Revascularization For Chronic Limb-threatening Ischemia Research Articles

The Impact of Diabetes Mellitus on the Outcomes of Revascularization for Chronic Limb-Threatening Ischemia in the BEST-CLI trial

Several observational studies have demonstrated an association between diabetes mellitus (DM) and above ankle amputation after lower extremity revascularization (LER). However, data from prospective randomized trials is lacking. This analysis compares the outcomes of patients with and without DM enrolled in the Best Endovascular versus Best Surgical Therapy in patients with Chronic Limb-Threatening Ischemia (CLTI) (BEST-CLI) trial. Baseline characteristics were compared between patients with and without DM in the BEST-CLI trial. Cox regression was used to determine the association between DM and major outcomes of major adverse limb events (MALE), reintervention, above ankle amputation, and all-cause death. Among 1,777 patients who underwent LER, 69.2% had DM. Compared to patients without DM, those with DM were significantly younger, less likely to be White, and more likely to be Hispanic. Patients with DM were more likely to have hypertension, hyperlipidemia, coronary artery disease, congestive heart failure, and renal disease and be on optimal medical therapy (antiplatelets and statins) while patients without DM were significantly more likely to be smokers and have chronic obstructive pulmonary disease. Patients with DM were significantly more likely to present with late Wound Ischemia foot Infection (WIfI) stages (3-4) (73.7% vs 45.9%, P<0.001) that were driven predominantly by differences in wound and infection grade. Conversely, patients without DM had significantly lower ankle pressures and toe pressures and were significantly more likely to have WIfI ischemia grade 3 compared to patients with DM (60% vs 52.5%, P=0.016). At three years, patients with DM exhibited higher rates of above ankle amputation and all-cause death compared to patients without DM. Kaplan-Meier analysis demonstrated significantly higher MALE or all-cause death compared to patients without DM (3-year estimate: 53.5% vs 46.4%, P<0.001). After adjusting for potential confounders, regression analysis demonstrated that DM was independently associated with increased above ankle amputation (1.75 [1.22-2.51]), all-cause death (1.63 [1.31-2.03]), and MALE or all-cause death (1.24 [1.04-1.47]). Patients with DM undergoing LER for CLTI experienced a greater incidence of MALE or all-cause death compared to patients without DM. The impact of DM seems to be mediated by more severe wounds and infections at the time of presentation, and a higher prevalence of cardiac and renal disease.

The Impact of Revascularization Strategy on Clinical Failure, Hemodynamic Failure and Chronic Limb Threatening Ischemia Symptoms in the BEST-CLI Trial

ObjectivesSustained clinical and hemodynamic benefit following revascularization for chronic limb-threatening ischemia (CLTI) is needed to resolve symptoms and prevent limb loss. We sought to compare rates of clinical and hemodynamic failure as well as resolution of initial and prevention of recurrent CLTI following endovascular (ENDO) vs bypass (OPEN) revascularization in the BEST-CLI trial. MethodsAs planned secondary analyses of the BEST-CLI trial, we examined the rates of A) clinical failure (a composite of all-cause death, above-ankle amputation, major reintervention, and degradation of WIfI stage); B) hemodynamic failure (a composite of above-ankle amputation, major and minor reintervention to maintain index limb patency, failure to initially increase or a subsequent decrease in ankle brachial index of 0.15 or toe brachial index of 0.10, and radiographic evidence of treatment stenosis or occlusion); C) time to resolution of presenting CLTI symptoms; and D) incidence of recurrent CLTI. Time-to-event analyses were by intention-to-treat assignment in both trial cohorts (cohort 1: suitable single segment great saphenous vein [SSGSV], N=1434; cohort 2: lacking suitable SSGSV, N= 396) and multivariate stratified Cox regression models were created. ResultsIn cohort 1, there was a significant difference in time to clinical failure (log-rank p<0.001), hemodynamic failure (log-rank p<0.001), and resolution of presenting symptoms (log-rank p=0.009) in favor of OPEN. In cohort 2, there was a significantly lower rate of hemodynamic failure (log-rank p=0.006) favoring OPEN, and no significant difference in time to clinical failure or resolution of presenting symptoms. Multivariate analysis revealed that assignment to OPEN was associated with significantly lower risk of clinical and hemodynamic failure in both cohorts, and a significantly higher likelihood of resolving initial and preventing recurrent CLTI symptoms in cohort 1, including after adjustment for key baseline patient covariates (end stage renal disease (ESRD), prior revascularization, smoking, diabetes, age>80, WIfI stage, tissue loss, infrapopliteal disease). Factors independently associated with clinical failure included age>80 in cohort 1 and ESRD across both cohorts. ESRD was associated with hemodynamic failure in cohort 1. Factors associated with slower resolution of presenting symptoms included diabetes in cohort 1 and WIfI stage in cohort 2. ConclusionsDurable clinical and hemodynamic benefit following revascularization for CLTI is important to avoid persistent and recurrent CLTI, reinterventions and limb loss. When compared with ENDO, initial treatment with OPEN surgical bypass, particularly with available saphenous vein, is associated with improved clinical and hemodynamic outcomes and enhanced resolution of CLTI symptoms.

The impact of travel distance in patient outcomes following revascularization for chronic limb-threatening ischemia

BackgroundPatient travel distance to the hospital is a key metric of individual and social disadvantage and its impact on the management and outcomes following intervention for chronic limb-threatening ischemia (CLTI) is likely underestimated. We sought to evaluate the effect of travel distance on outcomes in patients undergoing first-time lower extremity revascularization at our institution. MethodsWe retrospectively reviewed all consecutive patients undergoing first-time lower extremity revascularization, both endovascular and open, for CLTI from 2005 to 2014. Patients were stratified into 2 groups based on travel distance from home to hospital greater than or less than 30 miles. Outcomes included reintervention, major amputation, restenosis, primary patency, wound healing, length of stay, length of follow-up and mortality. Kaplan-Meier estimates were used to determine event rates. Logistic and cox regression was used to evaluate for an independent association between travel distance and these outcomes. ResultsOf the 1293 patients were identified, 38% traveled >30 miles. Patients with longer travel distances were younger (70 years vs 73 years; P = .001), more likely to undergo open revascularization (65% vs 41%; P < .001), and had similar Wound, Ischemia, foot Infection stages (P = .404). Longer distance travelled was associated with an increase in total hospital length of stay (9.6 days vs 8.6 days; P = .031) and shorter total duration of postoperative follow-up (2.1 years vs 3.0 years; P = .001). At 5 years, there was no definitive difference in the rate of restenosis (hzard ratio [HR], 1.3; 95% confidence interval [CI], 0.91-1.9; P = .155) or reintervention (HR, 1.4; 95% CI, 0.96-2.1; P = .065), but longer travel distance was associated with an increased rate of major amputation (HR, 2.1; 95% CI, 1.2-3.7; P = .011), and death (HR, 1.6; 95% CI, 1.2-2.2; P = .002). Longer travel distance was also associated with higher rate of nonhealing wounds (HR, 2.3; 95% CI, 1.5-3.5; P = .001). ConclusionsLonger patient travel distance was found to be associated with a lower likelihood of limb salvage and survival in patients undergoing first-time lower extremity revascularization for CLTI. Understanding and addressing the barriers to discharge, need for multidisciplinary follow-up, and appropriate postoperative wound care management will be key in improving outcomes at tertiary care regional specialty centers.

Surgery or endovascular therapy for patients with chronic limb-threatening ischemia requiring infrapopliteal interventions

ObjectiveThe recent publication of randomized trials comparing open bypass surgery to endovascular therapy in patients with chronic limb-threatening ischemia, namely, Best Endovascular vs Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI) and Bypass versus Angioplasty in Severe Ischaemia of the Leg-2 (BASIL-2), has resulted in potentially contradictory findings. The trials differed significantly with respect to anatomical disease patterns and primary end points. We performed an analysis of patients in BEST-CLI with significant infrapopliteal disease undergoing open tibial bypass or endovascular tibial interventions to formulate a relevant comparator with the outcomes reported from BASIL-2. MethodsThe study population consisted of patients in BEST-CLI with adequate single segment saphenous vein conduit randomized to open bypass or endovascular intervention (cohort 1) who additionally had significant infrapopliteal disease and underwent tibial level intervention. The primary outcome was major adverse limb event (MALE) or all-cause death. MALE included any major limb amputation or major reintervention. Outcomes were evaluated using Cox proportional regression models. ResultsThe analyzed subgroup included a total of 665 patients with 326 in the open tibial bypass group and 339 in the tibial endovascular intervention group. The primary outcome of MALE or all-cause death at 3 years was significantly lower in the surgical group at 48.5% compared with 56.7% in the endovascular group (P = .0018). Mortality was similar between groups (35.5% open vs 35.8% endovascular; P = .94), whereas MALE events were lower in the surgical group (23.3% vs 35.0%; P<.0001). This difference included a lower rate of major reinterventions in the surgical group (10.9%) compared with the endovascular group (20.2%; P = .0006). Freedom from above ankle amputation or all-cause death was similar between treatment arms at 43.6% in the surgical group compared with 45.3% the endovascular group (P = .30); however, there were fewer above ankle amputations in the surgical group (13.5%) compared with the endovascular group (19.3%; P = .0205). Perioperative (30-day) death rates were similar between treatment groups (2.5% open vs 2.4% endovascular; P = .93), as was 30-day major adverse cardiovascular events (5.3% open vs 2.7% endovascular; P = .12). ConclusionsAmong patients with suitable single segment great saphenous vein who underwent infrapopliteal revascularization for chronic limb-threatening ischemia, open bypass surgery was associated with a lower incidence of MALE or death and fewer major amputation compared with endovascular intervention. Amputation-free survival was similar between the groups. Further investigations into differences in comorbidities, anatomical extent, and lesion complexity are needed to explain differences between the BEST-CLI and BASIL-2 reported outcomes.

Food Insecurity is Associated with Poor Outcomes After Revascularization for Chronic Limb-threatening Ischemia

Food Insecurity is Associated with Poor Outcomes After Revascularization for Chronic Limb-threatening Ischemia

Outcomes for Patients With Chronic Limb-Threatening Ischemia After Direct and Indirect Endovascular and Surgical Revascularization: A Meta-Analysis and Systematic Review.

The purpose of this review and meta-analysis is to determine the clinical outcome differences between patients with chronic limb-threatening ischemia who underwent direct versus indirect angiosome revascularization using either the surgical or endovascular approach. The data sources used for article selection included PubMed, Embase/Medline, Cochrane reviews, and Web of Science (All studies were in English and included up to September 2023). All articles included were comparative in design, including retrospective, prospective, and randomized controlled trials that compared the clinical outcomes between direct and indirect angiosome-guided revascularization in chronic limb-threatening ischemia. A random-effects model was used to determine the measure of association between direct revascularization and amputation-free survival, wound healing, and overall survival. Publication bias was assessed with both Begg's and Egger's test, and heterogeneity was calculated using an I2. Data from 9 articles were analyzed and reported in this review. Direct revascularization was associated with improved amputation-free survival (odds ratio [OR]=2.632, confidence interval [CI]: 1.625, 4.265), binary wound healing (OR=2.262, CI: 1.518, 3.372), and overall survival (OR=1.757, CI: 1.176, 2.625). Time until wound healed was not associated with either direct or indirect revascularization (Standard Mean Difference [SMD]=-2.15, p=0.11). There was a low risk of bias across all studies according to the RoB 2.0 tool. Direct revascularization is associated with improved amputation-free survival, overall survival, and wound healing in chronic limb-threatening ischemic patients compared to the indirect approach. Preservation of the lower extremity is critical for preventing mortality and maintaining independence. The benefit of angiosome-guided revascularization for chronic limb-threatening ischemia remains controversial. The authors of this article aim to review the current literature and compare direct and indirect angiosome-guided intervention for preserving the lower extremity. Current findings suggest direct angiosome-guided intervention reduces amputation rates and improves survival; however, many trials neglect to address the multifactorial approach needed in wound care management.

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

ObjectiveThis study aimed to evaluate treatment outcomes after bypass surgery or endovascular therapy (EVT) in average- and high-risk patients with chronic limb-threatening ischemia (CLTI). MethodsWe retrospectively analyzed multicenter data of patients who underwent infra-inguinal revascularization for CLTI between 2015 and 2022. A high-risk patient was defined as one with estimated 30-day mortality rate ≥5% or 2-year survival rate ≤50%, as determined by the Surgical Reconstruction vs Peripheral Intervention in Patients With Critical Limb Ischemia (SPINACH) calculator. The amputation-free survival (AFS), limb salvage (LS), wound healing, and 30-day mortality were compared separately for the average- and high-risk patients between the bypass and EVT with propensity score matching. ResultsWe analyzed 239 and 31 propensity score-matched pairs in the average- and high-risk patients with CLTI. In the average-risk patients, the 2-year AFS and LS rates were 78.1% and 94.4% in the bypass group and 63.0% and 87.7% in the EVT group (P < .001 and P = .007), respectively. The 1-year wound healing rates were 88.6% in the bypass group and 76.8% in the EVT group, respectively (P < .001). The 30-day mortality was 0.8% in the bypass surgery and 0.8% in the EVT group (P = .996). In the high-risk patients, there was no differences in the AFS, LS, and wound healing between the groups (P = .591, P = .148, and P = .074). The 30-day mortality was 3.2% in the bypass group and 3.2% in the EVT group (P = .991). ConclusionsBypass surgery is superior to EVT with respect to the AFS, LS, and wound healing in the average-risk patients. EVT is a feasible first-line treatment strategy for high-risk patients with CLTI undergoing revascularization, based on the lack of significant differences in the 2-year AFS rate, between the bypass surgery and EVT cohorts.

Relevance of BEST-CLI trial endpoints in a tertiary care limb preservation program

ObjectiveMajor adverse limb event-free survival (MALE-FS) differed significantly by initial revascularization approach in the BEST-CLI randomized trial. The BEST-CLI trial represented a highly selected subgroup of patients seen in clinical practice; thus, we examined the endpoint of MALE-FS in an all-comers tertiary care practice setting. MethodsThis is a single-center retrospective study of consecutive, unique patients who underwent technically successful infrainguinal revascularization for chronic limb-threatening ischemia (2011-2021). MALE was major amputation (transtibial or above) or major reintervention (new bypass, open bypass revision, thrombectomy, or thrombolysis). ResultsAmong 469 subjects, the mean age was 70 years, and 34% were female. Characteristics included diabetes (68%), end-stage renal disease (ESRD) (16%), Wound, Ischemia, and foot Infection (WIfI) stage 4 (44%), Global Limb Anatomic Staging System (GLASS) stage 3 (62%), and high pedal artery calcium score (pMAC) (22%). Index revascularization was autogenous vein bypass (AVB) (30%), non-autogenous bypass (NAB) (13%), or endovascular (ENDO) (57%). The composite endpoint of MALE or death occurred in 237 patients (51%) at a median time of 189 days from index revascularization. In an adjusted Cox model, factors independently associated with MALE or death included younger age, ESRD, WIfI stage 4, higher GLASS stage, and moderate-severe pMAC, whereas AVB was associated with improved MALE-FS. Freedom from MALE-FS, MALE, and major amputation at 30 days were 90%, 92%, and 95%; and at 1 year were 63%, 70%, and 83%, respectively. MALE occurred in 144 patients (31%) and was associated with ESRD, WIfI stage, GLASS stage, pMAC score, and index revascularization approach. AVB had superior durability, with adjusted 2-year freedom from MALE of 72%, compared with 66% for ENDO and 51% for NAB. Within the AVB group, spliced vein conduit had higher MALE compared with single-segment vein (hazard ratio, 1.8; 95% confidence interval, 0.9-3.7; P = .008 after inverse propensity weighting), but there was no statistically significant difference in major amputation. Of the 144 patients with any MALE, the first MALE was major reintervention in 47% and major amputation in 53%. Major amputation as first MALE was associated with non-AVB index approach. Indications for major reintervention were symptomatic stenosis/occlusion (54%), lack of clinical improvement (28%), asymptomatic graft stenosis (16%), and iatrogenic events (3%). Conversion to bypass occurred after 6% of ENDO cases, two-thirds of which involved distal bypass targets at the ankle or foot. ConclusionsIn this consecutive, all-comers cohort, disease complexity was associated with procedural selection and MALE-FS. AVB independently provided the greatest MALE-FS and freedom from MALE and major amputation. Compared with the BEST-CLI randomized trial, MALE after ENDO in this series was more frequently major amputation, with relatively few conversions to open bypass.

Secondary interventions following open vs endovascular revascularization for chronic limb threatening ischemia in the BEST-CLI trial

ObjectivesPatients undergoing revascularization for chronic limb-threatening ischemia experience a high burden of target limb reinterventions. We analyzed data from the Best Endovascular versus Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI) randomized trial comparing initial open bypass (OPEN) and endovascular (ENDO) treatment strategies, with a focus on reintervention-related study endpoints. MethodsIn a planned secondary analysis, we examined the rates of major reintervention, any reintervention, and the composite of any reintervention, amputation, or death by intention-to-treat assignment in both trial cohorts (cohort 1 with suitable single-segment great saphenous vein [SSGSV], n = 1434; cohort 2 lacking suitable SSGSV, n = 396). We also compared the cumulative number of major and all index limb reinterventions over time. Comparisons between treatment arms within each cohort were made using univariable and multivariable Cox regression models. ResultsIn cohort 1, assignment to OPEN was associated with a significantly reduced hazard of a major limb reintervention (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.28-0.49; P < .001), any reintervention (HR, 0.63; 95% CI, 0.53-0.75; P < .001), or any reintervention, amputation, or death (HR, 0.68; 95% CI, 0.60-0.78; P < .001). Findings were similar in cohort 2 for major reintervention (HR, 0.53; 95% CI, 0.33-0.84; P = .007) or any reintervention (HR, 0.71; 95% CI, 0.52-0.98; P = .04). In both cohorts, early (30-day) limb reinterventions were notably higher for patients assigned to ENDO as compared with OPEN (14.7% vs 4.5% of cohort 1 subjects; 16.6% vs 5.6% of cohort 2 subjects). The mean number of major (mean events per subject ratio [MR], 0.45; 95% CI, 0.34-0.58; P < .001) or any target limb reinterventions (MR, 0.67; 95% CI, 0.57-0.80; P < .001) per year was significantly less in the OPEN arm of cohort 1. The mean number of reinterventions per limb salvaged per year was lower in the OPEN arm of cohort 1 (MR, 0.45; 95% CI, 0.35-0.57; P < .001 and MR, 0.66; 95% CI, 0.55-0.79; P < .001 for major and all, respectively). The majority of index limb reinterventions occurred during the first year following randomization, but events continued to accumulate over the duration of follow-up in the trial. ConclusionsReintervention is common following revascularization for chronic limb-threatening ischemia. Among patients deemed suitable for either approach, initial treatment with open bypass, particularly in patients with available SSGSV conduit, is associated with a significantly lower number of major and minor target limb reinterventions.

Comparison of direct oral anticoagulants and warfarin in chronic limb-threatening ischemia

ObjectiveThe role of direct oral anticoagulants (DOACs) in chronic limb-threatening ischemia after revascularization is unknown. Current evidence-based guidelines do not provide clear guidance on the role of anticoagulation or the selection of anticoagulant. Current practice is highly varied and based on provider and patient preference. The purpose of this study was to measure the impact of different anticoagulants on the incidence of major adverse limb events (MALEs) after revascularization for chronic limb-threatening ischemia, major adverse cardiovascular events (MACEs), all-cause mortality, and hospitalization for major bleeding events. MethodsThis was a single-center, observational, retrospective cohort study. Subjects were eligible if they were 18 years or older; underwent endovascular or open revascularization for chronic limb-threatening ischemia, rest pain, or tissue loss; and were subsequently prescribed apixaban, rivaroxaban, or warfarin. The primary end point was the incidence of MALEs, including above-ankle amputation or major index-limb reintervention, within 1 year of index event. Secondary end points included the rate of all-cause mortality, MACEs, and incidence of International Society on Thrombosis and Haemostasis (ISTH) major bleeding. ResultsFrom January 1, 2017, to September 20, 2022, 141 patients met the inclusion and exclusion criteria and were reviewed. The median age was 67 years, with 92 patients prescribed apixaban or rivaroxaban and 49 patients prescribed warfarin. Of these, 42 patients were prescribed triple antithrombotic therapy, 88 dual antithrombotic therapy, and 13 anticoagulant monotherapy. The primary outcome of 1-year MALEs occurred in 36.7% of the warfarin group and 33.7% of the DOAC group (relative risk [RR], 1.09; 95% CI, 0.53-2.25; P = .72). Secondary outcomes of 1-year MACEs (10.2% vs 4.3%; RR, 2.35; 95% CI, 0.60-9.18; P = .18) and 1-year all-cause mortality (26.5% vs 16.3%; RR, 1.63; 95% CI, 0.70-3.78; P = .15) did not differ between the groups. The secondary safety outcome of 1-year ISTH major bleeding occurred in 16.3% of the warfarin group and 4.3% of the DOAC group (RR, 3.76; 95% CI, 1.07-13.19; P = .015). ConclusionsIn patients with chronic limb-threatening ischemia who were revascularized and prescribed anticoagulation with apixaban, rivaroxaban, or warfarin on discharge, no difference in MALEs, MACEs, or all-cause mortality was found. However, 1-year admissions for ISTH major bleeding were significantly higher among patients prescribed warfarin. A randomized trial may confirm these findings.

Effect of health literacy and socioeconomic deprivation on outcomes after lower limb surgical revascularisation for chronic limb-threatening ischaemia: the HeaLTHI study

Introduction: Research has suggested a relationship between health literacy, socioeconomic status and health-related outcomes. The aim of the study was to study the association between health literacy, socioeconomic status and outcomes following infra-inguinal bypass surgery for chronic limb-threatening ischaemia (CLTI). Methods: Patients with CLTI undergoing lower limb surgical bypass graft operations between January 2016 and December 2018 were included in a cross-sectional observational study. The HLS19-Q12 questionnaire categorised participant’s health literacy as inadequate, problematic, sufficient or excellent. Socioeconomic status was assessed using the Index of Multiple Deprivation (IMD). Primary outcomes were major lower limb amputation (MLLA) and adverse cardiovascular events. Secondary outcomes included length of hospital stay, and early postoperative complications including pneumonia, surgical site and graft infection. Kaplan– Meier survival curves were used to compare health literacy and amputation, and Cox proportional regression analysis was conducted to identify differences in limb loss risk against health literacy and social deprivation levels. Results: The study consisted of 50 patients with an average age of 70±8.7 years. The participants' levels of health literacy were classified as inadequate (28%), problematic (38%), sufficient (24%) or excellent (10%). Approximately 40% of the patients lived in the most deprived areas. While all health literacy groups had similar postoperative outcomes, low health literacy was connected with lower socioeconomic status (r=0.308, p=0.029). IMD (p=0.017, HR 0.502 (95% CI 0.285 to 0.883)) and haemoglobin (p=0.001, HR 0.919 (95% CI 0.872 to 0.968)) were significant predictors of MLLA. Conclusion: Patients with lower health literacy are more likely to face higher levels of social deprivation, which may predict amputation following bypass surgery. Enhancing health literacy could play a role in reducing health disparities caused by social deprivation, thereby potentially addressing a vascular James Lind Alliance priority.

Minor amputation after revascularization in chronic limb-threatening ischemia: What is the optimal timing?

Patients with chronic limb-threatening ischemia (CLTI) have a high risk of lower limb amputation and loss of walking independence. Minor amputations play a key role in ensuring walking independence and they represent a challenge in terms of timing and level for vascular surgeons. A major cause of re-amputation is a defect in wound healing and a possible predictor of re-amputation for non-healing wounds could be the incorrect timing of minor amputation after revascularization. The lack of evidence in the literature leads to a wide variability of choices in clinical practice. The purpose of this study was to try to find the optimal timing analysing the risk of re-amputation in CLTI patients who have undergone successful revascularization and minor amputation focussing on timing of minor amputation. We conducted a single centre retrospective analysis on a cohort of 151 patients consecutively admitted to our hospital for CLTI (Rutherford 5) between January 2014 and April 2022. All the enrolled patients underwent successful revascularization of lower limbs and a minor amputation for dry acral necrosis. The characteristics of the patients and the revascularization procedures were collected and analysed. Patients were divided into two groups based on the timing of minor amputation performed before (group 1) or after the day (group 2) that best predicts the risk of re-amputation according to a Receiver Operating Characteristic (ROC) curve analysis. The primary outcome of this study was the risk of re-amputation during the first 60days of follow-up after a primary minor amputation, with revascularization still effective. The impact of the timing of minor amputation after revascularization, the type of revascularization and the presence of risk factors known to prolong the wound healing process were evaluated in a uni- and multi-variable logistic regression model. Systemic hypertension, and type of revascularization (i.e. open vs endovascular) were independent predictors of the risk of re-amputation at 60days (HR 4.26, 95% CI 1.30-14.04, p = .017 and HR 2.35, 95% CI 1.16-4.78, p = .018, respectively). Moreover, time ≤14days between revascularization and first amputation was associate with a clear, albeit not statistically significant, trend toward increased risk of re-amputation (HR 2.09, 95% CI 0.97-4.51, p = .06). In a cohort of patients who underwent a successful revascularization for CLTI and a minor amputation for dry gangrene in the first 14 days after revascularization, a higher -although not significant-risk of re-amputation was reported. In this cohort of patients, a delayed demolitive procedure should be considered to allow better tissue perfusion and to reduce the risk of re-amputation.

Perioperative complications following open or endovascular revascularization for chronic limb-threatening ischemia in the BEST-CLI Trial: Presented at the 2023 Vascular Annual Meeting of the Society for Vascular Surgery, National Harbor, MD, June 14-17, 2023.

Perioperative complications following open or endovascular revascularization for chronic limb-threatening ischemia in the BEST-CLI Trial: Presented at the 2023 Vascular Annual Meeting of the Society for Vascular Surgery, National Harbor, MD, June 14-17, 2023.

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

ObjectiveThe 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. MethodsA 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. ResultsThere 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). ConclusionsPedal 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.

Perioperative complications following open or endovascular revascularization for chronic limb-threatening ischemia in the BEST-CLI Trial

ObjectiveAnticipated perioperative morbidity is an important factor for choosing a revascularization method for chronic limb-threatening ischemia (CLTI). Our goal was to assess systemic perioperative complications of patients treated with surgical and endovascular revascularization in the Best Endovascular vs Best Surgical Therapy in Patients with CLTI (BEST-CLI) trial. MethodsBEST-CLI was a prospective randomized trial comparing open (OPEN) and endovascular (ENDO) revascularization strategies for patients with CLTI. Two parallel cohorts were studied: Cohort 1 included patients with adequate single-segment great saphenous vein (SSGSV), whereas Cohort 2 included those without SSGSV. Data were queried for major adverse cardiovascular events (MACE–composite myocardial infarction, stroke, death), non-serious (non-SAEs) and serious adverse events (SAEs) (criteria–death/life-threatening/requiring hospitalization or prolongation of hospitalization/significant disability/incapacitation/affecting subject safety in trial) 30 days after the procedure. Per protocol analysis was used (intervention received without crossover), and risk-adjusted analysis was performed. ResultsThere were 1367 patients (662 OPEN, 705 ENDO) in Cohort 1 and 379 patients (188 OPEN, 191 ENDO) in Cohort 2. Thirty-day mortality in Cohort 1 was 1.5% (OPEN 1.8%; ENDO 1.3%) and in Cohort 2 was 1.3% (2.7% OPEN; 0% ENDO). MACE in Cohort 1 was 4.7% for OPEN vs 3.13% for ENDO (P = .14), and in Cohort 2, was 4.28% for OPEN and 1.05% for ENDO (P = .15). On risk-adjusted analysis, there was no difference in 30-day MACE for OPEN vs ENDO for Cohort 1 (hazard ratio [HR] 1.5; 95% confidence interval [CI], 0.85-2.64; P = .16) or Cohort 2 (HR, 2.17; 95% CI, 0.48-9.88; P = .31). The incidence of acute renal failure was similar across interventions; in Cohort 1 it was 3.6% for OPEN vs 2.1% for ENDO (HR, 1.6; 95% CI, 0.85-3.12; P = .14), and in Cohort 2, it was 4.2% OPEN vs 1.6% ENDO (HR, 2.86; 95% CI, 0.75-10.8; P = .12). The occurrence of venous thromboembolism was low overall and was similar between groups in Cohort 1 (OPEN 0.9%; ENDO 0.4%) and Cohort 2 (OPEN 0.5%; ENDO 0%). Rates of any non-SAEs in Cohort 1 were 23.4% in OPEN and 17.9% in ENDO (P = .013); in Cohort 2, they were 21.8% for OPEN and 19.9% for ENDO (P = .7). Rates for any SAEs in Cohort 1 were 35.3% for OPEN and 31.6% for ENDO (P = .15); in Cohort 2, they were 25.5% for OPEN and 23.6% for ENDO (P = .72). The most common types of non-SAEs and SAEs were infection, procedural complications, and cardiovascular events. ConclusionsIn BEST-CLI, patients with CLTI who were deemed suitable candidates for open lower extremity bypass surgery had similar peri-procedural complications following either OPEN or ENDO revascularization: In such patients, concern about risk of peri-procedure complications should not be a deterrent in deciding revascularization strategy. Rather, other factors, including effectiveness in restoring perfusion and patient preference, are more relevant.

Secondary Interventions Following Open vs Endovascular Revascularization for Chronic Limb-threatening Ischemia in the BEST-CLI Trial

Patients undergoing revascularization for chronic limb-threatening ischemia experience a high burden of target limb reinterventions. We analyzed data from the BEST-CLI randomized trial comparing initial open and endovascular treatment strategies, with a focus on reintervention related study end points. In a planned secondary analysis from the BEST-CLI trial we examined the rates of major reintervention, any reintervention, and the composite of any reintervention, amputation or death (RAD) by intention-to-treat (ITT) assignment in both trial cohorts (cohort 1 with suitable single segment great saphenous vein [SSGSV], n = 1434; cohort 2 lacking suitable SSGSV, n = 396). We also compared the cumulative number of major and any reintervention over time. Comparisons between treatment arms within each cohort were made using a stratified Cox model adjusted for prespecified baseline covariates (end-stage renal disease, prior index limb revascularization, smoking, diabetes, age >80, WIfi stage, tissue loss, and significant infrapopliteal disease). In cohort 1, assignment to initial open treatment was associated with a significantly reduced incidence of a major limb reintervention (hazard ratio [HR], 0.35; 95% confidence interval, 0.27-0.47; P < .001), any reintervention (HR, 0.63; 95% CI, 0.53-0.75; P < .001), or RAD (HR, 0.69; 95% CI, 0.60-0.79; P < .001) (Fig 1). Findings were similar in cohort 2 for major reintervention (HR, 0.47; 95% CI, 0.29,0.76; P = .002) or any reintervention (HR, 0.68; 95% CI, 0.49, 0.95; P = .02). In both cohorts, early (30-day) limb reinterventions were notably higher for patients assigned to endovascular intervention as compared to open (15% vs 4.5% of cohort 1 subjects; 16.9% vs 5.8% of cohort 2 subjects). The cumulative incidence rate (IR) of major (IR, 0.50; 95% CI, 0.37-0.67; P < .001) (Fig 2) or any reinterventions (IR, 0.66; 95% CI, 0.54-0.81; P < .001) over time was significantly less in the open group of cohort 1. Rates of reintervention per limb salvaged were notably lower in the open arms of both study cohorts (IR 0.48 for both; P < .001 and P = .03, respectively). The majority of target limb reinterventions occurred over the first year following randomization, but events continued to accumulate over the duration of follow-up in the trial. Reintervention is common following revascularization for chronic limb-threatening ischemia. Initial treatment with open bypass, particularly in patients with an available SSGSV conduit, is associated with a significantly lower burden of major and minor target limb reinterventions.Fig 2Total number of cumulative major reinterventions by intention to treat (ITT), cohort 1.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The Impact of Revascularization Strategy on Clinical Failure, Hemodynamic Failure, and Chronic Limb-Threatening Ischemia Symptoms in the BEST-CLI Trial

Sustained clinical and hemodynamic benefit following revascularization for chronic limb-threatening ischemia (CLTI) is needed to resolve symptoms and prevent limb loss. We sought to compare rates of clinical and hemodynamic failure as well as resolution of initial and prevention of recurrent CLTI following endovascular vs bypass (OPEN) revascularization in the BEST-CLI trial. As planned secondary analyses of the BEST-CLI trial, we examined the rates of (A) clinical failure (a composite of all cause death, above ankle amputation, major reintervention, and degradation of WIfI stage); (B) hemodynamic failure (a composite of above ankle amputation, major and minor reintervention to maintain index limb patency, failure to initially increase or a subsequent decrease in ankle-brachial index of 0.15 or toe-brachial index of 0.10, and radiographic evidence of treatment stenosis or occlusion); (C) time to resolution of presenting CLTI symptoms; and (D) incidence of recurrent CLTI. Time-to-event analyses were by intention-to-treat assignment in both trial cohorts (cohort 1: suitable single segment great saphenous vein, n = 1434; cohort 2: lacking suitable single segment great saphenous vein, n = 396) and multivariate stratified Cox regression models were created. In cohort 1, there was a significant difference in time to clinical failure (Figure; log-rank P < .001), hemodynamic failure (log-rank P < .001), and resolution of presenting symptoms (log-rank P = .009) in favor of OPEN. In cohort 2, there was a significantly lower rate of hemodynamic failure (log-rank P = .006) favoring OPEN, and no significant difference in time to clinical failure or resolution of presenting symptoms. Multivariate analysis revealed that assignment to OPEN was associated with significantly lower risk of clinical and hemodynamic failure in both cohorts, and a significantly higher likelihood of resolving initial and preventing recurrent CLTI symptoms in cohort 1 (Table), including after adjustment for key baseline patient covariates (end stage renal disease [ESRD], prior revascularization, smoking, diabetes, age >80, WIfI stage, tissue loss, infrapopliteal disease). Factors independently associated with clinical failure included age >80 in cohort 1 and ESRD across both cohorts. ESRD was associated with hemodynamic failure in cohort 1. Factors associated with slower resolution of presenting symptoms included diabetes in cohort 1 and WIfI stage in cohort 2. Durable clinical and hemodynamic benefit following revascularization for CLTI is important to avoid persistent and recurrent CLTI, reinterventions and limb loss. Initial treatment with open surgical bypass, particularly with available saphenous vein, is associated with improved clinical and hemodynamic outcomes and enhanced resolution of CLTI symptoms.TableIncidence of clinical failure, hemodynamic failure, resolution of initial chronic limb-threatening ischemia (CLTI), and development of recurrent CLTIParameterCohort 1Cohort 2Open, n = 603, No. (%w event)Endovascular, n = 617, No. (%w event)Hazard ratio (95% confidence interval)P valueOpen, n = 171, No. (%w event)Endovascular, n = 173, No. (%w event)Hazard ratio (95% confidence interval)P valueClinical failure303 (50.25)419 (67.91)0.65 (0.56-0.76)<.00181 (47.37)104 (60.12)0.67 (0.50-0.90).009Hemodynamic failure377 (62.52)464 (75.20)0.71 (0.62-0.82)<.001112 (65.50)130 (75.14)0.65 (0.50-0.84).001Initial CLTI resolution514 (85.24)514 (83.31)1.22 (1.08-1.38).002142 (83.04)140 (80.92)1.08 (0.84-1.38).54Recurrent CLTI253 (0.15)a323 (0.18)a0.81b (0.68-0.95).0176 (0.23)a83 (0.23)a0.91b (0.67-1.25).57a Person-years of follow-up incidence rate.bIncidence rate ratio. Open table in a new tab

Patients Residing Afar From Tertiary Care Center Are More Likely to Receive Lower Extremity Revascularization for Chronic Limb-Threatening Ischemia: A Relationship Between the Distance From Hospital and Clinical Severity of Peripheral Arterial Disease

This study aimed to assess the association between the proximity to the hospital and the severity of peripheral arterial disease at the time of infrainguinal lower extremity bypass (LEB) in a rural-urban mixed region. Medical records of patients undergoing LEB from 2010 to 2020 at Penn State Milton S. Hershey Medical Center were reviewed and stratified into two study groups based on the median distance of their residence from the hospital (group I: ≥34 miles and group II: <34 miles). Patients’ demographic features, preoperative data including comorbidities, the severity of peripheral arterial disease (PAD), and medications were analyzed. Univariate analysis for the patient characteristics between the two study groups, evaluation of postoperative outcomes, and multivariate predictive modeling to study the PAD stage as the indication of LEB were performed. A P value of <.05 was set as a significant difference between the groups for all the analyses. A total of 351 patients met the inclusion criteria for this study. There were 175 (49.9%) patients in group I and 176 (50.1%) patients in group II, with a mean age of 65 ± 11.92 years (median: 64.61 years). No significant difference was observed in gender (P = .530), age (P = .906), and functional status (P = .830) between the study groups. It was observed that patients in group I were more overweight or obese (71.3% vs 57%, P = .007) and had a prior history of myocardial infarction (24.3% vs 15.3%, P = .036) compared with those in group II. No postoperative outcomes were found to be statistically different between the study groups. The multivariate analyses based on various confounders displayed that patients in group I were less likely to be treated for life-limiting claudication (adjusted odds ratio [AOR]: 0.36 [0.20-0.65]; P = .001) and had a 56% higher likelihood of LEB for chronic limb-threatening ischemia (AOR: 1.56 [0.92-2.62]; P = .042). Group I patients also had five times higher odds of LEB for acute limb ischemia (AOR: 5.07 [1.42-18.13]; P = .012). The Fig shows the distribution of patients by indication of LEB and patient’s residence in a zip code. Patient proximity to a major tertiary hospital may have implications for the disease progression of patients with PAD. It could be related to inadequate vascular services in primary and secondary hospitals. The lack of preventive care and disease management in regions afar from a tertiary hospital could be other factors. This highlights the need for vascular surgery outreach programs and the distribution of vascular specialists to reduce geographical disparities and ensure equity in access to care.

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

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. 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. 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±2.40years. 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). 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.

Pedal Arterial Calcification Is Associated With Progression From Transmetatarsal Amputation To Major Amputation Following Infrainguinal Revascularization For Chronic Limb-threatening Ischemia

The pedal medial arterial calcification (pMAC) score is associated with lack of hemodynamic improvement and major amputation despite technically successful infrainguinal revascularization for CLTI. We hypothesize that after transmetatarsal amputation (TMA) for limb salvage, severe pedal calcification burden is associated with progression to major amputation.