Chronic Limb-threatening Ischemia Patients Research Articles

Vascular Surgeons Have Improved Limb Salvage Compared to Nonvascular Surgeons in Chronic Limb-threatening Ischemia Patients

Vascular Surgeons Have Improved Limb Salvage Compared to Nonvascular Surgeons in Chronic Limb-threatening Ischemia Patients

Paclitaxel-coated Devices Improve Outcomes in Patients With Chronic Limb-threatening Ischemia

Paclitaxel (PTX) coated devices have been shown to decrease restenosis after femoropopliteal artery (FPA) intervention. Recently, they have been linked to a potential increase in late mortality and amputation based on data of patients predominantly presenting with claudication. Outcome of PTX in patients with chronic limb-threatening ischemia (CLTI) are unknown. The objective of this study was to compare outcome of CLTI patients treated with and without PTX.

Inflammation and Loss of Skeletal Muscle Mass in Chronic Limb Threatening Ischemia

Lower extremity peripheral arterial disease (PAD) is an atherosclerotic disease of the lower extremities. Atherosclerosis, inflammation, and sarcopenia are independently associated and potentiate each other. Inflammation is deeply involved in the formation and progression of atherosclerosis and is also involved in the pathophysiology of sarcopenia. Sarcopenia is defined as low muscle mass, with low muscle strength. This study aims to determine the differences in skeletal muscle characteristics and in inflammatory parameters between patients with claudication and with chronic limb threatening ischemia (CLTI). An observational, prospective study in patients with PAD was conducted from January 2018 to December 2020. The clinical characteristics and the cardiovascular risk factors were prospectively registered. The inflammatory parameters determined were: positive acute phase proteins (C-reactive Protein- CRP- and fibrinogen) and negative acute phase proteins albumin, total cholesterol and high-density lipoprotein (HDL). The skeletal muscle area and density were quantified with a computed topography (CT) scan. The strength was determined with a Jamar® hydraulic hand dynamometer. A total of 116 patients (mean age: 67.65±9.53 years-old) 64% with claudication and 46% with CLTI were enrolled in the study. No differences were registered between patients with claudication and CLTI on age, cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, and smoking habits) and medication. There was a higher prevalence of men in the claudication group (88.89% vs. 71.70%, P=0.019). Analyzing the inflammatory parameters, we noted that patients with CLTI had increased serum levels of positive acute phase proteins: CRP (37.53±46.61mg/L vs. 9.18±26.12mg/L, P=0.000), and fibrinogen (466.18±208.07mg/dL vs. 317.37±79.42mg/dL, P=0.000). CLTI patients had decreased negative acute phase proteins: albumin (3.53±0.85g/dL vs. 3.91±0.72g/dL, P=0.001), total cholesterol (145.41±38.59mg/dL vs. 161.84±34.94mg/dL, P=0.013) and HDL (38.70±12.19mg/dL vs. 51.31±15.85mg/dL, P=0.000). We noted that patients with CLTIhad lower skeletal muscle area and mass (14,349.77±3,036.60mm2 vs. 15,690.56±3,183.97mm2P=0.013; 10.11±17.03HU vs. 18.02±13.63HU P=0.013). After adjusting for the variable sex, the association between skeletal muscle density and CLTI persisted (r (97)=-0.232, P=0.021). The groups did not differ in strength (patients with claudication: 25.39±8.23 Kgf vs. CLTI: 25.17±11.95 Kgf P=0.910). CLTI patients have decreased skeletal muscle mass and a systemic inflammation status. Recognizing the deleterious triad of atherosclerosis, inflammation and loss of skeletal mass patients with CLTI is an opportunity to improve medical therapy and to perform a timely intervention to stop this vicious cycle.

Clinical course of patients with chronic limb-threatening ischemia developing COVID-19

BackgroundThe COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, has overwhelmed healthcare systems. Patients with lower extremity artery disease are at high risk of cardiovascular events, of whom chronic limb-threatening ischemia (CLTI) is the most severe manifestation of peripheral artery disease with an increased risk of mortality compared to patients with intermittent claudication. However, the clinical course of CLTI patients with COVID-19 has not been reported. MethodsWe retrospectively surveyed clinical course for 25 CLTI patients who developed COVID-19 during the “sixth wave” of the pandemic in Japan, which started in January 2022. The primary outcome measure was the 30-day mortality after the diagnosis of COVID-19. We also compared the mortality risk of the 18 COVID-19 patients who underwent initial endovascular treatment with that of 1867 CLTI patients who received initial endovascular treatment before December 2019 (i.e. before the COVID-19 pandemic) (control group). Cox proportional hazard regression model was used to evaluate the effect of COVID-19 on the mortality. To confirm the robustness of these results, we added the analysis with inverse probability weighting (IPW) based on the propensity score for the COVID-19. ResultsThe 30-day mortality after the diagnosis of COVID-19 reached 20 %; the 95 % confidence interval (CI) of the proportion was calculated to be 7 % to 41 % by the Clopper-Pearson exact method. Cox regression analysis demonstrated the mortality risk was significantly higher in patients developing COVID-19 than in control group [adjusted hazard ratio, 3.08 (95 % CI, 1.13–8.37); p = 0.027]. The IPW analysis also confirmed the significant association of COVID-19 with the mortality risk [hazard ratio, 3.97 (95 % CI 1.54–10.21, p = 0.004)]. ConclusionIn CLTI patients, the 30-day mortality after the diagnosis of COVID-19 reached 20 % (95 % CI, 7 % to 41 %) under the pandemic in January 2022, and patients developing COVID-19 had a significantly higher mortality risk than those treated before the pandemic.

Measuring Quality of Life in Chronic Limb-threatening Ischemia Patients and Informal Carers: A Scoping Review.

To review quality of life (QOL) instruments for chronic limb-threatening ischemia (CLTI) patients and informal carers, and their use in QOL and cost-utility analysis (CUA) studies. CLTI is a global health problem with significant morbidity affecting patients and informal carers. QOL is increasingly measured for holistic outcomes assessment and CUA. However, measurement instruments in CLTI are poorly understood. MEDLINE, EMBASE, PsycINFO, CINAHL, COSMIN, PROQOLID, CEA registry, and NHS EED databases were searched for all English language studies up to May 2021. Features of instruments, evidence of measurement property appraisal, and trends in use were assessed. Prospective protocol registration (Open Science Framework: https://doi.org/10.17605/OSF.IO/KNG9U ). A total of 146 studies on QOL instruments (n=43), QOL outcomes (n=97), and CUA (n=9) were included. Four disease-specific QOL instruments are available for lower extremity arterial disease (intermittent claudication or CLTI). VascuQoL-25 and VascuQoL-6 have been used in CLTI. There is no CLTI-specific instrument. Of 14 generic instruments, SF-36, EQ-5D-3L, NHP, and WHOQOL-BREF were most common. Studies reporting partial measurement property appraisal favored VascuQoL-25, VascuQoL-6, and SF-36. Feasibility considerations include mode of administration and responder burden. None of 4 available carer-specific instruments have been used in CLTI. Since 1992, the number of QOL studies has increased considerably, but CUA studies are scarce. Informal carers have not been assessed. This review provides a comprehensive reference for QOL measurement in CLTI that helps end-users with instrument selection, use, and interpretation. However, a CLTI-specific instrument is needed. There is an opportunity to benefit society through future CUA studies and evaluation of QOL in informal carers.

One year clinical outcomes of Rutherford 6 chronic limb threatening ischemia patients undergoing lower limb endovascular revascularisation from Singapore

BackgroundPercutaneous transluminal angioplasty (PTA) is widely used as a first-line revascularisation option in patients with chronic limb threatening ischemia (CLTI). This study aimed to evaluate the short-term endovascular revascularisation treatment outcomes of a cohort of Rutherford 6 (R6) CLTI patients, from a multi-ethnic Asian population in Singapore.Patients with R6 CLTI who underwent endovascular revascularisation from June 2019 to February 2020 at Singapore General Hospital, a tertiary vascular centre in Singapore, were included and followed up for one year. Primary outcome measures included number and type of reinterventions required, 3-, 6- and 12-month mortality, 6- and 12-month amputation free survival (AFS), wound healing success and changes in Rutherford staging after 3, 6 and 12 months.ResultsTwo hundred fifty-five procedures were performed on 86 patients, of whom 78 (90.7%) were diabetics, 54 (62.8%) had coronary artery disease (CAD) and 54 (62.8%) had chronic kidney disease (CKD). 42 patients (48.8%) required reintervention within 6 months. Multivariate analysis revealed that the presence of CAD was a significant independent predictor for reintervention. Mortality was 15.1%, 20.9% and 33.7% at 3, 6 and 12 months respectively. AFS was 64.0% and 49.4% at 6 and 12 months. Inability to ambulate, congestive heart failure (CHF), dysrhythmia and CKD were significant independent predictors of lower 12-month AFS.ConclusionsPTA for R6 CLTI patients was associated with relatively high mortality and reintervention rates at one year. CAD was an independent predictor of reintervention. More research is required to help risk stratify which CLTI patients would benefit from an endovascular-first approach versus conservative treatment or an immediate major lower extremity amputation policy.

Global Limb Anatomic Staging System Score correlates with the clinical outcomes in chronic limb threatening ischemia patients.

Chronic limb-threatening ischemia (CLTI) affects millions of people and causes health care burden around the globe. Global Limb Anatomic Staging System (GLASS) was proposed as a new anatomic system for integrating the complexity of threatened limb. We retrospectively classified computed tomography angiography images of threatened limbs into GLASS stages between January 2018 and April 2020. Comorbidities, limb treatments, and outcomes including amputation-free survival (AFS), reintervention and mortality were compared and the likelihood of benefit from revascularization was estimated according to GLASS. Kaplan-Meier estimate was used to determine the rates of endpoint events at 1 year. Multivariate analysis was performed to identify predictors of those outcomes. In our study, 285 threatened limbs in 263 patients were stratified including GLASS stage I disease (N.=53, 19%), stage II (N.=129; 45%) and stage III (N.=103; 36%) disease. The percentage of limbs undergoing endovascular revascularization and minor amputation increased significantly with increasing GLASS stage. On Kaplan-Meier analysis, increasing GLASS stage was associated with 1-year reduced AFS (stage I: 96.1%, stage II: 94.1%, stage III: 83.9%; log rank P=0.016). The percentage of 1-year reintervention rate in infrapopliteal GLASS grade 3-4 (15%) was significantly higher than the percentage of reintervention in infrapopliteal GLASS grade 0-2 (5%) (Log rank P=0.002). Infrapopliteal GLASS grade 3 and 4 was the independent predictor of reduced AFS. GLASS stage correlated with intensity of limb treatment and with clinical outcomes at 1 year. Infrapopliteal GLASS grade 3 and 4 independently predicted the reduced amputation-free survival.

Impact of Serum Zinc Level and Oral Zinc Supplementation on Clinical Outcomes in Patients Undergoing Infrainguinal Bypass for Chronic Limb-Threatening Ischemia.

Zinc (Zn) has been reported to play an important role in wound healing (WH). Nevertheless, the effect of Zn in chronic limb-threatening ischemia (CLTI) patients is unclear. This study investigated the effect of Zn on the clinical outcomes of CLTI patients undergoing bypass surgery.Methods and Results: This study reviewed 111 consecutive patients who underwent an infrainguinal bypass from 2012 to 2020. Patients with Zn deficiency (serum Zn level <60 μg/dL) received oral Zn supplementation and maintained a normal level until WH. This study aimed to explore: (1) the effect of Zn deficiency; and (2) Zn supplementation in Zn-deficient patients on the clinical outcomes of this cohort. Patients with Zn deficiency, Zn supplementation, and no Zn supplementation despite Zn deficiency accounted for 48, 21, and 42 patients, respectively. (1) Zn deficiency was associated with WH (HR, 0.47; 95% CI, 0.29-0.78: P=0.003), major adverse limb events (MALE) (HR, 2.53; 95% CI, 1.26-5.09: P=0.009), and major amputation or death (HR, 3.17; 95% CI, 1.51-6.63: P=0.002). (2) Zn supplementation was positively related to WH (HR, 2.30; 95% CI, 1.21-4.34: P=0.011). This result was confirmed using propensity score matching (HR, 2.24; 95% CI, 1.02-4.87: P=0.043). The current study revealed that Zn level was associated with clinical outcomes in CLTI patients after bypass surgery. Oral Zn supplementation could improve WH in these patients.

Paclitaxel-coated Devices Improve Outcomes in Patients Presenting With Chronic Limb-Threatening Ischemia

Paclitaxel (PTX)-coated devices decrease restenosis after femoropopliteal artery intervention. Recently, they have been linked to a potential increase in late mortality and amputation based on data of patients predominantly presenting with claudication. Outcome of PTX in patients with chronic limb-threatening ischemia (CLTI) are unknown. The objective of this study was to compare outcome of CLTI patients treated with and without PTX. Patients who underwent femoropopliteal artery interventions for CLTI from January 2016 to October 2020 (n = 35,533; 13,546 treated with PTX) in the Society for Vascular Surgery Vascular Quality Initiative were reviewed. Patients were divided based on PTX exposure and propensity matched to control for differences in symptoms, comorbidities, and perioperative medications. After matching there were 13,528 patients in each cohort. Primary outcome measures of overall survival (OS), limb salvage, freedom from target vessel revascularization (TVR), and freedom from major adverse limb events (MALE) were assessed using Kaplan-Meier survival analysis. After matching there were no significant differences in baseline characteristics. At 2-year follow-up, there was no significant difference in OS between PTX and no-PTX patients (81 vs 80%; P = .07). A significant benefit was observed with PTX treatment in limb salvage (90% vs 87%; P < .001) (Fig 1), freedom from MALE (73% vs 69%; P < .001) (Fig 2), and freedom from TVR (81% vs 78%; P < .001). Multivariable Cox regression analysis confirms that PTX is associated with improved limb salvage (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.69-0.83; P < .001), freedom from MALE (HR, 0.73; 95% CI, 0.68-0.78; P < .001), and freedom from TVR (HR, 0.72; 95% CI, 0.66-0.79; P < .001), with no difference in OS (HR, 0.95; 95% CI, 1.01-0.88; P = .11). At 2 years, CLTI patients treated with a PTX-coated device demonstrated improved limb salvage, freedom from TVR, and freedom from MALE with no difference in OS. This study suggests that the use of PTX-coated devices may be beneficial to patients presenting with CLTI and are not associated with adverse outcome as suggested by recent meta-analyses.Fig 2View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Multicomponent Prehabilitation as a Novel Strategy for Preventing Delirium in Older Chronic Limb Threatening Ischemia Patients: A Study Protocol.

ObjectiveChronic limb threatening ischemia is the final stage of peripheral arterial disease. Current treatment is based on revascularization to preserve the leg. In the older, hospitalized chronic limb threatening ischemia patient, delirium is a frequent and severe complication after revascularization. Delirium leads to an increased length of hospital stay, a higher mortality rate and a decrease in quality of life. Currently, no specific guidelines to prevent delirium in chronic limb threatening ischemia patients exist. We aim to evaluate the effect of a multicomponent, multidisciplinary prehabilitation program on the incidence of delirium in chronic limb threatening ischemia patients ≥65 years.DesignA prospective observational cohort study to investigate the effects of the program on the incidence of delirium will be performed in a large teaching hospital in the Netherlands. This manuscript describes the design of the study and the content of this specific prehabilitation program.MethodsChronic limb threatening ischemia patients ≥65 years that require revascularization will participate in the program. This program focuses on optimizing the patient’s overall health and includes delirium risk assessment, nutritional optimization, home-based physical therapy, iron infusion in case of anaemia and a comprehensive geriatric assessment in case of frailty. The primary outcome is the incidence of delirium. Secondary outcomes include quality of life, amputation-free survival, length of hospital stay and mortality. Exclusion criteria are the requirement of acute treatment or patients who are mentally incompetent to understand the procedures of the study or to complete questionnaires. A historical cohort from the same hospital is used as a control group.DiscussionThis study will clarify the effect of a prehabilitation program on delirium incidence in chronic limb threatening ischemia patients. New insights will be obtained on optimizing a patient’s preoperative mental and physical condition to prevent postoperative complications, including delirium.TrialThis protocol is registered at the Netherlands National Trial Register (NTR) number: NL9380.

An Evaluation of Pre-Operative Nutritional Assessment Methods in Patients with Chronic Limb Threatening Ischaemia Having Distal Bypass

The purpose of this study was to evaluate the influence of pre-operative nutritional status on long term outcomes of patients with chronic limb threatening ischaemia (CLTI) after distal bypass. Patients who underwent distal bypass for CLTI from 2011 to 2020 at a single centre were reviewed retrospectively in Japan. Comparisons were made between patients with malnutrition and normal nutrition, as diagnosed by four nutritional assessments: Controlling Nutritional Status (CONUT), Geriatric Nutritional Risk Index (GNRI), Glasgow Prognostic Score (GPS), and Prognostic Nutritional Index (PNI). The primary endpoint was survival, and the secondary endpoints were graft patency, limb salvage, and wound healing. A total of 314 distal bypasses were performed in 249 patients (169 males; median age, 76 years; diabetes mellitus, 70%; and end stage renal disease with haemodialysis, 40%). Malnutrition was observed in 103 patients (41%) evaluated by CONUT, 129 (52%) by GNRI, 76 (31%) by GPS, and 114 (46%) by PNI. The survival rates in the study cohort were 81% at one year, 55% at three years, and 47% at five years. Malnutrition in all assessments was statistically significantly associated with reduced survival rate (CONUT, p < .001; GNRI, p= .002; GPS, p < .001; PNI, p < .001). In multivariable analysis, CONUT was the best predictor of mortality (p= .014). Malnutrition did not affect graft patency and limb salvage, but malnutrition based on CONUT, GNRI, and GPS was statistically significantly associated with reduced wound healing (CONUT, p= .002; GNRI, p= .006; GPS, p= .011). In multivariable analysis, CONUT tended to be the best predictor of wound healing (p= .061). Malnutrition in patients with CLTI with distal bypass was associated with overall mortality and incomplete wound healing. CONUT assessment was most effective for prediction of survival and wound healing. Distal bypass for CLTI patients with malnutrition may be suboptimal, and endovascular treatment may be recommended as an initial revascularisation method.

Increased thrombogenicity is associated with revascularization outcomes in patients with chronic limb-threatening ischemia

ObjectivesClinically driven target lesion revascularization (CD-TLR) frequently occurs after endovascular therapy (EVT) in patients with chronic limb-threatening ischemia (CLTI). The total thrombus-formation analysis system (T-TAS) can quantitatively evaluate thrombogenicity. Therefore, we aimed to elucidate the association of the T-TAS parameters with CD-TLR. MethodsWe analyzed 34 patients with CLTI and 62 patients without CLTI who had undergone EVT. Blood samples collected on the day of EVT were used in the T-TAS to compute the thrombus formation area under the curve for the first 10 minutes for the platelet chip tested at a flow rate of 24 μL/min (PL24-AUC10) and area under the curve for the first 30 minutes for the atheroma chip tested at a flow rate of 10 μL/min (AR10-AUC30). After EVT, clinical follow-up was performed, and the presence of CD-TLR was assessed. ResultsDuring the follow-up period (median, 574 days), 10 patients (29%) in the CLTI group and 11 (18%) in the non-CLTI group had required CD-TLR. In the CLTI group, the patients with CD-TLR had had a higher AR10-AUC30 vs those without (median, 1694 [interquartile range, 1657-1799] vs median, 1561 [interquartile range, 1412-1697]; P = .01). In contrast, the PL24-AUC10 showed no significant differences when stratified by CD-TLR in either group. For the CLTI patients, multivariable Cox regression analysis using propensity score matching revealed that the AR10-AUC30 was an independent predictor of CD-TLR even after adjusting for baseline demographics, lesion characteristics, and anticoagulant use (hazard ratio, 2.04; 95% confidence interval, 1.18-3.88; P = .01; per 100-unit increase). In contrast, for those without CLTI, neither the AR10-AUC30 nor the PL24-AUC10 was significantly associated with CD-TLR. Receiver operating characteristics curve analysis identified an AR10-AUC30 level of 1646 as an optimal cutoff value to predict for CD-TLR (AUC, 0.85; sensitivity, 0.93; specificity, 0.56). ConclusionsFor patients with CLTI, but not for those without CLTI, the AR10-AUC30 showed potential to predict for CD-TLR. This finding suggests that hypercoagulability might play a predominant role in the progression of CLTI and that anticoagulant therapy might be useful in preventing revascularization.

The Geriatric Nutritional Risk Index predicts amputation after infrapopliteal angioplasty in critical limb ischemia patients

ObjectiveTo validate the Critical Limb Ischemia Frailty Index (CLIFI), and to identify independent predictors of 2-year amputation-free survival after infrapopliteal endovascular treatment for chronic limb-threatening ischemia (CLTI) in Thai patients. MethodsThis retrospective study was conducted during the June 2014 to February 2017 study period. CLTI patients treated with infrapopliteal angioplasty were enrolled and analyzed. A patient was defined as CLIFI positive if two or more of the following criteria were present: Geriatric Nutritional Risk Index (GNRI) < 89.8, low skeletal muscle mass index (<6.87 kg/m2 in males, and <5.46 kg/m2 in females), and/or non-ambulatory status. Kaplan–Meier survival analysis was used to assess 2-year amputation-free survival (AFS), and comparisons were performed using log-rank test. Univariate and multivariate Cox proportional hazards models were used to analyze for significant and independent association, respectively, between preoperative characteristics and AFS. ResultsA total of 266 patients and 286 limbs were included. Forty (15.0%) patients were CLIFI positive, and 226 (85.0%) patients were CLIFI negative. The 2-year amputation-free survival rate was 90.3% in the CLIFI positive group, and 86.6% in the CLIFI negative group (p = 0.59). Multivariate analysis revealed the GNRI to be an independent risk factor for amputation within two years after infrapopliteal revascularization (adjusted hazard ratio: 4.87, 95% confidence interval: 1.20–19.70; p = 0.02). ConclusionsThe GNRI was found to independently predict 2-year amputation after infrapopliteal angioplasty in Thai CLTI patients; however, the CLIFI was not found to significantly predict 2-year amputation in this patient population.

The Patency of Tibial/Peroneal Arteries Affects the Increment of Regional Tissue Saturation of Oxygen in Each Angiosome after Superficial Femoral Artery Revascularization.

Objective: The angiosome model is a controversial concept in the revascularization of patients with chronic limb-threatening ischemia (CLTI). The aim of this study was to demonstrate the importance of patency of the tibial/peroneal arteries for regional tissue oxygenation in each angiosome during endovascular therapy (EVT) of the superficial femoral artery (SFA).Materials and Methods: We devised a novel near-infrared spectroscopy oximeter, “TOE-20,” for real-time monitoring of regional tissue oxygen saturation (rSO2). Using TOE-20, we prospectively assessed rSO2 at each angiosome in 23 CLTI patients who underwent successful revascularization of the SFA. During EVT, three sensor probes were placed at the dorsal foot, plantar foot, and outer ankle for rSO2 monitoring.Results: At the end of EVT, rSO2 at all angiosomes was significantly elevated by SFA revascularization. The change in rSO2 in each angiosome was larger in patients with patent relevant arteries than in those with occluded relevant arteries (i.e., anterior tibial artery patency, posterior tibial artery patency, and peroneal artery patency).Conclusion: The patency of the tibial/peroneal arteries is important for regional tissue oxygenation in EVT. Using TOE-20 and rSO2-based revascularization, it may possible to anticipate whether an ischemic ulcer will heal or not.

Below-the-Ankle Orbital Atherectomy in Chronic Limb-Threatening Ischemia Patients as a Bailout Strategy for Limb Salvage: Early Clinical Experience

PurposeTo evaluate the feasibility and early outcomes of below the ankle orbital atherectomy in chronic limb-threatening ischemia in patients with calcified foot arteries. Methods12 patients (mean age 69.4 ± 14.7; range 57 to 85 years) who were affected by diabetes underwent orbital atherectomy below the knee and ankle arterial segments. Technical success was defined as orbital atherectomy passage and debulked the calcified lesion, delivery of adjunctive therapy, and < 30% residual stenosis at final angiogram. The procedural outcome included complications, amputation-free survival, and freedom from clinically-driven target lesion revascularization at 30-days and 6-months of follow-up. ResultsOrbital atherectomy was performed in 3 cases in Anterior tibial (AT) and dorsalis pedis (Ped) arteries + Posterior tibial (PT) and Lateral Plantar (Lat Plan), 5 cases in PT and Lat Plan arteries, 1 case of PT and Medial Plantar, 1 case of Peroneal and Plan Lat, and 2 cases of AT and Ped. After atherectomy, we used a drug-coated balloon (DCB) angioplasty.Technical success was achieved in 11 (91.6%) cases. No deaths were registered during the follow-up. The limb salvage rate was 100%, and no major amputations were registered. Amputation-free survival was 50%. Freedom from CD-TLR was 100% at 30 days and 91.7% at 6-months. One patient underwent a TLR at three months. No major cardiovascular events, limb events, or significant procedure-related complications were registered. ConclusionsCSI orbital atherectomy and DCB angioplasty appear a feasible and promissor treatment options in diabetic CLTI patients.

Individual patient data meta-analysis of patients treated with a heparin-bonded Viabahn in the femoropopliteal artery for chronic limb-threatening ischemia.

ObjectivesThe aim of the study was to analyze available data on patients treated for chronic limb‐threatening ischemia (CLTI) with the heparin‐bonded Viabahn endoprosthesis.BackgroundThe patency of self‐expanding covered stents in patients with complex femoropopliteal lesions is encouraging. However, data were mostly derived in patients with intermittent claudication. Patients with CLTI often have more advanced disease and worse outcome.MethodsAfter the abstract screening, full‐text papers were checked. Authors were approached to consider joining the consortium. Data were sent anonymously, databases were merged and an individual patient data meta‐analysis was performed. Kaplan–Meier curves were used to calculate the freedom from amputations, the amputation‐free survival, and patency rates.ResultsSeven studies were enrolled, representing 161 limbs that were treated for CLTI. Median lesion length was 28.0 cm (interquartile range 25.0–33.0 cm) and 82.7% were chronic total occlusions. The technical success rate was 98.1% and the 30‐day mortality 1.9%. Through 2‐year follow‐up, the freedom‐from‐major‐amputations was 99.3%, with an amputation‐free survival of 78.8%. The freedom‐from‐loss‐of primary, primary‐assisted, and secondary patency was 70.4%, 71.8%, and 88.2%, respectively, at 1‐year and 59.5%, 62.7%, and 86.1% at 2‐year follow‐up, respectively. The reintervention‐free survival was 62.2% at a 2‐year follow‐up.ConclusionsTreatment of femoropopliteal disease in CLTI patients with the use of the heparin‐bonded Viabahn is safe and effective with favorable clinical outcomes and low amputation rates. Reinterventions are needed in a subset of the population to maintain endoprosthesis patency. Close follow‐up using duplex is recommended to detect potential edge stenosis, allowing treatment before device occlusion.

Slow-flow phenomena following lower limb paclitaxel- and sirolimus-coated balloon angioplasty in the setting of chronic limb threatening ischaemia—a case series

The Achilles heel of plain old balloon angioplasty (POBA) is neointimal hyperplasia (NIH) and restenosis, caused from the barotrauma of ballooning. Drug-coated balloons using a paclitaxel-based platform (PCB) have been shown to retard the restenotic process, using the anti-proliferative effects of paclitaxel, and give longer vessel patency. This is important in the setting of chronic limb threatening ischemia (CLTI) and for the protracted wound healing process in these frail patients. However, during PCB application, more than 50% of the drug is lost downstream, a phenomenon termed particulate embolization. This is thought to account for the slow- or no-flow phenomenon encountered after PCB use. Recent data suggest that slow-flow phenomenon was associated with a lower target lesion revascularisation rate and worse amputation free survival (AFS). The use of sirolimus coated balloons (SCB) to impede the NIH cascade has been less well studied but recent data suggested excellent short-term efficacy and found no slow flow phenomenon with their use in the tibial arteries in CLTI patients. Aim of this case series is to highlight the difference in flow phenomena using PCB and SCB elution in the setting of CLTI. We evaluated the use of parametric colour coding and time attenuation curves (TAC) as a quantitative measure of blood flow. SCB may have an advantage over PCB use in the peripheral vasculature because of a reduced incidence of slow flow phenomenon following drug elution.

Association of wound, ischemia, and foot infection clinical stage with frailty and malnutrition in chronic limb-threatening ischemia patients undergoing endovascular intervention.

The Wound, Ischemia, and foot Infection (WIfI) clinical stage has been thought to have a prognostic value in Chronic limb-threatening ischemia (CLTI) patients, and frailty and nutritional status appear to represent pivotal factor affecting prognosis among CLTI patients. The purpose of this study was to examine clinical factors (including frailty and nutritional status) relevant to WIfI clinical stage. This retrospective study investigated 200 consecutive CLTI patients. We individually assessed WIfI clinical stage, frailty according to the Clinical Frailty Scale (CFS) score, and malnutrition according to Geriatric Nutritional Risk Index (GNRI). We then compared mortality after endovascular intervention between a WIfI stage 1, 2 group and a stage 3, 4 group, and investigated associations between baseline characteristics (including CFS and GNRI) and WIfI clinical stage. Among 200 patients, 123 patients (62%) showed WIfI stage 1 or 2, and the remaining 77 patients (38%) had WIfI stage 3 or 4. CFS score was significantly higher in the WIfI stage 3, 4 group [median 6.0, interquartile range (IQR) 5.5-7.0] compared with the WIfI stage 1, 2 group (median 5.0, IQR 4.0-6.0, p < 0.001), and GNRI was significantly lower in the WIfI stage 3, 4 group (median 88, IQR 80-97) than in the WIfI stage 1, 2 (median 103, IQR 94-111, p < 0.001). Forty patients (20%) died after endovascular intervention. Incidences of all-cause and cardiac deaths were higher in the WIfI stage 3, 4 group than in the WIfI stage 1, 2 group (27% vs. 15%, p = 0.047 and 12% vs. 3%, p = 0.040, respectively). Kaplan-Meier analysis showed a significantly lower survival rate in the WIfI stage 3, 4 group than in the WIfI stage 1, 2 group (p = 0.002 by log-rank test). Multivariate logistic regression analysis using relevant factors from univariate analysis showed CFS score [odds ratio (OR) 2.06, 95% confidence interval (CI) 1.41-3.13, p < 0.001), diabetes mellitus (OR 3.17, 95%CI 1.17-8.61, p = 0.023) and GNRI (OR 0.93, 95%CI 0.89-0.97, p = 0.002) significantly associated with WIfI stage 3 or 4. In addition, multivariate ordinal logistic regression analysis for WIfI clinical stage showed CFS score (OR 1.43, 95%CI 1.09-1.89, p = 0.011), diabetes mellitus (OR 1.77, 95%CI 1.26-2.54, p < 0.001), and high-sensitivity C-reactive protein (OR 1.14, 95%CI 1.02-1.28, p = 0.041) were positively associated with WIfI clinical stage, and GNRI correlated negatively with WIfI clinical stage (OR 0.95, 95%CI 0.91-0.97, p < 0.001). These results indicate that CLTI patients with high WIfI clinical stage may be more frail and malnourished, and be associated with poor prognosis after endovascular intervention.

Filgrastim, fibrinolysis, and neovascularization.

Segmental recanalization of chronically occluded arteries was observed in patients with chronic limb‐threatening ischemia (CLTI) treated with Filgrastim, a granulocyte colony stimulating factor, every 72 h for up to a month, and an infra‐geniculate programmed compression pump (PCP) for 3 h daily. Molecular evidence for fibrinolysis and neovascularization was sought. CLTI patients were treated with PCP alone (N = 19), or with Filgrastim and PCP (N = 8 and N = 6, at two institutions). Enzyme‐Linked Immunosorbent Assay was used to measure the plasma concentration of plasmin and of fibrin degradation products (FDP), and the serum concentration of proteins associated with neovascularization. In the PCP‐alone group, blood was sampled on Day 1 (baseline) and after 30 days of daily PCP. In the Filgrastim and PCP group, blood was drawn on Day 1, and 1 day after the 5th and the 10th Filgrastim doses. Each blood draw occurred before and after 2 h of supervised PCP. Significant (p < 0.01) PCP independent increases in the plasma concentration of plasmin (>10‐fold) and FDP (>5‐fold) were observed 1 day after both the 5th and the 10th Filgrastim doses, compared to Day 1. Significant (p < 0.05) increases in the concentration of pro‐angiogenic proteins (e.g., HGF, MMP‐9, VEGF A) were also observed. Filgrastim at this novel dosimetry induced fibrinolysis without causing acute hemorrhage, in addition to inducing a pro‐angiogenic milieu conducive to NV. Further clinical testing is warranted at this novel dosimetry in CLTI, as well as in other chronically ischemic tissue beds. Trial registration. https://clinicaltrials.gov/ct2/show/NCT02802852.

Team-Based Care in Patients with Chronic Limb-Threatening Ischemia

Team-based care has been proposed as a tool to improve health care delivery, especially for the treatment of complex medical conditions. Chronic limb-threatening ischemia (CLTI) is a complex disease associated with significant morbidity and mortality which often involves the care of multiple specialty providers. Coordination of efforts across the multiple physician specialists, nurses, wound care specialists, and administrators is essential to providing high-quality and efficient care. The aim of this review is to discuss the multiple facets of care of the CLTI patient and to describe components important for a team-based care approach. Observational studies have reported improved outcomes when using a team-based care approach in the care of the patients with CLTI, including reduction in mean wound healing times, decreasing rate of amputations, and readmissions. Team-based care can streamline care of CLTI patients by raising awareness, facilitating early recognition, and providing prompt vascular assessment, revascularization, and surveillance. This approach has the potential to improve patient outcomes and reduce downstream health care costs.