Revascularization For Chronic Limb-threatening Ischemia Research Articles

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.

The role of Braden scores in predicting outcomes following revascularisation for chronic limb-threatening ischaemia and their association with frailty

Introduction: Chronic limb-threatening ischaemia (CLTI) is a substantial healthcare burden associated with high rates of amputation, morbidity and mortality. Frailty measures have proved to be an asset in risk prediction but are not routinely universally collated. This study aimed to identify the utility of Braden scores, an assessment tool for pressure ulceration, as a prognostic indicator for patients with CLTI undergoing revascularisation. Methods: This is a retrospective study of a prospectively maintained database of all patients with CLTI who underwent lower limb revascularisation bypass surgery between 2016 and 2018 in the Northern Vascular Centre, Freeman Hospital, Newcastle upon Tyne, UK. Their Braden scores were obtained and their electronic Frailty Index (eFI) calculated. Patients were divided into subgroups for each scoring system and their post-revascularisation outcomes were compared. This allowed us to identify the ability of these scoring systems to predict outcomes. Results: Eighty-seven of 124 CLTI patients undergoing lower limb revascularisation bypass surgery had their Braden scores calculated. Nineteen patients (22%) had Braden scores &lt;18 (high risk for ulceration) with a higher risk of baseline sarcopenia (32% vs 12%, p=0.04, OR 1.4, CI 0.48 to 4.53), major amputation (53% vs 28%, p=0.04, OR 1.2, CI 0.48 to 3.02), longer hospital stay (median 33 vs 14 days, p=0.04) and overall complications of pneumonia, myocardial ischaemia and wound infection (58% vs 31%, p=0.035, OR 1.8, CI 0.59 to 5.53) considered as composite factors. These patients also had worse overall survival according to Kaplan–Meier analysis (p&lt;0.001), and the Braden scores were independently associated with death (hazard risk 1.157, CI 0.67 to 1.92; p=0.01). Braden scores were negatively correlated with an increasing eFI (p=0.016). Conclusion: Braden scores appear to be a promising prognostic indicator of adverse outcomes in patients with CLTI undergoing revascularisation surgery. Additionally, Braden scores may also be a surrogate marker of frailty. Further larger studies are required for the validation of Braden scores and their roles in improving outcomes of CLTI intervention.

Presenting limb severity is associated with long-term outcomes after infrainguinal revascularization for chronic limb-threatening ischemia

ObjectiveThe SVS Wound, Ischemia, foot Infection (WIfI) limb staging system was established to estimate risk of major amputation in chronic limb-threatening ischemia (CLTI) and better stratify outcomes comparisons. There is little data on treatment outcomes beyond 1 year based on presenting WIfI stage. MethodsThis is a single-institution retrospective study of 413 patients who underwent infrainguinal revascularization for CLTI (2011-2021) with data available for WIfI staging. Patient characteristics and outcomes were gathered from the electronic medical record. Data were analyzed based on presenting WIfI stage and initial treatment received at our center. ResultsPresenting WIfI stages were 1 to 2 (23%), 3 (27%), and 4 (50%). Index revascularization approach was endoluminal (59%), autogenous vein bypass (29%), or non-autogenous bypass (13%). Operative mortality within 30 days was 2.9% and was not associated with WIfI stage or revascularization approach. Median limb follow-up time was 502 days (interquartile range [IQR], 112-1256 days), and median survival follow-up time was 932 days (IQR, 343-1770 days). Major amputation or death occurred in 19% and 46% of patients at median times of 119 days (IQR, 28-314 days) and 739 days (IQR, 204-1475 days), respectively. WIfI stage was independently associated with major amputation (P = .001), as was initial revascularization approach (P = .01). In a Cox proportional hazards model, factors independently associated with major amputation were male sex (hazard ratio [HR], 1.4; 95% confidence interval [CI], 1.04-2.0; P = .03), diabetes (HR, 1.8; 95% CI, 1.3-2.5; P = .001), WIfI stage 4 (HR, 2.3; 95% CI, 1.5-3.5; P < .001), and non-autogenous bypass (HR, 2.9; 95% CI, 2.1-4.2; P < .001). In a Cox proportional hazards model for mortality, independently associated factors were age (HR, 1.04; 95% CI, 1.02-1.05; P < .001), end-stage renal disease (HR, 2.8; 95% CI, 1.9-4.0; P < .001), congestive heart failure (HR, 1.9; 95% CI, 1.4-2.5; P < .001), chronic obstructive pulmonary disease (HR, 1.5; 95% CI, 1.1-2.1; P = .02), and WIfI stage 4 (HR, 1.6; 95% CI, 1.04-2.2; P = .03). Among those presenting with WIfI stage 4 limbs, Kaplan-Meier estimated rates of freedom from major amputation or death at 2 years were 71% ± 3.7% and 68% ± 3.5%, respectively. In an inverse propensity weighted Cox proportional hazards model, non-white race (HR, 1.5; 95% CI, 1.01-2.2; P = .047), diabetes (HR, 2.0; 95% CI, 1.2-3.3; P = .008), Global Anatomic Staging System infrapopliteal grade (HR, 1.2; 95% CI, 1.05-1.3; P = .005), non-autogenous bypass (HR, 3.2; 95% CI, 1.9-5.3; P < .001), and endoluminal revascularization (HR, 2.6; 95% CI, 1.6-4.3; P < .001) were independently associated with major amputation in the WIfI stage 4 subgroup. ConclusionsPresenting WIfI stage is strongly associated with long-term risks of major amputation and death following infrainguinal revascularization for CLTI and should be used to stratify outcomes comparisons. Effective revascularization is critical in WIfI stage 4 disease, and autogenous vein bypass provides durable long-term limb preservation.

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

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

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

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

Wound Healing on the Cutting Plane of Ankle Bones after Incomplete Revascularization for Chronic Limb-Threatening Ischemia in an Elderly Patient: A Case Report.

Chronic limb-threatening ischemia (CLTI) is an important issue for elderly patients with peripheral artery disease. Here, we present the case of a 91-year-old man with CLTI, residing in a rural district. The onset of CLTI rapidly deprived him of ambulation because of a foot infection. Given that he had difficulty with long-distance transportation, limb salvage for extensive tissue loss was performed at a district facility, based on his and his family’s request. Finally, skin grafting on the cutting plane of the right ankle bones resulted in wound healing in six months after incomplete revascularization and multiple minor amputations.

Severe Inframalleolar Disease is an Independent Predictor of Adverse Limb Outcomes After Revascularization in Patients With Chronic Limb-threatening Ischemia

In the present study, we evaluated the impact of inframalleolar disease (IM) on major adverse limb events (MALE) in patients undergoing endovascular revascularization for chronic limb-threatening ischemia (CLTI).

Efficacy of Early Closed Toe Amputation for Toe Ulcers with Suspected Osteomyelitis after Revascularization for Chronic Limb-Threatening Ischemia.

Objective: In this study, we aim to evaluate the efficacy of early closed toe amputation on the wound management of toe ulcers with suspected osteomyelitis after revascularization for chronic limb-threatening ischemia (CLTI).Methods: This retrospective study included patients who have underwent revascularization for toe ulcers associated with CLTI at Shizuoka Red Cross Hospital from 2015 to 2021. Wound management comprised early closed toe amputation for toe ulcers with suspected osteomyelitis (19 toes in 17 patients) or conservative treatment (35 toes in 26 patients). The primary endpoint was wound healing after revascularization. We compared the wound healing rate at 90 days and median healing time of early closed toe amputation versus conservative treatment.Results: Compared with the conservative treatment, early closed toe amputation was able to achieve a better wound healing rate at 90 days (89.5% vs. 68.6%; P<0.01) and a shorter median healing time (19 days vs. 62 days; P=0.01).Conclusion: There remains no established wound management for toe lesions associated with CLTI. Despite its several disadvantages including wound infection and possible foot deformity, early closed toe amputation for toe ulcers with suspected osteomyelitis can be considered a safe approach in terms of wound management.

Limb-based patency as a measure of effective revascularization for chronic limb-threatening ischemia

ObjectiveIn 2019, the Global Vascular Guidelines on chronic limb-threatening ischemia (CLTI) introduced the concept of limb-based patency (LBP) defined as maintained patency of a target artery pathway after intervention. The purpose of this study was to investigate the relationship between LBP and major adverse limb events (MALE) after infrainguinal revascularization for CLTI. MethodsConsecutive patients undergoing revascularization for CLTI between 2016 and 2019 at a single tertiary institution with a dedicated limb preservation team were included. Subjects with aortoiliac disease, prior infrainguinal stents, or existing bypass grafts were excluded. Demographics, Global Limb Anatomic Staging System scores, Wound, Ischemia, foot Infection (WIfI) stages, revascularization details, and limb-specific outcomes were reviewed. LBP was defined by the absence of reintervention, occlusion, critical stenosis (>70%), or hemodynamic compromise with ongoing symptoms of CLTI. MALE included thrombectomy or thrombolysis, new bypass, open surgical graft revision and/or major amputation. ResultsWe analyzed 184 unique limbs in 163 patients. This cohort was composed of 66.9% male patients with a mean age of 72 years. Baseline characteristics included diabetes (66%), tissue loss (91%), and advanced WIfI stages (30% stage 3, 51% stage 4). Global Limb Anatomic Staging System stage 3 anatomic patterns were common (n = 119 [65%]). Sixty limbs were treated with open bypass (65% involving tibial targets) and 124 underwent endovascular intervention (70% including infrapopliteal targets). The 12-month freedom from MALE and loss of LBP were 74.0% ± 3.7% and 48.6% ± 4.2%, respectively. Diabetes (hazard ratio [HR], 2.56; 95% confidence interval [CI], 1.13-5.83; P = .025) and loss of LBP (HR, 4.12; 95% CI, 1.96-8.64; P < .001) were independent predictors of MALE in a Cox proportional hazard model. Loss of LBP was the sole independent predictor of major limb amputation after revascularization (HR, 4.97; 95% CI, 1.89-13.09; P = .001). Loss of LBP impacted both intermediate-risk limbs (HR, 2.85; 95% CI, 1.02-7.97; P = .047 in WIfI stages 1-3) and high-risk limbs (HR, 3.99; 95% CI, 1.32-12.11; P = .014 in WIfI stage 4). However, the loss of LBP had the greatest impact on patients presenting with WIfI stage 4 disease (31% vs 8% major limb amputation at 12 months in limbs without vs with maintained LBP). ConclusionsThe anatomic durability of revascularization, as measured by LBP, is a key determinant of treatment outcomes in CLTI regardless of the initial mode of intervention undertaken. Loss of LBP is most detrimental in patients presenting with advanced limb threat (WIfI stage 4).

WIfI Staging and Long-term Outcomes After Infrainguinal Revascularization for Chronic Limb-threatening Ischemia

The Society for Vascular Surgery wound, ischemia, foot infection (WIfI) limb staging system was established to estimate risk of major amputation in chronic limb-threatening ischemia (CLTI) and to better stratify outcomes comparisons. There is little data on treatment outcomes beyond 1 year based on presenting WIfI stage.

Racial and Ethnic Disparities in Long-term Outcomes After Open Revascularization for Chronic Limb-Threatening Ischemia

Black and Hispanic patients have higher rates of chronic limb-threatening ischemia (CLTI) and suffer worse perioperative outcomes after lower extremity bypass compared with White patients. The underlying reasons for these disparities are unclear, and data on long-term outcomes are limited. Therefore, we examined differences in 3-year outcomes after open infrainguinal revascularization for CLTI by race and ethnicity and explored potential factors contributing to these differences.

Applicability of the Vascular Quality Initiative mortality prediction model for infrainguinal revascularization in a tertiary limb preservation center population

ObjectivePatients undergoing revascularization for chronic limb-threatening ischemia (CLTI) are at elevated risk for both mortality and limb loss. To facilitate therapeutic decision-making, a mortality prediction model derived from the Vascular Quality Initiative (VQI) database has stratified patients into low, medium, and high risk, defined by 30-day mortality estimates of ≤3%, 3%-5%, or >5% and 2-year mortality estimates of ≤30%, 30%-50%, or ≥50%, respectively. The purpose of this study was to compare expected mortality risk derived from this model with observed outcomes in a tertiary center. MethodsConsecutive patients treated at a single center between 2016 and 2019 were analyzed. Baseline demographics, approach, and mortality events were reviewed. Observed mortality was obtained using life-table methods and compared using a log-rank test with the expected mortality risk that was calculated using the VQI model. ResultsThis study cohort consisted of 195 revascularization procedures in 169 unique patients stratified into 128 (66%) low-, 50 (26%) medium-, and 17 (8%) high-risk cases based on the VQI model. Ninety percent of revascularizations were performed for tissue loss. Compared with the VQI population, comorbidities were prevalent and included unstable angina or myocardial infarction within 6 months (6% vs 2.4% in VQI; P < .001), congestive heart failure (30% vs 23%; P < .001), and dialysis dependence (14% vs 0.9%; P < .001). Patients were also older (31% vs 21% ≥80 years old; P < .001) and more likely to be frail (45% vs 64% independent; P < .001). High-risk patients were more prevalent in the endovascular group (11% of 132 endovascular interventions vs 3% of 63 bypasses; P = .056). Thirty-day observed mortality exceeded expected VQI prediction model mortality in all groups, although was not statistically significant. The VQI model adequately stratified the studied population into risk groups (P < .001). Low-risk patients with CLTI (65% of the overall cohort) experienced 2-year mortality of 18.9%. However, observed mortality rates for medium- and high-risk VQI strata were similar. After a median follow-up of 28 months, medium-risk patients incurred a significantly higher mortality than predicted (53.5% ± 2.1% vs 36.8% ± 1.1%; P = .016). ConclusionsThe VQI mortality prediction model discriminates mortality risk after limb revascularization in CLTI, accurately identifying a majority subgroup of patients who are suitable for either open or endovascular intervention. However, it may underestimate mortality in a tertiary referral population with high comorbidity burden and was not well calibrated for the medium-risk group. It may be more appropriate to dichotomize patients with CLTI who are candidates for limb salvage into an average-risk and high-risk group.

Contemporary outcomes of limb-salvage procedures using Vascular Quality Initiative–Medicare-linked data: Racial and ethnic disparities persist

BackgroundSeveral reports have shown that ethnic and racial minority patients with chronic limb-threatening ischemia (CLTI) are more likely to undergo major amputation. Whether this disparity is driven by limited access to care, statistical discrimination, or biologic factors has remained a matter of debate. We studied the effects of race and ethnicity on the short- and long-term outcomes of limb-salvage procedures among patients with new-onset CLTI. MethodsWe identified all patients who had undergone first time (open or endovascular) revascularization for CLTI between January 2010 and December 2016 in the Vascular Quality Initiative–Medicare-linked database. These patients were divided into two groups: non-Hispanic White (NHW) and racial and ethnic minority (REM). The early end points included length of stay and operative mortality. The 2-year outcomes included major amputation, freedom from subsequent revascularization, number of limb salvage reinterventions, and all-cause mortality. Subanalyses comparing NHW and Hispanic patients and NHW and Black patients were also performed. ResultsOf 16,249 patients presenting with CLTI, 73.9% were NHW. The REM patients were younger (mean age, 69.9 ± 11.3 years vs 74.2 ± 10.5 years; P < .001) and more likely to be women (45.9% vs 37.7%; P < .001). Other baseline differences included a higher rate of smoking history, coronary artery disease, chronic obstructive pulmonary disease, and chronic kidney disease for the NHW group. In contrast, the REM patients were more likely to have diabetes and hypertension and were more likely to present with tissue loss (78% vs 76.6%; P = .04). The preoperative ankle brachial index and procedure type (endovascular vs open) were similar between the two groups. On multivariable analysis, the NHW group had had a 13% increase in the length of stay and a 25% decrease in operative mortality. Of the 2-year outcomes, the limb salvage estimate was 86% for the NHW group and 77.1% for the REM group (P < .001). A comparison between the two groups showed similar rates of freedom from subsequent revascularization (67.9% vs 67.1%; P =.2). The REM patients had had higher rates of overall survival (70.3% vs 68.4%; P = .01) compared with their NHW counterparts. The patients in the REM group were also more likely to have undergone more than two limb salvage reinterventions during follow-up (14.2% vs 8.6%; P < .001). After adjusting for potential confounders, the REM patients had significantly greater odds of major amputation at 2 years (adjusted hazard ratio, 1.49; 95% confidence interval, 1.36-1.63; P < .001). ConclusionsThe results from the present Vascular Quality Initiative–Medicare-matched study have shown that REM patients continue to face a higher major amputation risk despite equivalent attempts at limb salvage. Further studies to identify the risk factors and evaluate intervention strategies that might be more effective in preventing amputation in this particular population are warranted.

Two-year clinical outcomes following lower limb endovascular revascularisation for chronic limb-threatening ischaemia at a tertiary Asian vascular centre in Singapore.

Percutaneous transluminal angioplasty (PTA) is commonly used to treat patients with chronic limb-threatening ischaemia (CLTI). This study aimed to examine the mortality and functional outcomes of patients with CLTI who predominantly had diabetes mellitus in a multi-ethnic Asian population in Singapore. Patients with CLTI who underwent PTA between January 2015 and March 2017 at the Vascular Unit at Singapore General Hospital, Singapore, were studied. Primary outcome measures were 30-day unplanned readmission, two-year major lower extremity amputation (LEA), mortality rates, and ambulation status at one, six and 12 months. A total of 221 procedures were performed on 207 patients, of whom 184 (88.9%) were diabetics. The one-, six- and 12-month mortality rate was 7.7%, 16.4% and 21.7%, respectively. The two-year LEA rate was 30.0%. At six and 12 months, only 96 (46.4%) and 93 (44.9%) patients were ambulant, respectively. Multivariate analysis revealed that preoperative ambulatory status, haemoglobin, Wound Ischaemia and foot Infection (WIfI) score, and end-stage renal failure (ESRF) were independent predictors of one-year ambulatory status. Predictors of mortality at one, six and 12 months were ESRF, preoperative albumin level, impaired functional status and employment status. PTA for CLTI was associated with low one-year mortality and two-year LEA rates but did not significantly improve ambulation status. ESRF and hypoalbuminaemia were independent predictors of mortality. ESRF/CKD and WIfI score were independent predictors of loss of ambulation at six months and one year. We need better risk stratification for patients with CLTI to decide between initial revascularisation and an immediate LEA policy.

Effect of postoperative antithrombotic therapy on lower extremity outcomes after infrapopliteal bypass for chronic limb-threatening ischemia

ObjectiveAlthough the current guidelines have recommended single antiplatelet therapy (SAPT) for patients undergoing revascularization for chronic limb-threatening ischemia (CLTI), antithrombotic management has varied by patient and provider. Our aim was to examine the effects of different postoperative antithrombotic regimens on 3-year clinical outcomes after infrapopliteal bypass for CLTI. MethodsWe identified patients who had undergone infrapopliteal bypass for CLTI in the Vascular Quality Initiative (VQI) registry from 2003 to 2017 with linkage to Medicare claims for long-term outcomes. We divided the patients into three cohorts according to the discharge antithrombotic regimen: SAPT (aspirin or clopidogrel), dual antiplatelet therapy (DAPT; aspirin and clopidogrel), or anticoagulation (AC) plus any antiplatelet (AP) agent. To reduce selection bias, we restricted the analysis cohorts to patients treated by providers who discharged >50% of patients with each antithrombotic regimen. Our primary outcome was 3-year major adverse limb events (MALE; major amputation or reintervention). The secondary outcomes included 3-year major amputation, reintervention, and mortality. We used Kaplan-Meier and Cox regression analyses to assess these outcomes stratified by antithrombotic regimen and adjusted for demographic, comorbid, clinical, and operative differences between the treatment groups with clustering at the center level. ResultsAmong 1812 patients (median follow-up, >2 years), 693 (38%) were discharged with SAPT, 544 (30%) with DAPT, and 575 (32%) with AC+AP. At 3 years, the MALE rates were 75% with DAPT, 74% with AC+AP, and 68% with SAPT. In adjusted analyses with SAPT as the reference group, no differences were found in 3-year MALE with DAPT (adjusted hazard ratio [aHR], 1.0; 95% confidence interval [CI], 0.85-1.3; P = .71) or AC+AP (aHR, 1.1; 95% CI, 0.96-1.3; P = .14). Across the treatment groups, we also found no differences in the individual end points of 3-year major amputation (DAPT: aHR, 0.98; 95% CI, 0.72-1.3; AC+AP: aHR, 1.3; 95% CI, 0.96-1.7), reintervention (DAPT: aHR, 1.0; 95% CI, 0.84-1.3; AC+AP: aHR, 1.1; 95% CI, 0.96-1.3), or mortality (DAPT: aHR, 1.1; 95% CI, 0.88-1.4; AC+AP: aHR, 0.95; 95% CI, 0.74-1.2). In a sensitivity analysis evaluating patients treated by providers who discharged >60%, >70%, or >80% of patients with these regimens, the association between antithrombotic regimen and MALE was unchanged. ConclusionsCompared with SAPT, DAPT and anticoagulation therapy were not associated with improved outcomes among Medicare beneficiaries who had undergone infrapopliteal bypass for CLTI at VQI participating centers. These findings support current guidelines recommending SAPT after lower extremity bypass and suggest that the routine use of DAPT or anticoagulation therapy might not provide clinical benefit in this high-risk, elderly population. However, further evaluation of the risks and benefits of various antithrombotic regimens in relevant subgroups is warranted.