Surgery or Endovascular Therapy for Chronic Limb-Threatening Ischemia.

BACKGROUND: Patients with chronic limb-threatening ischemia (CLTI) require revascularization to improve limb perfusion and thereby limit the risk of amputation. It is uncertain whether an initial strategy of endovascular therapy or surgical revascularization for CLTI is superior for improving limb outcomes. METHODS: In this international, randomized trial, we enrolled 1830 patients with CLTI and infrainguinal peripheral artery disease in two parallel-cohort trials. Patients who had a single segment of great saphenous vein that could be used for surgery were assigned to cohort 1. Patients who needed an alternative bypass conduit were assigned to cohort 2. The primary outcome was a composite of a major adverse limb event - which was defined as amputation above the ankle or a major limb reintervention (a new bypass graft or graft revision, thrombectomy, or thrombolysis) - or death from any cause. RESULTS: In cohort 1, after a median follow-up of 2.7 years, a primary-outcome event occurred in 302 of 709 patients (42.6%) in the surgical group and in 408 of 711 patients (57.4%) in the endovascular group (hazard ratio, 0.68; 95% confidence interval [CI], 0.59 to 0.79; P<0.001). In cohort 2, a primary-outcome event occurred in 83 of 194 patients (42.8%) in the surgical group and in 95 of 199 patients (47.7%) in the endovascular group (hazard ratio, 0.79; 95% CI, 0.58 to 1.06; P = 0.12) after a median follow-up of 1.6 years. The incidence of adverse events was similar in the two groups in the two cohorts. CONCLUSIONS: Among patients with CLTI who had an adequate great saphenous vein for surgical revascularization (cohort 1), the incidence of a major adverse limb event or death was significantly lower in the surgical group than in the endovascular group. Among the patients who lacked an adequate saphenous vein conduit (cohort 2), the outcomes in the two groups were similar. (Funded by the National Heart, Lung, and Blood Institute; BEST-CLI ClinicalTrials.gov number, NCT02060630.).

Impact of wound management strategies after revascularization for chronic limb-threatening ischemia.

OBJECTIVE: There is no established consensus or guidelines for wound management after revascularization for patients with chronic limb-threatening ischemia (CLTI) without severe infection. This study is designed to evaluate the clinical effect of the wound management strategy on toe wounds after revascularization for CLTI. METHODS: This retrospective cohort study was performed at eight institutions affiliated with Keio University School of Medicine in Japan and included 261 patients who underwent revascularization for CLTI between April 2019 and July 2021. We identified 132 patients with toe wounds from the database who had restored in-line blood flow to the foot. Patients were divided into two groups by the timing of toe resection after revascularization, which dictated the wound management policy. Group A (62 patients) underwent early toe amputation for suspected osteomyelitis, whereas group B (70 patients) underwent watchful waiting. The primary outcome was wound healing after revascularization; the secondary outcome was major amputation. We compared outcomes between groups A and B after propensity score matching. RESULTS: Using propensity score matching, each patient in group A (33 patients) was matched with a patient in group B (33 patients). Wound healing in matched group A was significantly better than that in matched group B (respectively: 1-year wound healing rate: 90.0% vs 68.2%, P < .001; median wound healing time: 65 days vs 258 days, P < .01). Although five major amputations were necessary in matched group B, none were required in matched group A (P = .05). The high rate of major amputations in group B was attributed to the sudden exacerbation of infection. Limb salvage rate in matched group A exceeded matched group B (100.0% vs 90.5%: 1-year limb salvage rate, P = .02). CONCLUSIONS: Early toe amputation for highly suspected osteomyelitis in patients with CLTI with toe wounds may expedite wound healing compared with watchful waiting, potentially avoiding unnecessary major amputation. Considering the wound management strategy is crucial when evaluating wound healing outcomes in patients with CLTI with revascularization.

Comparison of limb outcomes between bypass surgery and endovascular therapy in dialysis-dependent and -independent patients with chronic limb-threatening ischemia.

OBJECTIVE: To examine limb salvage (LS) and wound healing in dialysis-dependent and -independent patients with chronic limb-threatening ischemia (CLTI) after infrainguinal bypass surgery or endovascular therapy (EVT). METHODS: We retrospectively analyzed the multi-center data of patients who underwent infrainguinal revascularization for CLTI with Wound, Ischemia, and foot Infection (WIfI) stage 2 to 4 between 2015 and 2020. The primary endpoint was LS. The secondary endpoint included wound healing, amputation-free survival (AFS), periprocedural complications, and 2-year survival. Comparison of these outcomes were made after propensity score matching. RESULTS: We analyzed 252 dialysis-dependent (318 limbs) and 305 dialysis-independent (354 limbs) patients. Propensity score matching extracted 202 pairs with no significant differences in characteristics. The LS rate in bypass surgery was better than that in EVT in dialysis-dependent patients (P < .001). There was no significant difference in the LS rates between bypass surgery and EVT in dialysis-independent patients (P = .168). The wound healing rate of bypass surgery was better than that of EVT both dialysis-dependent and -independent patients with CLTI. The AFS rate of bypass surgery was better than that of EVT in dialysis-dependent patients (P < .001). There was no significant difference in the AFS rates between bypass surgery and EVT in dialysis-independent patients (P = .099). There was no significant difference in the occurrence of Clavien-Dindo ≥ IV and V between bypass surgery and EVT in dialysis-dependent and -independent patients. Age ≥75 years, serum albumin levels <3.5 g/dL, and non-ambulatory status were risk factors for 2-year mortality in dialysis-dependent patients. The 2-year survival rates in dialysis-dependent patients with risk factors of 0, 1, 2, and 3 were 82.5%, 67.1%, 49.5%, and 10.2%, respectively (P < .001). CONCLUSIONS: For LS and wound healing, bypass surgery was preferred for revascularization in dialysis-dependent patients with WIfI stage 2 to 4. Although dialysis dependency was one of the risk factors for 2-year mortality, dialysis-dependent patients, who have 0 to 1 risk factors, may benefit from bypass surgery, as 2-year survival of >50% is expected.

Clinical Utility of Infrapopliteal Calcium Score for the Evaluation of Severity of Peripheral Artery Disease.

PURPOSE: To identify associations between computed tomography (CT)-based lower-extremity calcium score (LECS) across different anatomic segments and the presence, severity, and clinical outcomes of peripheral artery disease (PAD). MATERIALS AND METHODS: In a mixed retrospective and prospective cohort study, 139 patients without prior lower-extremity intervention who underwent CT angiography of the aorta and lower extremities were identified. Subjects were classified as asymptomatic, claudicants, or having chronic limb-threatening ischemia (CLTI). LECS was measured using the Agatston method. Univariate and multivariate analyses were performed across categories of PAD severity. Receiver operating characteristic (ROC) analysis was performed, and an optimal cutoff point for LECS was identified. Claudicants were followed prospectively for CLTI and mortality. RESULTS: Higher infrapopliteal calcium score (CS) was independently associated with CLTI versus claudication (odds ratio [OR], 3.24 per unit increase in log10-transformed CS; P < .001) in addition to hemodialysis dependence and poor functional status. One hundred eighty-eight Agatston units was identified as the optimal cutoff for infrapopliteal CS in assessing the risk of CLTI versus claudication (area under the ROC curve, 0.84 [SD ± 0.049]). This cutoff was validated in an independent cohort to be associated with progression to CLTI (OR, 12.8; P = .0039). In the claudicant group followed prospectively, infrapopliteal CS ≥188 predicted increased risk of CLTI or death after adjusting for functional status and hemodialysis dependence (Cox hazard ratio, 4.92; P = .0202). CONCLUSIONS: Higher infrapopliteal CS was associated with CLTI among those with symptomatic PAD. An infrapopliteal CS cutoff of 188 Agatston units may serve as a useful tool to identify patients with increased risk of CLTI and mortality.

Inflammation Is a Histological Characteristic of Skeletal Muscle in Chronic Limb Threatening Ischemia.

BACKGROUND: The loss of skeletal muscle is a prognostic factor in several diseases including in patients with chronic limb threatening ischemia (CLTI). Patients with CLTI also have a lower skeletal mass and area when compared to those with claudication. However, there are no currently available data regarding the histological characteristics of core muscles in patients with CLTI. This study aims to determine the differences in core skeletal muscles between patients with claudication and those with CLTI. The second aim is to evaluate the differences in myokines, which are molecules secreted by skeletal muscle, between patients with claudication and those with CLTI. METHODS: An observational, prospective study was conducted from January 2018 to July 2022 involving consecutive patients with peripheral arterial disease (PAD). The clinical characteristics were registered. In PAD patients with surgical indication for common femoral artery approach, samples of sartorius skeletal muscle (and not from the limb muscles directly involved in the ischemic process) were collected. The samples were submitted to histological characterization on hematoxylin-eosin and to immunohistochemical analysis to detect CD45+ leukocytes and CD163+ macrophages. The extent of the inflammatory cells (leukocytes and macrophages) was semiquantitatively assessed using a 0-to-4 grade scale as follows: absent (0†), mild (†), moderate (††), severe (†††), and very severe (††††). Serum levels of myokines: irisin, myostatin, IL-8, and lL-6 were determined with multiplex bead-based immunoassay. RESULTS: 119 patients (mean age: 67.58 ± 9.60 years old, 79.80% males) 64 with claudication and 54 with CLTI were enrolled in the study. No differences were registered between patients with claudication and those with CLTI on age, gender, cardiovascular risk factors, and medication, except on smoking habits. There was a significantly higher prevalence of smokers and a higher smoking load in the claudication group. Samples of sartorius skeletal muscle from 40 patients (14 with claudication and 26 with CLTI) were submitted to histological analysis. No differences were found in skeletal muscle fibers preservation, trauma, or hemorrhage (on hematoxylin-eosin staining). However, in the immunohistochemistry study, we found more inflammatory cells CD45+ leukocytes in patients with CLTI when compared to those with claudication [CD45+ ≥ moderate (††): claudication (n = 14): 4; 28.57%; CLTI (n = 25): 16; 64.00%; P = 0.034]. Patients with CLTI also had higher tissue levels of CD163+ macrophages, but this difference was not significant [CD163+ ≥ moderate (††): claudication (n = 13): 7; 53.85%; CLTI (n = 27): 21; 77.78%; P = 0.122]. The serum levels of the myokines, irisin, and myostatin were below the lower limit of detection, in the majority of patients, so no valid results were obtained. However, patients with CLTI had a higher serum level of Interleukin (IL)-6 and IL-8. CONCLUSIONS: CLTI patients exhibit increased quantities of leukocytes in their sartorius muscle, as well as elevated serum levels of myokines IL-8 and IL-6. Inflamed skeletal muscle can contribute to the loss of muscle mass and account for the lower density of skeletal muscle observed in CLTI. Additionally, inflamed skeletal muscle may contribute to the development of systemic inflammation through the secretion of pro-inflammatory cytokines into the systemic circulation. Halting the inflammatory process could eventually improve the prognosis of CLTI patients.

Cross-Limb Vascular Shunting for Traumatic Popliteal Artery Injury.

BACKGROUND: Popliteal artery injury (PAI) is a challenging trauma that requires prompt and accurate treatment since the probability of lower-limb amputation increases with the ischemic time. Intravascular shunting and cross-limb vascular shunting (CLS) are used as temporary vascular shunting (TVS) methods to shorten the ischemic time for limb vascular injury. CLS involves sending blood from an artery in a healthy body part to a peripheral vessel in an injured part to immediately resume blood flow to the injured limb. For closed injuries including PAI, CLS may be performed without exploring and identifying the arterial stumps and it enables early reperfusion to the ischemic limb. We report the case series of traumatic PAI treated using CLS and verify the usefulness of CLS. METHODS: All patients with traumatic PAI treated with CLS at our institution between August 2013 and December 2021 were included. Demographic and clinical patient characteristics were extracted from the medical records. Comorbid injuries, severity of acute limb ischemia based on the Rutherford grading scale, time from injury to reperfusion by CLS, time from injury to completion of artery, and the use of fasciotomy were investigated. As outcomes, we investigated the presence or absence of lower extremity amputation during the course of treatment. RESULTS: We used CLS as treatment for 5 cases with traumatic PAI. Based on the Rutherford grading scale for acute limb ischemia, there were one limb with grade 2B and 4 with grade 3. Amputation of the lower extremities was avoided except for 1 extremity in which arterial reconstruction was not achieved due to unexplained cardiac arrest during surgery. CONCLUSIONS: CLS enables early reperfusion of the injured limb and is effective as a TVS method for traumatic PAI with severe ischemia or soft tissue damage.

Insulin Requirement and Infrainguinal Bypass Outcomes in Patients with Peripheral Arterial Disease.

BACKGROUND: Diabetes mellitus (DM) is a major risk factor for peripheral artery disease. The association of DM with major adverse limb events (MALE) after lower extremity revascularization remains controversial, as patients with diabetes are typically analyzed as a single, homogenous group. Using a large national database, this study examines the impact of insulin use and glycemic control on the outcomes following infrainguinal bypass. The hypothesis is that prevalent insulin therapy and elevated hemoglobin A1c (HbA1c) are associated with an increased risk of MALEs after infrainguinal bypass in patients with DM and could therefore be used for risk stratification. METHODS: The Vascular Quality Initiative database files for infrainguinal bypass (2007-2021) were retrospectively reviewed. Patients with DM undergoing bypass for peripheral artery disease were included. Patients on dialysis or with prior kidney transplantation were excluded. The characteristics and outcomes of patients with insulin-requiring diabetes mellitus (IRDM) were compared to those of patients not requiring insulin (noninsulin-requiring diabetes mellitus [NIRDM]) prior to the bypass procedure. RESULTS: A total of 9,686 patients with DM (56% IRDM) underwent bypass. Patients with IRDM were significantly younger than patients with NIRDM, more likely to be female (P < 0.01), African American (P < 0.01), and Hispanic (P = 0.031), and more likely to have comorbidities and be categorized into American Society of Anesthesiologist classes IV-V. They were more likely to be treated for chronic limb-threatening ischemia (P < 0.001). Patients with IRDM had significantly higher perioperative complications with no difference in perioperative mortality between the 2 groups. Beyond the perioperative period, with a mean follow-up of 427 days, patients with IRDM had significantly lower crude rates of primary patency and higher crude rates of major amputation, MALE, and mortality compared to patients with NIRDM. Regression analyses demonstrated that insulin requirement, but not HbA1c, was independently associated with a higher risk of MALE (hazard ratio = 1.17 [1.06-1.29]) and mortality (hazard ratio = 1.28 [1.16-1.43]). CONCLUSIONS: Insulin requirement, but not HbA1c, is significantly associated with MALEs and survival after infrainguinal bypass in the Vascular Quality Initiative. Stratification of patients with DM based on their prevalent insulin use prior to infrainguinal bypass surgery could improve the prediction of outcomes of peripheral arterial bypass surgery in patients with diabetes.

Risk Analysis and Clinical Outcomes in Chronic Limb-threatening Ischemia Patients with Surgical Site Infection after Distal Bypass.

BACKGROUND: A recent randomized control study showed that long-term outcomes after surgical revascularization were superior to those after endovascular treatment for cases with chronic limb-threatening ischemia (CLTI) with an appropriate single-segment great saphenous vein. However, surgical site infection (SSI) in CLTI cases after infrapoplital bypass also resulted in a prolonged hospital stay and poor outcomes, including graft disruption. The aim of the current study was to analyze risk factors for SSI in CLTI patients after distal bypass and to compare outcomes in patients with and without SSI. METHODS: A total of 515 cases that underwent distal bypass at a single center between 2009 and 2022 were analyzed retrospectively. Comparisons were made between patients with and without SSI after distal bypass. The primary end point was limb salvage after distal bypass. RESULTS: Of the 515 cases that underwent distal bypass, 79 (15%) had SSI. The risk factors for SSI were preoperative antibacterial drug use (P = 0.001), pedal bypass (P = 0.001), and prolonged operation time (≥150 min) (P = 0.010). The median hospital stay in SSI cases was longer than that in non-SSI cases (P < 0.001). Of 515 distal bypasses, 7 (1.3%) bypass grafts ruptured postoperatively due to SSI, and of these 7 cases, 6 ruptured during the day, 5 cases occurred within 1 month postoperatively, and 2 patients (29%) are alive without amputation. The mean follow-up period was 34 ± 30 months. During follow-up, 62 limbs (SSI cases, 19; non-SSI cases, 43) required major amputation and there were 234 deaths (SSI cases, 46; non-SSI cases, 188). The 1-, 3-, and 5-year limb salvage rates of 82%, 71%, and 62%, respectively, in SSI cases were significantly lower than those in non-SSI cases (P < 0.001). The 5-year survival rate of 29% in SSI cases showed a tendency to be lower than that in non-SSI cases (P = 0.058). CONCLUSIONS: The limb salvage rate in SSI cases was lower than in non-SSI cases after distal bypass. Graft rupture due to SSI occurred at a rate of 1.3% and resulted in poor outcomes in most cases. SSIs adversely affect outcomes and further study is needed to identify methods to avoid SSI following distal bypass.

Are current wound classifications valid for predicting prognosis in people treated for limb-threatening diabetic foot ulcers?

This study aims to investigate whether the current wound classifications were valid for the treatment prognosis of subjects treated for limb-threatening diabetic foot ulcers (LTDFU). A total of 1548 patients with LTDFU and infection were studied, with wounds recorded using the Wagner, Texas, PEDIS and WIfI classifications while major lower extremity amputations (LEAs) or in-hospital mortality incidences were defined as poor outcomes. Among them, 153 (9.9%) patients received major LEAs and 38 (2.5%) patients died. After adjustments, the Wagner classification and Texas stage as well as clinical factors such as comorbidity with major adverse cardiac events (MACE), being under dialysis and having serum levels of C-reactive protein (CRP) and albumin were independent factors for prognosis. For patients without dialysis, Wagner and Texas stage stood out independently for prognosis. For patients on dialysis, only levels of CRP (odds ratio [OR] = 2.2 in Wagner, OR = 2.0 in WIfI, OR = 2.2 in Texas, OR = 2.3 in PEDIS) and albumin (OR = 0.4 in four classifications) were valid predictors. The Wagner system and Texas stage were valid for predicting prognosis in treatment for LTDFUs, suggesting a role of vascular perfusion. MACE history, levels of CRP and albumin level should assist in prediction; more significantly, only levels of CRP and albumin appeared valid for those subjects undergoing dialysis.

Severe inframalleolar disease is an independent predictor of adverse limb outcomes after endovascular revascularization in chronic limb-threatening ischemia.

OBJECTIVE: In the present study, we evaluated the effects of inframalleolar (IM) disease on the occurrence of major adverse limb events (MALE) in patients undergoing endovascular revascularization for chronic limb-threatening ischemia (CLTI). METHODS: Patients who had undergone endovascular revascularization for CLTI between January 2015 and December 2019 at two university-affiliated hospitals were reviewed retrospectively. Patients with severe IM disease (pedal score of 2) were compared with those with mild to moderate IM disease (score of 0 or 1) using the Global Vascular Guidelines. The primary outcome was MALE (open revascularization, acute leg ischemia, major amputation). The secondary outcomes were mortality, reintervention, major adverse cardiac events, and perioperative complications ≤30 days after endovascular revascularization, primary limb-based patency, and the occurrence of any limb event (defined as any amputation, acute leg ischemia, or open revascularization). Kaplan-Meier estimates were used to compare the primary outcome, and the Cox proportion hazard model was used to assess the effects of IM disease. RESULTS: The study included 167 limbs in 149 patients (36% female; mean age, 74 ± 12 years). Severe IM disease was identified in 71 limbs (43%). No differences were found in the baseline characteristics, except for a higher prevalence of dyslipidemia in the patients with severe IM disease (66% vs 43%; P = .003). Most patients in both groups had had a WIfI (Wound, Ischemia, foot Infection) score of 4 (severe IM disease, 64%; vs mild to moderate IM disease, 57%; P = .462) and GLASS (global limb anatomic severity scale) III anatomy (severe IM disease, 54%; vs mild to moderate IM disease, 48%; P = .752). The Kaplan-Meier estimates showed that severe IM disease was associated with lower freedom from MALE (69% vs 82%; P = .026). The Cox proportion hazard regression model showed that severe IM disease was an independent predictor of increased MALE and amputation risk (hazard ratio, 1.715; 95% confidence interval, 1.015-2.896; P = .044) after adjusting for covariates. During follow-up, patients with severe IM disease had had mortality (27% vs 31%; P = .567) and reintervention (42% vs 38%; P = .608) similar to those for patients with mild to moderate IM disease. Primary limb-based patency was also similar (79% vs 84%; P = .593) at a mean follow-up of 3.8 ± 0.8 years. CONCLUSIONS: Severe IM disease was prevalent in 43% of limbs that had undergone endovascular revascularization for CLTI and was associated with lower freedom from MALE. Severe IM disease also independently increased the hazard of adverse limb outcomes and amputations in patients with CLTI by >70%, highlighting its importance as a measure of foot perfusion.

Poor utilization of palliative care among Medicare patients with chronic limb-threatening ischemia.

OBJECTIVE: Patients with chronic limb-threatening ischemia (CLTI) experience high annual mortality and would benefit from timely palliative care intervention. We sought to better characterize use of palliative care among patients with CLTI in the Medicare population. METHODS: Using Medicare data from 2017 to 2018, we identified patients with CLTI, defined as two or more encounters with a CLTI diagnosis code. Palliative care evaluations were identified using ICD-10-CM Z51.5 "Encounter for palliative care." Time intervals between CLTI diagnosis, palliative consultation, and death or end of follow-up were calculated. Associations between patient demographics, comorbidities, and palliative care consultation were assessed. RESULTS: A total of 12,133 Medicare enrollees with complete data were categorized as having CLTI. Of these, 7.4% (894) underwent a palliative care evaluation at a median of 170 days (interquartile range, 45-352 days) from their CLTI diagnosis. Compared with those who did not undergo evaluation, palliative patients were more likely to be dual eligible for Medicaid (45.2% vs 38.1%; P < .001) and had more comorbid conditions (P < .001). After controlling for gender and race, age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.02-1.04), dual eligibility (OR, 1.40; 95% CI, 1.22-1.62), solid organ malignancy (OR, 2.82; 95% CI, 1.92-4.14), hematologic malignancy (OR, 2.24; 95% CI, 1.27-3.98), congestive heart failure (OR, 1.44; 95% CI, 1.15-1.88), complicated diabetes (OR, 1.35; 95% CI, 1.11-1.65), dementia (OR, 1.32; 95% CI, 1.04-1.66), and severe renal failure (OR, 1.56; 85% CI. 1.24-1.98) were independently associated with palliative care evaluation. During mean follow up of 410 ± 220 days, 16.9% (2044) of patients died at a mean of 268 (±189) days after their CLTI diagnosis. Among living patients, only 3.2% (325) underwent palliative evaluation. Comparatively, 27.8% (569) of patients who died received palliative care at a median of 196 days (interquartile range, 55-362 days) after their diagnosis and 15 days (interquartile range, 5-63 days) prior to death. CONCLUSIONS: Despite high mortality, palliative care services were rarely provided to Medicare patients with CLTI. Age, medical complexity, and income status may play a role in the decision to consult palliative care. When obtained, evaluations occurred closer to time of death than to time of CLTI diagnosis, suggesting misuse of palliative care as end-of-life care.

Medial arterial calcification score is associated with increased risk of major limb amputation.

OBJECTIVE: The pedal medial arterial calcification (MAC) score has been associated with risk of major limb amputation in patients with chronic limb-threatening ischemia. This study aimed to validate the pedal MAC scoring system in a multi-institutional analysis to validate its usefulness in limb amputation risk prediction. METHODS: A multi-institution, retrospective study of patients who underwent endovascular or open surgical infrainguinal revascularization for chronic limb-threatening ischemia was performed. MAC scores of 0 to 5 were assigned based on visible calcified arteries on foot X ray then trichotomized (0-1, 2-4, 5) for analysis. The primary outcome was major limb amputation at 6 months. Adjusted Kaplan-Meier models were used to analyze time-to-major amputation across groups. RESULTS: There were 176 patients with 184 affected limbs (mean age, 66 years; 61% male; 60% White), of whom 97% presented with a wound. The MAC score was 0 in 41%, 1 in 9%, 2 in 13%, 3 in 11%, 4 in 13%, and 5 in 13% of the limbs. There were 26 major amputations (14%) and 16 deaths (8.7%) within 6 months. Patients with MAC 5 had a significantly higher risk of major limb amputation than both the 0 to 1 and 2 to 4 groups (P = .001 and P = .044, respectively), and lower overall amputation-free survival (log-rank P = .008). CONCLUSIONS: Pedal MAC score is a reproducible and generalizable measure of inframalleolar arterial disease that can be used with Wound, Ischemia, and foot Infection staging to predict major limb amputation in patients with chronic limb-threatening ischemia.

A systematic review and meta-analysis of early and late outcomes after endovascular angioplasty among patients with thromboangiitis obliterans and chronic limb ischemia.

BACKGROUND: No consensus has yet been reached regarding the optimal treatment of patients with thromboangiitis obliterans (TO) and chronic limb ischemia. In the present study, we aimed to summarize the results on endovascular treatment of such patients. METHODS: We performed a meta-analysis using the following databases: PubMed, Scopus, and the Cochrane Library. The eligible studies had been reported up to December 2021 and had evaluated endovascular angioplasty to treat patients with TO and chronic limb ischemia. The early (mortality and technical success) and late (primary/secondary patency and limb salvage) outcomes were evaluated. StatsDirect (StatsDirect Ltd, Merseyside, UK) was used for the statistical analysis. RESULTS: Overall, 15 eligible studies were included (only endovascular in 11 studies and both endovascular and open repair in 4 studies). Among 601 patients, 402 endovascular procedures (416 limbs) were recorded (angioplasty plus stenting for 7.2% and angioplasty plus thrombolysis for 3.7%). The clinical presentation was intermittent claudication (stage II-III) for 7.9% of the patients and critical ischemia (stage IV-VI) for 92.1% of the patients. Most of the patients had had lesions below the knee, and five had had upper extremity lesions. The pooled technical success rate was 86% (range, 81.1%-90.3%), with no in-hospital mortality. The other complications included perforations (1.9%), wound complications (2.2%), and distal embolism (0.2%). Primary patency was 65.7% (range, 52.7%-77.6%) at 12 months and 50.7% (range, 23.3%-77.9%) at 36 months. Secondary patency was 76.2% (range, 57.5%-90.8%) at 12 months and 64.5% (range, 32.3%-90.6%) at 36 months. The limb salvage rate was 94.1% (range, 90.7%-96.7%) at 12 months and 89.1% (range, 80.6%-95.4%) at 36 months. CONCLUSIONS: Endovascular angioplasty for patients with TO and chronic limb ischemia was associated with optimal safety and low complication rates. The technical success and late outcomes were acceptable.

Impact of ambulatory status change on survival in patients with chronic limb-threatening ischemia undergoing infrainguinal surgical or endovascular revascularization.

OBJECTIVE: This study aimed to evaluate the influence of change in ambulatory status on the prognosis of patients with chronic limb-threatening ischemia (CLTI) undergoing infrainguinal bypass surgery or endovascular therapy (EVT). METHODS: We retrospectively analyzed data from two vascular centers for patients who underwent revascularization for CLTI between 2015 and 2020. The primary endpoint was overall survival (OS), and the secondary endpoints were changes in ambulatory status and postoperative complications. RESULTS: Throughout the study, 377 patients and 508 limbs were analyzed. In the preoperative nonambulation cohort, the average body mass index (BMI) was lower in the postoperative nonambulatory group than in the postoperative ambulatory group (P < .01). The percentage of cerebrovascular disease (CVD) was higher in the postoperative nonambulatory group than in the postoperative ambulatory group (P = .01). In the preoperative ambulation cohort, the average controlling nutritional status (CONUT) score was higher in the postoperative nonambulatory group than in the postoperative ambulatory group (P < .01). There was no difference in the bypass percentage and the EVT in the preoperative nonambulation (P = .32) and ambulation (P = .70) cohorts. According to the change in ambulatory status before and after revascularization, the 1-year OS rates were 86.8% in the ambulatory → ambulatory group, 81.1% in the nonambulatory → ambulatory group, 54.7% in the nonambulatory → nonambulatory group, and 23.9% in the ambulatory → nonambulatory group (P < .01). On multivariate analysis, increased age (P = .04), higher Wound, Ischemia, and foot Infection stage (P = .02), and increased CONUT score (P < .01) were independent risk factors for the decline in ambulatory status in patients with preoperative ambulation. In patients with preoperative nonambulation, increased BMI (P < .01) and absence of CVD (P = .04) were independent factors related to the improved ambulatory status. The percentages of postoperative complications were 31.0% and 17.0% in the preoperative nonambulation and the preoperative ambulation in the overall cohort (P < .01). Preoperative nonambulatory status (P < .01), CONUT score (P < .01), and bypass surgery (P < .01) were risk factors for postoperative complications. CONCLUSIONS: Improved ambulatory status is associated with better OS in patients with preoperative nonambulatory status after infrainguinal revascularization for CLTI. Although patients with preoperative nonambulatory status have a risk of postoperative complication, some may benefit from revascularization if they have no factors such as low BMI and CVD, improving their ambulatory status.

The management of patients with popliteal artery aneurysms presenting with acute limb ischemia.

OBJECTIVE: Endovascular popliteal artery aneurysm (PAA) repair has acceptable outcomes compared with open repair for elective therapy. Endovascular repair for urgent PAA causing acute limb ischemia (ALI) has not been well-studied. This project compares outcomes of urgent endovascular and open repair of PAA with ALI. METHODS: The Vascular Quality Initiative database for peripheral vascular interventions (PVIs) and infrainguinal bypass were reviewed for PAAs with ALI from 2010 to 2021. Only patients entered as having symptoms of ALI in the PVI module and ALI as indication in the infrainguinal bypass module were included. In addition, patients undergoing elective treatment were excluded and the sample analyzed was restricted to patients undergoing urgent and emergent open and endovascular repair. Patient demographics and comorbidities as well as procedural details were compared between the two groups. Perioperative complications up to 30 days were compared as well as long-term outcomes including major amputation and mortality at 1 year. RESULTS: Urgent PAA repair for ALI constituted 10.5% (n = 571) of all PAAs. Most urgent repairs were open (80.6%; n = 460) with 19.4% (n = 111) endovascular. The proportion of endovascular repair significantly increased from 16.7% in 2010 to 85.7% in 2021. Patients undergoing endovascular repair were older (71.2 ± 12.5 vs 68.0 ± 11.8; P = .011) than patients undergoing open repair. They were also more likely to have coronary artery disease (32.4% vs 21.7%; P = .006). Open PAA repair was associated with more bleeding complications (20.8% vs 2.7%; P < .001), longer postoperative length of stay (8.1 ± 9.3 days vs 4.9 ± 5.6 days; P < .001), and less likelihood of discharge to home (64.9% vs 70.3%; P = .051). Perioperative major amputation rate was 7.5% with no difference between the two treatment strategies up to 1 year. However, patients receiving endovascular repair had higher inpatient (1.1% vs 0%; P < .001), 30-day (6.3% vs 0.4%; P < .001), and 1-year (16.5% vs 8.4%; P = .02) mortality. Multivariable regression analysis suggested that endovascular repair was possibly associated with increased 30-day mortality, but not 1-year mortality. CONCLUSIONS: Endovascular PAA has exponentially increased from 2010 to 2021. Endovascular repair is associated with decreased complications and hospital length of stay. The increased perioperative mortality seen in this group is likely due to selection bias.

Distal Endarterectomy Combined With Endovascular Proximal Treatment: The Hybrid DEEP Retrograde Technique for High-Complexity Infrainguinal Disease.

Purpose: We present a hybrid technique for the treatment of chronic limb-threatening ischemia (CLTI) due to complex, multilevel infrainguinal disease. It consists of an open distal endarterectomy combined with endovascular proximal treatment (the DEEP technique). Materials and Methods: This was a prospective cohort study. Thirty-three limbs (30 patients) were treated. Main inclusion criteria were absence of significant disease in femoral bifurcation associated with a complex infrainguinal pattern. This approach was specially considered in absence of suitable vein for bypass, obesity, hostile groin, and overall high surgical risk. Results: Mean age was 72.8 ± 10 years (ranging 50-93). Most cases presented with severe limb threatening onset (90.9% Rutherford >4 and 81.8% WIfi >3) due to high-complexity infrainguinal disease pattern (Global Limb Anatomic Staging System [GLASS] stage III) in 31/33 (93.9%), chronic total occlusions (CTOs) in 24/33 (72.7%), and severe calcification (Peripheral Arterial Calcium Scoring System [PACSS] grade 4) in 22/33 (66.6%). Mean lesion length was 228.2 mm ± 83 (ranging 40-340 mm). In all procedures, a covered-stent (25 cm length Viabahn) was implanted in a retrograde fashion as the endovascular component. Effective revascularization was achieved in all cases, showing significant clinical and hemodynamic improvement (median pre- and postprocedure ankle-brachial index [ABI]: 0.3 and 0.9, respectively). Results at 12 months follow-up were as follows: 93.9% limb salvage ratio, 75.7% primary patency, 84.6% assisted primary patency, and 90.9% secondary patency. Major adverse limb events (MALE) and cardiovascular events (MACE) occurred in 8/33 (24.2%) and 2/33 (6%), respectively. Mean length of postoperative stay was 7.5 ± 6.92 days (3-27). Conclusion: This less invasive hybrid technique has promising short-term results for limb salvage and it is worth to be included in vascular armamentarium for CLTI revascularization in selected patients.

Global Limb Anatomic Staging System Inframalleolar Modifier Predicts Limb Salvage and Wound Healing in Patients with Chronic Limb Threatening Ischaemia Undergoing Endovascular Infrainguinal Revascularisation.

OBJECTIVE: This study aimed to analyse the influence of the Global Anatomic Staging System (GLASS) and inframalleolar (IM) disease on the treatment outcomes of patients with chronic limb threatening ischaemia (CLTI) who undergo endovascular treatment (EVT) METHODS: Data of patients who underwent infrainguinal endovascular therapy (EVT) for CLTI between 2015 and 2019 at two centres were analysed retrospectively. The endpoints were major amputation, major adverse limb events (MALE), and wound healing. RESULTS: Overall, 276 patients and 340 limbs were analysed. The number of revascularisations for an infrapopliteal lesion was 48 (70.6%), 63 (63.0%), and 142 (82.6%) in the GLASS I, GLASS II, and GLASS III stages, respectively (p < .001). There was no statistically significant difference in limb salvage among the GLASS stages (p = .78). The limb salvage rates at one year were 94.6%, 88.0%, and 70.0% in the IM P0 P1, and P2 groups, respectively (p < .001). Multivariable analysis showed that Wound, Ischemia, and foot Infection (WIfI) stage, and IM grade were risk factors for major amputation. The freedom from MALE rates at two years were 60.5%, 45.3%, and 41.1% in the GLASS I, II, and III stages, respectively (p = .003) and 64.1%, 43.5%, and 18.4% in the IM P0, P1, and P2 groups, respectively (p < .001). Multivariable analysis demonstrated that WIfI stage, GLASS stage, IM grade, and infrapopliteal revascularisation were risk factors for MALE. There was no significant difference in wound healing among GLASS I - III (p = .75). The wound healing rates at 365 days were 78.6%, 68.6%, and 42.0% in the IM P0, P1, and P2 groups, respectively (p = .065). Multivariable analysis showed that WIfI stage and IM P2 were risk factors for incomplete wound healing. CONCLUSION: GLASS IM was associated with major amputation, MALE, and wound healing, while GLASS stage was associated with only MALE.

The Relationship Between the Global Limb Anatomic Staging System Inframalleolar Modifier and the Outcomes of Diabetic Foot Ulcer with Peripheral Artery Disease.

BACKGROUND: We aimed to investigate the relationship between the condition of the inframalleolar (IM) arteries, as assessed by the Global Limb Anatomic Staging System Inframalleolar (GLASS IM) modifier, and the outcomes of patients with diabetic foot ulcers. METHODS: The data of 215 patients, who underwent endovascular therapy from January 2016 to May 2020 at our center, were retrospectively reviewed. Patients were divided into the P0, P1, and P2 groups according to the angiography results. The rates of ulcer healing, limb salvage, survival, and amputation-free survival were compared during the 2-year period after discharge. RESULTS: Of the 216 affected limbs, 35 (16%) were classed as P0, 122 (57%) as P1, and 59 (27%) as P2. Compared with the P2 group, the P0 + P1 group had a higher ulcer healing rate (P = 0.001), a shorter ulcer healing time (P = 0.004), and a higher survival rate (P = 0.044). GLASS IM Modifier classification P2 was an independent predictor of nonhealing ulcers. No significant difference was observed between the P0 versus P1 groups. CONCLUSIONS: GLASS IM modifier classification P2 is an independent risk factor for a poor outcome. GLASS IM modifier classification P0 versus P1 demonstrates similar outcomes to each other.

Validity of the Global Vascular Guidelines in Predicting Outcomes Based on First-Time Revascularization Strategy.

BACKGROUND: The Global Vascular Guidelines (GVG) recommend selecting an endovascular versus open-surgical approach to revascularization for chronic limb-threatening ischemia (CLTI), based on the Global Limb Anatomic Staging System (GLASS) and wound, ischemia, and foot infection (WIfI) classification systems. We assessed the utility of GVG-recommended strategies in predicting clinical outcomes. METHODS: We conducted a single-center, retrospective review of first-time lower-extremity revascularizations within a comprehensive limb-preservation program from 2010 to 2018. Procedures were stratified by (1) treatment concordance with GVG-recommended strategy (concordant versus nonconcordant groups), (2) GLASS stages I-III, and (3) endovascular versus open strategies. The primary outcome was 5-year freedom from major adverse limb events (FF-MALE), defined as freedom from reintervention or major amputation, and secondary outcomes included 5-year overall survival, freedom from major amputation, freedom from reintervention, and immediate technical failure (ITF) during initial revascularization. Kaplan-Meier (KM) survival analysis and multivariate analysis with Cox proportional hazard models were performed on the primary and secondary outcomes. RESULTS: Of 281 first-time revascularizations for CLTI, 251 (89.3%) were endovascular and 186 (66.2%) were in the concordant group, with a mean clinical follow-up of 3.02 ± 2.40 years. Within the concordant group alone, 167 (89.8%) of revascularizations were endovascular. The concordant group had a higher rate of chronic kidney disease (60.8% vs. 45.3%, P = 0.02), WIfI foot infection grade (0.81 ± 1.1 vs. 0.56 ± 0.80, P = 0.03), and WIfI stage (3.1 ± 0.79 vs. 2.8 ± 1.2, P < 0.01) compared to the non-concordant group. After both KM and multivariate analyses, there were no significant differences in 5-year FF-MALE or overall survival between concordant and non-concordant groups. There was higher freedom from major amputation in the non-concordant group on KM analysis (83.9% vs. 74.2%, P = 0.025), though this difference was non-significant on multivariate analysis (hazard ratio [HR]: 0.49, 95% confidence interval [CI]: 0.21-1.15, P = 0.10). The open group had lower MALE compared to the endovascular group (HR: 0.39, 95% CI: 0.17-0.91, P = 0.029) attributed to a lower reintervention rate in the open group (HR: 0.31, 95% CI: 0.11-0.87, P = 0.026). GLASS stage was not associated with significant differences in outcomes, but the severity of GLASS stage was associated with ITF (2.1% in stage 1, 6.4% in stage 2, and 11.7% in stage 3, P = 0.01). CONCLUSIONS: In this study, CLTI treatment outcomes did not differ significantly based on whether treatment was received in concordance with GVG-recommended strategy. There was no difference in overall survival between the endovascular and open groups, though there was a higher reintervention rate in the endovascular group. The GVG guidelines are an important resource to help guide the management of CLTI patients. However, in this study, both concordance with GVG guidelines and GLASS staging were found to be indeterminate in differentiating outcomes between complex CLTI patients treated primarily with an endovascular-first approach. The revascularization approach for a CLTI patient is a nuanced decision that must take into account patient anatomy and clinical status, as well as physician skill and experience and institutional resources.

Risk Factors for Major Amputation in Chronic Limb-Threatening Ischemia Patients Classified as Wound, Ischemia, and Foot Infection Stage 4 following Infrainguinal Revascularization.

BACKGROUND: To evaluate limb salvage outcomes and risk factors for major amputation in chronic limb-threatening ischemia (CLTI) patients classified as stage 4 per the wound, ischemia, and foot infection (WIfI) classification following infrainguinal revascularization. METHODS: We retrospectively analyzed multicenter data of patients who had undergone infrainguinal revascularization for CLTI between 2015 and 2020. The endpoint was secondary major amputation defined as an above- or below-knee amputation following infrainguinal revascularization. RESULTS: We analyzed 243 patients with CLTI and 267 limbs. Bypass surgery was performed in 14 (25.5%) and 120 (56.6%) limbs from the secondary major amputation and limb salvage groups, respectively (P < 0.01). Endovascular therapy (EVT) was performed in 41 limbs (74.5%) in the secondary major amputation group and 92 limbs (43.4%) in the limb salvage group (P < 0.01). The average serum albumin levels were 3.0 ± 0.6 and 3.4 ± 0.5 g/dL in the secondary major amputation and limb salvage groups, respectively (P < 0.01). The percentage of congestive heart failure (CHF) was 36.4% and 14.2% in secondary major amputation and limb salvage groups, respectively (P < 0.01). The number of limbs with infra-malleolar (IM) P0, P1, and P2 were 4 (7.3%), 37 (67.3%), and 14 (25.5%), respectively, in the secondary major amputation group and 58 (27.4%), 140 (66.0%), and 14 (6.6%), respectively, in the limb salvage group (P < 0.01). Limb salvage rates at 1 year were 91.0% and 68.6% in the bypass and EVT groups, respectively (P < 0.01). Limb salvage rates at 1 year in patients with IM P0, P1, and P2 were 91.8%, 79.9%, and 53.1%, respectively (P < 0.01). Multivariate analysis revealed that serum albumin level [hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.36-0.89; P = 0.01], hypertension (HR, 0.39; 95% CI, 0.21-0.75; P < 0.01), CHF (HR, 2.10; 95% CI, 1.09-4.05; P = 0.03), wound grade (HR, 1.72; 95% CI, 1.03-2.88; P = 0.04), IM P (HR, 2.08; 95% CI, 1.27-3.42; P < 0.01), and EVT (HR, 3.31; 95% CI, 1.77-6.18; P < 0.01) as independent risk factors for secondary major amputation being required. CONCLUSIONS: Among CLTI patients with WIfI stage 4, the limb salvage rate was poor in those with IM P1-2 following infrainguinal EVT. Low serum albumin levels, CHF, high wound grade, IM P1-2, and EVT were independent risk factors for CLTI patients requiring major amputation.