One-year clinical outcomes of delayed referral and subsequent management in chronic limb-threatening ischemia.

Background: Although hemodialysis vintage and serum phosphorus level adversely impact on outcomes in the field of general population on hemodialysis, it has not systematically studied whether these have similar prognostic impacts on clinical outcomes in population with chronic limb-threatening ischemia (CLTI). Methods: The current study retrospectively analyzed 374 hemodialysis patients with CLTI presenting ischemic tissue loss (age: 72.3±9.0 years, male: 73.3%, diabetes mellitus: 39.6%, Rutherford 5: 75.9%, 6: 24.1%, WIFI stage 4: 50.0%) primarily treated with endovascular therapy (EVT) between April 2007 and December 2016. Primary outcome measure was 1-year amputation-free survival (AFS), while secondary outcome measure was 1-year wound healing. Predictors for each outcome were evaluated by Cox proportional hazards model. Result: One-year rate of AFS and wound healing rate were 70.5±2.5%, and 57.1±3.0%, respectively. Multivariate analysis demonstrated that body mass index (hazard ratio [HR], 0.918; 95% confidence interval [CI], 0.859-0.981; p=0.012), non-ambulatory status (HR, 1.887; 95% CI, 1.222-2.913; p=0.004), lower serum albumin level (HR, 0.591; 95% CI, 0.414-0.844; p=0.004), WIfI stage 4 (HR, 1.782; 95% CI, 1.156-2.748; p=0.009) and longer vintages for hemodialysis with higher serum phosphorus levels (HR, 1.670; 95% CI, 1.099-2.537; p=0.016) were significantly associated with 1-year AFS (Figure), while WIfI stage 4 (HR, 0.713; 95% CI, 0.519-0.979; p=0.037) was associated and longer vintages for hemodialysis with higher serum phosphorus levels was close to significant association (HR, 0.684; 95% CI, 0.467-1.000; p=0.050) with 1-year wound healing. Conclusion: Longer hemodialysis vintage with higher serum phosphorus level would adversely affect clinical outcomes after EVT for hemodialysis patients with CLTI presenting ischemic tissue loss.

This study investigated the effect of patency of the pedal arch (PA) on wound healing rate and time, amputation-free survival (AFS), limb salvage, and limb-based patency (LBP) in chronic limb-threatening ischemia (CLTI) patients undergoing endovascular revascularization of infrainguinal arterial lesions. This prospective study included all CLTI patients presenting with wound, ischemia, and foot infection (WIfI) stages 2 to 4 (WIfI ischemia grades 2-3) who underwent endovascular revascularization of infrainguinal arterial disease between April 2019 and April 2021. Pedal angioplasty was attempted in all patients with significant steno-occlusive pedal artery disease. Patients were stratified according to Kawarada PA types. Successful PA revascularization (PAR) was counted when at least 1 pedal vessel is patent. Wound healing rate and time and Kaplan-Meier estimate of AFS and LBP at 2 years were evaluated and compared among the patient groups. A total of 120 patients were categorized according to PA type into type 1 (n = 34; 28.3%), type 2 (n = 64; 53.3%), and type 3 (n = 22; 18.3%). Pedal angioplasty was attempted in 97 patients and was technically successful in 75 patients (77.3%). Successful PAR (with or without pedal angioplasty) was achieved in 98 patients (81.7%). During the follow-up, successful PAR resulted in a better wound healing rate (86.7% vs 59.1%; P = 0.007), major amputation rates (5.1% vs 40.9%; P ≤ 0.001), and AFS (92.9% vs 72.7%; P = 0.018) compared with unsuccessful PAR. There were no significant differences between the 2 groups in wound healing time (3.76 ± 1.99 months vs 3.64 ± 1.94 months; P = 0.798, respectively) or LBP (80.6% vs 72.7%; P = 0.594, respectively). Global Limb Anatomic Staging System (GLASS) stage (odds ratio [OR] = 6.84; 95% CI, 1.30-36.03; P = 0.023) and unsuccessful PAR (OR = 21.64; 95% CI, 4.01-116.69; P ≤ 0.001) were independently associated with failure of wound healing, whereas site of wound lesion (OR = 5.52; 95% CI, 1.15-26.48; P = 0.033), GLASS stage (OR = 24.93; 95% CI, 2.84-218.69; P = 0.004), and unsuccessful PAR (OR = 22.44; 95% CI, 3.53-142.67; P = 0.001) were significant predictors of major amputation. Successful PAR is important for improving clinical outcomes of endovascular revascularization of CLTI patients such as wound healing, amputation-free survival, and limb salvage. Predictors of limb salvage were site of foot lesion, GLASS stage, and successful PAR, whereas GLASS stage and successful PAR were independently associated with improved wound healing. Pedal arch patency positively influences clinical outcomes in patients with chronic limb-threatening ischemia who have ischemic wounds undergoing endovascular revascularization. This study demonstrated that successful pedal arch revascularization (PAR) significantly improved wound healing, amputation-free survival, and limb salvage rates when compared to patients who did not achieve successful PAR. Additionally, the study identified the predictors of limb salvage as the site of foot lesions, GLASS staging, and successful PAR, while both GLASS staging and successful PAR were found to be independently associated with improved wound healing.

Surgical Revascularization Versus Endovascular Therapy to Treat Chronic Limb-Threatening Ischemia: Perhaps Less Invasive Is Not Always Better

Impact of angiosome- and nonangiosome-targeted peroneal bypass on limb salvage and healing in patients with chronic limb-threatening ischemia

In the current study, we hypothesized that the Japanese below-the-knee chronic total occlusion score could be used to stratify the lesion difficulty of endovascular therapy for below-the-knee chronic total occlusion through angiographic evaluation. We thus aimed to evaluate the prognostic impact of the Japanese below-the-knee chronic total occlusion score in patients with chronic limb-threatening ischemia after successful endovascular therapy for below-the-knee chronic total occlusion. This was a retrospective, single-center observational study. We enrolled 139 consecutive patients with chronic limb-threatening ischemia (149 limbs), who underwent successful endovascular therapy for chronic total occlusion between February 2008 and December 2017. The Japanese below-the-knee chronic total occlusion score was assessed based on the definition of the target arterial path. The evaluation items were the rate of amputation-free survival and wound healing at 1 year, and the association between wound healing at 1 year and the Japanese below-the-knee chronic total occlusion score. The rates of amputation-free survival and wound healing at 1 year were 88.0 and 56.4%, respectively. Multivariate Cox proportional hazard analysis identified direct flow to the wound (hazard ratio: 2.34, 95% confidence interval: 1.28-4.66; p<0.01); Wound, Ischemia, and foot Infection stages 1-3 (hazard ratio: 2.81, 95% confidence interval: 1.63-5.18; p<0.01); and a Japanese below-the-knee chronic total occlusion score ≤1 (hazard ratio: 1.70, 95% confidence interval: 1.02-2.98; p=0.04) to be predictors of wound healing. A Japanese below-the-knee chronic total occlusion score ≤1, direct flow to the wound, and Wound, Ischemia, and foot Infection stages 1-3 were found to be associated with wound healing after successful endovascular therapy for below-the-knee chronic total occlusion in patients with chronic limb-threatening ischemia. This study was conducted to evaluate the prognostic impact of the Japanese below-the-knee chronic total occlusion (J-BTK CTO) score in patients with chronic limb-threatening ischemia (CLTI) after successful endovascular treatment (EVT). The results showed that the J-BTK CTO score not only evaluates the difficulty of EVT but also can predict limb prognosis. Using the J-BTK CTO score, it seems possible to predict the limb prognosis and make it useful in clinical practice.

Introduction: The nutrition status plays a key role in the pathogenesis of frailty, and is strongly associated with the prognosis of patients with chronic limb-threatening ischemia (CLTI). The Geriatric Nutritional Risk Index (GNRI) is a widely used, simple, and well established nutritional status screening method. The association between the GNRI and wound healing in patients with CLTI has not been established. Hypothesis: We assessed the hypothesis that GNRI is associated with wound healing in patients with CLTI. Methods: We conducted a single-center retrospective analysis for 172 consecutive CLTI patients who were admitted to our hospital from August 2017 to April 2019 (age 70±14 years; men 62.2%). The GNRI on admission was calculated as follows: [14.89 х albumin (g/dL)] + [41.7 х (bodyweight/ideal body weight)]. According to the GNRI values, 4 grades of nutrition-related risk are defined as major risk (GNRI:&lt;82), moderate risk (GNRI: 82 to &lt;92), low risk (GNRI: 92 to 98), and no risk (GNRI: &gt;98). The amputation-free survival (AFS) and the cumulative wound healing rate are calculated by the log-rank test. The receiver operating characteristic curve was used to obtain a cutoff value for wound heal. Cox proportional hazards regression analysis was performed to explore the independent association between the GNRI and wound heal. Results: The follow-up period was 12±6.7 months. The 1-year AFS in no risk, low risk, moderate risk, and major risk groups were 90%, 74%, 66%, and 62%, respectively ( P =0.045). GNRI was significantly associated with WIfI wound score (W1, 95±8.8; W2, 87±8.0; W3, 84±9.3, P &lt;0.001). The 1-year cumulative wound healing rate in no risk, low risk, moderate risk, and major risk groups were 56%, 45%, 37%, and 32%, respectively ( P =0.036). GNRI=95 was selected as cutoff value with maximum discriminative power for wound healing (sensitivity 70%, specificity 60%; Area under the curve, 0.67; 95% confidence interval, 0.59-0.76). GNRI&gt;95 was an independent predictor of wound healing (Hazard ratio, 1.9; 95% confidence interval, 1.0-3.7; P =0.046). Conclusions: The GNRI was significantly associated with AFS and wound healing in patients with CLTI. GNRI=95 is a novel cutoff value to predict wound healing during follow-up.

Purpose: To investigate the prognostic impact of infrapopliteal (IP) artery anatomic severity according to the Global Limb Anatomic Staging System (GLASS) on delayed wound healing in patients with chronic limb-threatening ischemia (CLTI). Materials and Methods: This study retrospectively analyzed 639 limbs with tissue loss in 484 CLTI patients (mean age 74±10 years; 300 men) presenting IP lesions treated with endovascular therapy between April 2010 and December 2015. Two-thirds of patients had diabetes (323, 67%) and over half were on hemodialysis (255, 53%). More than a third of the limbs (251, 39%) were classified as clinical stage 4 according to the Wound, Ischemia, and foot Infection (WIfI) system. IP anatomic severity was classified based on preprocedural angiography according to the GLASS. Severity of arterial calcification was assessed using high-intensity fluoroscopy and classified into 3 groups: none (grade 0), unilateral (grade 1), and bilateral (grade 2). Poor below-the-ankle (BTA) runoff was defined as the lack of a pedal arch with 0 to 1-vessel runoff within the dorsal pedis artery and the lateral and medial plantar arteries. The outcome measure was 1-year wound healing. The association of anatomic characteristics with delayed wound healing was evaluated using Cox proportional hazards regression analysis. Outcomes are presented as the adjusted hazard ratio (HR) with 95% confidence interval (CI). Results: During a mean follow-up of 22±19 months, the 1-year cumulative wound healing rate was estimated to be 59.0% (95% CI 54.5% to 63.5%). Multivariable analysis demonstrated independent associations between delayed wound healing and IP calcification grade (HR 1.24, 95% CI 1.02 to 1.50, p=0.027) and poor BTA runoff (HR 1.39, 95% CI 1.04 to 1.85, p=0.025) but not the GLASS IP grade (HR 0.92, 95% CI 0.82 to 1.14, p=0.21). Conclusion: The current study revealed that IP arterial calcification and poor BTA runoff were significantly associated with delayed wound healing, whereas the GLASS was not predictive of wound healing.

Infra-inguinal bypass surgery vs endovascular revascularization for chronic limb-threatening ischemia in average- and high-risk patients

ObjectiveInadequate vein quality or prior harvest precludes use of autologous single segment greater saphenous vein (ssGSV) in many patients with chronic limb-threatening ischemia (CLTI). Predictors of patient outcome after infrainguinal bypass with alternative (non-ssGSV) conduits are not well-understood. We explored whether limb presentation, bypass target, and conduit type were associated with amputation-free survival (AFS) after infrainguinal bypass using alternative conduits. MethodsA single-center retrospective study (2013-2020) was conducted of 139 infrainguinal bypasses performed for CLTI with cryopreserved ssGSV (cryovein) (n = 71), polytetrafluoroethylene (PTFE) (n = 23), or arm/spliced vein grafts (n = 45). Characteristics, Wound, Ischemia, and foot Infection (WIfI) stage, and outcomes were recorded. Multivariable Cox proportional hazards and classification and regression tree analysis modeled predictors of AFS. ResultsWithin 139 cases, the mean age was 71 years, 59% of patients were male, and 51% of cases were nonelective. More patients undergoing bypass with cryovein were WIfI stage 4 (41%) compared with PTFE (13%) or arm/spliced vein (27%) (P = .04). Across groups, AFS at 2 years was 78% for spliced/arm, 79% for PTFE, and 53% for cryovein (adjusted hazard ratio for cryovein, 2.5; P = .02). Among cases using cryovein, classification and regression tree analysis showed that WIfI stage 3 or 4, age >70 years, and prior failed bypass were predictive of the lowest AFS at 2 years of 36% vs AFS of 58% to 76% among subgroups with less than two of these factors. Although secondary patency at 2 years was worse in the cryovein group (26% vs 68% and 89% in arm/spliced and PTFE groups; P < .01), in patients with tissue loss there was no statistically significant difference in wound healing in the cryovein group (72%) compared with other bypass types (72% vs 87%, respectively; P = .12). ConclusionsIn patients with CLTI lacking suitable ssGSV, bypass with autogenous arm/spliced vein or PTFE has superior AFS compared with cryovein, although data were limited for PTFE conduits for distal targets. Despite poor patency with cryovein, wound healing is achieved in a majority of cases, although it should be used with caution in older patients with high WIfI stage and prior failed bypass, given the low rates of AFS.

Endovascular Management of Chronic Limb-Threatening Ischemia (CLTI) in the Elderly: A Focus on Frailty, Wound Healing, and Outcomes

Prognostic Significance of Preoperative Functional Independence Measure (FIM) on Long-Term Outcomes in Patients with Chronic Limb-Threatening Ischemia (CLTI)

Commonly used chronic limb-threatening ischemia (CLTI) classifications lack granularity and detail to precisely stratify patients according to risk of limb loss, expected revascularization benefit and mortality. The aim of this study is to evaluate in a Portuguese population the prognostic value of an updated CLTI classification based on Wound, Ischemia, and foot Infection (WIfI) proposed by the Society for Vascular Surgery. Single-center retrospective evaluation of prospectively collected data of consecutive patients with CLTI submitted to lower limb revascularization from January to December of 2017. All consecutive patients with chronic peripheral artery disease with ischemic rest pain or tissue loss were included. The exclusion criteria were patients with intermittent claudication, vascular trauma, acute ischemia, non-atherosclerotic arterial disease and isolated iliac intervention. The primary end-point was major limb amputation, mortality and amputation-free survival (AFS) at 30 days, 1 year and 2 year follow-up. Secondary end-points were minor amputation, wound healing time (WHT) and rate (WHR). A total of 111 patients with CLTI were submitted to infra-inguinal revascularization: 91 endovascular and 20 open surgery. After categorizing them according to the WIfI: 20 had stage 1 (18.52%), 29 stage 2 (26.85%), 38 stage 3 (35.19%) and 21 stage 4 (19.44%). Overall mortality rate was 1.8%, 17% and 22.3% at 30 days, 1 year and 2 years follow-up. Major amputation rate was 0.9%, 2.7% and 2.7% at 30 days, 1 year and 2 years follow-up. AFS rate was 97.3%, 82.1%, and 76.8% at 30 days, 1 year, 2 years follow-up. In multi-variable analysis, higher WIfI score was the only predictive factor for mortality and AFS. WIfI 3 and 4 were also associated with increased risk of non-healing ulcer. This study proved the prognostic value of the WIfI classification in a Portuguese population by showing an association between higher scores and increased mortality, lower AFS and non-healing ulcer.

Vascular specialist response to medicare evidence development coverage advisory committee (MEDCAC) panel on peripheral artery disease of the lower extremities.

BackgroundApproximately 20% of patients with chronic limb-threatening ischemia have no revascularization options, leading to above-ankle amputation. Transcatheter arterialization of the deep veins is a percutaneous approach that creates an artery-to-vein connection for delivery of oxygenated blood by means of the venous system to the ischemic foot to prevent amputation.MethodsWe conducted a prospective, single-group, multicenter study to evaluate the effect of transcatheter arterialization of the deep veins in patients with nonhealing ulcers and no surgical or endovascular revascularization treatment options. The composite primary end point was amputation-free survival (defined as freedom from above-ankle amputation or death from any cause) at 6 months, as compared with a performance goal of 54%. Secondary end points included limb salvage, wound healing, and technical success of the procedure.ResultsWe enrolled 105 patients who had chronic limb-threatening ischemia and were of a median age of 70 years (interquartile range, 38 to 89). Of the patients enrolled, 33 (31.4%) were women and 45 (42.8%) were Black, Hispanic, or Latino. Transcatheter arterialization of the deep veins was performed successfully in 104 patients (99.0%). At 6 months, 66.1% of the patients had amputation-free survival. According to Bayesian analysis, the posterior probability that amputation-free survival at 6 months exceeded a performance goal of 54% was 0.993, which exceeded the prespecified threshold of 0.977. Limb salvage (avoidance of above-ankle amputation) was attained in 67 patients (76.0% by Kaplan–Meier analysis). Wounds were completely healed in 16 of 63 patients (25%) and were in the process of healing in 32 of 63 patients (51%). No unanticipated device-related adverse events were reported.ConclusionsWe found that transcatheter arterialization of the deep veins was safe and could be performed successfully in patients with chronic limb-threatening ischemia and no conventional surgical or endovascular revascularization treatment options. (Funded by LimFlow; PROMISE II study ClinicalTrials.gov number, NCT03970538.)

Wound care-first strategies provide superior amputation-free survival in patients with chronic limb-threatening ischemia Wound, Ischemia, and foot Infection clinical stages 1 and 2.