Endovascular and Surgical Venous Arterialization for No-Option Patients With Chronic Limb-Threatening Ischemia: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic limb-threatening ischemia (CLTI) is known for its high rates of major amputation and mortality. Conventional revascularization techniques often fail in CLTI patients due to the heavily diseased arteries. Foot vein arterialization (FVA) has been proposed as an alternative technique to provide arterial blood to the foot by using the disease-free venous bed. OBJECTIVES: This systematic review and meta-analysis aimed to determine outcomes of surgical FVA (sFVA) and percutaneous FVA (pFVA) at 6 and 12 months post-procedure. DATA SOURCES: PubMed, Scopus, Web of Science, and the Cochrane Library databases were searched to identify papers reporting clinical outcomes of sFVA and pFVA published between January 1966 and March 2023. METHODS: Databases were searched for eligible studies. A meta-analysis was performed to evaluate the limb salvage rate, overall survival rate, and wound healing rate at 6 and 12 months. RESULTS: A total of 27 studies were included, with 753 patients and 793 limbs. Of the included studies, 16 analyzed the sFVA technique and 11 the pFVA technique. Of the included patients, 86.3% were Rutherford 5/6 in the sFVA group versus 98.4% in the pFVA group. The pooled limb salvage rate at 6 and 12 months was 78.1% and 74.1% in the sFVA group and 81.7% and 78.6% in the pFVA group, respectively. Wound healing rates were not reported in the sFVA group. In the pFVA group, the pooled wound healing rates were 48.1% and 64.5% at 6 and 12 months, respectively. CONCLUSION: This study showed promising results after FVA among a large population of CLTI patients. In high-risk patients, pFVA is a feasible option with favorable limb salvage and wound healing rates.

The Elephant in the Room.

Despite its increasing prevalence, severity, and mortality, Diabetic foot syndrome (DFS) still remains an unaddressed critical issue. The management of DFS is adequately performed only in few centers, and clinical outcomes vary, depending on the possibility of patients to access optimal standards of care. To focus on the critical aspects of the management of DFS in Italy with the purpose of suggesting arguments that might have a more general audience, to improve the quality of therapy and accessibility to optimal care, we have written this article.

Medial Sclerosis-Epidemiology and Clinical Significance.

BACKGROUND: Medial sclerosis (MeS) is a chronic systemic vascular disease that mainly affects the arteries of the lower limb. Its prevalence in the general population is approximately 2.5% (range: 1.6% to 10.0%). It is more common in men than in women. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed. RESULTS: MeS is the final common pathway of a wide variety of diseases; its pathogenesis is not fully understood. It often remains clinically silent for decades and is usually diagnosed as an incidental finding or in a late stage. MeS with or without atherosclerosis is the most common histologic finding after limb amputation. MeS of the below-the-knee arteries is a major risk factor for chronic critical leg ischemia (OR:13.25, 95% confidence interval: [1.69; 104.16]) and amputation (RR 2.27, [1.89; 2.74]). Patients with peripheral arterial occlusive disease and marked calcification have a much higher risk of amputation (OR 2.88, [1.18; 12.72]) and a higher mortality (OR 5.16, [1.13; 21.61]). MeS is a risk factor for the failure of endovascular treatment of the pedal arteries (OR 4.0, [1.1; 16.6]). The more marked the calcification, the higher the risk of major amputation (HR 10.6 [1.4; 80.7] to HR 15.5 [2.0; 119]). Patients with vascular calcifications have been found to have lower patency rates and higher treatment failure rates two years after open surgical revascularization of the below-the-knee arteries. No pharmacotherapy for MeS is available to date. CONCLUSION: MeS is an important risk factor for chronic critical lower limb ischemia, amputation, morbidity, and complications, particularly after endovascular and surgical procedures.

International Union of Angiology Position Statement on no-option chronic limb threatening ischemia.

This position paper, written by members of International Union of Angiology (IUA) Youth Committee and senior experts, shows an overview of therapeutical approaches for patients with chronic limb-threatening ischemia (CLTI) and absence of 'standard' solutions for revascularization. The aim was to demonstrate the accurate management of the 'no-option' CLTI patient including the wound treatment and the rehabilitation, considering always the goal of the increase of quality of life of the patients.

Pedal arterial calcification score is associated with hemodynamic change and major amputation after infrainguinal revascularization for chronic limb-threatening ischemia.

OBJECTIVE: Pedal medial arterial calcification (pMAC) is associated with major amputation in patients with chronic limb-threatening ischemia (CLTI). We hypothesize that this association would be related to unresolved distal ischemia. We investigated relationships across pMAC score, hemodynamic change, and major amputation after infrainguinal revascularization for CLTI. METHODS: This is a single-institution, retrospective study of 306 patients who underwent technically successful infrainguinal revascularization for CLTI (2011-2020) and had foot x-rays for blinded pMAC scoring (0-5). A total of 136 (44%) patients had toe pressure measurements performed within 90 days before and 60 days after revascularization. Ischemia grade (0-3) was assigned using the Society for Vascular Surgery Wound, Ischemia, foot Infection (WIfI) system. RESULTS: The revascularization approach was open bypass in 118 (38%) and endovascular in 188 (62%) patients. pMAC scores were trichotomized (0-1 [125; 41%], 2-4 [116; 38%], 5 [65; 21%]). Post-revascularization WIfI ischemia grade was improved in 78 of 136 (57%) and unchanged/worsened in 58 of 136 (43%). A lower pMAC score was associated with hemodynamic improvement (P = .004). Failure to improve the ischemia grade was associated with major amputation (P = .0002). In the endovascular subgroup, WIfI ischemia grade was improved in 43 of 90 (48%) with available measurements, and 37 of 188 (20%) underwent major amputation. In a multivariate logistic model, pMAC 5 was the only factor independently associated with unimproved ischemia grade after endovascular treatment (odds ratio: 4.0 [1.1-16.6], P = .04). In a Cox proportional hazards model, factors independently associated with major amputation after endoluminal revascularization were WIfI stage 4 (hazard ratio [HR]: 2.7 [1.3-5.7], P = .007) and pMAC score (pMAC: 2-4: HR: 10.6 [1.4-80.7], P = .02; pMAC: 5: HR: 15.5 [2.0-119], P = .008). In the bypass subgroup, WIfI ischemia grade was improved in 35 of 46 (76%) with available measurements but was not associated with pMAC score (P = .88) or any other baseline patient or limb characteristics. A total of 19 of 118 (16%) patients underwent major amputation. In a Cox proportional hazards model including bypass conduit, WIfI stage, and pMAC score, the only factor independently associated with major amputation after bypass was use of nonautologous conduit (HR: 5.6 [1.8-17.6], P = .003). CONCLUSIONS: The pMAC score is independently associated with persistent distal ischemia and major amputation after technically successful revascularization for CLTI. These data suggest that pMAC may be a marker for hemodynamic response to revascularization and risk of limb loss, and it may have a stronger influence on the outcome of endoluminal interventions.

Leadless pacemakers as a new alternative for pacemaker lead-related superior vena cava syndrome: A case report.

Superior vena cava (SVC) syndrome is a rare disease induced by thrombosis and consequent occlusion of SVC, negatively affecting morbidity and mortality. The incidence of SVC syndrome from central venous catheters and pacemaker or defibrillator leads is increasing. Optimal treatment of pacemaker or defibrillator-related SVC syndrome is not well defined. Lead extraction causes mechanical trauma to the vessel wall. In addition, subsequent device implantation on the contralateral side can be an added factor for venous occlusion. The use of leadless pacemakers could be an interesting option to reduce the risk of SVC restenosis after lead extraction. We report a clinical case of PM leads-related SVC syndrome referred to our centers and treated with transvenous lead extraction, leadless pacemaker implantation and subsequent percutaneous angioplasty and stenting of the SVC and left innominate vein.

Percutaneous Transluminal Angioplasty for Below-the-Elbow Critical Hand Ischemia: A Systematic Review.

PURPOSE: To perform a systematic review assessing the safety and efficacy of percutaneous transluminal angioplasty (PTA) for treatment of critical hand ischemia (CHI) due to below-the-elbow (BTE) obstructive arterial disease. MATERIALS AND METHODS: MEDLINE and EMBASE systematic searches were performed from inception to December 2020 to identify studies assessing PTA for management of BTE obstructive arterial disease. Three independent reviewers performed abstract selection, data extraction, and quality assessment. The Newcastle-Ottawa Scale was used to assess individual study bias for non-randomized controlled trials. RESULTS: Eight studies comprising 176 patients with obstructive BTE vessel disease were included. All studies had a score >5 on the Newcastle-Ottawa Scale, indicative of high quality. All studies used low-profile balloons (1.5-4 mm) for PTA of stenotic lesions or chronic total occlusions (CTOs). The weighted average technical success and clinical success rates were 89.3% (range = 82%-100%) and 69.9% (range = 19%-100%), respectively, at a mean follow-up of 29.7 ± 17.1 months. The short-term (<30 days) complication rate was low at 4.7% and most commonly included access site hematomas, pseudoaneurysms, and radial artery perforation or re-thrombosis. Nearly 20% of patients required an amputation, and most (96%) were minor (either distal phalanges or digits). Only 2 patients required above-wrist amputations. The primary and secondary patency rate at 5 years were 38% and 54%, respectively. The cumulative 5-year mortality rate was 33.1%. CONCLUSIONS: PTA for CHI due to BTE obstructive arterial disease is feasible with a high technical success rate and a low short-term complication rate. Additional long-term comparative studies are required to unequivocally establish the clinical benefit of endovascular treatment compared with conservative management or surgical bypass.

Pedal arterial calcification score is associated with the risk of major amputation in chronic limb-threatening ischemia.

OBJECTIVE: The medial arterial calcification (MAC) score is a simple metric that describes the burden of inframalleolar calcification using a plain foot radiograph. We hypothesized that a higher MAC score would be independently associated with the risk of major amputation in patients with chronic limb-threatening ischemia (CLTI). METHODS: We performed a single-institution, retrospective study of 250 patients who had undergone infrainguinal revascularization for CLTI from January 2011 to July 2019 and had foot radiographs available for MAC score calculation. A single blinded reviewer assigned MAC scores of 0 to 5 using two-view minimum plain foot radiographs, with 1 point each for calcification of >2 cm in the dorsalis pedis, plantar, and metatarsal arteries and >1 cm in the hallux and non-hallux digital arteries. RESULTS: The MAC score was 0 in 36%, 1 in 5.2%, 2 in 8.4%, 3 in 14%, 4 in 14%, and 5 in 21%. The MAC score was trichotomized to facilitate analysis and clinical utility (mild, MAC score 0-1; moderate, MAC score 2-4; and severe, MAC score 5). The variables independently associated with a higher MAC score were male sex, diabetes, end-stage renal disease, and the global limb anatomic staging system pedal score. The MAC score was not associated with the Society for Vascular Surgery WIfI (wound, ischemia, foot infection) grade or overall WIfI stage (P = .58). The median follow-up was 759 days (interquartile range, 264-1541 days). A higher MAC score was significantly associated with the risk of major amputation (P < .0001). In a Cox proportional hazards multiple regression model for major amputation that included the trichotomized MAC score, diabetes, end-stage renal disease, and WIfI stage (1-3 vs 4). The MAC score (MAC score 5: hazard ratio [HR], 4.9; 95% confidence interval [CI], 1.9-13.1; P = .001; MAC score 2-4: HR, 3.4; 95% CI, 1.3-8.8; P = .01) and WIfI stage (WIfI stage 4: HR, 2.1; 95% CI, 1.1-3.9; P = .03) were significantly associated with the risk of major amputation. In the subsets of patients with the most advanced WIfI stage of 3 to 4 (191 of 250; 76%) and patients with diabetes (185 of 250; 74%), the MAC score further stratified the risk of major amputation on univariate and multivariate analyses. CONCLUSIONS: The MAC score is a simple, practical tool and a strong independent predictor of major amputation in patients with CLTI. It provides novel clinical data that are currently unmeasured using any validated CLTI staging system. The MAC score is a promising standardized measure of inframalleolar disease burden that can be used in conjunction with the WIfI staging system to help improve outcomes stratification and determine the optimal treatment strategies for patients with CLTI.

Medial Arterial Calcification: JACC State-of-the-Art Review.

Medial arterial calcification (MAC) is a chronic systemic vascular disorder distinct from atherosclerosis that is frequently but not always associated with diabetes mellitus, chronic kidney disease, and aging. MAC is also a part of more complex phenotypes in numerous less common diseases. The hallmarks of MAC include disseminated and progressive precipitation of calcium phosphate within the medial layer, a prolonged and clinically silent course, and compromise of hemodynamics associated with chronic limb-threatening ischemia. MAC increases the risk of complications during vascular interventions and mitigates their outcomes. With the exception of rare monogenetic defects affecting adenosine triphosphate metabolism, MAC pathogenesis remains unknown, and causal therapy is not available. Implementation of genetics and omics-based approaches in research recognizing the critical importance of calcium phosphate thermodynamics holds promise to unravel MAC molecular pathogenesis and to provide guidance for therapy. The current state of knowledge concerning MAC is reviewed, and future perspectives are outlined.

Association of infrapopliteal medial arterial calcification with lower-limb amputations in high-risk patients: A systematic review and meta-analysis.

Medial arterial calcification (MAC) is a known risk factor for cardiovascular morbidity. The association between vascular calcifications and poor outcome in several vascular districts suggest that infrapopliteal MAC could be a risk factor for lower-limb amputation (LLA). This study's objective is to review the available literature focusing on the association between infrapopliteal MAC and LLA in high-risk patients. The PubMed and Embase databases were systematically searched. We selected original studies reporting the association between infrapopliteal MAC and LLAs in patients with diabetes and/or peripheral artery disease (PAD). Estimates were pooled using either a fixed-effects or a random-effects model meta-analysis. Heterogeneity was evaluated using the Q and I2 statistics. Publication bias was investigated with a funnel plot and Egger test. The trim-and-fill method was designed to estimate the possibly missing studies. Influence analysis was conducted to search studies influencing the final result. Test of moderators was used to compare estimates in good versus non-good-quality studies. Fifteen articles satisfied the selection criteria (n = 6489; median follow-up: 36 months). MAC was significantly associated with LLAs (pooled adjusted risk ratio (RR): 2.27; 95% CI: 1.89-2.74; I2 = 25.3%, Q-test: p = 0.17). This association was kept in the subgroup of patients with diabetes (RR: 2.37; 95% CI: 1.76-3.20) and patients with PAD (RR: 2.48; 95% CI: 1.72-3.58). The association was maintained if considering as outcome only major amputations (RR: 2.11; 95% CI: 1.46-3.06). Our results show that infrapopliteal MAC is associated with LLAs, thus suggesting MAC as a possible new marker of the at-risk limb.

GLASS (Global Limb Anatomic Staging System): a critical appraisal.

BACKGROUND: THE Global Vascular Guidelines (GVGs) propose a new Global Anatomic Staging System (GLASS) resulting in three stages of complexity for intervention. The aim of this study was to retrospectively classify a large cohort of CLTI patients according to the GLASS, evaluating its distribution in a real-world setting. METHODS: Retrospective, single center, observational study enrolling all consecutive CLTI patients submitted to infra-inguinal endovascular revascularization in our institution, between June 2014 and September 2019. Patients were categorized according to the GLASS for femoro-popliteal (FP), infra-popliteal (IP) and infra-malleolar grading. FP and IP grades were merged to get the final GLASS stage for each limb. RESULTS: The study included 1995 CLTI patients who underwent 2850 endovascular procedures in which 6009 arterial lesions were successfully treated. The FP segment was classified as: 1292 (45.3%) grade 0, 475 (16.6%) grade 1, 159 (5.6%) grade 2, 209 (7.4%) grade 3, and 715 (25.1%) grade 4. The IP segment was classified as: 1529 (53.6%) grade 0, 183 (6.4%) grade 1, 80 (2.8%) grade 2, 207 (7.3%) grade 3, and 851 (29.9%) grade 4. The combination of FP and IP grading led to GLASS stages: 922 (32.3%) stage 1, 375 (13.2%) stage 2, 1472 (51.6%) stage 3. CONCLUSIONS: The distribution of the FP, IP and final GLASS grading was mainly grouped at the two extremes, letting the intermediate grades rather scarce. The majority of patients present with an absent or severely diseased pedal arch, stressing the need to incorporate infra-malleolar disease into the GLASS.

A Novel Scoring System for Small Artery Disease and Medial Arterial Calcification Is Strongly Associated With Major Adverse Limb Events in Patients With Chronic Limb-Threatening Ischemia.

PURPOSE: To evaluate the roles of small artery disease (SAD) and medial arterial calcification (MAC) in patients with chronic limb-threatening ischemia (CLTI) and to identify any correlation between these factors and peripheral artery disease (PAD) or outcomes after treatment. MATERIALS AND METHODS: A retrospective review was conducted of 259 limbs with tissue loss among 223 CLTI patients (mean age 72.2±11.4 years; 194 men) having an angiographic foot vessel study, foot radiography, and at least 6 months of follow-up after intervention. SAD and MAC were quantified using a 3-level score (0=absent, 1=moderate, 2=severe) based on angiography for SAD and foot radiographs for MAC. The MAC score was validated and compared with the SAD score, evaluating their associations with PAD distribution and clinical outcomes. RESULTS: Based on the MAC score, the 259 limbs were classified as 55 group 0 (21.2%), 89 group 1 (34.4%), and 115 group 2 (44.4%). The SAD score stratified the 259 limbs as 67 group 0 (25.9%), 76 group 1 (29.3%), and 116 group 2 (44.8%). Interobserver reproducibility of the MAC score was high (correlation coefficient 0.96). Sensitivity and specificity of the MAC score in detecting SAD was 100% and 98.1%, respectively, in SAD groups 0 and 2 vs 99.1% and 92.7%, respectively, for SAD group 1. PAD was more proximal in MAC and SAD groups 0 and more distal in groups 1 and 2. Both MAC and SAD scores were able to predict clinical endpoints. Multivariable analysis demonstrated that the MAC score represents an independent risk factor for adverse limb events. CONCLUSION: SAD and MAC must be considered expressions of the same obstructing disease, able to adversely impact the fate of CLTI patients. SAD and MAC scores are powerful prognostic indicators of major adverse limb events in CLTI patients.

Foot Angiosomes: Instructions for Use.

In the last 15 years an abundance of literature has demonstrated that angiosome-targeted revascularization, either endovascular or open, can lead to better clinical results in patients with chronic limb-threatening ischemia. According to this literature, the angiosome concept should guide our treatment strategy in every chronic limb-threatening ischemia patient. However, in our daily practice, its application is often difficult or impossible. Most foot wounds spread over multiple angiosomes and, moreover, the value of an angiosome-guided revascularization approach can vary according to vascular anatomy, collateral vessel network, type of revascularization, and wound. The aim of this article is to explore values and limits of the angiosome concept, and to propose some "instructions for use" regarding its application in our daily practice.

High-pressure, non compliant balloon angioplasty for long and calcified infrapopliteal and inframalleolar lesions is feasible.

BACKGROUND: To evaluate the safety, feasibility and effectiveness of high-pressure, noncompliant balloon angioplasty in the management of long infrapopliteal calcified lesions. METHODS: Consecutive patients, presenting with chronic limb-threatening ischemia (CLTI) and long (>100 mm) calcified infrapopliteal lesions who were treated with a high pressure, noncompliant balloon (JADE, OrbusNeich, Hong Kong) between January 2016 and July 2016 were retrospectively analyzed. Angioplasty was performed by inflating the balloon to a pressure of 22 to 24 atm for 90 seconds. Primary outcome was technical success. Secondary outcomes were procedure-related complications, limb salvage, amputation-free survival (AFS), wound healing, overall survival, freedom from clinically driven target lesion reintervention (CD-TLR), and resolution of CLTI at 2 and 3 years. RESULTS: Overall, 23 lesions in 21 limbs of 20 patients were treated. All patients had tissue loss (Rutherford 5 or 6). The mean lesion length was 374.8 mm. Of all lesions, 56.5% were occlusions, 91.3% were classified as TransAtlantic Inter-Society Consensus (TASC) C and D lesions, and 78.3% had severe calcification classification. Of all lesions, 52.2% extended into the below-the-ankle arteries. Technical success was achieved in 22 lesions (95.7%). There were no procedure-related complications. No bailout stenting was required. At 2 and 3 years, limb salvage was 84.7% and 78.7%, AFS was 71.4% and 56.1%, wound healing was 81.0% and 85.7%, overall survival was 75.0% and 64.3% and freedom from CD-TLR was 77.6% and 63.5%, respectively. Resolution of CLTI without TLR was 81.0% at 2 and 3 years. CONCLUSIONS: This study is the first to analyze safety and feasibility of a high-pressure, noncompliant balloon for long, calcified infrapopliteal and inframalleolar lesions.

Midterm Outcomes of Percutaneous Deep Venous Arterialization With a Dedicated System for Patients With No-Option Chronic Limb-Threatening Ischemia: The ALPS Multicenter Study.

Purpose: To evaluate the midterm results of patients suffering from no-option chronic limb-threatening ischemia (CLTI) treated with a dedicated system for percutaneous deep venous arterialization (pDVA). Materials and Methods: Thirty-two consecutive CLTI patients (mean age 67±14 years; 20 men) treated with pDVA using the Limflow device at 4 centers between 11 July 2014 and 11 June 2018 were retrospectively analyzed. Of all patients, 21 (66%) had diabetes, 8 (25%) were on immunosuppression, 4 (16%) had dialysis-dependent renal failure, 9 (28%) had Rutherford category 6 ischemia, and 25 (78%) were deemed at high risk of amputation. The primary outcome was amputation-free survival (AFS) at 6 months. Secondary outcomes were wound healing, limb salvage, and survival at 6, 12, and 24 months. Results: Technical success was achieved in 31 patients (96.9%). The median follow-up was 34 months (range 16-63). At 6, 12, and 24 months, estimates were 83.9%, 71.0%, and 67.2% for AFS, 86.8%, 79.8% and 79.8% for limb salvage, and 36.6%, 68.2%, and 72.7% for complete wound healing, respectively. Median time to complete wound healing was 4.9 months (range 0.5-15). The DVA circuit occluded during follow-up in 21 patients; the median time to occlusion was 2.6 months. Reintervention for occlusion was performed in 17 patients: 16 because of unhealed wounds and 1 for a newly developed ulcer. Conclusion: This study represents the largest population of patients with no-option CLTI treated with pDVA using the LimFlow device with midterm results. In this complex group of patients, pDVA using the LimFlow device has been shown to be feasible, with a high technical success rate and AFS at 6 up to 24 months coupled with wound healing. In selected patients with no-option CLTI, pDVA could be a recommended treatment to prevent amputation and heal wounds.

Below-the-Ankle Angioplasty in Patients with Critical Limb Ischemia: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the safety and effectiveness of below-the-ankle (BTA) angioplasty and to assess whether additional BTA angioplasty after below-the-knee (BTK) angioplasty would improve clinical outcomes in patients with critical limb ischemia. MATERIALS AND METHODS: Two authors independently performed the search, study selection, assessment of methodological quality, and data extraction for this systematic review and meta-analysis. MEDLINE, Embase, and the Cochrane Database of Systematic Reviews were searched. Articles were eligible if it was reported that BTA angioplasty was performed and if the articles were published in English and had the full text available. Methodological quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) score. The primary outcome was 12-month limb salvage rate. Secondary outcomes were 12-month amputation-free survival, technical success, complications, survival, and freedom from reintervention. RESULTS: Ten articles met the inclusion criteria, reporting a total of 478 patients with BTA angioplasty performed in 524 legs. Three of the 10 included studies compared BTK angioplasty only to BTK angioplasty and additional BTA angioplasty. The pooled 12-month limb salvage rate was 92% (95% confidence interval [CI], 0.88-0.96). No statistically significant difference was found in limb salvage when additional BTA angioplasty was compared to BTK angioplasty only (odds ratio [OR], 1.23; 95% CI, 0.61-2.49). The pooled 12-month amputation-free survival was 78% (95% CI, 0.69-0.87). No statistically significant difference was found in amputation-free survival rate when additional BTA angioplasty was compared to BTK angioplasty only (OR, 1.58; 95% CI, 0.95-2.64). The methodological quality of the studies included was moderate, according to the MINORS score. CONCLUSIONS: This systematic review and meta-analysis showed that additional BTA angioplasty is a safe and feasible procedure, with a 92% pooled proportion of limb salvage at 12 months.