopliteal critical limb ischemia through interventional therapy and determining the clinical significance of collateral vessels.
      • Azuma N.
      • Uchida H.
      • Kokubo T.
      • Koya A.
      • Akasaka N.
      • Sasajima T.
      Factors influencing wound healing of critical ischaemic foot after bypass surgery: is the angiosome important in selecting bypass target artery?.
      • Kret M.R.
      • Cheng D.
      • Azarbal A.F.
      • Mitchell E.L.
      • Liem T.K.
      • Moneta G.L.
      • et al.
      Utility of direct angiosome revascularization and runoff scores in predicting outcomes in patients undergoing revascularization for critical limb ischemia.
      Eight studies (1293 limbs) enrolled diabetic patients alone.
      • Acín F.
      • Varela C.
      • López De Maturana I.
      • De Haro J.
      • Bleda S.
      • Rodriguez-Padilla J.
      Results of infrapopliteal endovascular procedures performed in diabetic patients with critical limb ischemia and tissue loss from the perspective of an angiosome-oriented revascularization strategy.
      • Söderström M.
      • Albäck A.
      • Biancari F.
      • Lappalainen K.
      • Lepäntalo M.
      • Venermo M.
      Angiosome-targeted infrapopliteal endovascular revascularization for treatment of diabetic foot ulcers.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      • Troisi N.
      • Turini F.
      • Chisci E.
      • Ercolini L.
      • Frosini P.
      • Lombardi R.
      • et al.
      Pedal arch patency and not direct-angiosome revascularization predicts outcomes of endovascular interventions in diabetic patients with critical limb ischemia.
      • Alexandrescu V.-A.
      • Hubermont G.
      • Philips Y.
      • Guillaumie B.
      • Ngongang C.
      • Vandenbossche P.
      • et al.
      Selective primary angioplasty following an angiosome model of reperfusion in the treatment of Wagner 1–4 diabetic foot lesions: practice in a multidisciplinary diabetic limb service.
      • Fossaceca R.
      • Guzzardi G.
      • Cerini P.
      • Cusaro C.
      • Stecco A.
      • Parziale G.
      • et al.
      Endovascular treatment of diabetic foot in a selected population of patients with below-the-knee disease: is the angiosome model effective?.
      • Jeon E.Y.
      • Cho Y.K.
      • Yoon D.Y.
      • Kim D.J.
      • Woo J.J.
      Clinical outcome of angiosome-oriented infrapopliteal percutaneous transluminal angioplasty for isolated infrapopliteal lesions in patients with critical limb ischemia.
      • Lejay A.
      • Georg Y.
      • Tartaglia E.
      • Gaertner S.
      • Geny B.
      • Thaveau F.
      • et al.
      Long-term outcomes of direct and indirect below-the-knee open revascularization based on the angiosome concept in diabetic patients with critical limb ischemia.
      Post-operative anticoagulation regimen, consisting of either single or dual antiplatelets, were specifically stated in seven studies (1743 limbs, no data for the remaining studies).
      • Kabra A.
      • Suresh K.R.
      • Vivekanand V.
      • Vishnu M.
      • Sumanth R.
      • Nekkanti M.
      Outcomes of angiosome and non-angiosome targeted revascularization in critical lower limb ischemia.
      • De Athayde Soares R.
      • Brochado Neto F.C.
      • Matielo M.F.
      • Lehn C.N.
      • Nakamura E.T.
      • Godoy M.R.
      • et al.
      Concept of angiosome does not affect limb salvage in infrapopliteal angioplasty.
      • Söderström M.
      • Albäck A.
      • Biancari F.
      • Lappalainen K.
      • Lepäntalo M.
      • Venermo M.
      Angiosome-targeted infrapopliteal endovascular revascularization for treatment of diabetic foot ulcers.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      • Zheng X.T.
      • Zeng R.C.
      • Huang J.Y.
      • Pan L.M.
      • Su X.
      • Wu Z.H.
      • et al.
      The use of the angiosome concept for treating infrapopliteal critical limb ischemia through interventional therapy and determining the clinical significance of collateral vessels.
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      • Fossaceca R.
      • Guzzardi G.
      • Cerini P.
      • Cusaro C.
      • Stecco A.
      • Parziale G.
      • et al.
      Endovascular treatment of diabetic foot in a selected population of patients with below-the-knee disease: is the angiosome model effective?.
      Twelve studies (2419 limbs) specified a clinical or radiological post-operative surveillance programme to which patients were enrolled (further details given in Appendix III).
      • Kabra A.
      • Suresh K.R.
      • Vivekanand V.
      • Vishnu M.
      • Sumanth R.
      • Nekkanti M.
      Outcomes of angiosome and non-angiosome targeted revascularization in critical lower limb ischemia.
      • Acín F.
      • Varela C.
      • López De Maturana I.
      • De Haro J.
      • Bleda S.
      • Rodriguez-Padilla J.
      Results of infrapopliteal endovascular procedures performed in diabetic patients with critical limb ischemia and tissue loss from the perspective of an angiosome-oriented revascularization strategy.
      • De Athayde Soares R.
      • Brochado Neto F.C.
      • Matielo M.F.
      • Lehn C.N.
      • Nakamura E.T.
      • Godoy M.R.
      • et al.
      Concept of angiosome does not affect limb salvage in infrapopliteal angioplasty.
      • Söderström M.
      • Albäck A.
      • Biancari F.
      • Lappalainen K.
      • Lepäntalo M.
      • Venermo M.
      Angiosome-targeted infrapopliteal endovascular revascularization for treatment of diabetic foot ulcers.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      • Troisi N.
      • Turini F.
      • Chisci E.
      • Ercolini L.
      • Frosini P.
      • Lombardi R.
      • et al.
      Pedal arch patency and not direct-angiosome revascularization predicts outcomes of endovascular interventions in diabetic patients with critical limb ischemia.
      • Varela C.
      • Acín F.
      • de Haro J.
      • Bleda S.
      • Esparza L.
      • March J.R.
      The role of foot collateral vessels on ulcer healing and limb salvage after successful endovascular and surgical distal procedures according to an angiosome model.
      • Zheng X.T.
      • Zeng R.C.
      • Huang J.Y.
      • Pan L.M.
      • Su X.
      • Wu Z.H.
      • et al.
      The use of the angiosome concept for treating infrapopliteal critical limb ischemia through interventional therapy and determining the clinical significance of collateral vessels.
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      • Fossaceca R.
      • Guzzardi G.
      • Cerini P.
      • Cusaro C.
      • Stecco A.
      • Parziale G.
      • et al.
      Endovascular treatment of diabetic foot in a selected population of patients with below-the-knee disease: is the angiosome model effective?.
      • Iida O.
      • Takahara M.
      • Soga Y.
      • Yamauchi Y.
      • Hirano K.
      • Tazaki J.
      • et al.
      Impact of angiosome-oriented revascularization on clinical outcomes in critical limb ischemia patients without concurrent wound infection and diabetes.
      • Lejay A.
      • Georg Y.
      • Tartaglia E.
      • Gaertner S.
      • Geny B.
      • Thaveau F.
      • et al.
      Long-term outcomes of direct and indirect below-the-knee open revascularization based on the angiosome concept in diabetic patients with critical limb ischemia.
      Four studies (1132 limbs) provided propensity score matched groups,
      • Söderström M.
      • Albäck A.
      • Biancari F.
      • Lappalainen K.
      • Lepäntalo M.
      • Venermo M.
      Angiosome-targeted infrapopliteal endovascular revascularization for treatment of diabetic foot ulcers.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      • Azuma N.
      • Uchida H.
      • Kokubo T.
      • Koya A.
      • Akasaka N.
      • Sasajima T.
      Factors influencing wound healing of critical ischaemic foot after bypass surgery: is the angiosome important in selecting bypass target artery?.
      • Iida O.
      • Takahara M.
      • Soga Y.
      • Yamauchi Y.
      • Hirano K.
      • Tazaki J.
      • et al.
      Impact of angiosome-oriented revascularization on clinical outcomes in critical limb ischemia patients without concurrent wound infection and diabetes.
      which were extracted preferentially to non-matched data outcomes. No papers reported patient reported outcomes or quality of life data. Ten papers had a NO score of ≥ 6.
      • Rashid H.
      • Slim H.
      • Zayed H.
      • Huang D.Y.
      • Wilkins C.J.
      • Evans D.R.
      • et al.
      The impact of arterial pedal arch quality and angiosome revascularization on foot tissue loss healing and infrapopliteal bypass outcome.
      • Ricco J.B.
      • Gargiulo M.
      • Stella A.
      • Abualhin M.
      • Gallitto E.
      • Desvergnes M.
      • et al.
      Impact of angiosome- and nonangiosome-targeted peroneal bypass on limb salvage and healing in patients with chronic limb-threatening ischemia.
      • Söderström M.
      • Albäck A.
      • Biancari F.
      • Lappalainen K.
      • Lepäntalo M.
      • Venermo M.
      Angiosome-targeted infrapopliteal endovascular revascularization for treatment of diabetic foot ulcers.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      • Zheng X.T.
      • Zeng R.C.
      • Huang J.Y.
      • Pan L.M.
      • Su X.
      • Wu Z.H.
      • et al.
      The use of the angiosome concept for treating infrapopliteal critical limb ischemia through interventional therapy and determining the clinical significance of collateral vessels.
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      • Azuma N.
      • Uchida H.
      • Kokubo T.
      • Koya A.
      • Akasaka N.
      • Sasajima T.
      Factors influencing wound healing of critical ischaemic foot after bypass surgery: is the angiosome important in selecting bypass target artery?.
      • Fossaceca R.
      • Guzzardi G.
      • Cerini P.
      • Cusaro C.
      • Stecco A.
      • Parziale G.
      • et al.
      Endovascular treatment of diabetic foot in a selected population of patients with below-the-knee disease: is the angiosome model effective?.
      • Iida O.
      • Takahara M.
      • Soga Y.
      • Yamauchi Y.
      • Hirano K.
      • Tazaki J.
      • et al.
      Impact of angiosome-oriented revascularization on clinical outcomes in critical limb ischemia patients without concurrent wound infection and diabetes.
      • Kret M.R.
      • Cheng D.
      • Azarbal A.F.
      • Mitchell E.L.
      • Liem T.K.
      • Moneta G.L.
      • et al.
      Utility of direct angiosome revascularization and runoff scores in predicting outcomes in patients undergoing revascularization for critical limb ischemia.
      GRADE quality assessment was very low for all outcomes (Table 3).
      Table 1Demographic data and Newcastle–Ottawa (NO) score of included studies.
      First author (year)Retrospective or ProspectiveNumber of centresConsecutive patientsVascular interventionPatients: Diabetic only (DM), Mixed or non-DMPropensity score matched groupsFollow up (months)Patients (n)Limbs (n)DR (n)IR (n)NO score (max. 9)
      Acin (2014)RetrospectiveSingleYesEndovascularDMNo12, 24ND8546395
      Alexandrescu (2008)RetrospectiveMultipleNDEndovascularDMNo17.8ND10285174
      Ambler (2017)RetrospectiveSingleYesBothMixedNo12, 24, 362212501151139
      Azuma (2012)RetrospectiveSingleNDBypass surgeryMixedYes24ND9648489
      Fossaceca (2013)RetrospectiveSingleNDEndovascularDMNo17.5201201167347
      Jeon (2015)RetrospectiveNDNDEndovascularDMNo12708263195
      Iida (2014)RetrospectiveMultipleYesEndovascularMixedYes183643641821828
      Kabra (2013)ProspectiveSingleNDBypass surgeryMixedNo6646439254
      Kret (2014)RetrospectiveNDYesBypass surgeryMixedNoND9710654526
      Lejay (2013)RetrospectiveSingleYesBypass surgeryDMNo12545836225
      Neville (2009)RetrospectiveSingleYesBypass surgeryMixedNoNDND4322214
      Osawa (2013)RetrospectiveSingleNDEndovascularNo dataNoND385129224
      Oshima (2012)NDNDYesEndovascularNo dataNo12556031294
      Rashid (2013)RetrospectiveSingleYesBypass surgeryMixedNo12ND14166757
      Ricco (2017)RetrospectiveMultipleYesBypass surgeryMixedNo3612012055656
      Soares (2016)RetrospectiveSingleYesEndovascularMixedNo149210948445
      Soderstrom (2013)RetrospectiveSingleYesEndovascularDMYes12ND16884848
      Soon (2012)RetrospectiveNDNDEndovascularMixedNoND3503811971844
      Spillerova (2015)RetrospectiveSingleYesBothDMYes12, 24, 36, 485045042522528
      Troisi (2017)RetrospectiveSingleNDEndovascularDMNo16939355384
      Varela (2010)RetrospectiveNDYesBothMixedNo12707645315
      Zheng (2016)RetrospectiveMultipleNDEndovascularMixedNo124864861523346
      DR = direct revascularisation; IR = indirect revascularisation; ND = no data.
      Table 2Target vessels revascularised (either to named artery or branch of named artery) for DR and IR, as provided in five papers.
      First author (year)Direct revascularisationIndirect revascularisation
      AT/DPPosterior tibial/plantar arteriesPeroneal arteryAT/DPPosterior tibial/plantar arteriesPeroneal artery
      Iida (2012)1057246775454
      Kret (2014)2726115631
      Lejay (2013)31321732
      Neville (2009)1165886
      Varela (2010)376210120
      Total211 (55.5%)113 (29.7%)56 (14.7%)127 (40.1%)72 (23.1%)113 (36.2%)
      Note. The number of limbs that underwent DR to the anterior tibial (AT)/dorsalis pedis (DP) was significantly higher compared with those that underwent IR (p < .0001, chi-square test). Fewer limbs had revascularisation to the peroneal artery in the DR group compared with the IR group (p < .0001, chi-square test). Totals greater than limb number given owing to multiple angioplasties.
      Table 3Grading of recommendations assessment, development and evaluation analysis, and assessment of quality of evidence (GRADE).
      OutcomeLimbs (studies)Risk of biasInconsistencyIndirectnessImprecisionPublication BiasOverall quality of evidence
      Wound healing (overall)2998 (18)YesYesNANoYesVery low
      Wound healing (time)647 (5)YesYesNANoNAVery low
      Limb salvage3144 (20)YesYesNANoNoVery low
      Mortality1213 (9)NoYesNAYesNAVery low
      Re-intervention rate369 (2)YesYesNANoNAVery low
      Risk of bias was assessed for each included paper and was assumed to be present when a non-consecutive or non-propensity score matched cohort was analysed, or follow up did not reach 12 months.

      Outcomes

      Wound healing

      Eighteen studies reported on wound healing rates (DR, 1557 limbs; IR, 1441 limbs).
      • Kabra A.
      • Suresh K.R.
      • Vivekanand V.
      • Vishnu M.
      • Sumanth R.
      • Nekkanti M.
      Outcomes of angiosome and non-angiosome targeted revascularization in critical lower limb ischemia.
      • Acín F.
      • Varela C.
      • López De Maturana I.
      • De Haro J.
      • Bleda S.
      • Rodriguez-Padilla J.
      Results of infrapopliteal endovascular procedures performed in diabetic patients with critical limb ischemia and tissue loss from the perspective of an angiosome-oriented revascularization strategy.
      • Neville R.F.
      • Attinger C.E.
      • Bulan E.J.
      • Ducic I.
      • Thomassen M.
      • Sidawy A.N.
      Revascularization of a specific angiosome for limb salvage: does the target artery matter?.
      • Osawa S.
      • Terashi H.
      • Tsuji Y.
      • Kitano I.
      • Sugimoto K.
      Importance of the six angiosomes concept through arterial-arterial connections in CLI.
      • Rashid H.
      • Slim H.
      • Zayed H.
      • Huang D.Y.
      • Wilkins C.J.
      • Evans D.R.
      • et al.
      The impact of arterial pedal arch quality and angiosome revascularization on foot tissue loss healing and infrapopliteal bypass outcome.
      • Ricco J.B.
      • Gargiulo M.
      • Stella A.
      • Abualhin M.
      • Gallitto E.
      • Desvergnes M.
      • et al.
      Impact of angiosome- and nonangiosome-targeted peroneal bypass on limb salvage and healing in patients with chronic limb-threatening ischemia.
      • Söderström M.
      • Albäck A.
      • Biancari F.
      • Lappalainen K.
      • Lepäntalo M.
      • Venermo M.
      Angiosome-targeted infrapopliteal endovascular revascularization for treatment of diabetic foot ulcers.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      • Troisi N.
      • Turini F.
      • Chisci E.
      • Ercolini L.
      • Frosini P.
      • Lombardi R.
      • et al.
      Pedal arch patency and not direct-angiosome revascularization predicts outcomes of endovascular interventions in diabetic patients with critical limb ischemia.
      • Alexandrescu V.-A.
      • Hubermont G.
      • Philips Y.
      • Guillaumie B.
      • Ngongang C.
      • Vandenbossche P.
      • et al.
      Selective primary angioplasty following an angiosome model of reperfusion in the treatment of Wagner 1–4 diabetic foot lesions: practice in a multidisciplinary diabetic limb service.
      • Varela C.
      • Acín F.
      • de Haro J.
      • Bleda S.
      • Esparza L.
      • March J.R.
      The role of foot collateral vessels on ulcer healing and limb salvage after successful endovascular and surgical distal procedures according to an angiosome model.
      • Zheng X.T.
      • Zeng R.C.
      • Huang J.Y.
      • Pan L.M.
      • Su X.
      • Wu Z.H.
      • et al.
      The use of the angiosome concept for treating infrapopliteal critical limb ischemia through interventional therapy and determining the clinical significance of collateral vessels.
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      • Azuma N.
      • Uchida H.
      • Kokubo T.
      • Koya A.
      • Akasaka N.
      • Sasajima T.
      Factors influencing wound healing of critical ischaemic foot after bypass surgery: is the angiosome important in selecting bypass target artery?.
      • Fossaceca R.
      • Guzzardi G.
      • Cerini P.
      • Cusaro C.
      • Stecco A.
      • Parziale G.
      • et al.
      Endovascular treatment of diabetic foot in a selected population of patients with below-the-knee disease: is the angiosome model effective?.
      • Jeon E.Y.
      • Cho Y.K.
      • Yoon D.Y.
      • Kim D.J.
      • Woo J.J.
      Clinical outcome of angiosome-oriented infrapopliteal percutaneous transluminal angioplasty for isolated infrapopliteal lesions in patients with critical limb ischemia.
      • Iida O.
      • Takahara M.
      • Soga Y.
      • Yamauchi Y.
      • Hirano K.
      • Tazaki J.
      • et al.
      Impact of angiosome-oriented revascularization on clinical outcomes in critical limb ischemia patients without concurrent wound infection and diabetes.
      • Kret M.R.
      • Cheng D.
      • Azarbal A.F.
      • Mitchell E.L.
      • Liem T.K.
      • Moneta G.L.
      • et al.
      Utility of direct angiosome revascularization and runoff scores in predicting outcomes in patients undergoing revascularization for critical limb ischemia.
      Heterogeneity was significant (I2 = 56%, p = .002). Meta-analysis showed that DR was significantly associated with improved wound healing rates compared to IR (OR 0.51; 95% CI 0.39–0.68, p < 0.001, Fig. 3; Table 4), a finding maintained on sensitivity analysis for endovascular revascularisation, for larger studies, for propensity score matched groups, for studies with NO score ≥6, for those papers reporting follow up at one year, and for studies in which only diabetic patients were enrolled. This significance was lost for studies performing surgical revascularisation (OR 0.64; 95% CI 0.39–1.07, p = .09, Table 4). Time to wound healing was given in five studies (DR 339 limbs; IR 308 limbs).
      • Neville R.F.
      • Attinger C.E.
      • Bulan E.J.
      • Ducic I.
      • Thomassen M.
      • Sidawy A.N.
      Revascularization of a specific angiosome for limb salvage: does the target artery matter?.
      • Varela C.
      • Acín F.
      • de Haro J.
      • Bleda S.
      • Esparza L.
      • March J.R.
      The role of foot collateral vessels on ulcer healing and limb salvage after successful endovascular and surgical distal procedures according to an angiosome model.
      • Iida O.
      • Takahara M.
      • Soga Y.
      • Yamauchi Y.
      • Hirano K.
      • Tazaki J.
      • et al.
      Impact of angiosome-oriented revascularization on clinical outcomes in critical limb ischemia patients without concurrent wound infection and diabetes.
      • Kret M.R.
      • Cheng D.
      • Azarbal A.F.
      • Mitchell E.L.
      • Liem T.K.
      • Moneta G.L.
      • et al.
      Utility of direct angiosome revascularization and runoff scores in predicting outcomes in patients undergoing revascularization for critical limb ischemia.
      • Lejay A.
      • Georg Y.
      • Tartaglia E.
      • Gaertner S.
      • Geny B.
      • Thaveau F.
      • et al.
      Long-term outcomes of direct and indirect below-the-knee open revascularization based on the angiosome concept in diabetic patients with critical limb ischemia.
      DR was associated with a more rapid wound healing time ((SMD): −1.70; 95% CI –3.34 to −0.07, p = 0.04, I2 = 98%, Table 4).
      Figure 3
      Figure 3DR vs. IR revascularisation: Forest plot for wound healing. Data were extracted from Špillerová et al.
      • Špillerová K.
      • Settembre N.
      • Biancari F.
      • Albäck A.
      • Venermo M.
      Angiosome targeted PTA is more important in endovascular revascularisation than in surgical revascularisation: analysis of 545 patients with ischaemic tissue lesions.
      for wound healing and limb salvage sensitivity analysis in the endovascular and bypass revascularisation groups and Špillerová et al.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      was used for all other sensitivity analysis. CI = confidence interval; DR = direct revascularisation; IR = indirect revascularisation; M−H = Mantel–Haenszel; NO = Newcastle–Ottawa.
      Table 4Summary of findings for outcomes of DR and IR.
      Sensitivity analysisNo. of studies (total limbs)DR (n)IR (n)HG I2 (%)HG pOR (95% CI)Overall effect Zp
      Wound healing (overall)
      All studies18 (2998)1557144156.0020.51 (0.39–0.68)4.57<0.001
      Endovascular revascularisation11 (2174)1147102761.0040.48 (0.34–0.67)4.30<.0001
      Bypass revascularisation8 (865)48238348.060.64 (0.39–1.07)1.71.09
      Larger studies9 (2300)1157114333.150.54 (0.43–0.69)4.94<0.001
      Propensity score-matched groups4 (1132)56656637.190.60 (0.42–0.87)2.71.007
      NO ≥ 610 (2414)1175123954.020.62 (0.46–0.84)3.16.002
      1 year FU10 (2201)1103109843.070.46 (0.34–0.62)5.19<0.001
      Diabetic patients alone7 (1233)75048365.0090.43 (0.26–0.70)3.35.0008
      Wound healing (time)5 (647)33930898<0.001−1.70 (−3.34 to −0.07)2.040.04
      Limb salvage
      All studies20 (3144)1613153173<0.0010.37 (0.24–0.58)4.36<.0001
      Endovascular revascularisation12 (2243)1158108581<0.0010.36 (0.20–0.66)3.30.001
      Bypass revascularisation8 (866)48238433.170.56 (0.33–0.94)2.18.03
      Larger studies8 (2215)1087112887<0.0010.40 (0.20–0.81)2.57.01
      Propensity score matched groups3 (768)3843840.650.63 (0.44–0.89)2.60.009
      NO ≥ 69 (2050)993105784<0.0010.44 (0.22–0.88)2.34.02
      1 year FU11 (2032)957107516.290.62 (0.46–0.83)3.17.002
      Diabetic patients alone7 (1191)70348811.340.31 (0.11–0.87)2.22.03
      Mortality
      All studies9 (1213)64157256.020.73 (0.45–1.18)1.29.2
      Endovascular revascularisation3 (303)1511520.541.16 (0.69–1.96)0.57.57
      Bypass revascularisation3 (237)138990.610.35 (0.16–0.78)2.59.01
      Larger studies3 (778)39038868.040.89 (0.42–1.90)0.30.76
      Propensity score matched groups2 (672)3363360.411.29 (0.94–1.77)1.60.11
      NO ≥ 63 (778)39038868.040.89 (0.42–1.90)0.30.76
      1 year FU5 (884)4484360.460.91 (0.67–1.25)0.56.58
      Diabetic patients alone5 (898)46343556.060.96 (0.57–1.61)0.16.87
      Re-intervention
      All studies2 (369)25111870.070.44 (0.10–1.88)1.10.27
      Note. Špillerová et al.
      • Špillerová K.
      • Settembre N.
      • Biancari F.
      • Albäck A.
      • Venermo M.
      Angiosome targeted PTA is more important in endovascular revascularisation than in surgical revascularisation: analysis of 545 patients with ischaemic tissue lesions.
      was used in the sensitivity analysis for endovascular and bypass revascularisation, however Spillerova et al.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      was used in all other appropriate sensitivity analysis with propensity score matched data. HG = heterogeneity; OR = odds ratio; CI = confidence interval; NO = Newcastle–Ottawa; FU = follow up; ND = no data.

      Limb salvage

      Limb salvage rates were provided by 20 studies (DR, 1613 limbs; IR 1531 limbs).
      • Kabra A.
      • Suresh K.R.
      • Vivekanand V.
      • Vishnu M.
      • Sumanth R.
      • Nekkanti M.
      Outcomes of angiosome and non-angiosome targeted revascularization in critical lower limb ischemia.
      • Acín F.
      • Varela C.
      • López De Maturana I.
      • De Haro J.
      • Bleda S.
      • Rodriguez-Padilla J.
      Results of infrapopliteal endovascular procedures performed in diabetic patients with critical limb ischemia and tissue loss from the perspective of an angiosome-oriented revascularization strategy.
      • Neville R.F.
      • Attinger C.E.
      • Bulan E.J.
      • Ducic I.
      • Thomassen M.
      • Sidawy A.N.
      Revascularization of a specific angiosome for limb salvage: does the target artery matter?.
      • Osawa S.
      • Terashi H.
      • Tsuji Y.
      • Kitano I.
      • Sugimoto K.
      Importance of the six angiosomes concept through arterial-arterial connections in CLI.
      • Oshima S.
      • Noda K.
      • Sumida H.
      • Fukushima H.
      • Nishijima T.
      • Morihisa K.
      • et al.
      Impact of the angiosome concept for endovascular therapy in patients with critical limb ischemia due to isolated below-the knee lesions.
      • Rashid H.
      • Slim H.
      • Zayed H.
      • Huang D.Y.
      • Wilkins C.J.
      • Evans D.R.
      • et al.
      The impact of arterial pedal arch quality and angiosome revascularization on foot tissue loss healing and infrapopliteal bypass outcome.
      • Ricco J.B.
      • Gargiulo M.
      • Stella A.
      • Abualhin M.
      • Gallitto E.
      • Desvergnes M.
      • et al.
      Impact of angiosome- and nonangiosome-targeted peroneal bypass on limb salvage and healing in patients with chronic limb-threatening ischemia.
      • De Athayde Soares R.
      • Brochado Neto F.C.
      • Matielo M.F.
      • Lehn C.N.
      • Nakamura E.T.
      • Godoy M.R.
      • et al.
      Concept of angiosome does not affect limb salvage in infrapopliteal angioplasty.
      • Söderström M.
      • Albäck A.
      • Biancari F.
      • Lappalainen K.
      • Lepäntalo M.
      • Venermo M.
      Angiosome-targeted infrapopliteal endovascular revascularization for treatment of diabetic foot ulcers.
      • Soon C.
      • Tay K.
      • Taneja M.
      • Teo T.
      • Lo R.
      • Burgmans M.C.
      • et al.
      Angiosome directed angioplasty for limb salvage in critical limb ischemia.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      • Troisi N.
      • Turini F.
      • Chisci E.
      • Ercolini L.
      • Frosini P.
      • Lombardi R.
      • et al.
      Pedal arch patency and not direct-angiosome revascularization predicts outcomes of endovascular interventions in diabetic patients with critical limb ischemia.
      • Varela C.
      • Acín F.
      • de Haro J.
      • Bleda S.
      • Esparza L.
      • March J.R.
      The role of foot collateral vessels on ulcer healing and limb salvage after successful endovascular and surgical distal procedures according to an angiosome model.
      • Zheng X.T.
      • Zeng R.C.
      • Huang J.Y.
      • Pan L.M.
      • Su X.
      • Wu Z.H.
      • et al.
      The use of the angiosome concept for treating infrapopliteal critical limb ischemia through interventional therapy and determining the clinical significance of collateral vessels.
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      • Azuma N.
      • Uchida H.
      • Kokubo T.
      • Koya A.
      • Akasaka N.
      • Sasajima T.
      Factors influencing wound healing of critical ischaemic foot after bypass surgery: is the angiosome important in selecting bypass target artery?.
      • Fossaceca R.
      • Guzzardi G.
      • Cerini P.
      • Cusaro C.
      • Stecco A.
      • Parziale G.
      • et al.
      Endovascular treatment of diabetic foot in a selected population of patients with below-the-knee disease: is the angiosome model effective?.
      • Jeon E.Y.
      • Cho Y.K.
      • Yoon D.Y.
      • Kim D.J.
      • Woo J.J.
      Clinical outcome of angiosome-oriented infrapopliteal percutaneous transluminal angioplasty for isolated infrapopliteal lesions in patients with critical limb ischemia.
      • Kret M.R.
      • Cheng D.
      • Azarbal A.F.
      • Mitchell E.L.
      • Liem T.K.
      • Moneta G.L.
      • et al.
      Utility of direct angiosome revascularization and runoff scores in predicting outcomes in patients undergoing revascularization for critical limb ischemia.
      • Lejay A.
      • Georg Y.
      • Tartaglia E.
      • Gaertner S.
      • Geny B.
      • Thaveau F.
      • et al.
      Long-term outcomes of direct and indirect below-the-knee open revascularization based on the angiosome concept in diabetic patients with critical limb ischemia.
      Heterogeneity was high (I2 = 73%, p < 0.001). DR was associated with a significantly greater limb salvage rate than IR (OR 0.37; 95% CI 0.24–0.58, p < .001), a finding maintained on all sensitivity analyses (Fig. 4; Table 4).
      Figure 4
      Figure 4DR vs. IR revascularisation: Forest plot for limb salvage. Data were extracted from Špillerová et al.
      • Špillerová K.
      • Settembre N.
      • Biancari F.
      • Albäck A.
      • Venermo M.
      Angiosome targeted PTA is more important in endovascular revascularisation than in surgical revascularisation: analysis of 545 patients with ischaemic tissue lesions.
      for wound healing and limb salvage sensitivity analysis in the endovascular and bypass revascularisation groups and Spillerova et al.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      was used for all other sensitivity analysis. CI = confidence interval; DR = direct revascularisation; IR = indirect revascularisation; M−H = Mantel–Haenszel; NO = Newcastle–Ottawa.

      Mortality

      Nine studies presented mortality rates (DR, 641 limbs; IR, 572).
      • Kabra A.
      • Suresh K.R.
      • Vivekanand V.
      • Vishnu M.
      • Sumanth R.
      • Nekkanti M.
      Outcomes of angiosome and non-angiosome targeted revascularization in critical lower limb ischemia.
      • Acín F.
      • Varela C.
      • López De Maturana I.
      • De Haro J.
      • Bleda S.
      • Rodriguez-Padilla J.
      Results of infrapopliteal endovascular procedures performed in diabetic patients with critical limb ischemia and tissue loss from the perspective of an angiosome-oriented revascularization strategy.
      • Oshima S.
      • Noda K.
      • Sumida H.
      • Fukushima H.
      • Nishijima T.
      • Morihisa K.
      • et al.
      Impact of the angiosome concept for endovascular therapy in patients with critical limb ischemia due to isolated below-the knee lesions.
      • Söderström M.
      • Albäck A.
      • Biancari F.
      • Lappalainen K.
      • Lepäntalo M.
      • Venermo M.
      Angiosome-targeted infrapopliteal endovascular revascularization for treatment of diabetic foot ulcers.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      • Troisi N.
      • Turini F.
      • Chisci E.
      • Ercolini L.
      • Frosini P.
      • Lombardi R.
      • et al.
      Pedal arch patency and not direct-angiosome revascularization predicts outcomes of endovascular interventions in diabetic patients with critical limb ischemia.
      • Varela C.
      • Acín F.
      • de Haro J.
      • Bleda S.
      • Esparza L.
      • March J.R.
      The role of foot collateral vessels on ulcer healing and limb salvage after successful endovascular and surgical distal procedures according to an angiosome model.
      • Kret M.R.
      • Cheng D.
      • Azarbal A.F.
      • Mitchell E.L.
      • Liem T.K.
      • Moneta G.L.
      • et al.
      Utility of direct angiosome revascularization and runoff scores in predicting outcomes in patients undergoing revascularization for critical limb ischemia.
      • Lejay A.
      • Georg Y.
      • Tartaglia E.
      • Gaertner S.
      • Geny B.
      • Thaveau F.
      • et al.
      Long-term outcomes of direct and indirect below-the-knee open revascularization based on the angiosome concept in diabetic patients with critical limb ischemia.
      Heterogeneity was significant (I2 of 56%; p = .02). Mode of revascularisation had no effect on mortality rates when all studies were compared (OR 0.73; 95% CI 0.45–1.18, p = .2; Fig. 4; Table 4); however, mortality was significantly less with DR compared to IR on sensitivity analysis for bypass revascularisation (OR 0.35; 95% CI 0.16–0.78, p = .01, Fig. 4; Table 4). There was no difference in mortality rates between DR and IR for other sensitivity analyses (Fig. 5, Table 4).
      Figure 5
      Figure 5DR vs. IR revascularisation: forest plot for mortality rates. CI = confidence interval; DR = direct revascularisation; IR = indirect revascularisation; M−H = Mantel–Haenszel; NO = Newcastle–Ottawa.

      Re-intervention

      Two papers provided rates of re-intervention (DR, 251 limbs; IR, 118 limbs).
      • Söderström M.
      • Albäck A.
      • Biancari F.
      • Lappalainen K.
      • Lepäntalo M.
      • Venermo M.
      Angiosome-targeted infrapopliteal endovascular revascularization for treatment of diabetic foot ulcers.
      • Fossaceca R.
      • Guzzardi G.
      • Cerini P.
      • Cusaro C.
      • Stecco A.
      • Parziale G.
      • et al.
      Endovascular treatment of diabetic foot in a selected population of patients with below-the-knee disease: is the angiosome model effective?.
      Mode of revascularisation had no effect on re-intervention rates (OR 0.44, 95% CI 0.10–1.88, p = .27; Fig. 6; Table 4).
      Figure 6
      Figure 6DR vs. IR revascularisation: forest plot for re-intervention rates. CI = confidence interval; DR = direct revascularisation; IR = indirect revascularisation; M−H = Mantel–Haenszel; NO = Newcastle–Ottawa.

      Discussion

      This updated systematic review and meta-analysis comparing direct with indirect angiosomal revascularisation identified a total of 22 studies comprising 4146 limbs for analysis. Wound healing rates, time to wound healing and limb salvage were significantly better with DR than IR. Sensitivity analyses were concordant with the primary analysis for these outcomes, with the exception of the effect of wound healing rates between DR and IR, which was lost on sensitivity analysis for bypass surgery. Mode of revascularisation had no effect on mortality or on re-intervention rates.

      Strengths and weaknesses

      This review was undertaken using an extensive literature search, and has identified a number of recently published papers. Sensitivity analyses were generally concordant with the primary analysis. Unlike a previously published review,
      • Bosanquet D.C.
      • Glasbey J.C.D.
      • Williams I.M.
      • Twine C.P.
      Systematic review and meta-analysis of direct versus indirect angiosomal revascularisation of infrapopliteal arteries.
      data on time to wound healing has been analysed to complement data on overall wound healing rates. Furthermore, sensitivity analysis of studies enrolling diabetic patients alone was undertaken, with this analysis having very similar results to the main analyses. However, all studies were observational, most were retrospective, and a number were of poor quality. The resultant GRADE scores were very low for all outcomes. Owing to a lack of funding for translation, non-English articles were excluded, and other important articles could have been missed. Different authors employed different decision making regarding the importance of the angiosome concept when revascularising, with approximately half of the cohort comprised patients undergoing treatment where the angiosome concept was considered at the time of revascularisation. By implication a proportion of patients undergoing IR would have had a failed attempt at DR, which would imply a greater burden of disease and potentially poorer outcomes. Post-procedural anticoagulation and follow up practice were poorly reported and may have been significantly different between studies. Re-intervention in the angioplasty groups were also poorly reported and differences in practice between studies may influence outcome. Some authors have suggested that other factors, such as the presence of adequate foot collaterals or pedal arch
      • Zheng X.T.
      • Zeng R.C.
      • Huang J.Y.
      • Pan L.M.
      • Su X.
      • Wu Z.H.
      • et al.
      The use of the angiosome concept for treating infrapopliteal critical limb ischemia through interventional therapy and determining the clinical significance of collateral vessels.
      • Špillerová K.
      • Settembre N.
      • Biancari F.
      • Albäck A.
      • Venermo M.
      Angiosome targeted PTA is more important in endovascular revascularisation than in surgical revascularisation: analysis of 545 patients with ischaemic tissue lesions.
      or undertaking both DR and IR during endovascular revascularisation,
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      are as important as the angiosome revascularised. Although only a few papers gave data on artery revascularised, there was clearly a greater use of AT/PD revascularisation in DR, and peroneal artery revascularisation in IR, and this factor alone may account for the improved outcomes in the DR group. Cohorts varied as to their target revascularisation vessel being either tibial or pedal, the conduit used for bypass procedures (prosthetic vs. autologous vein) and to the number of “inflow” procedures performed in conjunction with distal revascularisation. Despite four papers presenting propensity score matched groups, no randomised data exist comparing angiosomal revascularisation, and therefore causation (that DR truly does improve outcomes) is only implied. Often there is only one suitable outflow tibial vessel or angioplasty target, in which case the angiosome concept is only of value in prognosis, and does not change patient management. Most papers did not give data on the extent of tissue loss for which revascularisation was performed, and even when given
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      this was not suitable for extraction and separate sensitivity analysis. Few data were given on the exact definitions used for wound healing, and on dressings or other adjunctive procedures (such as skin grafting) used between revascularisation and wound healing. Other key factors contributing to healing (DM, renal failure, malnutrition, etc.) were also unaccounted for in data derived from non-propensity score matched series. No data on patient reported outcomes or quality of life was included in any paper.

      Explanation of findings and implications for practice

      The overall result of this meta-analysis, that DR is associated with improved limb salvage and wound healing outcomes compared with IR, is concordant with the majority of reviews on this topic.
      • Jongsma H.
      • Bekken J.A.
      • Akkersdijk G.P.
      • Hoeks S.E.
      • Verhagen H.J.
      • Fioole B.
      Angiosome-directed revascularization in patients with critical limb ischemia.
      • Khor B.Y.C.
      • Price P.
      The comparative efficacy of angiosome-directed and indirect revascularisation strategies to aid healing of chronic foot wounds in patients with co-morbid diabetes mellitus and critical limb ischaemia: a literature review.
      This would imply that when possible, revascularisation should be direct. However, there are a number of caveats to this statement.
      • Stimpson A.L.
      • Dilaver N.
      • Bosanquet D.C.
      • Ambler G.K.
      • Twine C.P.
      Angiosome specific revascularisation, does the evidence support it?.
      The recently published European Society of Cardiology (ESC) guidelines highlight that when a vessel directly feeds an area of tissue loss, and is open to foot, clinician preference would almost invariably be to revascularise this vessel.
      • Aboyans V.
      • Ricco J.-B.
      • Bartelink M.-L.E.L.
      • Björck M.
      • Brodmann M.
      • Cohnert T.
      • et al.
      2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European society for vascular surgery (ESVS).
      However not infrequently, revascularisation options are limited to one or two tibial vessels, in which case a suitable surgical or angioplasty target is of more importance than their angiosome, especially when the risk of graft failure is considered. As a result, ESC guidelines state that the angiosome model should not be used as an absolute for guiding revascularisation.
      • Aboyans V.
      • Ricco J.-B.
      • Bartelink M.-L.E.L.
      • Björck M.
      • Brodmann M.
      • Cohnert T.
      • et al.
      2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European society for vascular surgery (ESVS).
      Some data suggest that in the presence of good foot collaterals, the importance of the angiosome concept is lost. When adequate foot collaterals exist, certain authors have demonstrated equivalent outcomes with DR and IR.
      • Zheng X.T.
      • Zeng R.C.
      • Huang J.Y.
      • Pan L.M.
      • Su X.
      • Wu Z.H.
      • et al.
      The use of the angiosome concept for treating infrapopliteal critical limb ischemia through interventional therapy and determining the clinical significance of collateral vessels.
      Others have found either minimal or no difference in outcomes between DR and IR, but significant outcome differences when pedal arch quality has been analysed.
      • Rashid H.
      • Slim H.
      • Zayed H.
      • Huang D.Y.
      • Wilkins C.J.
      • Evans D.R.
      • et al.
      The impact of arterial pedal arch quality and angiosome revascularization on foot tissue loss healing and infrapopliteal bypass outcome.
      • Ricco J.B.
      • Gargiulo M.
      • Stella A.
      • Abualhin M.
      • Gallitto E.
      • Desvergnes M.
      • et al.
      Impact of angiosome- and nonangiosome-targeted peroneal bypass on limb salvage and healing in patients with chronic limb-threatening ischemia.
      • Troisi N.
      • Turini F.
      • Chisci E.
      • Ercolini L.
      • Frosini P.
      • Lombardi R.
      • et al.
      Pedal arch patency and not direct-angiosome revascularization predicts outcomes of endovascular interventions in diabetic patients with critical limb ischemia.
      Owing to the way data were presented pooled analysis by pedal arch status was not possible.
      Bypass patency is dependent on identifying a suitable outflow vessel that crosses the ankle, which is of paramount importance. On sensitivity analysis, the effect of DR on wound healing in bypass surgery was lost. It may be that restoration of pulsatile flow to the ankle in a previously ischaemic limb provides such a significant effect on wound healing that the importance of the angiosome is lost. Relatively small observational studies have suggested there is a greater improvement in post-procedural arterial pressures following bypass surgery than endovascular treatment.
      • Malas M.B.
      • Enwerem N.
      • Qazi U.
      • Brown B.
      • Schneider E.B.
      • Reifsnyder T.
      • et al.
      Comparison of surgical bypass with angioplasty and stenting of superficial femoral artery disease.
      • Feinglass J.
      • McCarthy W.J.
      • Slavensky R.
      • Manheim L.M.
      • Martin G.J.
      Functional status and walking ability after lower extremity bypass grafting or angioplasty for intermittent claudication: results from a prospective outcomes study.
      This may account for observational data from larger studies, including revascularisation to tibial and more proximal vessels, which demonstrate better wound healing in bypass than endovascular revascularisation.
      • Darling J.D.
      • McCallum J.C.
      • Soden P.A.
      • Korepta L.
      • Guzman R.J.
      • Wyers M.C.
      • et al.
      Results for primary bypass versus primary angioplasty/stent for lower extremity chronic limb-threatening ischemia.
      Series employing propensity score matching have found bypass performs consistently better than angioplasty for rate of wound healing.
      • Spillerova K.
      • Biancari F.
      • Leppäniemi A.
      • Albäck A.
      • Söderström M.
      • Venermo M.
      Differential impact of bypass surgery and angioplasty on angiosome-targeted infrapopliteal revascularization.
      The results of the BASIL2
      • Popplewell M.A.
      • Davies H.
      • Jarrett H.
      • Bate G.
      • Grant M.
      • Patel S.
      • et al.
      Bypass versus angioplasty in severe ischaemia of the leg – 2 (BASIL-2) trial: study protocol for a randomised controlled trial.
      and the BEST-CLI
      • Farber A.
      • Rosenfield K.
      • Menard M.
      The BEST-CLI Trial: a multidisciplinary effort to assess which therapy is best for patients with critical limb ischemia.
      trials will help illuminate which factors account for improvements in wound healing. Post-hoc analysis of these trials evaluating DR versus IR may provide the most conclusive evidence for the angiosomal model.
      DR was far less likely to be undertaken via the peroneal artery. It is often relatively spared from atherosclerotic processes.
      • Dible H.
      The Pathology of Limb Ischaemia.
      • Karmody A.M.
      • Leather R.P.
      • Shah D.M.
      • Corson J.D.
      • Naraynsingh V.
      Peroneal artery bypass: a reappraisal of its value in limb salvage.
      Historic data have demonstrated adequate patency and limb salvage following open bypass,
      • Raftery K.B.
      • Belkin M.
      • Mackey W.C.
      • O'Donnell T.F.
      • Pomposelli F.
      • Grabowski E.
      • et al.
      Are peroneal artery bypass grafts hemodynamically inferior to other tibial artery bypass grafts?.
      • Abou-Zamzam Jr., A.M.
      • Moneta G.L.
      • Lee R.W.
      • Nehler M.R.
      • Taylor Jr., L.M.
      • Porter J.M.
      Peroneal bypass is equivalent to inframalleolar bypass for ischemic pedal gangrene.
      and more recent data have suggested endovascular revascularisation of the peroneal artery is sufficient for healing tissue loss.
      • Dosluoglu H.H.
      • Cherr G.S.
      • Lall P.
      • Harris L.M.
      • Dryjski M.L.
      Peroneal artery-only runoff following endovascular revascularizations is effective for limb salvage in patients with tissue loss.
      However, unlike the other tibial vessels, it does not cross the ankle and is reliant on cross collateralisation to supply the foot. It is impossible from the current literature to determine if some of the beneficial effects seen in DR is simply a result of improved results from AT and PT revascularisation. To date propensity score matched studies have not matched for which vessel was revascularised, which would be of value in teasing this data out.
      Endovascular revascularisation gives an option of treating more than one tibial vessel. Ambler et al.
      • Ambler G.K.
      • Stimpson A.L.
      • Wardle B.G.
      • Bosanquet D.C.
      • Hanif U.K.
      • Germain S.
      • et al.
      Infrapopliteal angioplasty using a combined angiosomal reperfusion strategy.
      have shown that undertaking “combined revascularisation” of both a direct and indirect angiosome during angioplasty (i.e., two or three tibial arteries treated) is associated with improved wound healing outcomes compared with IR. This is concordant with a large observational series (>1200 patients) presented by Peregrin et al.,
      • Peregrin J.H.
      • Koznar B.
      • Kovác J.
      • Lastovicková J.
      • Novotný J.
      • Vedlich D.
      • et al.
      PTA of infrapopliteal arteries: long-term clinical follow-up and analysis of factors influencing clinical outcome.
      who demonstrated the most important variable determining limb salvage in their cohort was the number of tibial arteries opened. A recent small randomised control trial (RCT) has suggested this correlation holds in a randomised cohort of patients undergoing tibial angioplasty, with patients undergoing more than one tibial artery angioplasty having quicker wound healing rates and a trend towards improved limb salvage than single vessel treatment.
      • Biagioni R.B.
      • Biagioni L.C.
      • Nasser F.
      • Burihan M.C.
      • Ingrund J.C.
      • Neser A.
      • et al.
      Infrapopliteal angioplasty of one or more than one artery for critical limb ischaemia: a randomised clinical trial.
      The greater the number of tibial vessels opened the greater likelihood of revascularisation being direct, and the effect of this confounding variable is difficult to tease out in the literature.
      • Khan S.Z.
      • Dosluoglu H.H.
      Should multiple vessels be recanalised for tissue loss irrespective of pedal anatomy and angiosome?.
      Importantly in the above RCT, DR demonstrated no difference over IR in terms of wound healing and limb salvage, although numbers involved in this analysis were small.
      In conclusion, DR appears to result in improved outcomes over IR, although it may only be in a minority of patients where the option to choose between the two, and therefore alter patient management, is available. In open surgery the importance of the angiosome concept appears to be less important.

      Funding

      None.

      Conflict of Interest

      None.

      Appendix I. Rating of the quality of evidence and strength of recommendation using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

      • Quality was assessed based on the following five parameters:
      • 1.
        Risk of bias, defined as either non-representative cohort (unless propensity score matched) or inadequate FU (<12/12)
      • 2.
        Inconsistency (defined as an I2 of >50%)
      • 3.
        Indirectness of evidence (assumed not to occur in this setting)
      • 4.
        Imprecision of results (defined as fewer than 50 patients in either cohort)
      • 5.
        Publication bias, assessed using funnel plots for outcomes with >10 studies
      The resultant evidence strength can be “high”, “medium”, “low”, or “very low”. Cohort studies, by definition, have a “low” quality of evidence prior to further quality assessment. The presence of one or more serious limitations results in a