Objectives
The Society for Vascular Surgery has proposed the Wound, Ischaemia, and foot Infection (WIfI) classification system as a prognostic tool for the one year amputation risk and the added value of revascularisation in patients with chronic limb threatening ischaemia (CLTI). This systematic review summarises the current evidence on the prognostic value of the WIfI classification system in clinical practice.
Design
Systematic review and meta-analysis following the PRISMA guidelines.
Materials
The Embase, MEDLINE, and Cochrane databases were searched up to June 2018.
Methods
All studies using the WIfI classification for patients with CLTI were eligible. Outcomes of interest were major amputation, limb salvage, and amputation free survival in relation to WIfI clinical stage. The methodological quality of studies was appraised with the Quality in Prognosis Studies (QUIPS) tool. If possible, data were pooled and analysed using a random effects model. Study selection, quality assessment, and data extraction were carried out by two authors independently.
Results
The search yielded 12 studies comprising 2669 patients, most of whom underwent endovascular or open revascularisation. Overall study quality was moderate. All but one were retrospective studies, including a variety of subpopulations of patients with CLTI, such as only haemodialysis dependent, diabetic or non-diabetic patients. The WIfI classification was derived from chart data or prospectively maintained databases, both documented before the WIfI classification was published. Estimated one year major amputation rates from four studies comprising 569 patients were 0%, 8% (95% CI 3–21%), 11% (95% CI 6–18%) and 38% (95% CI 21–58%), for WIfI stages I–IV, respectively.
Conclusions
The likelihood of an amputation after one year in patients with CLTI increases with higher WIfI stages, which is important prognostic information. Prospective evaluations are needed to determine its role in clinical practice.
Keywords
What this paper adds
The Society for Vascular Surgery Wound Ischaemia and foot Infection (WIfI) classification has been developed as a tool to help clinical decision making in patients with CLTI. This systematic review shows that the WIfI classification can, to some extent, predict major amputation after one year. However, the current evidence is not sufficient for the instrument to be helpful in clinical decision making for patients with CLTI.
Introduction
Since critical limb ischaemia was defined in 1982, the epidemiology of patients presenting with this diagnosis has changed.
1
To reflect these changes the 2017 ESC/ESVS (European Society of Cardiology/European Society for Vascular Surgery) guideline on the diagnosis and treatment of peripheral arterial disease has replaced the term critical limb ischaemia with chronic limb threatening ischaemia (CLTI).2
Three arguments were given for this change; first, not all patients suffering from this disease are ‘critical’ at risk of losing their affected limb even in the absence of revascularisation. Second, due to the increase in diabetes and neuro-ischaemic ulcers it was pointed out that severe ischaemia is not the only underlying cause.3
The third reason was that the risk of amputation does not entirely depend on the extent of ischaemia but also on the presence of a wound and infection.Separate classification systems have been used for patients with ischaemia (i.e. Rutherford and Fontaine) or for patients with a diabetic foot (i.e. Wagner and Texas). In 2014, Mills et al.
4
stated that the existing classification systems neither took into account the natural history of CLTI nor assessed or graded the major risk factors that influence limb loss and clinical management. Hence, they presented a new classification system to be used to predict the one year amputation risk and the added value of a revascularisation. The determinants of these two outcomes were the presence and dimensions of wound or tissue loss, the presence and grade of infection, and the severity of ischaemia, each scored on a scale from 0 to 3. By means of a Delphi consensus these three determinants were combined into a clinical risk score, ranging from very low (1) to high (4). This is currently known as the Wound, Infection, and Ischaemia (WIfI) classification system for the risk of amputation after one year, and the benefit or requirement of revascularisation. The classification and the clinical scores are shown in Tables S2 and S3.Multiple studies have evaluated the prognostic value of the WIfI classification as summarised in the scoping review by Mills.
5
Some of these studies showed that the risk of amputation increased with a higher WIfI grade but predominantly included diabetic patients or those who underwent revascularisation.6
, 7
In order to evaluate the prognostic value of this new classification system in all CLTI patients, the available evidence was reviewed regarding the value of the WIfI classification in patients presenting with CLTI to predict the one year major amputation risk and the benefit of revascularisation.Materials and Methods
This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement.
8
The protocol was registered as PROSPERO CRD42018086641.Literature search
With the aid of a clinical librarian a systematic literature search was created to query the Embase, MEDLINE, and Cochrane databases from their inception to June 2018. The full search strategy is shown in Table S1. No language or other restrictions were applied.
Eligibility criteria
Studies were eligible if they included patients with diabetic foot ulcers and/or CLTI and evaluated the prognostic value of the WIfI classification system regardless of revascularisation or revascularisation method and duration of follow up. Articles published before 2014 were excluded since the original article on the WIfI classification was published in 2014. Titles and abstracts were screened independently by two reviewers (N.R., K.P.). Discrepancies were resolved by discussion or by a third arbitrator. Subsequently, full texts were retrieved and screened independently by two reviewers (N.R., K.P.). Again, discrepancies were resolved by discussion.
Data extraction and outcomes
Data were extracted independently by the same two authors (N.R., K.P.) and recorded on a predefined form. Study characteristics extracted were study design, inclusion and exclusion criteria, type of treatment, endpoints, follow up period, restaging of the WIfI classification, and baseline patient characteristics such as age, gender, diabetes, renal disease, or dialysis dependence. The outcomes of interest were major amputation (amputation level at which the foot is not sufficiently functional to allow walking without a prosthesis), limb salvage (no major amputation with healing of ulcers), and amputation free survival (AFS, composite of patient being alive without major amputation).
9
Disparities were checked and resolved.Risk of bias assessment
The methodological quality assessment of the individual studies was performed independently by two reviewers (N.R., K.P.) using the Quality in Prognosis Studies (QUIPS) tool.
10
A GRADE table was created with GRADEPRO for the certainty of evidence on the three outcomes, namely major amputation, AFS, and limb salvage after one year.11
Data analysis
If continuous data were presented as medians, with (interquartile) ranges, the means and standard deviations were estimated.
12
The DerSimonian and Laird random effects model was chosen a priori to calculate the pooled risk and 95% confidence interval (CI) for major amputation after one year, limb salvage after one year, and one year AFS because of presumed clinical heterogeneity between studies. The amount of statistical heterogeneity between studies was assessed using the I2
statistic. Statistical analyses were conducted using R-Studio (R-Studio Inc., Boston, MA, USA). Analysis of publication bias was not carried out because of the low number of studies eventually included in the systematic review.Results
Study selection
The search yielded a total of 1702 studies of which 12 were included for qualitative analysis (Fig. 1).
6
, 7
, 13
, 14
, 15
, 16
, 17
, 18
, - Robinson W.P.
- Loretz L.
- Hanesian C.
- Flahive J.
- Bostrom J.
- Lunig N.
- et al.
Society for Vascular Surgery Wound, Ischemia, foot Infection (WIfI) score correlates with the intensity of multimodal limb treatment and patient-centered outcomes in patients with threatened limbs managed in a limb preservation center.
J Vasc Surg. 2017; 66 (488–98.e2)
19
, 20
, 21
, 22
One of the main reasons for exclusion of full text articles was overlapping patient samples. One of the included papers presented midterm results16
and the excluded paper reported on the short term results of virtually the same cohort.23
A second paper on a subgroup of patients who underwent infrapopliteal angioplasty24
was excluded since this was a subgroup analysis of a series of patients with first time revascularisation.- Darling J.D.
- McCallum J.C.
- Soden P.A.
- Meng Y.
- Wyers M.C.
- Hamdan A.D.
- et al.
Predictive ability of the Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification system following infrapopliteal endovascular interventions for critical limb ischemia.
J Vasc Surg. 2016; 64: 616-622
14
The remaining reasons for exclusion are listed in Fig. 1. Eventually, eight studies were available for quantitative synthesis.
Figure 1PRISMA flow diagram. PRISMA = Preferred Reporting Items for Systematic reviews and Meta-Analyses; WIFI = wound, ischemia and foot infection.
Study characteristics
The 12 included studies reported on a total of 2669 patients (Table 1). One study was conducted in Japan,
22
three studies in Europe,6
, 17
, 21
the other eight in the United States (Table 2). The studies included different populations of patients presenting with CLTI. For example, one study included only patients with diabetes,15
whereas another excluded patients with diabetes.6
Treatments also varied among the studies: six studies included patients treated by revascularisation which was surgical in only one,17
endovascular in only two others,6
, 22
and both surgical and endovascular in yet another.14
In two studies the nature of invasive treatment was not specified.13
, 20
The other six studies included also patients with conservative treatment (Table 3). The WIfI classification was determined either at presentation, admission, or pre-operatively, two studies did not specify this (Table 2).14
, 19
In another two studies the WIfI classification was determined at baseline as well as during follow up or after intervention.13
, 20
Table 1Baseline characteristics of individual studies.
| Study | Included–excluded (n) | Age (years, mean) | F:M (n) | Diabetes (n) | Renal disease (n) | Treatment (n) |
|---|---|---|---|---|---|---|
| Beropoulis 6 | 126 Excl: 17 | 77 | 52:74 | 0 | 42 CKD 12 ESRD/Dialysis | Endovascular revascularisation |
| Cull 13 | 139 151 Limbs Excl: 26 | 70 | 53:86 | 91 | 19 ESRD | Revascularisation, not specified |
| Darling 14 | 903 992 Limbs Excl: NR | 71 | 368:535 | 660 | 155 Dialysis | Revascularisation (limbs): 524 Open 468 Endovascular |
| Mathioudakis 15 | 217 Excl: NR | 58 | 91:126 | 217 | 39 CKD 27 Dialysis | 60 Revascularisation: 16 Open 29 Endovascular 6 Open after endovascular 9 Hybrid 157 Conservative |
| Leithead 20 | 172 Excl: NR | 64 | 72:100 | 89 | 8 Dialysis | Revascularisation, not specified |
| Zhan 7 | 201 Excl: NR | 58 | 42:159 | 187 | 77 CKD 41 Dialysis | 48 Revascularisation, not specified 153 Conservative |
| Ramanan 16 | 128 157 Limbs Excl: NR | 66 | 61:96 (limbs) | 118 | 37 ESRD | 91 Revascularisation (Limbs): 51 Open 40 Endovascular 46 Conservative |
| Ricco 17 | 120 Excl: NR | 72 | 33:87 | 69 | 31 CKD | Surgical revascularisation |
| Robinson 18
Society for Vascular Surgery Wound, Ischemia, foot Infection (WIfI) score correlates with the intensity of multimodal limb treatment and patient-centered outcomes in patients with threatened limbs managed in a limb preservation center. J Vasc Surg. 2017; 66 (488–98.e2) | 257 280 Limbs Excl: NR | 65 | 73:184 | 7 Diet 27 N-insulin 179 Insulin | 154 CKD 30 ESRD | 106 Revascularisation (Limbs): 60 Endovascular 59 Open 15 Hybrid 174 Conservative |
| Ward 19 | 92 98 Limbs Excl: 119 | 63 | 40:52 | 71 | 17 CKD | 84 Revascularisation (Limbs): 37 Open 34 Endovascular 13 Hybrid 14 Conservative |
| Tokuda 22 | 163 Excl: 240 limbs | 71 | 53:110 | 112 | 163 Dialysis | Endovascular revascularisation |
| Van Haelst 21 | 150 Excl: 10 | 67 | 47:103 | 55 | 34 CKD | 81 Bone marrow – mononuclear cells 79 Conservative |
CKD = chronic kidney disease; ESRD = end stage renal disease; NR = not reported; Excl = number of patients excluded; F = females; M = males.
∗ Numbers are reported as patients, if noted per limbs.
Table 2Characteristics of individual studies.
| Study | Inclusion criteria | Exclusion criteria | Study design | Endpoints | FU (mean, SD) | Timing of staging | Restaging |
|---|---|---|---|---|---|---|---|
| Beropoulis 6 Germany 2016 | CLI: ABI ≤ 0.40 and/or rest pain and/or with(out) tissue loss in presence of PAD, Rutherford 4–6, >2 weeks CLI. Only one leg per patient, first treatment | Acute ischaemia, trauma, isolated iliac interventions, non-atherosclerotic disease, hypercoagulable states, diabetes, no endovascular treatment | Retrospective Prospective data Jan ‘13 – Sep ‘14 Single centre | Primary: death and major amputation, Major amputation, death | 14 months (SD 8) | Pre-operatively | No |
| Cull 13 US 2016 | CLI Rutherford V-VI scheduled to undergo revascularisation | Vasospastic, collagen vascular disease, vasculitis, Buerger's disease, acute limb ischaemia, athero-embolic disease, arterial trauma | Retrospective Prospective data 2007–2011 Single centre | Major amputation at one year, wound healing, amputation free survival | 27.5 months (SD 11) | Wound and infection, pre-operative Ischaemia post-operative | Secondary intervention <6 weeks after initial; restaging ischaemia positive >6 weeks after, with improvement restaging Ischaemia positive |
| Darling 14 US 2017 | First time revascularisation CLTI | No symptoms CLTI, aborted endovascular procedures, missing data on WIFI | Retrospective Chart review 2005–2014 Single centre | Major amputation, RAS, death | 1.6 years | NR | No |
| Mathioudakis 15 US 2017 | All patients presenting at Diabetic Foot Ulcer service | NR | Retrospective Prospective data 2012–2015 Single centre | Major amputation, wound healing | NR | Initial presentation | No |
| Leithead 20 US 2017 | Threatened limb, patients who underwent revascularisation, also patients without tissue loss but with rest pain | Missing WIfI component, acute limb ischaemia, arteritis, non-healing incisions, emergency major amputation | Retrospective EMR review Jan ‘14 – Jun ‘15 Single centre | Major amputation, AFS | NR | Initial presentation, immediately post-operatively, one and six months after intervention | Yes |
| Zhan 7 US 2015 | Consecutive threatened limbs due to varying degrees tissue loss, with or without ischaemia or infection with complete follow up | Patients presenting and managed entirely on outpatient clinic | Retrospective Chart review Jan ’10 – Dec ‘11 Single centre | Major amputation, AFS, Wound healing time | Not reported, methods state at least two years | Initial presentation, before intervention. | No |
| Ramanan 16 US 2017 | All consecutive admissions to a limb preservation service | Non-atherosclerotic disease, acute limb ischaemia, trauma | Retrospective Prospective grading of WIfI Jul ’13 – Oct ‘14 Single centre | Major amputation, mortality, wound healing | 391 days (SD 107) | On admission | No |
| Ricco 17 France/Italy 2017 | All patients with CLTI, Rutherford 5–6, only a patent peroneal artery to the ankle, lower limb bypass | If also contralateral peroneal bypass, contralateral limb not included | Retrospective Prospective data Jan ’04 – Oct ‘15 Multicentre | Limb salvage, amputation free survival, wound healing | 79 months (SD 6) | Pre-operatively | No |
| Robinson 18
Society for Vascular Surgery Wound, Ischemia, foot Infection (WIfI) score correlates with the intensity of multimodal limb treatment and patient-centered outcomes in patients with threatened limbs managed in a limb preservation center. J Vasc Surg. 2017; 66 (488–98.e2) US 2017 | CLI or diabetic foot ulceration | NR | Retrospective Prospective data Oct ’13 – May ‘15 Single centre | Wound healing, limb salvage, AFS and mortality | 214 days (SD 183) | At presentation | No |
| Ward 19 US 2017 | Patients treated for CLI, who survived 12 months and had FU for limb status at 12 months | NR | Retrospective Prospective data Feb ‘10 – Jun ‘14 Single centre | Major amputation | Not reported, methods state 12 months | Retrospectively, not clearly defined. | No |
| Tokuda 22 Japan 2018 | Haemodialysis patients undergoing a successful infrapopliteal EVT for CLI | Unsuccessful EVT, bypass surgery, absence of HD, contralateral limb of same patient | Retrospective Retrospective data Apr ’07 – Dec ‘15 Single centre | Amputation free survival, Wound healing | 784 days (SD 650) | Pre-operatively | No |
| Van Haelst 21 Netherlands 2018 | Age >18 years, Rutherford IV or higher, ineligible for surgical or radiological revascularisation | History of malignancy in past 10 years, life expectancy less than one year, HIV, Hepatitis B/C, Follow up impossible, inability to determine WIfI | Retrospective Prospective data Sep ’06 – Jun ‘12 Single centre | Mortality, Major Amputation | 2 years (SD 1.7) | Pre-treatment | No |
CLI = critical limb ischaemia; EVT = endovascular therapy; NR = not reported; RAS = revascularisation, amputation, stenosis; SD = standard deviation; EMR = electronic medical record; HD = haemodialysis dependent; WIfI = wound, ischemia and foot infection; CLTI = chronic limb-threatening ischemia; PAD = peripheral arterial disease; US = United States; AFS = amputation-free survival; FU = follow up; ABI = ankle brachial index.
Table 3Methodological assessment of individual studies (Quality in Prognosis Studies).
Methodological quality assessment
The methodological quality assessment of the studies is presented in Table 3. Statistical analysis and reporting was good in all studies. Five of the 12 studies did not report attrition of patients during the study period,
7
, 14
, 15
, 16
, 22
while in four studies the reasons for loss to follow up were unknown.13
, 17
, 18
, - Robinson W.P.
- Loretz L.
- Hanesian C.
- Flahive J.
- Bostrom J.
- Lunig N.
- et al.
Society for Vascular Surgery Wound, Ischemia, foot Infection (WIfI) score correlates with the intensity of multimodal limb treatment and patient-centered outcomes in patients with threatened limbs managed in a limb preservation center.
J Vasc Surg. 2017; 66 (488–98.e2)
20
The prognostic value of the WIfI classification was determined retrospectively in all but one study,
16
which implies a certain risk of information bias. Seven studies conducted retrospective analyses of prospectively maintained databases,6
, 13
, 15
, 16
, 17
, 18
, - Robinson W.P.
- Loretz L.
- Hanesian C.
- Flahive J.
- Bostrom J.
- Lunig N.
- et al.
Society for Vascular Surgery Wound, Ischemia, foot Infection (WIfI) score correlates with the intensity of multimodal limb treatment and patient-centered outcomes in patients with threatened limbs managed in a limb preservation center.
J Vasc Surg. 2017; 66 (488–98.e2)
19
, 21
four studies were retrospective analyses of (electronic) medical charts.7
, 14
, 20
, 22
Lastly, one study used another classification and converted these scores into the WIfI score retrospectively.13
The certainty of evidence was low to very low for all three outcomes according to the GRADE approach. Full details are presented in Table S4.Outcomes
An overview of the outcomes extracted from the studies is shown in Table 4, Table 5. The outcomes were either reported per patient or if noted, per limb. Three studies were excluded from meta-analysis, because they did not report their outcomes after one year of follow up.
17
, 18
, - Robinson W.P.
- Loretz L.
- Hanesian C.
- Flahive J.
- Bostrom J.
- Lunig N.
- et al.
Society for Vascular Surgery Wound, Ischemia, foot Infection (WIfI) score correlates with the intensity of multimodal limb treatment and patient-centered outcomes in patients with threatened limbs managed in a limb preservation center.
J Vasc Surg. 2017; 66 (488–98.e2)
20
In addition, the study by Mathioudakis et al.15
was excluded from the meta-analysis on clinical grounds because they only included diabetic foot ulcer patients with and without peripheral arterial disease. Five studies performed a multivariable analysis for the WIfI classification on major amputation, as shown in Table 4.13
, 14
, 18
, - Robinson W.P.
- Loretz L.
- Hanesian C.
- Flahive J.
- Bostrom J.
- Lunig N.
- et al.
Society for Vascular Surgery Wound, Ischemia, foot Infection (WIfI) score correlates with the intensity of multimodal limb treatment and patient-centered outcomes in patients with threatened limbs managed in a limb preservation center.
J Vasc Surg. 2017; 66 (488–98.e2)
19
, 21
Table 4Outcome in WIfI stages
| Study | WIfI I (n=patients) | WIfI II (n=patients) | WIfI III (n=patients) | WIfI IV (n=patients) | Multivariable analysis WIfI for Major amputation |
|---|---|---|---|---|---|
| Beropoulis 6 FU: 1 year | 29 AFS 87% Amp 0% | 42 AFS 81% Amp 2% | 29 AFS 81% Amp 3% | 26 AFS 62% Amp 12% | |
| Cull 13 FU: 1 year | 36 (37 Limbs) Limb Sal 97% AFS 86% | 58 (63 Limbs) Limb Sal 89% AFS 83% | 37 (43 Limbs) Limb Sal 77% AFS 70% | 8 (8 limbs) Limb Sal 63% AFS 38% | WIfI stage I OR 1 - reference II OR 4.8 (95% CI 0.6-40.5) III OR 10.8 (95% CI 1.3-88.8) IV OR 23.4 (95% CI 2.2-270.2) |
| Darling 14 FU: 1 year | 12 Limbs Limb sal 100% | 293 Limbs Limb sal 96% | 249 Limbs Limb sal 96% | 438 Limbs Limb sal 79% | HR 2.4 ( 95% CI 1.7-3.2) Clinical stage or reference not reported |
| Mathioudakis 15 FU: 1 year | 61 Limbs Amp 4% | 24 Limbs Amp 3% | 72 Limbs Amp 5% | 60 Limbs Amp 6% | |
| Zhan 7 FU: 1 year | 39 Amp 0% AFS 100% Limb Sal 100% | 50 Amp 0% AFS 100% Limb Sal 100% | 53 Amp 8% AFS 92% Limb Sal 92% | 59 Amp 64% AFS 63% Limb Sal 36% | |
| Ramanan 16 FU: 391 days | 20 Limbs AFS 75% Limb Sal 92% | 48 Limbs AFS 62% Limb Sal 81% | 41 Limbs AFS 69%) Limb Sal 93% | 48 Limbs AFS 57% Limb Sal 63% | |
| Ricco 17 FU: 3 years WIfI I-II and III-IV combined | 1311 AFS WIfI I/II 87.4% +/- 8.3% | 4947 AFS WIfI III/IV 48.4% +/- 5.3 % | |||
| Robinson 18
Society for Vascular Surgery Wound, Ischemia, foot Infection (WIfI) score correlates with the intensity of multimodal limb treatment and patient-centered outcomes in patients with threatened limbs managed in a limb preservation center. J Vasc Surg. 2017; 66 (488–98.e2) FU: 214 days | 48 Amp 2% AFS 84% | 67 Amp 5% AFS 75% | 64 Amp 8% AFS 80% | 83 Amp 17% AFS 69% | WIfI stage IV HR 12 (95% CI 1.6-94) Reference not reported |
| Ward 19 FU: 1 year | 5 Limbs Amp 0% | 21 Limbs Amp 14% | 14 Limbs Amp 21% | 58 Limbs Amp 34% | OR 1.84 (95% CI 1.0-3.39) Clinical stage or reference not reported |
| Tokuda 22 FU: 1 year | 16 AFS 76% | 30 AFS 58% | 56 AFS 61% | 61 AFS 46% | |
| Van Haelst 21 FU: 1 year | 15 Amp 0% | 50 Amp 16% | 32 Amp 13% | 53 Amp 42% | WIfI stage IV HR 2.39 (95% CI 0.93 – 6.20) Reference not reported |
Amp = major amputation; AFS = amputation free survival; Limb sal = limb salvage; FU = follow up; WIfI = Wound, Ischaemia, and foot Infection; OR = odds ratio; CI = confidence interval.
∗ Numbers are reported as patients, if noted per limbs.
Table 5Divergent reporting of WIfI classification.
| Study | |||
|---|---|---|---|
| Leithead 20 FU: NR Individual determinants WIfI post-operatively reported | Wound 1 month post-op Total: 148, Amp = 16 0–1 4,9% 2–3 34,5% 6 months post-op Total: 115, Amp = 5 0–1 2,7% 2–3 22,2% | Ischaemia 1 month post-op 0–1 11% 2–3 9,5% 6 months post-op 0–1 2,2% 2–3 11,5% | Infection 1 month post-op 0 5,3% > 0 50% 6 months post-op 0 3,5% > 0 20% |
| Darling 14 FU: one year | WIfI Composite 1–3 336 Limbs Limb sal 96% WIfI Mean Score I 12 Limbs Limb sal 100% | WIfI Composite 4–6 557 Limbs Limb sal 89% WIfI Mean Score II 542 Limbs Limb sal 96% | WIfI Composite 7–9 100 Limbs Limb sal 67% WIfI Mean Score III 438 Limbs Limb sal 79% |
Amp = major amputation; FU = follow up; Limb sal = limb salvage; NR = not reported; WIfI = Wound, Ischaemia, and foot Infection.
WIfI Composite: individual determinants of classification added together and score divided in presented scores.
WIfI Mean Score: individual determinants added together and divided by number of known individual determinants.
∗ Amounts are reported as patients, if noted per limbs.
Two studies applied the WIfI classification differently (Table 5). Leithead et al.
20
used it as a tool for post-revascularisation staging and expressed the outcomes per determinant (i.e. wound, ischaemia, foot infection) and not per clinical stage. Darling et al.14
reported a WIfI composite score (i.e. a cumulative score of the individual determinants) and a WIfI mean score (i.e. the cumulative score of the individual determinants divided by the number of known determinants). This was done in order to weigh the individual determinants equally. The mean score allowed use of the classification in case not all determinants were known.Meta-analyses
Major amputation after one year
Data for each WIfI stage from four studies (569 patients, 575 limbs) reporting on major amputation were pooled.
6
, 7
, 19
, 21
The estimated risk of a major amputation after one year was 0% for WIfI stage I patients, 8% (95% CI 3–21%, I2
= 58%) for stage II, 11% (95% CI 6–19%, I2
= 18%) for stage III, and 38% (95% CI 21–58%, I2
= 85%) for stage IV. The level of evidence for this outcome ranged from low to very low (Table 6, Table S4).Table 6Meta-analyses.
| Major amputation after one year | WIfI I | WIfI II | WIfI III | WIfI IV |
|---|---|---|---|---|
| Beropoulis 6 | 29 0% | 42 2% | 29 3% | 26 12% |
| Zhan 7 | 39 0% | 50 0% | 53 8% | 59 64% |
| Ward 19 | 5 0% | 21 14% | 14 21% | 58 34% |
| Van Haelst 21 | 15 0% | 50 16% | 32 13% | 53 42% |
| Pooled data, random effects model (95% CI) | 88 0% N.E. | 163 8% (3–21%) I 2 = 58% | 128 11% (6–19%) I 2 = 18% | 196 38% (21–58%) I 2 = 85% |
| GRADE certainty of evidence | LOW | VERY LOW | LOW | VERY LOW |
| Amputation free survival after one year | ||||
| Beropoulis 6 | 29 87% | 42 81% | 29 81% | 26 62% |
| Cull 13 | 36 86% | 58 83% | 37 70% | 8 38% |
| Zhan 7 | 39 100% | 50 100% | 53 92% | 59 63% |
| Ramanan 16 | 20 75% | 48 62% | 41 69% | 48 57% |
| Tokuda 22 | 16 76% | 30 58% | 56 61% | 61 46% |
| Pooled data, random effects model (95% CI) | 140 83% (73–91%) I 2 = 32% | 228 76% (60–87%) I 2 = 76% | 216 75% (62–84%) I 2 = 70% | 202 55% (47–63%) I 2 = 18% |
| GRADE certainty of evidence | LOW | VERY LOW | VERY LOW | LOW |
| Limb salvage after one year | ||||
| Cull 13 | 37 97% | 63 89% | 43 77% | 8 63% |
| Darling 14 | 12 100% | 293 96% | 249 96% | 438 79% |
| Zhan 7 | 39 100% | 50 100% | 53 92% | 59 36% |
| Ramanan 16 | 20 92% | 48 81% | 41 93% | 48 63% |
| Pooled data, random effects model (95% CI) | 108 95% (88–98% I 2 = 0% | 454 92% (81–97%) I 2 = 81% | 386 91% (79–97%) I 2 = 82% | 553 61% (36–82%) I 2 = 93% |
| GRADE certainty of evidence | LOW | VERY LOW | VERY LOW | VERY LOW |
CI = confidence interval; WIfI = Wound, Ischaemia, and foot Infection; N.E. = Not estimable.
Amputation free survival after one year
Five studies comprising 757 patients and 786 limbs reported on AFS.
6
, 7
, 13
, 16
, 22
The estimated one year AFS was 83% (95% CI 73–91%, I2
= 32%) for patients classified as WIFI stage I, 76% (95% CI 60–87%, I2
= 76%) for stage II, 75% (95% CI 62–84%, I2
= 70%) for stage III, and IV 55% (95% CI 47–63%, I2
= 18%) for stage IV. The certainty of evidence on AFS after one year was low to very low (Table 6, Table S4).Limb salvage after one year
Four studies,
7
, 13
, 14
, 16
totalling 1369 patients and 1501 limbs, reported on limb salvage after one year, which was 95% (95% CI 88–98%, I2
= 0%) for patients having WIfI stage I, 92% (95% CI 81–97%, I2
= 81%) for stage II, 91% (95% CI 79–97%, I2 = 82%) for stage III, and 61% (95% CI 36–82%, I2
= 93%) for stage IV). The GRADE certainty of evidence on limb salvage ranged from low to very low (Table 6, Table S4).Discussion
The Society for Vascular Surgery introduced the WIfI classification to provide information regarding the risk of major amputation within one year and the benefit of revascularisation in patients with CLTI. This review shows that the likelihood of a major amputation after one year in patients with CLTI does increase with higher clinical WIfI stages, especially in stage IV. Similarly, the higher the WIfI stage, the lower AFS and limb salvage rates after one year.
Sufficient evidence was not found to support the use of the WIfI classification to predict the benefit of revascularisation. The study by Robinson et al.
18
presented these results only for the ischaemia determinant but not the complete WIfI classification. In addition, Leithead et al.- Robinson W.P.
- Loretz L.
- Hanesian C.
- Flahive J.
- Bostrom J.
- Lunig N.
- et al.
Society for Vascular Surgery Wound, Ischemia, foot Infection (WIfI) score correlates with the intensity of multimodal limb treatment and patient-centered outcomes in patients with threatened limbs managed in a limb preservation center.
J Vasc Surg. 2017; 66 (488–98.e2)
20
presented the benefit of restaging the classification after revascularisation but only presented the outcomes of the individual determinants (i.e. wound, ischaemia, foot infection) and not the clinical stage. Furthermore, they only presented post-operative results of staging WIfI, which makes the interpretation of their results on the benefit of restaging, and therefore benefit of revascularisation difficult. This review has some limitations. The included studies comprised a diverging range of patients: hospitalised vs. outpatient treatment, patients requiring haemodialysis, invasively or conservatively treated patients, and diabetic or non-diabetic patients. For this reason, individual studies showed different results. For example, major amputation rates after one year in the study of Beropoulis et al.,6
who included non-diabetic patients treated by endovascular revascularisation, were not considerably different for clinical WIfI stages I and IV (0% and 12%, respectively). In contrast, in the study by Zhan et al.,7
in which only hospitalised, mostly diabetic patients were included and a large proportion of patients were treated conservatively, one year amputation rates were 0% and 64%, respectively. This could partly explain the statistical heterogeneity in the meta-analyses for WIfI stage IV on Major amputation and stage II–IV on Limb salvage (Table 6).Second, after the WIfI classification was published in 2014, it has been evaluated in only one prospective study.
16
The other studies were retrospective analyses of data from charts or electronic medical records, or from prospectively maintained databases in which the data were collected before the introduction of the WIfI classification. Hence, only patients with sufficient data to determine the WIfI classification were suitable to be included in these studies. However, we do not think this has skewed the findings.Furthermore, it is possible that, due to the inclusion criteria of the individual studies, only patients with either a good or a poor prognosis were included. This would yield results of outliers and not the average patient with CLTI. Also, it is conceivable that converting information from medical charts on wounds and infection to grade WIfI stages is imprecise, because the exact information islikely to be missing. This could result in information bias.
Finally, although the concept of the classification is promising, it only takes into account the status of the affected limb and not the patients’ comorbidities or overall condition. These determinants are well known to influence the course and management of the affected limb.
25
, 26
Also, the vascular anatomy can restrict possible revascularisation options.The WIfI classification is only part of the puzzle in the prognosis and decision on the treatment of patients with CLTI.
5
In daily practice, vascular surgeons determine the optimum treatment not solely on the clinical status of the leg but on a more comprehensive view of the patient. Unfortunately, the multivariable analyses by Darling et al.14
and Cull et al.13
did not include determinants other than WIfI, which ignores the association of other predictive factors for AFS, mortality, and amputation. In the study by Robinson et al.18
revascularisation lowered the risk of amputation, whereas this risk increased with a higher WIfI stage. However, in four studies reporting on the WIfI classification in multivariable analyses on major amputation, the reference group was not presented (Table 4).- Robinson W.P.
- Loretz L.
- Hanesian C.
- Flahive J.
- Bostrom J.
- Lunig N.
- et al.
Society for Vascular Surgery Wound, Ischemia, foot Infection (WIfI) score correlates with the intensity of multimodal limb treatment and patient-centered outcomes in patients with threatened limbs managed in a limb preservation center.
J Vasc Surg. 2017; 66 (488–98.e2)
At present the classification gives a global indication of the prognosis, the logical next step is to determine its value as an instrument to guide clinical decision making. Ideally, this is done in future multicentre studies registering the WIfI classification prospectively in all patients presenting with CLTI.
Conclusion
The likelihood of an amputation after one year in patients with CLTI increases with higher WIfI stages, which is important prognostic information. Prospective evaluations are needed to determine its role in clinical practice.
Conflict of Interest
None.
Funding
This work was supported by the Netherlands Organisation for Health Research and Development (ZonMw) grant no. 843004106 . ZonMw did not play any role in the conduct and writing of this research.
Acknowledgements
We would like to thank Faridi S. van Etten-Jamaludin, clinical librarian and medical information specialist, for her advice on the search strategies for this review.
Appendix A. Supplementary data
The following is the Supplementary data to this article:
- Multimedia component 1
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Article Info
Publication History
Published online: June 20, 2019
Accepted:
March 29,
2019
Received:
October 24,
2018
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© 2019 European Society for Vascular Surgery. Published by Elsevier B.V.
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- WIfI: Highlighting Hotspots of Limb Loss?European Journal of Vascular and Endovascular SurgeryVol. 58Issue 3
- PreviewThe past three decades have established that limb loss is a multifactorial process. Alongside this growing appreciation, tools have been developed to aid clinicians in stratifying patients into high and low risk groups. The Society for Vascular Surgery Wound, Ischaemia and foot Infection (WIfI) classification was born out of the recognition that existing classification systems had deficiencies in the description of at least one domain.1 For example the Rutherford classification provides a granular description of the effects of tissue ischaemia, but fails to account for the role of foot infection in limb loss.
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