Background
Critical limb ischaemia
Revascularisation
The angiosome concept
Patients with Diabetes | Patients without Diabetes | |
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Age of onset | Younger | Older |
Disease progression | Aggressive | Gradual |
Anatomical localisation | • Mainly distal • Distinctly infrapopliteal affliction, frequently involving all three tibial region arteries: Anterior Tibial, Posterior Tibial and Peroneal artery • Relative sparing of inframalleolar pedal arteries (e.g. Dorsalis Pedis) and supragenicular arteries (e.g. Femoral and Aortic-iliac arteries). | • Mainly proximal • Lesions tend to affect the Femoral and Aortic-iliac arteries more frequently than the distal arteries |
Type of atherosclerotic lesions | • Stenosis < Occlusions (severe) • Diffuse, and occurring over long segments | • Stenosis > Occlusions • Focal, and occurring over short segments |
Calcification | Commonly present | Absent |
Collateral network | Poor | Unaffected |
Diabetic population: unique challenges
Clinical relevance
Statement of purpose
Methods
Search strategy
Search terms | S1–“critical limb isch?emia” OR “isch?emi*” S2–“peripheral arter* disease” OR “peripheral vascular disease” S3–“diabetic foot” OR “diabet*” S4–“bypass” OR “angioplasty” OR “endovascular” OR “revasculari?ation” OR “reconstruct*” S5–“angiosom*” OR “direct revasculari?ation” OR “indirect revasculari?ation” S6–S1 OR S2 OR S3 S7–S4 AND S5 AND S6 |
Databases searched | EBSCOhost (AMED, CINAHL), The Cochrane Library, ProQuest (ProQuest Health & Medicine Complete, ProQuest Nursing & Allied Health Source), PubMed, ScienceDirect, TRIP database |
Part of journals searched | Title and Abstract |
Years of search | No limits set |
Language | No limits set |
Identification of studies
Inclusion Criteria | Exclusion Criteria | |
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Study design | • Full-text available in English • Cohort studies (retrospective/prospective) | • Non-English • Case reports, commentaries, reviews |
Population (P) | • Human • Chronic limb ischaemia with tissue loss (Fontaine IV or Rutherford 5, 6) • Studies of interventions in patients with diabetes | • Cadaver or animal • Acute limb ischaemia • Chronic limb ischaemia without tissue loss (e.g. rest pain only; Fontaine III or Rutherford 4) • Mixed cohorts (i.e. not all patients have diabetes) |
Intervention (I), Comparison (C) | • Arterial revascularisations • Revascularisation with application of the angiosome concept • Comparative study of DR and IR | • Non-arterial revascularisations • Revascularisation without application of the angiosome concept • Non-comparative studies of DR and IR |
Outcome (O) | • Studies which utilised wound healing as an outcome measure | • Studies where wound healing was not utilised as an outcome measure |
Inclusion/exclusion criteria
Population (P)
Intervention (I)/comparison (C)
Outcome (O)
Quality appraisal tools
Results
Fossaceca et al., 2013 [36] | Söderström et al., 2013 [37] | Acín et al., 2014 [38] | Lejay et al., 2014 [39] | Jeon et al., 2016 [40] | |
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Participants | Italy, single-centre Retrospective, non-randomised Study period: 2005–2011 • 201 subjects (201 limbs) • Mean age: 75.5 (range 66–85) • PAD anatomical locations: Isolated BTK lesions • All foot ulcers | Finland, single-centre Retrospective, non-randomised Study period: 2007–2011 • 226 subjects (250 limbs) • Mean age: 71.1 (range 56.5–84.9) • PAD anatomical locations: Isolated infrapopliteal lesions • Ulcers distal to malleolus | Spain, single-centre Retrospective, non-randomised Study period: 1999–2009 • 92 subjects (101 limbs) • Mean age: 72 (range 64–77) • PAD anatomical locations: Femoropopliteal & infrapopliteal lesions • All foot ulcers | France, single-centre Retrospective, non-randomised Study period: 2003–2009 • 54 subjects (58 limbs) • Mean age: 69.1 (range 58–81) • PAD anatomical locations: Isolated BTK lesions • Ulcers distal to malleolus | South Korea, unspecified number of centres Retrospective, non-randomised Study period: 2011–2013 • 70 subjects (82 limbs) • Mean age: 69.6 (range 59.6–79.6) • PAD anatomical locations: Isolated infrapopliteal lesions • Ulcers distal to calcaneus |
Diagnostic criterion for diabetes | Diagnostic criterion unstated in-text, however the following information was tabulated: • Time from diagnosis of diabetes: 12.5 ± 5.2 years • HbA1c (%): 7.9 ± 1.6 • Insulin therapy: 113 (56.2%) | • On hyperglycaemia reducing diet • Taking oral hypoglycaemic drugs • Undergoing insulin treatment | • Baseline blood glucose levels >120 g/dL, or • Require treatment with hypoglycaemic drugs | — | Diagnostic criterion unstated, however the following information was provided: • Mean duration of diabetes: 17.1 ± 9.7 years (range 1–50) • HbA1c (%): 8.5 ± 1.9 |
Intervention | Angioplasty: PTA • Primary endoluminal approach • Secondary subintimal approach | Angioplasty: PTA • Primary intraluminal approach | Stents used selectively Angioplasty: PTA • Primary endoluminal approach | Bypass • Autologous saphenous vein conduits only | Angioplasty: PTA • Primary intraluminal approach • Secondary subintimal approach |
Guiding principle for interventions | Angiosome concept • i.e. all patients primarily considered for DR, subsequently undergoing IR when all DR options was not technically feasible | Best vessel strategy • i.e. retrospective grouping of patients into DR or IR, determined if the best quality vessel utilised supplied the ischaemic site via a source artery or via existing collaterals | Best vessel strategy • i.e. retrospective grouping of patients into DR or IR, determined if the best quality vessel utilised supplied the ischaemic site via a source artery or via existing collaterals | Angiosome concept • i.e. all patients primarily considered for DR, subsequently undergoing IR when DR was not technically feasible | Angiosome concept • i.e. all patients primarily considered for DR, subsequently undergoing IR when all DR options was not technically feasible |
Pre-revascularisation care | |||||
- Wound care | • Debridement of necrotic tissue | Local wound care tailored to lesion characteristics. • Debridement of devitalised tissue, surgical revision and indicated microbial therapy for infected ulcers; negative-pressure wound therapy and off-loading where indicated. | • Early debridement, abscess drainage, minor amputations, and wet dressings. | — | • Unstated. |
- Medications | • Prophylaxis broad-spectrum antibiotic therapy • (The antibiotic utilised and the route of administration unstated.) • Dual anti-platelet therapy (Aspirin 100 mg/day, Clopidogrel 75 mg/day). | • Aspirin (100 mg/day), if not contraindicated. | • Broad-spectrum antibiotic therapy for severe infections in accordance with a general protocol. • (Protocol unstated, hence the drug utilised as well as the route of administration is not known.) | — | • Dual anti-platelet therapy at least 72 h before the procedure. (Aspirin 100 mg/day, Clopidogrel 75 mg/day) |
Post-revascularisation care | |||||
- Medications | • Dual anti-platelet therapy maintained (Aspirin 100 mg/day and Clopidogrel 75 mg/day) for 6 weeks, then Aspirin alone indefinitely. | • Lifelong Aspirin therapy, accompanied by Clopidogrel (75 mg/day) for 3 months after PTA | — | — | • Dual anti-platelet therapy maintained (Aspirin 100 mg/day and Clopidogrel 75 mg/day) once daily for at least 3 months if there were no contraindications to either drug. |
Outcome measures | |||||
- Wound healing |
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✓
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✓
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✓
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✓
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partial/complete at 1, 6, 12 months | at 12 months | at 12 months | at 3, 6, 12 months | at 12 months | |
- Limb salvage |
✓
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✓
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✓
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✓
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✓
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at 1, 6, 12 months | at 12 months | at 24 months | at 12 months | at 12, 24 months | |
- Additional measures | Amputation (minor and major), Average TcPO2, Mortality, PTA retreatment, Restenosis, Technical success | AFS, AFS with healed ulcer, Median time to ulcer healing, Survival, Vascular Re-intervention | AFS, Major amputation at 30 days, MACE, MALE, Freedom from MALE + POD, Freedom from RAS, Freedom from RAO, Overall survival at 24 months | Median Ulcer Healing Time, Primary Patency, Survival, TcPO2
| Amputation, Angiosome Score, Major and minor complications, Mortality, PTA reintervention, Technical Success, Wound Healing Time |
Wound classification | — | UTWCS | — | UTWCS | Wagner |
Presence of infection accounted for | — |
✓
| Graded according to CDC/NHSN surveillance definition [81] |
✓
| — |
Follow-up (months) | • Protocol: 1, 6, 12 • Mean: 17.5 • Range 5.5–29.5 | • Protocol: 1 month, and at 1–3 months thereafter depending on clinical condition of the foot • Mean: — • Range: — Surveillance of ulcer continued until healing occurred, with follow-up ending 1 year after intervention or death whichever occurred first. | • Protocol: 1, 3 and every 6 months thereafter. • Median: 19 • Range: 9–38 | • Protocol: 1, 3, and every 6 months thereafter. • Mean: 20 • Range: 4–36 | • Protocol: 12, 24 • Mean: 13 • Range: 0–25 The status of the wound was regularly checked until complete healing occurred. |
Main findings: wound healing rate | No statistically significant difference found in therapeutic efficacy. (p-values: —) | • DR had a highly statistically significant improvement in wound healing rates at 12 months (p < 0.001) • Results were still highly statistically significant after adjustments with propensity score (HR 1.97; 95% CI, 1.34–2.90) (p = 0.001) | • DR had a highly statistically significant improvement in wound healing rates as compared to IR ‘without collaterals’ group at 12 months (p = 0.001) • No statistically significant differences were found between DR and IR ‘through collaterals’ groups for wound healing at 12 months (p = 0.38) | • DR had a statistically significant improvement in wound healing rates as compared to IR at 3, 6 and 12 months (p = 0.04) | • DR had a statistically significant improvement in wound healing rates as compared to IR at 12 months (p < 0.05) |
Strengths of study | • TASC-II diagnostic criteriona for CLI satisfied • Complete follow-up of all subjects • Diagnostic criteria of diabetes indicated • Subjects’ duration of diabetes provided | • TASC-II diagnostic criteriona for CLI satisfied • Complete follow-up of all subjects • Diagnostic criteria of diabetes indicated • Consecutive sample • Employment of wound classification system • Presence of infection accounted for • Use of propensity score | • TASC-II diagnostic criteriona for CLI satisfied • Diagnostic criteria of diabetes indicated • Consecutive sample • Presence of infection accounted for • Comparable baseline characteristics of subjects between groups | • TASC-II diagnostic criteriona for CLI satisfied • Complete follow-up of all subjects • Consecutive sample • Employment of wound classification system • Presence of infection accounted for • Comparable baseline characteristics of subjects between groups | • TASC-II diagnostic criteriona for CLI satisfied • Diagnostic criteria of diabetes indicated • Subjects’ duration of diabetes provided • Employment of wound classification system |
Limitations of study | • Non-consecutive sample • Wound classification system not employed • Presence of infection not accounted for • Omission of subjects’ baseline characteristics | • No data on subjects’ duration of diabetes | • No data on subjects’ duration of diabetes • Drop-outs unaccounted • Wound classification system not employed • Patients with ESRD excluded | • No data on diagnostic criteria for diabetes • No data on subjects’ duration of diabetes | • Drop-outs unaccounted • Non-consecutive sample • Presence of infection not accounted for • Omission of subjects’ baseline characteristics |
NOS scores | 6/9 | 8/9 | 5/9 | 7/9 | 5/9 |
Population characteristics
No. of patients | No. of limbs | Age | Male/Female | Ethnicity | HTN | DLP | History of smoking | ESRD/on dialysis | CAD | CVD | |
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Fossaceca et al., 2013 [36] | |||||||||||
DR | 201 | - | 75.5 ± 9.5 | 136 M/65 F | - | 124 (62%) | - | - | 15 (7%) | 65 (32%) | - |
IR | |||||||||||
p-values | NA | - | - | - | - | - | - | - | - | - | - |
Söderström et al., 2013 [37] | |||||||||||
DR | 226 | 121 | 68.4 ± 11.9 | 89 M/32 F | - | 89 (74%) | 78 (65%) | 24 (18%) | 26 (22%) | 69 (57%) | 29 (24%) |
IR | 129 | 73.8 ± 11.1 | 71 M/58 F | - | 102 (79%) | 84 (65%) | 20 (24%) | 13 (10%) | 90 (70%) | 24 (19%) | |
p-values | NA | NA | 0.001 | 0.002 | - | NS | NS | NS | 0.012 | 0.044 | NS |
DR: propensity score matched pairs | - | 84 | 71.7 ± 11.0 | 59 M/25 F | - | 63 (75%) | 50 (60%) | 18 (25%) | 14 (17%) | 53 (63%) | 20 (24%) |
IR: propensity score matched pairs | 84 | 70.3 ± 10.9 | 58 M/26 F | - | 63 (75%) | 60 (71%) | 15 (20%) | 12 (14%) | 55 (66%) | 17 (20%) | |
p-values: propensity score matched pairs | NA | NA | NS | NS | - | NS | NS | NS | NS | NS | NS |
Acín et al., 2014 [38] | |||||||||||
DR | 46 | - | 72 (63–78) | 30 M/16 F | - | 31 (67%) | 13 (28%) | 36 (78%) | Excluded | 17 (37%) | 9 (20%) |
IR ‘through collaterals’ | 22 | - | 72 (68–75) | 11 M/11 F | - | 18 (82%) | 9 (41%) | 15 (68%) | Excluded | 5 (23%) | 6 (27%) |
IR ‘without collaterals’ | 17 | - | 69 (63–77) | 9 M/8 F | - | 14 (82%) | 4 (24%) | 11 (65%) | Excluded | 4 (24%) | 3 (17%) |
p-values: DR vs IR ‘through collaterals’ | NA | - | NS | NS | - | NS | NS | NS | NS | NS | NS |
p-values: DR vs IR ‘without collaterals’ | NA | - | NS | NS | - | NS | NS | NS | NS | NS | NS |
Lejay et al., 2014 [39] | |||||||||||
DR | 36 | - | 68 ± 10 | 25 M/11 F | - | 34 (95%) | 19 (53%) | 25 (69%) | 19 (53%) | 19 (53%) | 4 (11%) |
IR | 22 | - | 71 ± 10 | 15 M/7 F | - | 21 (96%) | 12 (55%) | 16 (73%) | 12 (55%) | 12 (55%) | 2 (9%) |
p-values | NA | - | NS | NS | - | NS | NS | NS | NS | NS | NS |
Jeon et al., 2016 [40] | |||||||||||
DR | 70 | 63 | 69.6 ± 10 | 51 M/19 F | - | 63 (90%) | - | - | 24 (34%) | 31 (44%) | - |
IR | 19 | ||||||||||
p-values | NA | NA | - | - | - | - | - | - | - | - | - |
Intervention
Outcome measures
Analysis
Population characteristics
Intervention
Outcome measures
Completeness of follow-up
Methodological rigour
Primary outcome measure: wound healing rates
Discussion
Implications for practice
Multidisciplinary implications
Limitations
Recommendations for future research
Conclusion
Acknowledgements
Funding
Availability of data and materials
Authors’ contributions
Competing interests
Consent for publication
Ethics approval and consent to participate
Additional declarations
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Oral presentation at Multidisciplinary European Endovascular Therapy (i-MEET) Conference, Nice, France, 2–3 June 2016.
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Oral presentation at NHS Greater Glasgow and Clyde’s Podiatry Development Day, Queen Elizabeth University Hospital, Glasgow, 10 June 2016.
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Poster presentation at College of Podiatry Conference, Glasgow, 17–19 November 2016.