Effectiveness of revascularisation for the ulcerated foot in patients with diabetes and peripheral artery disease: A systematic review.

INTRODUCTION: Peripheral artery disease (PAD) is associated with an increased likelihood of delayed or non-healing of a diabetes-related foot ulcer, gangrene, and amputation. The selection of the most effective surgical technique for revascularisation of the lower limb in this population is challenging and there is a lack of conclusive evidence to support the choice of intervention. This systematic review aimed to determine, in people with diabetes and tissue loss, if direct revascularisation is superior to indirect revascularisation and if endovascular revascularisation is superior to open revascularisation for the outcomes of wound healing, minor or major amputation, and adverse events including mortality. METHODS: Title and abstract searches of Medline, Embase, PubMed, and EBSCO were conducted from 1980 to 30th November 2022. Cohort and case-control studies and randomised controlled trials reporting comparative outcomes of direct (angiosome) revascularisation (DR) and indirect revascularisation (IR) or the comparative outcomes of endovascular revascularisation and open or hybrid revascularisation for the outcomes of healing, minor amputation, and major amputation in people with diabetes, PAD and tissue loss (including foot ulcer and/or gangrene) were eligible. Methodological quality was assessed using the Cochrane risk-of-bias tool for randomised trials, the ROBINS-I tool for non-randomised studies, and Newcastle-Ottawa Scale for observational and cohort studies where details regarding the allocation to intervention groups were not provided. RESULTS: From a total 7086 abstracts retrieved, 26 studies met the inclusion criteria for the comparison of direct angiosome revascularisation (DR) and indirect revascularisation (IR), and 11 studies met the inclusion criteria for the comparison of endovascular and open revascularisation. One study was included in both comparisons. Of the included studies, 35 were observational (31 retrospective and 4 prospective cohorts) and 1 was a randomised controlled trial. Cohort study quality was variable and generally low, with common sources of bias related to heterogeneous participant populations and interventions and lack of reporting of or adjusting for confounding factors. The randomised controlled trial had a low risk of bias. For studies of DR and IR, results were variable, and it is uncertain if one technique is superior to the other for healing, prevention of minor or major amputation, or mortality. However, the majority of studies reported that a greater proportion of participants receiving DR healed compared with IR, and that IR with collaterals may have similar outcomes to DR for wound healing. For patients with diabetes, infrainguinal PAD, and an adequate great saphenous vein available for use as a bypass conduit who were deemed suitable for either surgical procedure, an open revascularisation first approach was superior to endovascular therapy to prevent a major adverse limb event or death (Hazard Ratio: 0.72; 95% CI 0.61-0.86). For other studies of open and endovascular approaches, there was generally no difference in outcomes between the interventions. CONCLUSIONS: The majority of available evidence for the effectiveness of DR and IR and open and endovascular revascularisation for wound healing and prevention of minor and major amputation and adverse events including mortality in people with diabetes, PAD and tissue loss is inconclusive, and the certainty of evidence is very low. Data from one high quality randomised controlled trial supports the use of open over endovascular revascularisation to prevent a major limb event and death in people with diabetes, infrainguinal disease and tissue loss who have an adequate great saphenous vein available and who are deemed suitable for either approach.

Effectiveness of bedside investigations to diagnose peripheral artery disease among people with diabetes mellitus: A systematic review.

As a progressive disease process, early diagnosis and ongoing monitoring and treatment of lower limb peripheral artery disease (PAD) is critical to reduce the risk of diabetes-related foot ulcer (DFU) development, non-healing of wounds, infection and amputation, in addition to cardiovascular complications. There are a variety of non-invasive tests available to diagnose PAD at the bedside, but there is no consensus as to the most diagnostically accurate of these bedside investigations or their reliability for use as a method of ongoing monitoring. Therefore, the aim of this systematic review was to first determine the diagnostic accuracy of non-invasive bedside tests for identifying PAD compared to an imaging reference test and second to determine the intra- and inter-rater reliability of non-invasive bedside tests in adults with diabetes. A database search of Medline and Embase was conducted from 1980 to 30 November 2022. Prospective and retrospective investigations of the diagnostic accuracy of bedside testing in people with diabetes using an imaging reference standard and reliability studies of bedside testing techniques conducted in people with diabetes were eligible. Included studies of diagnostic accuracy were required to report adequate data to calculate the positive likelihood ratio (PLR) and negative likelihood ratio (NLR) which were the primary endpoints. The quality appraisal was conducted using the Quality Assessment of Diagnostic Accuracy Studies and Quality Appraisal of Reliability quality appraisal tools. From a total of 8517 abstracts retrieved, 40 studies met the inclusion criteria for the diagnostic accuracy component of the review and seven studies met the inclusion criteria for the reliability component of the review. Most studies investigated the diagnostic accuracy of ankle -brachial index (ABI) (N = 38). In people with and without DFU, PLRs ranged from 1.69 to 19.9 and NLRs from 0.29 to 0.84 indicating an ABI <0.9 increases the likelihood of disease (but the extent of the increase ranges from a small to large amount) and an ABI within the normal range (≥0.90 and <1.3) does not exclude PAD. For toe-brachial index (TBI), a threshold of <0.70 has a moderate ability to rule PAD in and out; however, this is based on limited evidence. Similarly, a small number of studies indicate that one or more monophasic Doppler waveforms in the pedal arteries is associated with the presence of PAD, whereas tri- or biphasic waveform suggests that PAD is less likely. Several forms of bedside testing may also be useful as adjunct tests and 7 studies were identified that investigated the reliability of bedside tests including ABI, toe pressure, TBI, transcutaneous oxygen pressure (TcPO2 ) and pulse palpation. Inter-rater reliability was poor for pulse palpation and moderate for TcPO2. The ABI, toe pressure and TBI may have good inter- and intra-rater reliability, but margins of error are wide, requiring a large change in the measurement for it to be considered a true change rather than error. There is currently no single bedside test or a combination of bedside tests that has been shown to have superior diagnostic accuracy for PAD in people with diabetes with or without DFU. However, an ABI <0.9 or >1.3, TBI of <0.70, and absent or monophasic pedal Doppler waveforms are useful to identify the presence of disease. The ability of the tests to exclude disease is variable and although reliability may be acceptable, evidence of error in the measurements means test results that are within normal limits should be considered with caution and in the context of other vascular assessment findings (e.g., pedal pulse palpation and clinical signs) and progress of DFU healing.

Performance of non-invasive bedside vascular testing in the prediction of wound healing or amputation among people with foot ulcers in diabetes: A systematic review.

INTRODUCTION: The presence of peripheral artery disease (PAD) confers a significantly increased risk of failure to heal and major lower limb amputation for people with diabetes-related foot ulcer (DFU). Determining performance of non-invasive bedside tests for predicting likely DFU outcomes is therefore key to effective risk stratification of patients with DFU and PAD to guide management decisions. The aim of this systematic review was to determine the performance of non-invasive bedside tests for PAD to predict DFU healing, healing post-minor amputation, or need for minor or major amputation in people with diabetes and DFU or gangrene. METHODS: A database search of Medline and Embase was conducted from 1980 to 30 November 2022. Prospective studies that evaluated non-invasive bedside tests in patients with diabetes, with and without PAD and foot ulceration or gangrene to predict the outcomes of DFU healing, minor amputation, and major amputation with or without revascularisation, were eligible. Included studies were required to have a minimum 6-month follow-up period and report adequate data to calculate the positive likelihood ratio (PLR) and negative likelihood ratio for the outcomes of DFU healing, and minor and major amputation. Methodological quality was assessed using the Quality in Prognosis Studies tool. RESULTS: From 14,820 abstracts screened 28 prognostic studies met the inclusion criteria. The prognostic tests evaluated by the studies included: ankle-brachial index (ABI) in 9 studies; ankle pressures in 10 studies, toe-brachial index in 4 studies, toe pressure in 9 studies, transcutaneous oxygen pressure (TcPO2 ) in 7 studies, skin perfusion pressure in 5 studies, continuous wave Doppler (pedal waveforms) in 2 studies, pedal pulses in 3 studies, and ankle peak systolic velocity in 1 study. Study quality was variable. Common reasons for studies having a moderate or high risk of bias were poorly described study participation, attrition rates, and inadequate adjustment for confounders. In people with DFU, toe pressure ≥30 mmHg, TcPO2 ≥25 mmHg, and skin perfusion pressure of ≥40 mmHg were associated with a moderate to large increase in pretest probability of healing in people with DFU. Toe pressure ≥30 mmHg was associated with a moderate increase in healing post-minor amputation. An ABI using a threshold of ≥0.9 did not increase the pretest probability of DFU healing, whereas an ABI <0.5 was associated with a moderate increase in pretest probability of non-healing. Few studies investigated amputation outcomes. An ABI <0.4 demonstrated the largest increase in pretest probability of a major amputation (PLR ≥10). CONCLUSIONS: Prognostic capacity of bedside testing for DFU healing and amputation is variable. A toe pressure ≥30 mmHg, TcPO2 ≥25 mmHg, and skin perfusion pressure of ≥40 mmHg are associated with a moderate to large increase in pretest probability of healing in people with DFU. There are little data available evaluating the prognostic capacity of bedside testing for healing after minor amputation or for major amputation in people with DFU. Current evidence suggests that an ABI <0.4 may be associated with a large increase in risk of major amputation. The findings of this systematic review need to be interpreted in the context of limitations of available evidence, including varying rates of revascularisation, lack of post-revascularisation bedside testing, and heterogenous subpopulations.

The intersocietal IWGDF, ESVS, SVS guidelines on peripheral artery disease in people with diabetes and a foot ulcer.

Diabetes related foot complications have become a major cause of morbidity and are implicated in most major and minor amputations globally. Approximately 50% of people with diabetes and a foot ulcer have peripheral artery disease (PAD) and the presence of PAD significantly increases the risk of adverse limb and cardiovascular events. The International Working Group on the Diabetic Foot (IWGDF) has published evidence based guidelines on the management and prevention of diabetes related foot complications since 1999. This guideline is an update of the 2019 IWGDF guideline on the diagnosis, prognosis and management of peripheral artery disease in people with diabetes mellitus and a foot ulcer. For this guideline the IWGDF, the European Society for Vascular Surgery and the Society for Vascular Surgery decided to collaborate to develop a consistent suite of recommendations relevant to clinicians in all countries. This guideline is based on three new systematic reviews. Using the Grading of Recommendations, Assessment, Development, and Evaluation framework clinically relevant questions were formulated, and the literature was systematically reviewed. After assessing the certainty of the evidence, recommendations were formulated which were weighed against the balance of benefits and harms, patient values, feasibility, acceptability, equity, resources required, and when available, costs. Through this process five recommendations were developed for diagnosing PAD in a person with diabetes, with and without a foot ulcer or gangrene. Five recommendations were developed for prognosis relating to estimating likelihood of healing and amputation outcomes in a person with diabetes and a foot ulcer or gangrene. Fifteen recommendations were developed related to PAD treatment encompassing prioritisation of people for revascularisation, the choice of a procedure and post-surgical care. In addition, the Writing Committee has highlighted key research questions where current evidence is lacking. The Writing Committee believes that following these recommendations will help healthcare professionals to provide better care and will reduce the burden of diabetes related foot complications.

Major Adverse Limb Events in Patients Undergoing Revascularisation for Lower Limb Peripheral Arterial Disease: A Nationwide Observational Study.

OBJECTIVE: Major adverse limb events (MALEs) are frequent in patients with lower extremity peripheral arterial disease (PAD). However, routine care MALE rate estimations after revascularisation are scarce. This study aimed to determine post-procedural MALE rates in revascularised patients with PAD and identify predictors of post-procedural MALEs. METHODS: This was a population based observational study on merged national registry data. Patients with PAD undergoing lower limb revascularisation between 2008 and 2016 were retrieved from the Swedish National Registry for Vascular Surgery. Information on comorbidities, medications, and post-procedural MALE endpoints were identified in national healthcare registries. Primary outcomes of interest were categorised as 2 - 4 point MALE composites that included limb amputation, acute lower limb ischaemia, progression to or relapse of chronic limb threatening ischaemia (CLTI), and ipsilateral re-interventions regardless of indication. Patients with intermittent claudication (IC) and CLTI were analysed separately using Kaplan-Meier estimates. Stepwise Cox proportional hazard models were used for predictor candidate analysis. RESULTS: Overall, 28 021 revascularised patients with PAD were analysed (IC, n = 10 506, 37.5%; CLTI, n = 17 515, 62.5%). During a mean follow up ± standard deviation of 3.2 ± 2.4 years, 5 226 (18.7%), 9 423 (33.6%), and 12 696 (45.3%) patients experienced a 2, 3, and 4 point MALE, respectively. The estimated one year 4 point MALE rates were 21.4% (95% confidence interval [CI] 20.6 - 22.2%) in IC and 46.9% (95% CI 46.1 - 47.7%) in CLTI. Adjusted predictors for experiencing a 4 point MALE in IC were chronic kidney disease (CKD) (hazard ratio [HR] 1.33, 95% CI 1.12 - 1.59) and previous lower limb revascularisation (HR 1.29, 95% CI 1.19 - 1.40). In CLTI, previous contralateral lower limb amputation (HR 1.60, 95% CI 1.47 - 1.73) and CKD (HR 1.25, 95% CI 1.17 - 1.34) were adjusted predictors. CONCLUSION: This study emphasises the very high MALE rates in revascularised patients with lower limb PAD, especially in CLTI. Prior lower limb revascularisation correlated with increased MALE rates in IC patients, while prior lower limb amputation was linked to subsequent MALEs in CLTI. In both IC and CLTI, CKD was associated with poorer outcomes, regardless of applied MALE definition.

Two or More Ischaemic Events Within Seven Days Before Carotid Endarterectomy Increases the Risk of Peri-operative Stroke or Death.

OBJECTIVE: The aim of this study was to determine how many pre-operative ischaemic events occurring within a specific timeframe before carotid endarterectomy (CEA) are needed to increase the peri-operative 30 day risk of stroke or death. METHODS: This was a secondary exploratory analysis based on pooled data from three observational studies sourced from a single centre. Patients with recently symptomatic conventional ≥ 50% carotid stenosis were included. The principal analysis was limited to patients presenting with stroke or transient ischaemic attack (TIA). The primary outcome was 30 day risk of peri-operative stroke or death. Whether one, two, three, or four or more ipsilateral pre-operative ischaemic events within three, seven, 14, or 30 days before CEA were associated with the primary outcome was assessed. RESULTS: The study included 382 patients who underwent CEA with symptomatic conventional ≥ 50% carotid stenosis with stroke or TIA as the presenting event. Mean patient age ± standard deviation was 72 ± 7 years, 117 (30.6%) were female, and 5% were treated with dual antiplatelet therapy. The primary outcome occurred in 21 patients (5.5%). Two or more events within 7 days before CEA was the most discriminative definition of repeated events, with a 14.3% (8/56) risk of the primary outcome. Those who fell outside this definition of two or more events within seven days before CEA had a 4.0% (13/326; p = .006) risk of experiencing the primary outcome (adjusted odds ratio 4.1, 95% confidence interval 1.6 - 10.5). Several alternative definitions were assessed, but patients with two or more events within seven days before CEA and negative for these alternatives still had a > 10% risk of the primary outcome. CONCLUSION: Two or more ipsilateral ischaemic events within seven days before CEA is associated with an increased risk of peri-operative stroke or death in cases with symptomatic conventional ≥ 50% carotid stenosis and TIA or stroke as the presenting event. Studies assessing whether delayed or immediate CEA is preferable for this patient group are warranted.

Endovascular revascularization strategies for aortoiliac and femoropopliteal artery disease: a meta-analysis.

AIMS: Optimal endovascular management of intermittent claudication (IC) remains disputed. This systematic review and meta-analysis compares efficacy and safety outcomes for balloon angioplasty (BA), bare-metal stents (BMS), drug-coated balloons (DCB), drug-eluting stents (DES), covered stents, and atherectomy. METHODS AND RESULTS: Electronic databases were searched for randomized, controlled trials (RCT) from inception through November 2021. Efficacy outcomes were primary patency, target-lesion revascularization (TLR), and quality-of-life (QoL). Safety endpoints were all-cause mortality and major amputation. Outcomes were evaluated at short-term (<1 year), mid-term (1-2 years), and long-term (≥2 years) follow-up. The study was registered on PROSPERO (CRD42021292639). Fifty-one RCTs enrolling 8430 patients/lesions were included. In femoropopliteal disease of low-to-intermediate complexity, DCBs were associated with higher likelihood of primary patency [short-term: odds ratio (OR) 3.21, 95% confidence interval (CI) 2.44-4.24; long-term: OR 2.47, 95% CI 1.93-3.16], lower TLR (short-term: OR 0.33, 95% CI 0.22-0.49; long-term: OR 0.42, 95% CI 0.29-0.60) and similar all-cause mortality risk, compared with BA. Primary stenting using BMS was associated with improved short-to-mid-term patency and TLR, but similar long-term efficacy compared with provisional stenting. Mid-term patency (OR 1.64, 95% CI 0.89-3.03) and TLR (OR 0.50, 95% CI 0.22-1.11) estimates were comparable for DES vs. BMS. Atherectomy, used independently or adjunctively, was not associated with efficacy benefits compared with drug-coated and uncoated angioplasty, or stenting approaches. Paucity and heterogeneity of data precluded pooled analysis for aortoiliac disease and QoL endpoints. CONCLUSION: Certain devices may provide benefits in femoropopliteal disease, but comparative data in aortoiliac arteries is lacking. Gaps in evidence quantity and quality impede identification of the optimal endovascular approach to IC.

Mortality with Paclitaxel-Coated Devices in Peripheral Artery Disease.

BACKGROUND: The results of a recent meta-analysis aroused concern about an increased risk of death associated with the use of paclitaxel-coated angioplasty balloons and stents in lower-limb endovascular interventions for symptomatic peripheral artery disease. METHODS: We conducted an unplanned interim analysis of data from a multicenter, randomized, open-label, registry-based clinical trial. At the time of the analysis, 2289 patients had been randomly assigned to treatment with drug-coated devices (the drug-coated-device group, 1149 patients) or treatment with uncoated devices (the uncoated-device group, 1140 patients). Randomization was stratified according to disease severity on the basis of whether patients had chronic limb-threatening ischemia (1480 patients) or intermittent claudication (809 patients). The single end point for this interim analysis was all-cause mortality. RESULTS: No patients were lost to follow-up. Paclitaxel was used as the coating agent for all the drug-coated devices. During a mean follow-up of 2.49 years, 574 patients died, including 293 patients (25.5%) in the drug-coated-device group and 281 patients (24.6%) in the uncoated-device group (hazard ratio, 1.06; 95% confidence interval, 0.92 to 1.22). At 1 year, all-cause mortality was 10.2% (117 patients) in the drug-coated-device group and 9.9% (113 patients) in the uncoated-device group. During the entire follow-up period, there was no significant difference in the incidence of death between the treatment groups among patients with chronic limb-threatening ischemia (33.4% [249 patients] in the drug-coated-device group and 33.1% [243 patients] in the uncoated-device group) or among those with intermittent claudication (10.9% [44 patients] and 9.4% [38 patients], respectively). CONCLUSIONS: In this randomized trial in which patients with peripheral artery disease received treatment with paclitaxel-coated or uncoated endovascular devices, the results of an unplanned interim analysis of all-cause mortality did not show a difference between the groups in the incidence of death during 1 to 4 years of follow-up. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT02051088.).

The intersocietal IWGDF, ESVS, SVS guidelines on peripheral artery disease in people with diabetes mellitus and a foot ulcer.

Diabetes related foot complications have become a major cause of morbidity and are implicated in most major and minor amputations globally. Approximately 50% of people with diabetes and a foot ulcer have peripheral artery disease (PAD) and the presence of PAD significantly increases the risk of adverse limb and cardiovascular events. The International Working Group on the Diabetic Foot (IWGDF) has published evidence based guidelines on the management and prevention of diabetes related foot complications since 1999. This guideline is an update of the 2019 IWGDF guideline on the diagnosis, prognosis, and management of peripheral artery disease in people with diabetes mellitus and a foot ulcer. For this updated guideline, the IWGDF, the European Society for Vascular Surgery, and the Society for Vascular Surgery decided to collaborate to develop a consistent suite of recommendations relevant to clinicians in all countries. This guideline is based on three new systematic reviews. Using the Grading of Recommendations, Assessment, Development and Evaluation framework clinically relevant questions were formulated, and the literature was systematically reviewed. After assessing the certainty of the evidence, recommendations were formulated which were weighed against the balance of benefits and harms, patient values, feasibility, acceptability, equity, resources required, and when available, costs. Through this process five recommendations were developed for diagnosing PAD in a person with diabetes, with and without a foot ulcer or gangrene. Five recommendations were developed for prognosis relating to estimating likelihood of healing and amputation outcomes in a person with diabetes and a foot ulcer or gangrene. Fifteen recommendations were developed related to PAD treatment encompassing prioritisation of people for revascularisation, the choice of a procedure and post-surgical care. In addition, the Writing Committee has highlighted key research questions where current evidence is lacking. The Writing Committee believes that following these recommendations will help healthcare professionals to provide better care and will reduce the burden of diabetes related foot complications.

Disease Specific Health Related Quality of Life in Patients With Chronic Limb Threatening Ischaemia Undergoing Revascularisation of Femoropopliteal Lesions.

OBJECTIVE: Patients with chronic limb threatening ischaemia (CLTI) suffer from pain and non-healing ulcers, which impact negatively on both their physical and mental health. While maintaining and improving quality of life is a principal aim with all treatments, little is known about the health related quality of life (HRQoL) of CLTI patients and how revascularisation procedures impact on HRQoL endpoints. The aim of this study was to investigate disease specific HRQoL before and after revascularisation in patients with CLTI undergoing femoropopliteal revascularisation. METHODS: HRQoL was prospectively analysed in 190 CLTI patients with main atherosclerotic target lesions in the femoropopliteal segment, who were planned for endovascular or open revascularisation. The choice of revascularisation method was made by the vascular team, represented by both open and endovascular expertise. The Vascular Quality of Life (VascuQoL) questionnaire was used to assess disease specific HRQoL before revascularisation and one month, one year, and two years after the procedure. Main endpoints were mean VascuQoL score changes, effect sizes of observed changes and the proportion reaching a minimally important difference (half a standard deviation change from baseline) during two years after revascularisation. RESULTS: Patient reported VascuQoL scores were low at baseline (mean 2.68, 95% CI 1.18 - 4.17). After revascularisation, the mean VascuQoL score improved statistically significantly over time, with the largest improvement observed after one year (difference from baseline 2.02, 95% CI 1.75 - 2.29; p < .001). No differences in HRQoL change over time were observed between patients treated with endovascular approaches compared with bypass surgery. Approximately half the patients reached the minimally important threshold at one year (53%), which was largely maintained also at two years (41%). CONCLUSION: While CLTI profoundly affected HRQoL, a large and clinically meaningful HRQoL increase was observed after revascularisation. This confirms the value of CLTI revascularisation on HRQoL and underlines the importance of including patient reported outcomes when evaluating revascularisation procedures in CLTI patients.

The Intersocietal IWGDF, ESVS, SVS Guidelines on Peripheral Artery Disease in People With Diabetes Mellitus and a Foot Ulcer.

Diabetes related foot complications have become a major cause of morbidity and are implicated in most major and minor amputations globally. Approximately 50% of people with diabetes and a foot ulcer have peripheral artery disease (PAD) and the presence of PAD significantly increases the risk of adverse limb and cardiovascular events. The International Working Group on the Diabetic Foot (IWGDF) has published evidence based guidelines on the management and prevention of diabetes related foot complications since 1999. This guideline is an update of the 2019 IWGDF guideline on the diagnosis, prognosis, and management of peripheral artery disease in people with diabetes mellitus and a foot ulcer. For this updated guideline, the IWGDF, the European Society for Vascular Surgery, and the Society for Vascular Surgery decided to collaborate to develop a consistent suite of recommendations relevant to clinicians in all countries. This guideline is based on three new systematic reviews. Using the Grading of Recommendations, Assessment, Development and Evaluation framework clinically relevant questions were formulated, and the literature was systematically reviewed. After assessing the certainty of the evidence, recommendations were formulated which were weighed against the balance of benefits and harms, patient values, feasibility, acceptability, equity, resources required, and when available, costs. Through this process five recommendations were developed for diagnosing PAD in a person with diabetes, with and without a foot ulcer or gangrene. Five recommendations were developed for prognosis relating to estimating likelihood of healing and amputation outcomes in a person with diabetes and a foot ulcer or gangrene. Fifteen recommendations were developed related to PAD treatment encompassing prioritisation of people for revascularisation, the choice of a procedure and post-surgical care. In addition, the Writing Committee has highlighted key research questions where current evidence is lacking. The Writing Committee believes that following these recommendations will help healthcare professionals to provide better care and will reduce the burden of diabetes related foot complications.

Impact of walk advice alone or in combination with supervised or home-based structured exercise on patient-reported physical function and generic and disease-specific health related quality of life in patients with intermittent claudication, a secondary analysis in a randomized clinical trial.

BACKGROUND: Supervised exercise is an integral part of the recommended first-line treatment for patients with intermittent claudication (IC). By reflecting the patients' perspectives, patient-reported outcome measurements provide additional knowledge to the biomedical endpoints and are important outcomes to include when evaluating exercise interventions in patients with IC. We aimed to evaluate the one-year impact of three strategies: unsupervised Nordic pole walk advice (WA), WA + six months of home-based structured exercise (HSEP) or WA + six months of hospital-based supervised exercise (SEP) on health-related quality of life and patient-reported physical function in patients with IC. METHODS: This secondary exploratory analysis of a multi-center, randomized clinical trial compared three exercise strategies. The primary outcome of the secondary analysis was the one-year change in the 36-Item Short-Form (SF-36). Secondary outcomes were three- and six-months SF-36 changes alongside three, six- and 12-months changes in the disease-specific Vascular Quality of Life instrument (VascuQoL) and the Patient-Specific Functional Scale (PSFS). The Kruskal-Wallis test with Bonferroni-adjusted post-hoc tests were used for between-group comparisons. Effect size calculations were used to describe the size of observed treatment effects, and the clinical meaningfulness of observed changes in the VascuQoL summary score at one year was studied using established minimally important difference (MID) thresholds. RESULTS: A total of 166 patients with IC, mean age: 72.1 (SD 7.4) years, 41% women, were randomized. No significant between-group differences were observed over time for the SF-36 or the PSFS scores whereas some significant between-group differences were observed in the VascuQoL domain and summary scores over time, favoring SEP and/or HSEP over WA. The observed SF-36 and VascuQoL domain and summary score effect sizes were small to moderate, and many domain score effect sizes also remained unchanged over time. A significantly higher proportion of the patients in the SEP group reached the VascuQoL summary score MID of improvement in one year. CONCLUSION: Clinically important improvements were observed in SEP using the VascuQoL, while we did not observe any significant between-group differences using the SF-36. Whereas effect sizes for the observed changes over time were generally small, a significantly higher proportion of patients in SEP reached the VascuQoL MID of improvement. TRIAL REGISTRATION: NCT02341716, January 19, 2015 (retrospectively registered).

Poor inter-observer agreement in anatomical classifications of infrapopliteal arterial disease due to mandatory selection of only one target artery.

BACKGROUND: Established anatomical classifications of infrapopliteal arterial lesion severity are based on assessment of only one target artery, not including all infrapopliteal arteries although multivessel revascularization is common. PURPOSE: To investigate the reproducibility of one of these classifications and a new aggregated score. MATERIAL AND METHODS: A total of 68 patients undergoing endovascular infrapopliteal revascularization at Sahlgrenska University Hospital during 2008-2016 were included. Preoperative magnetic resonance angiographies (MRA) and digital subtraction angiographies (DSA) were evaluated by three blinded observers in random order, using the infrapopliteal TransAtlantic Inter-Society Consensus (TASC) II classification. An aggregated score, the Infrapopliteal Total Atherosclerotic Burden (I-TAB) score, including all infrapopliteal arteries, was constructed and used for comparison. RESULTS: Inter-observer agreement on lesion severity for each evaluated artery was good; Krippendorff's α for MRA 0.64-0.79 and DSA 0.66-0.84. Inter-observer agreement on TASC II grade, based on the selected target artery as stipulated, was poor; Krippendorff's α 0.14 (95% confidence interval [CI]=-0.05 to 0.30) for MRA and 0.48 (95% CI=0.33-0.61) for DSA. Inter-observer agreement for the new I-TAB score was good; Krippendorff's α 0.76 (95% CI=0.70-0.81) for MRA and 0.79 (95% CI=0.74-0.84) for DSA. CONCLUSION: Reproducible assessment of infrapopliteal lesion severity can be achieved for separate arteries with both MRA and DSA using the TASC II definitions. However, poor inter-observer agreement in selecting the target artery results in low reproducibility of the overall infrapopliteal TASC II grade. An aggregated score, such as I-TAB, results in less variability and may provide a more robust evaluation tool of atherosclerotic disease severity.

A Delphi Consensus on Patient Reported Outcomes for Registries and Trials Including Patients with Intermittent Claudication: Recommendations and Reporting Standard.

OBJECTIVE: This study aimed to develop a core set of patient reported outcome quality indicators (QIs) for the treatment of patients with intermittent claudication (IC), that allow a broad international implementation across different vascular registries and within trials. METHODS: A rigorous modified two stage Delphi technique was used to promote consensus building on patient reported outcome QIs among an expert panel consisting of international vascular specialists, patient representatives, and registry members of the VASCUNET and the International Consortium of Vascular Registries. Potential QIs identified through an extensive literature search or additionally proposed by the panel were validated by the experts in a preliminary survey and included for evaluation. Consensus was reached if ≥ 80% of participants agreed that an item was both clinically relevant and practical. RESULTS: Participation rates in two Delphi rounds were 66% (31 participants of 47 invited) and 90% (54 of 60), respectively. Initially, 145 patient reported outcome QIs were documented. Following the two Delphi rounds, 18 quality indicators remained, all of which reached consensus regarding clinical relevance. The VascuQoL questionnaire (VascuQoL-6), currently the most common patient reported outcome measurement (PROM) used within vascular registries, includes a total of six items. Five of these six items also matched with high rated indicators identified in the Delphi study. Consequently, the panel recommends the use of the VascuQoL-6 survey as a preferred core PROM QI set as well as an optional extension of 12 additional patient reported QIs that were also identified in this study. CONCLUSION: The current recommendation based on the Delphi consensus building approach, strengthens the international harmonisation of registry data collection in relation to patient reported outcome quality. Continuous and standardised quality assurance will ensure that registry data may be used for future quality benchmarking studies and, ultimately, positively impact the overall quality of care provided to patients with peripheral arterial occlusive disease.

Editor's Choice - Structured Computed Tomography Analysis can Identify the Majority of Patients at Risk of Post-Endovascular Aortic Repair Rupture.

OBJECTIVE: The main objective was to report mechanisms and precursors for post-endovascular aneurysm repair (EVAR) rupture. The second was to apply a structured protocol to explore whether these factors were identifiable on follow up computed tomography (CT) prior to rupture. The third objective was to study the incidence, treatment, and outcome of post-EVAR rupture. METHODS: This was a multicentre, retrospective study of patients treated with standard EVAR at five Swedish hospitals from 2008 to 2018. Patients were identified from the Swedvasc registry. Medical records were reviewed up to 2020. Index EVAR and follow up data were recorded. The primary endpoint was post-EVAR rupture. CT at follow up and at post-EVAR rupture were studied, using a structured protocol, to determine rupture mechanisms and identifiable precursors. RESULTS: In 1 805 patients treated by EVAR, 45 post-EVAR ruptures occurred in 43 patients. The cumulative incidence was 2.5% over a mean follow up of 5.2 years. The incidence rate was 4.5/1 000 person years. Median time to post-EVAR rupture was 4.1 years. A further six cases of post-EVAR rupture in five patients found outside the main cohort were included in the analysis of rupture mechanisms only. The rupture mechanism was type IA in 20 of 51 cases (39%), IB in 20 of 51 (39%) and IIIA/B in 11 of 51 (22%). One of these had type IA + IB combined. One patient had an aortoduodenal fistula without another mechanism being identified. Precursors had been noted on CT follow up prior to post-EVAR rupture in 16 of 51 (31%). Retrospectively, using the structured protocol, precursors could be identified in 43 of 51 (84%). In 17 of 27 (63%) cases missed on follow up but retrospectively identifiable, the mechanisms were type IB/III. Overall, the 30 day mortality rate after post-EVAR rupture was 47% (n = 24/51) and the post-operative mortality rate was 21% (n = 7/33). CONCLUSIONS: Most precursors of post-EVAR rupture are underdiagnosed but identifiable before rupture using a structured follow up CT protocol. Precursors of type IB and III failures caused the majority of post-EVAR ruptures.

The OAC3-PAD Risk Score Predicts Major Bleeding Events one Year after Hospitalisation for Peripheral Artery Disease.

OBJECTIVE: There is a paucity of evidence concerning the risk of bleeding after hospitalisation for symptomatic peripheral artery disease (PAD) in everyday clinical practice, as randomised clinical trials commonly exclude patients with heightened risk. The current study aimed to develop a pragmatic risk score that enables prediction of major bleeding during the first year after index discharge. METHODS: Unselected retrospective data from the second largest insurance fund in Germany, BARMER, were used to identify patients with a first hospitalisation for PAD registered between 1 January 2010 and 31 December 2018. Within a separate training cohort, final predictors were selected using penalised Cox regression (least absolute shrinkage and selection operator with ten fold cross validation) with one year major bleeding requiring hospitalisation as outcome. The risk score was internally validated. Four different risk groups were constructed. RESULTS: A total of 81 930 patients (47.2% female, 72.3 years) underwent hospitalisation for symptomatic PAD. After one year, 1 831 (2.2%) of the patients had a major bleeding event. Independent predictors were previous oral anticoagulation, age over 80, chronic limb threatening ischaemia, congestive heart failure, severe chronic kidney disease, previous bleeding event, anaemia, and dementia. The OAC3-PAD risk score exhibited adequate calibration and discrimination between four risk groups (c = 0.69, 95% confidence interval 0.67 - 0.71) from low risk (1.3%) to high risk (6.4%). CONCLUSION: A pragmatic risk score was developed to predict the individual major bleeding risk classifying a fifth of the cohort as high risk patients. Individual prediction scores such as the one proposed here may help to inform the risk and benefit of intensified antithrombotic strategies.

Validation of an automated measurement method for determination of the ankle-brachial index.

Objective. Lower extremity atherosclerotic disease (LEAD) diagnosis is largely based on ankle-brachial index (ABI) recordings. Equipment that could automatically determine ABI may facilitate LEAD identification within a broad range of health services. We aimed to test the measurement properties of an automated oscillometric ABI measurement device (MESI ABPI MD®) as compared to manual reference ABI measurements in patients with and without LEAD. Design. A total of 153 patients with and without LEAD visiting a vascular surgery clinic underwent manual and automated ABI measurements. In total, 306 limbs were investigated. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess the automated ABI device overall validity, with the manual method as reference. Correlation analysis (Spearman) was used to assess patterns of correlation between measurement methods while Bland-Altman plots were used to quantify measurement agreement. Results. Sensitivity and specificity for the automated ABI device were 75 and 67% whereas PPV and NPV were 72 and 71%, respectively. The correlation coefficient (automated versus manual measurements) was r = 0.552, p < .01. Bland-Altman plots revealed proportional bias and a tendency by the automated device to overestimate lower ABI values and underestimate higher ABI values. The best agreement between automated and manual ABI recordings was observed within the normal ABI range. Conclusions. The ABPI MD® device performance was unfavorable. The automated device tended to overestimate lower ABI values while underestimating higher values, which may lead to underdiagnosis of LEAD. Our data do not support the use of this automated ABI measurement device in clinical practice.

SGLT2 Inhibitors and Peripheral Vascular Events: A Review of the Literature.

Fifty articles comprising 18 randomized controlled trials (RCTs), 16 observational studies, and 16 meta-analyses on the safety and effectiveness of sodium-glucose cotransporter 2 inhibitors were evaluated in the current review. Only one-fourth of the cohorts of recent trials had peripheral arterial disease (PAD), whereas this subgroup was at high risk for amputations. Despite a remarkable heterogeneity of RCTs, only 2 trials on canagliflozin suggested excess amputation rates, whereas several observational studies generated conflicting conclusions and remained short on possible explanations. Preliminary evidence from observational research suggested that patients with PAD may even benefit from SGLT-2 inhibitor treatment due to lower observed heart failure hospitalization rates.

Misdiagnosis of ruptured abdominal aortic aneurysms is common and is associated with increased mortality.

OBJECTIVE: To investigate the rate of misdiagnosis in the emergency department in patients with ruptured abdominal aortic aneurysms (rAAAs), and to investigate how misdiagnosis affects rAAA mortality. METHODS: Data were extracted from the Swedish Cause of Death Registry and the Swedish National Registry for Vascular Surgery from 2010 to 2015. All rAAA patients registered in the health care system in the west of Sweden were identified. Medical charts for rAAA patients were reviewed, and patients who were correctly diagnosed at the first assessment in the emergency department were compared with patients who were misdiagnosed. RESULTS: Altogether, 455 patients with rAAA were identified, including both patients who underwent surgery and those who did not. One hundred seventy-seven (38.9%) were initially misdiagnosed. The mortality rate was 74.6% in patients who were misdiagnosed, as compared with 62.9% in correctly diagnosed patients (P = .01). The adjusted odds ratio for mortality in misdiagnosed patients relative to correctly diagnosed patients was 1.83 (95% confidence interval, 1.13-2.96) (P = .01). When excluding patients offered palliative care (n = 134) after detection of the rAAA, the mortality in initially misdiagnosed patients was 65.1% as compared with 46.4% in correctly diagnosed patients (P = .001). In patients reaching surgical intervention, 37 (45.1%) of the primarily misdiagnosed patients died (30-day or in-hospital mortality) as compared with 63 (38.0%) of the correctly diagnosed (P = .34). CONCLUSIONS: Misdiagnosis is common in patients with rAAA, and it is associated with a substantially higher risk of dying from the ruptured aneurysm.

Editor's Choice - Cost Effectiveness of Primary Stenting in the Superficial Femoral Artery for Intermittent Claudication: Two Year Results of a Randomised Multicentre Trial.

OBJECTIVE: Invasive treatment of intermittent claudication (IC) is commonly performed, despite limited evidence of its cost effectiveness. IC symptoms are mainly caused by atherosclerotic lesions in the superficial femoral artery (SFA), and endovascular treatment is performed frequently. The aim of this study was to investigate its cost effectiveness vs. non-invasive treatment. METHODS: One hundred patients with IC due to lesions in the SFA were randomised to treatment with primary stenting, best medical treatment (BMT) and exercise advice (stent group), or to BMT and exercise advice alone (control group). Patients were recruited at seven hospitals in Sweden. For this analysis of cost effectiveness after 24 months, 84 patients with data on quality adjusted life years (QALY; based on the EuroQol Five Dimensions EQ-5D 3L™ questionnaire) were analysed. Patient registry and imputed cost data were used for accumulated costs regarding hospitalisation and outpatient visits. RESULTS: The mean cost per patient was €11 060 in the stent group and €4 787 in the control group, resulting in a difference of €6 273 per patient between the groups. The difference in mean QALYs between the groups was 0.26, in favour of the stent group, which resulted in an incremental cost effectiveness ratio (ICER) of € 23 785 per QALY. CONCLUSION: The costs associated with primary stenting in the SFA for the treatment of IC were higher than for exercise advice and BMT alone. With concurrent improvement in health related quality of life, primary stenting was a cost effective treatment option according to the Swedish national guidelines (ICER < €50 000 - €70 000) and approaching the UK's National Institute for Health and Care Excellence threshold for willingness to pay (ICER < £20 000 - £30 000). From a cost effectiveness standpoint, primary stenting of the SFA can, in many countries, be used as an adjunct to exercise training advice, but it must be considered that successful implementation of structured exercise programmes and longer follow up may alter these findings.