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Angiosome-Guided Endovascular Revascularization for Treatment of Diabetic Foot Ulcers with Peripheral Artery Disease

Open AccessPublished:March 04, 2022DOI:https://doi.org/10.1016/j.avsg.2022.02.012

      Background

      Because diabetic foot ulcers (DFUs) are difficult to heal and cause huge economic losses to the society, accelerating their healing has become extremely important. The purpose of this study was to evaluate the effect of revascularization based on the angiosome concept on DFU.

      Methods

      Between January 2018 and July 2020, 112 consecutive legs with DFUs, in 111 patients who were discharged from the vascular surgery department of our hospital were retrospectively evaluated. The legs were assigned to two groups depending on whether direct arterial flow to the foot ulcer based on the angiosome concept was achieved. Comparisons of the ulcer healing rate, mean time to ulcer healing, major amputation rate, survival rate, and major amputation-free survival rate between the angiosome direct revascularization (DR) and angiosome indirect revascularization (IR) groups were performed.

      Results

      DR was achieved in 71 legs (63%) compared with IR in 41 legs. The ulcer healing rate (70.4% in the DR group versus 34.1% in the IR group, P < 0.01), the mean time to ulcer healing (7.01 ± 4.26 months versus 10.09 ± 3.24 months, P < 0.01), the survival rate (90.1 vs. 53.7%, P < 0.01), and the major amputation-free survival rate (81.7 vs. 48.8%, P < 0.01) were significantly higher in the DR group than in the IR group. Undergoing DR did not significantly reduce the major amputations rate compared to IR (13.4 and 34.1%, respectively, P = 0.15), but there might be a trend. In multivariate models, DR remained a significant predictor for ulcer healing (HR, 7.07; 95% confidence interval (CI), 6.54–7.60, P < 0.01). Opening multiple infrapopliteal arteries in the DR group compared with restoring only one infrapopliteal artery did not significantly improve the ulcer healing rate (P = 0.59), the mean time to ulcer healing (P = 0.70), major amputation rate (P = 0.83), the survival rate (P = 0.31), and the major amputation-free survival rate (P = 0.40).

      Conclusions

      Attaining a direct arterial flow based on the angiosome concept may be important for ulcer healing, survival, and amputation-free survival in diabetic foot patients. Opening multiple infrapopliteal arteries in DR patients may not improve the ulcer healing, survival, major amputation or amputation-free survival compared with single DR vessel patency.

      Introduction

      Diabetic foot ulcer (DFU) is one of the main complications of the diabetic foot, and is the leading cause of non-traumatic amputation in the United States.
      • Gregg E.W.
      • Sorlie P.
      • Paulose-Ram R.
      • et al.
      Prevalence of lower-extremity disease in the US adult population ≥40 years of age with and without diabetes: 1999-2000 national health and nutrition examination survey.
      Of DFU patients, 85% are at risk of amputation, 5–8% will undergo major amputation within one year,
      • Apelqvist J.
      • Larsson J.
      • Agardh C.D.
      Long-term prognosis for diabetic patients with foot ulcers.
      and 70% will die within 5 years of amputation.
      • Hingorani A.
      • LaMuraglia G.M.
      • Henke P.
      • et al.
      The management of diabetic foot: a clinical practice guideline by the society for vascular surgery in collaboration with the American podiatric medical association and the society for vascular medicine.
      Among diabetic patients with DFU, more than 50% display peripheral artery disease (PAD),
      • Prompers L.
      • Huijberts M.
      • Apelqvist J.
      • et al.
      High prevalence of ischaemia, infection and serious comorbidity in patients with diabetic foot disease in Europe. Baseline results from the Eurodiale study.
      and the combination with PAD will make DFU more difficult to heal.
      • Spreen M.I.
      • Gremmels H.
      • Teraa M.
      • et al.
      Diabetes is associated with decreased limb survival in patients with critical limb ischemia: pooled data from two randomized controlled trials.
      In an earlier clinical practice, physicians normally selected the least impaired arteries for revascularization.
      • Jongsma H.
      • Bekken J.A.
      • Akkersdijk G.P.
      • et al.
      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.
      Then in 1987, Taylor and Palmer
      • Taylor G.I.
      • Palmer J.H.
      The vascular territories (angiosomes) of the body: experimental study and clinical applications.
      proposed the concept of the angiosome, which is a three-dimensional unit of tissue fed by a source artery. In recent years, the implementation of the angiosome concept has shown positive effects in ulcer healing and limb salvage therapy in chronic limb-threatening ischemia (CLTI) patients.
      • Stimpson A.L.
      • Dilaver N.
      • Bosanquet D.C.
      • et al.
      Angiosome specific revascularisation: does the evidence support it?.
      In addition, angiosome-guided revascularization appears to be more meaningful in endovascular therapy compared with bypass surgery.
      • Jongsma H.
      • Bekken J.A.
      • Akkersdijk G.P.
      • et al.
      Angiosome-directed revascularization in patients with critical limb ischemia.
      Previous studies have, however, mainly focused on CLTI patients, and only a few studies excluded patients without diabetes. The evaluation indexes (including Wagner grade and Rutherford grade) used in many studies could not effectively evaluate the complex limb conditions of the affected limb of diabetic foot patients.
      • Forsythe R.O.
      • Apelqvist J.
      • Boyko E.J.
      • et al.
      Effectiveness of bedside investigations to diagnose peripheral artery disease among people with diabetes mellitus: a systematic review.
      The present study retrospectively analyzed DFU patients to evaluate the effect of revascularization based on the angiosome concept.

      Materials and Methods

      Ethics

      The study was approved by the Ethics Committee of the First Affiliated Hospital of Fujian Medical University (Fuzhou, Fujian, China).

      Patients and Data Collection

      This study was performed according to the STROBE guidelines. Patient data were collected retrospectively from the database of our department from January 2018 to July 2020. The patients’ characteristics (age, sex, body mass index, smoking, and alcohol consumption), comorbidities (hypertension, cardiovascular, and cerebrovascular events), low density lipoprotein (LDL), serum creatinine, triglyceride, glycosylated hemoglobin (HbA1c), ankle-brachial index (ABI), transcutaneous oxygen pressure (TcPO2), the local condition of the affected limb, and the details of digital subtraction angiography (DSA) operation were obtained. Patients who had previously undergone revascularization in the past 6 months, major amputations, dialysis history or incomplete information were excluded (Fig. 1).
      Patients were assigned to the direct revascularization (DR) group or the indirect revascularization (IR) group according to the angiosome model. The WIfI classification was applied to evaluate the overall condition of the affected limb, and the WIfI stage was used as the baseline comparison of the preoperative condition of the patients.

      Surgical Procedure

      All patients received preoperative antiplatelet therapy (aspirin 100 mg/d combined with clopidogrel 75 mg/d) for at least 3 days and continued lifelong aspirin and statins therapy postoperatively, which was combined with clopidogrel for a minimum of 1 month. Percutaneous transluminal angioplasty (PTA) or PTA combined stent implantation was performed according to the characteristics of the lesion, with stent implantation only performed for above knee lesions. Selections for DR or IR were done before the intervention based on preoperative evaluation. When the ulcer was located on the dorsal side of the foot, revascularization of the anterior tibial artery was preferred; ulcers or gangrene located in the plantar should be prioritized for posterior tibial artery revascularization; for an ulcer located on the lateral heel and lateral malleolus area the focus should be on reopening the peroneal artery. If the angiosome-directed artery was almost patent before surgery, we attempted to revascularize other angiosome-indirected arteries.
      For patients with combined infection, appropriate antibiotics were selected perioperatively according to the culture results. Following revascularization, debridement was performed according to the local ulcer condition of the patient and digit amputation was performed for patients with gangrene.

      Follow-up

      Patients were followed up 1 year after discharge. Ulcer healing was defined as full-thickness healing of epidermis of the lesion, including healing of the remaining foot tissue after debridement or minor amputation. The major amputation event was defined as the amputation of the affected limb above the ankle. Patients who did not undergo major amputation but died during the follow-up period were excluded in the major amputation rate analysis.

      Statistical Analysis

      Statistical software package SPSS version 22.0 (SPSS Inc, Chicago, IL) was used for statistical analysis. Comparisons of univariate categorical variables in each group were computed using χ2 test and Fisher exact test when appropriate. After the Kolmogorow-Smironov test, comparisons of univariate continuous variables between the two groups were computed via the Student's t-test (normal distribution) or Mann-Whitney U-test (skewed distribution). Baseline risk factors having P < 0.30 in univariable analysis were included in the regression analysis. Kaplan-Meier univariable analysis was used to estimate the mean time to ulcer healing with differences compared using the log rank test. A two-tailed P value < 0.05 was considered to be statistically significant.

      Results

      A total of 111 patients with a diabetic foot and 112 legs were included in the study, with 67 males and 45 females with a mean age of 71.61 ± 9.25 years. Direct flow (Fig. 2) to the foot ulcer according to the angiosome concept was achieved in 71 legs (63%) compared with 41 legs (37%) in which direct flow was not achieved (Fig. 3). There were no statistical differences in other baseline characteristics between the two groups (Table I).
      Figure thumbnail gr2
      Fig. 2DR instance: A 79-year-old woman with ulceration of the forth toe of the right foot, W2I3fI1, WIfI Stage4, with preoperative angiography on the left and postoperative angiography on the right. The anterior tibial artery was revascularized intraoperatively and the ulcer healed 6 months after discharge.
      Figure thumbnail gr3
      Fig. 3IR instance: An 81-year-old woman with ulceration of the first toe of the left foot, W1I3fI1, WIfI Stage3, with preoperative angiography on the left and postoperative angiography on the right. The distal peroneal artery and plantar arch were revascularized during the operation, and the ulcer did not heal 1 year after discharge.
      Table ICharacteristics of patients with DR and IR according to the angiosome concept
      FactorsTotal (n = 112)DR (n = 71)IR (n = 41)P (DR versus IR)
      Age (year)71.61 ± 9.2570.76 ± 8.4473.09 ± 10.440.19
      WIfI stage11271410.28
       Stage 12 (2%)2 (3%)0 (0%)
       Stage 22 (2%)2 (3%)0 (0%)
       Stage 344 (39%)28 (39%)16 (39%)
       Stage 464 (57%)39 (55%)25 (61%)
      Male67 (60%)46 (65%)21 (51%)0.16
      LDL (mmol/L)2.42 ± 0.892.48 ± 0.832.32 ± 0.990.37
      SCr(umol/L)74.70 ± 58.9674.58 ± 33.7174.90 ± 87.510.97
      TG (mmol/L)1.22 ± 0.761.27 ± 0.851.12 ± 0.590.34
      HbA1c (%)8.52 ± 2.198.65 ± 2.358.32 ± 1.920.48
      BMI23.02 ± 2.9923.29 ± 3.0622.54 ± 2.840.27
      Cardiovascular event14 (13%)8 (11%)6 (14%)0.60
      Celebrovascular event14 (13%)9 (13%)5 (12%)0.94
      Hypertension63 (56%)39 (55%)24 (59%)0.71
      Smoking30 (27%)20 (28%)10 (24%)0.66
      Drinking12 (11%)9 (13%)3 (7%)0.38
      LDL, low density lipoprotein; SCr, Serum creatinine; TG, triglyceride; HbA1c, glycosylated hemoglobin; BMI, body mass index; DR, direct revascularization; IR, indirect revascularization.
      Of all the patients who underwent endovascular revascularization, in ten (9%) DR could not be achieved and they were thus transferred to IR because the vessels directly supplying the ulcerated area could not be opened. One year after discharge, a total of 17 patients had undergone major amputation, while 13 patients were not included in the statistics for major amputation rates because they died during the follow-up period without major amputation.
      One year after discharge, the ulcer healing rate (70.4% in the DR group versus 34.1% in the IR group, P < 0.01), the mean time to ulcer healing (7.01 ± 4.26 months in the DR group versus 10.09 ± 3.24 months in the IR group, P < 0.01), the survival rate (90.1% in the DR group versus 53.7% in the IR group, P < 0.01), and the major amputation-free survival rate (81.7% in the DR group versus 48.8% in the IR group, P < 0.01) were significantly different between the two groups. There was a trend in the one-year major amputation rate to be lower for patients in the DR group than in the IR group (13.4 vs. 25.0%, P = 0.15) (Table II). The description of the ulcer healing time in the two groups is presented in Figure 4. Multivariate analyses of ulcer healing are shown in Table III, which showed that DR was an independent factor for predicting whether ulcer healing could be achieved (HR, 7.07; 95% confidence interval: 6.54–7.60, P < 0.01).
      Table IIOutcomes of patients one year after discharge
      OutcomeDRIRP value
      Healing rate70.4%34.1%<0.01
      P < 0.05.
      Mean time to ulcer healing7.01 ± 4.26 months10.09 ± 3.24 months<0.01
      P < 0.05.
      Major amputation13.4%25.0%0.15
      Survival90.1%53.7%<0.01
      P < 0.05.
      Major amputation-free survival81.7%48.8%<0.01
      P < 0.05.
      a P < 0.05.
      Figure thumbnail gr4
      Fig. 4Ulcer healing rates in DR patients and IR patients after endovascular revascularization.
      Table IIIMultivariate analysis of factors of ulcer healing in diabetic foot patients one year after discharge
      Multivariate analysis
      FactorsHR95% CIP Value
      Age0.990.71,1.270.62
      WIfI stage0.950.54,1.360.91
      male0.30−0.24,0.830.57
      BMI0.880.79,0.960.12
      DR7.076.54,7.60<0.01
      P < 0.05.
      LDL, low density lipoprotein; SCr, Serum creatinine; TG, triglyceride; DR, direct revascularization.
      a P < 0.05.
      Of the 17 patients who underwent a major amputation, only 3 (18%) were able to ambulate (with the aid of a prosthetic limb) after the major amputation. Healing of foot ulcers significantly increased the one-year survival rate (90.6 vs. 58.3%, HR = 6.91, P < 0.01). Patients in the DR group with multiple patent infrapopliteal arteries did not show significantly increased ulcer healing, survival, major amputation or amputation-free survival compared with patients with only one patent artery (Table IV).
      Table IVComparison between single infrapopliteal artery patented and multiple infrapopliteal arteries patented in DR group
      OutcomeSingle infrapopliteal artery patentedMultiple infrapopliteal arteries patentedP Value
      Healing rate63.6%71.7%0.59
      Mean time to ulcer healing7.5 ± 4.35 months6.9 ± 4.28 months0.70
      Major amputation11.1%13.8%0.83
      Survival81.8%91.7%0.31
      Major amputation-free survival72.7%83.0%0.40

      Discussion

      Researchers have investigated the concept of angiosome in the limb-salvage treatment of CLTI patients and many studies suggested that DR was more beneficial than IR for ulcer healing in CLI patients.
      • Stimpson A.L.
      • Dilaver N.
      • Bosanquet D.C.
      • et al.
      Angiosome specific revascularisation: does the evidence support it?.
      ,
      • Dilaver N.
      • Twine C.P.
      • Bosanquet D.C.
      Editor's choice - direct vs. Indirect angiosomal revascularisation of infrapopliteal arteries, an updated systematic review and meta-analysis.
      ,
      • Fujii M.
      • Terashi H.
      Angiosome and tissue healing.
      However, other studies have suggested that IR can achieve the same effect as DR in promoting ulcer healing when there is abundant collateral circulation in the affected limb.
      • Hata Y.
      • Iida O.
      • Mano T.
      Is angiosome-guided endovascular therapy worthwhile?.
      Patients with PAD complicated with diabetes differed from patients without diabetes in their clinical manifestation and outcomes.
      • Hinchliffe R.J.
      • Brownrigg J.R.
      • Apelqvist J.
      • et al.
      IWGDF guidance on the diagnosis, prognosis and management of peripheral artery disease in patients with foot ulcers in diabetes.
      PAD with diabetes normally involves more distant vessels (i.e., infrapopliteal arteries).
      • Jude E.B.
      • Oyibo S.O.
      • Chalmers N.
      • et al.
      Peripheral arterial disease in diabetic and nondiabetic patients: a comparison of severity and outcome.
      These patients have an impaired collateral circulation
      • Dilaver N.
      • Twine C.P.
      • Bosanquet D.C.
      Editor's choice - direct vs. Indirect angiosomal revascularisation of infrapopliteal arteries, an updated systematic review and meta-analysis.
      and they normally lack a complete dorsalis pedis arch or collaterals of the peroneal artery in the foot. Therefore, the establishment of indirect blood perfusion may not be able to supply sufficient blood flow for ulcer healing. Compared with IR, DR can effectively promote ulcer healing, reduce the amputation rate, and increase the survival rate.
      • Jongsma H.
      • Bekken J.A.
      • Akkersdijk G.P.
      • et al.
      Angiosome-directed revascularization in patients with critical limb ischemia.
      In such patients, establishing a direct blood flow to supply the ulcer region is more meaningful than opening multiple blood vessels for limb salvage.
      • Iida O.
      • Nanto S.
      • Uematsu M.
      • et al.
      Importance of the angiosome concept for endovascular therapy in patients with critical limb ischemia.
      The ultimate goal of revascularization in DFU patients is to prolong survival, salvage limbs (i.e., avoid major amputation), and improve the quality of life.
      • Serra R.
      • Grande R.
      • Scarcello E.
      • et al.
      Angiosome-targeted revascularisation in diabetic foot ulcers.
      Ulcer healing and the time required thereof are closely associated with the quality of life of DFU patients and medical costs.
      • Spiliopoulos S.
      • Brountzos E.
      • Lazaris A.
      Commentary: wound-directed revascularization for the treatment of diabetic foot ulcers: comments on a newly proposed algorithm.
      Fossaceca et al.
      • Fossaceca R.
      • Guzzardi G.
      • Cerini P.
      • et al.
      Endovascular treatment of diabetic foot in a selected population of patients with below-the-knee disease: is the angiosome model effective?.
      reviewed the local conditions of affected limbs in 201 diabetic foot patients before and after PTA, and found that DR compared with IR could significantly improve the TcPO2 level. Alexandrescu et al.
      • Alexandrescu V.A.
      • Brochier S.
      • Limgba A.
      • et al.
      Healing of diabetic neuroischemic foot wounds with vs without wound-targeted revascularization: preliminary observations from an 8-year prospective dual-center registry.
      reported the preliminary results of a prospective study on the effect of DR and IR on ulcer healing in 167 DFU patients. Ulcer healing was achieved in 70% of patients with DR and 20% of patients with IR, and the ulcer healing time in the DR group was significantly shorter than that in the IR group. Our study used WIfI classification and included the most recent patients. Similarly, the ulcer healing rate in the DR group was significantly higher than that in the IR group. Multivariate analyses showed that DR had a statistically significant effect on ulcer healing in DFU patients. The mean time to ulcer healing of patients in the DR group was also significantly shorter than that of patients in the IR group in the present study. In addition, the Kaplan-Meier analysis suggested that patients in the DR group had a higher healing rate at any time within 1 year of discharge than patients in the IR group.
      In the present study, the major amputation rate of the DR group was decreased compared with the IR group, although this was not significantly different. A subgroup analysis of patients with non-healing ulcers in the DR group showed a high one-year major amputation rate of 51.6%, comparable to that of 50–54% in DFU patients in whom revascularization was not possible.
      • Elgzyri T.
      • Larsson J.
      • Thörne J.
      • et al.
      Outcome of ischemic foot ulcer in diabetic patients who had no invasive vascular intervention.
      We hypothesize that DR may provide blood flow to the ulcer region of DFU patients that is not compensated by IR. However, some studies have suggested that the distribution of lower limb vessels in patients with severe DF may be inconsistent with the traditional angiosome model.
      • Stimpson A.L.
      • Dilaver N.
      • Bosanquet D.C.
      • et al.
      Angiosome specific revascularisation: does the evidence support it?.
      ,
      • Kret M.R.
      • Cheng D.
      • Azarbal A.F.
      • et al.
      Utility of direct angiosome revascularization and runoff scores in predicting outcomes in patients undergoing revascularization for critical limb ischemia.
      In the report of Alexandrescu et al., approximately 16% of CLTI patients with diabetes develop this type of vascular variation.
      • Alexandrescu V.A.
      • Hubermont G.
      • Philips Y.
      • 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.
      IR could also increase the skin perfusion pressure on both the dorsal and plantar surfaces.
      • Ichihashi S.
      • Takahara M.
      • Fujimura N.
      • et al.
      Changes in skin perfusion pressure after endovascular treatment for chronic limb-threatening ischemia.
      Although the blood flow provided by IR may be insufficient to heal the ulcer, it can maintain tissue vitality to a certain extent and avoid major amputation.
      • 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.
      ,
      • Biancari F.
      • Juvonen T.
      Angiosome-targeted lower limb revascularization for ischemic foot wounds: systematic review and meta-analysis.
      In addition, patients in the IR group had a higher mortality rate, and some patients may have died before amputation, resulting in an underestimation of the amputation rate.
      Similar to the results of Iacopi et al.,
      • Iacopi E.
      • Coppelli A.
      • Goretti C.
      • et al.
      Direct endovascular revascularization based on the angiosome model reduces risk of major amputations and increases life expectancy in type 2 diabetic patients with critical limb ischemia and foot ulceration.
      the survival rate of the DR group was significantly higher than that of the IR group. Iacopi et al. suggested that DR may benefit the patient's overall body rather than merely improving the limb perfusion. Compared with IR, DR can significantly improve the survival rate of patients, which may be speculated to be because 93% of the patients included in our study were complicated with different degrees of infection. Sepsis caused by the spread of limb infection will pose a great threat to the life of the patient, such that improvement of the ulcer healing rate will significantly reduce the systemic infection of the patient and thus improve the patient survival rate. The reason that the amputation-free survival rate in the DR group was significantly higher than that in the IR group may be attributed to the significantly improved survival rate in the DR group. In the study of Kret et al.,
      • Kret M.R.
      • Cheng D.
      • Azarbal A.F.
      • et al.
      Utility of direct angiosome revascularization and runoff scores in predicting outcomes in patients undergoing revascularization for critical limb ischemia.
      the mortality of patients in the IR group was higher than that of patients in the DR group because of the persistence of the ulcers.
      Compared with bypass surgery, endovascular revascularization offers DFU patients the possibility to open multiple major branches at the same time.
      • Dilaver N.
      • Twine C.P.
      • Bosanquet D.C.
      Editor's choice - direct vs. Indirect angiosomal revascularisation of infrapopliteal arteries, an updated systematic review and meta-analysis.
      Theoretically, opening multiple blood vessels can provide greater blood flow to the foot. However, in the studies of Acin et al.
      • Varela C.
      • Acín F.
      • de Haro J.
      • et al.
      The role of foot collateral vessels on ulcer healing and limb salvage after successful endovascular and surgical distal procedures according to an angiosome model.
      and Soares et al.,
      • Soares R.D.A.
      • Matielo M.F.
      • Neto F.C.B.
      • et al.
      Number of infrapopliteal arteries undergoing endovascular treatment is not associated with the limb salvage rate in patients with critical limb ischemia.
      it was not found that opening multiple infrapopliteal arteries could promote a more rapid ulcer healing rate or lower the major amputation rate in DFU patients. Similarly, in the DR group in the present study, there was no significant difference in the ulcer healing, survival, or amputation rates between a single patented infrapopliteal artery and multiple patent infrapopliteal arteries. Prolonged surgery, trying to open multiple blood vessels, can lead to increased perioperative complications. When DR has already been successfully performed, additional revascularization may be less important to the patient's outcome. Near-infrared fluorescence imaging can reflect the foot blood flow distribution before revascularization and after the opening of one branch or of multiple branches in real time.
      • van den Hoven P.
      • Ooms S.
      • van Manen L.
      • et al.
      A systematic review of the use of near-infrared fluorescence imaging in patients with peripheral artery disease.
      Future studies could use this technique to determine whether the opening of multiple branches in the DR group leads to a greater local blood flow perfusion at the ulcer.
      Jongsma et al.
      • Jongsma H.
      • Bekken J.A.
      • Akkersdijk G.P.
      • et al.
      Angiosome-directed revascularization in patients with critical limb ischemia.
      suggested that, unlike bypass surgery, endovascular revascularization provides the opportunity to open multiple arteries, and, therefore, attempts to open branches that directly supply the ulcerated angiosome should be given priority during endovascular revascularization. However, in clinical practice, the target vessels corresponding to ulcerated angiosome are frequently more serious than non-target vasculature, and not all patients can realize DR. For example, in the present study, a total of ten patients were converted to IR because the target vessels of DR could not be revascularized. The reason for choosing IR may be due to the preoperative clinical decision of physicians, but it may also be because DR cannot be performed during the operation and IR must be applied instead , which may have led to a certain bias in the results of the present study. Since most of the studies on DF patients with PAD revascularization have considered DR superior to IR, prospective studies in this area may to some extent face ethical problems. In a current clinical practice, the angiosome concept can at least predict the prognosis of patients with DFU and PAD, although not all patients can be ideally revascularized under the guidance of the angiosome concept. With the progress of endovascular technology, it will be possible to revascularize ever more vessels that were previously considered to be untreatable, and new drug-coated balloons will bring long-term patency.
      The present study had some limitations. First, this was a non-randomized retrospective study. Second, the total number of patients included was small, and the follow-up time was relatively short. Some patients with incomplete information were excluded from this study, which may also introduce bias. Third, since some patients were switched to the IR group because DR could not be performed, this may also cause some bias. Further studies that evaluate long-term outcomes of diabetic foot ulcers versus non-diabetic foot ulcers comparing DR versus IR revascularization should be conducted in the future.

      Conclusions

      Angiosome concept-guided DR may be important for the ulcer healing, survival, and amputation-free survival rates in patients with DFU. Opening multiple infrapopliteal arteries in DR patients may not improve the ulcer healing, survival, major amputation or amputation-free survival rates compared with single DR vessel patency.

      Funding

      This study was financially supported by Natural Science Foundation of Fujian Province ( 2020J01960 ).

      Availability of Data and Materials

      All data generated or analyzed during this study are included in this published article.

      Ethics Approval and Consent to Participate

      This study was approved by the Ethics Committee of the First Affiliated Hospital of Fujian Medical University (Fuzhou, Fujian, China).

      Competing Interests

      The authors declare that they have no conflict of interests.
      We thank Robert Blakytny, DPhil, from Liwen Bianji (Edanz) (www.liwenbianji.cn) for editing the English text of a draft of this manuscript.

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