Major Adverse Limb Events Research Articles

High-Dose Drug-Coated Balloon Versus Polymer-Based Drug-Eluting Stent for Femoropopliteal Artery Disease Treatment.

Clinical trials have demonstrated that high-dose drug-coated balloon (HD-DCB) and polymer-based drug-eluting stent (PB-DES) treatments for femoropopliteal (FP) artery disease have favorable outcomes. However, which one would be better remained unrevealed. This study used the databases of 2 large-scale multicenter prospective drug-coated balloon (DCB) and drug-eluting stent (DES) registries. The study included 2470 patients with symptomatic FP lesion treated with IN.PACT Admiral DCB or Eluvia DES at 69 centers. A propensity-score-based paired analysis was conducted. Primary endpoint was 1-year restenosis rate. Secondary endpoints were 1-year reocclusion rate, target lesion revascularization (TLR), acute thrombosis, bypass conversion, major amputation, major adverse limb event (MALE), and all-cause death. A total of 1535 patients were treated with HD-DCB, and 935 patients were treated with PB-DES. The propensity-score matching extracted 678 pairs, with no remarkable intergroup difference in baseline characteristics. The 1-year restenosis rate was significantly lower in the PB-DES group than in the HD-DCB group (16.0% vs 22.0%, p=0.016). The other endpoints (reocclusion rate, TLR, acute thrombosis, bypass conversion, major amputation, MALE, and all-cause death) did not differ between the groups. No baseline characteristics had any significant interaction effect on the association of HD-DCB vs PB-DES with restenosis risk (all p>0.05). This study demonstrated that the 1-year TLR, reocclusion rate, and other endpoints did not differ between the PB-DES group and the HD-DCB group despite the lower restenosis in the PB-DES group. One-year restenosis rate was significantly lower in the polymer-based DES group than in the high-dose DCB group for foemoropopliteal disease. However, there is no difference in the other endpoints between two groups.

Blood Hemoglobin Concentrations and the Incidence of Lower Extremity Peripheral Arterial Disease in Patients Undergoing Hemodialysis: 10-Year Outcomes of the Q-Cohort Study.

Lower extremity peripheral arterial disease is a potentially lethal cardiovascular complication in patients undergoing hemodialysis. Anemia is a risk factor for cardiovascular disease among the hemodialysis population. However, whether blood hemoglobin concentration is associated with the risk of peripheral arterial disease progression in this population remains undetermined. This is an extension of a 4-year multicenter, prospective, observational cohort study to 10 years. A total of 3504 Japanese patients undergoing maintenance hemodialysis were recruited between 2006 and 2007. The primary exposure was blood hemoglobin concentration at baseline. The main outcome was the first-ever incidence of major adverse limb events (MALE), composed of endovascular treatment, bypass surgery, and amputation. Multivariable-adjusted Cox proportional hazards model, Fine-Gray subdistribution hazards model, restricted cubic spline analysis, and restricted mean survival time analysis were used to determine the association of blood hemoglobin concentration with the incidence of MALE. During a median follow-up of 8.0 years, 257 patients experienced MALE. A Cox proportional hazards model showed that the risk of MALE in patients with blood hemoglobin concentrations <10.0 g/dL was significantly higher than in patients with concentrations of 11.0 to 11.9 g/dL, even after adjusting for confounding factors. In contrast, elevated hemoglobin concentration (≥12.0 g/dL) was not significantly associated with increased risk of MALE. Similar associations were observed when the Fine-Gray subdistribution regression model was used by setting all-cause mortality as the competing risk. A low blood hemoglobin concentration is an independent risk factor for peripheral arterial disease progression in patients undergoing maintenance hemodialysis.

Clinical Outcomes of Non–Stent-Based Interventions for Symptomatic Below-the-Knee Peripheral Artery Disease in the Excellence in Peripheral Artery Disease (XLPAD) Registry

BackgroundFor endovascular treatment of below-the-knee (BTK) peripheral artery disease (PAD), independently adjudicated real-world outcomes comparing non-stent (balloon angioplasty or PTA and adjunctive treatment) with or without a concomitant ipsilateral femoropopliteal (FP) artery intervention are scarce. Methods1060 patients from the multicenter XLPAD Registry between 2006-2021 with non-stent based BTK PAD intervention are included. Primary outcome: 1-year incidence of major adverse limb events (MALE), a composite of all-cause death, any amputation, or clinically driven repeat revascularization. Results566 patients underwent BTK and 494 BTK + FP interventions; 72% men, with mean age 68.4 ± 10.9 years. Diabetes mellitus is more prevalent in BTK only group (76.5% vs. 69%, p=0.006). Mean Rutherford class 4.2 ± 1.18; chronic limb threatening ischemia is more frequent in the BTK group (55.3% vs. 49%, p=0.040). Moderate to severe calcification is higher in BTK + FP (21.2% vs. 27.1%, p=0.024), so is lesion length (110.6 ± 77.3 vs. 135.4 ± 86.3 mm; p<0.001). Nearly, 81% lesions are treated with PTA. DCB (1.6% vs 14%, p<0.001) and atherectomy (38% vs. 58.5%; p<0.001) use is greater in BTK + FP. Procedural success is higher in BTK + FP group (86% vs. 91%, p=0.009), with amputation being the most common complication at 3.3% ≤30 days. One-year MALE (21.2% vs. 22.3%, p=0.675) and mortality (4.6% vs. 3.4%; p=0.3) are similar across BTK and BTK + FP groups. ConclusionNon-stent treatment for BTK PAD with concomitant FP intervention leads to high procedural success and similar rates of 1-year MALE compared with isolated BTK intervention. Condensed abstractThe vast majority of below-the-knee (BTK) peripheral artery disease (PAD) interventions are performed with balloon angioplasty. Presence of inflow femoropopliteal (FP) PAD in patients undergoing BTK interventions can affect the outcome of the procedure. This report explores the immediate procedural success and major adverse limb events at 1 year following balloon angioplasty treatment for isolated BTK and in those undergoing an additional FP PAD intervention.

Major Adverse Limb Events in Patients Undergoing Revascularisation for Lower Limb Peripheral Arterial Disease: A Nationwide Observational Study

Major adverse limb events (MALEs) are frequent in patients with lower extremity peripheral arterial disease (PAD). However, routine care MALE rate estimations after revascularisation are scarce. This study aimed to determine post-procedural MALE rates in revascularised patients with PAD and identify predictors for post-procedural MALEs. This was a population based observational study on merged national registry data. Patients with PAD undergoing lower limb revascularisation between 2008 and 2016 were retrieved from the Swedish National Registry for Vascular Surgery. Information on comorbidities, medications, and post-procedural MALE endpoints were identified in national healthcare registries. Primary outcomes of interest were categorised as 2 - 4 point MALE composites that included limb amputation, acute lower limb ischaemia, progression to or relapse of chronic limb threatening ischaemia (CLTI), and ipsilateral re-interventions regardless of indication. Patients with intermittent claudication (IC) and CLTI were analysed separately using Kaplan-Meier estimates. Stepwise Cox proportional hazard models were used for predictor candidate analysis. Overall, 28 021 revascularised patients with PAD were analysed (IC, n = 10 506, 37.5%; CLTI, n = 17 515, 62.5%). During a mean follow up ± standard deviation of 3.2 ± 2.4 years, 5 226 (18.7%), 9 423 (33.6%), and 12 696 (45.3%) patients experienced a 2, 3, and 4 point MALE, respectively. The estimated one year 4 point MALE rates were 21.4% (95% confidence interval [CI] 20.6 - 22.2%) in IC and 46.9% (95% CI 46.1 - 47.7%) in CLTI. Adjusted predictors for experiencing a 4 point MALE in IC were chronic kidney disease (CKD) (hazard ratio [HR] 1.33, 95% CI 1.12 - 1.59) and previous lower limb revascularisation (HR 1.29, 95% CI 1.19 - 1.40). In CLTI, previous contralateral lower limb amputation (HR 1.60, 95% CI 1.47 - 1.73) and CKD (HR 1.25, 95% CI 1.17 - 1.34) were adjusted predictors. This study emphasises the very high MALE rates in revascularised patients with lower limb PAD, especially in CLTI. Prior lower limb revascularisation correlated with increased MALE rates in IC patients, while prior lower limb amputation was linked to subsequent MALEs in CLTI. In both IC and CLTI, CKD was associated with poorer outcomes, regardless of applied MALE definition.

Markers of optimal medical therapy are associated with improved limb outcomes after elective revascularization for intermittent claudication

BackgroundOptimal medical therapy (OMT) is a modifiable factor that decreases mortality and cardiovascular events in patients with severe peripheral arterial disease. We hypothesized that preintervention OMT would be associated with improved 1-year reintervention and major adverse limb event (MALE) rates after elective endovascular revascularization for intermittent claudication (IC). MethodsUsing the Vascular Quality Initiative (2010-2020), we identified patients with IC undergoing elective endovascular, hybrid, and open surgical interventions. Preoperative antiplatelet, statin, and nonsmoking status defined OMT components and created three groups: complete (all components), partial (1-2 components), and no OMT. The primary outcome was 1-year reintervention. Secondary outcomes included MALE and factors associated with OMT usage. Multivariable logistic regression generated adjusted odds ratios (aOR). ResultsThere were 39,088 patients (14,907 [38.1%] complete, 22,054 [56.4%)] partial, 2127 [5.4%] no OMT) who met our criteria. Patients with any OMT were more frequently older with more cardiovascular diseases and diabetes (P < .0001). Patients without OMT were more likely to be Black or with Medicare or Medicaid (P < .05). Observed 1-year reintervention (5.3% complete OMT, 6.1% partial OMT, 8.3% no OMT; P < .001) and MALE (5.6% complete OMT, 6.3% partial OMT, 8.8% no OMT; P < .001) were decreased by partial or complete OMT compared with no OMT. Complete OMT significantly decreased the adjusted odds of reintervention and MALE by 28% (aOR, 0.72, 95% confidence interval [95% CI], 0.59-0.88) and 30% (aOR, 0.70; 95% CI, 0.58-0.85), respectively, compared with no OMT. Partial OMT decrease the adjusted odds of reintervention and MALE by 24% (aOR, 0.76; 95% CI, 0.63-0.92) and 26% (aOR, 0.74; 95% CI, 0.62-0.89), respectively. ConclusionsPreintervention OMT is an underused, modifiable risk factor associated with improved 1-year reintervention and MALE. Vascular surgeons are uniquely positioned to initiate and maintain OMT in patients with IC before revascularization to optimize patient outcomes.

Discrepancy in opioid prescription patterns for Black or African American patients following lower extremity bypass surgery for chronic limb-threatening ischemia

BackgroundDisparity in the allocation of medical services and resources based on race is present within the health care industry today, including the prescription of postoperative analgesics. The purpose of this study was to evaluate the presence of race-based disparity in the prescription of postdischarge opioids after lower extremity bypass (LEB) surgery for chronic limb-threatening ischemia (CLTI). MethodsRetrospective analysis was conducted on adult CLTI patients who underwent LEB from 2000 to 2023 in the TrinetX database. Patients were stratified into two groups based on race: White (group I) and black or African American (AA) (group II). Primary outcomes were defined as oral opioid prescriptions at 7 days and 30 days after discharge, and mortality at 1 year postoperatively. Secondary outcomes included length of stay and 30-day postoperative outcomes, including myocardial infarction, pulmonary embolism, cerebral vascular accident, deep vein thrombosis, acute kidney injury, major amputation, minor amputation, major adverse cardiac events, and major adverse limb events. Stratified analysis was conducted based on disease stage (rest pain vs lower extremity ulcer vs gangrene). Univariate analysis was performed via two-sample t test and χ2 test. Logistic regression was performed to estimate the association of Black or AA (vs White) race while controlling for pertinent preoperative potential confounders. ResultsThere were 3345 patients who met the inclusion criteria. Group I included 2661 White patients and group II included 684 Black or AA patients. Group II patients were more likely to be younger, female, present with gangrene, and have a history of hypertension, diabetes, chronic kidney disease, or diabetic neuropathy. At both 7 and 30 days after discharge, the Black or AA cohort had significantly lower rates of opioid prescriptions (33.2% vs 42.5% and 35.8% vs 47.2%, respectively) (all P < .05). Stratification by indication showed that opioid prescription disparity persisted despite black or AA patients presenting at worse stages of disease both at 7 and 30 days after discharge (7 days: rest pain 43.4% vs 33.7% [P = .013], ulcer 41.4% vs 31.7% [P = .027], gangrene, 42.7% vs 33.6% [P = .006] and 30 days: rest pain 47.8% vs 37.1% [P = .007], ulcer 45.4% vs 33.5% [P = .007], gangrene, 48.2% vs 36.1% [P < .001]). Adjusted analysis confirmed that Black or AA race was associated with lower rates of 7- (adjusted odds ratio, 0.607; P = .001) and 30-day (adjusted odds ratio, 0.56; P = .001) postdischarge opioid prescriptions. ConclusionsBlack or AA patients were less likely to receive postdischarge opioid prescriptions compared with their White counterparts at 7 and 30 days after LEB for CLTI.

Contemporary outcomes after endoscopic vein harvesting for lower extremity bypass in a multicenter subspecialty practice

BackgroundEndoscopic vein harvesting (EVH) is considered the standard of care for coronary bypass procedures given the lower early morbidity from surgical wound complications. However, the use of EVH for lower extremity (LE) bypass remains controversial owing to concerns about decreased graft patency. In 2022, the BEST-CLI Trial (Best Endovascular vs. Best Surgical Therapy in Patients With Critical Limb Ischemia) demonstrated patients undergoing surgical bypass with adequate great saphenous vein quality experienced a lower incidence of major adverse limb events and mortality than those who underwent endovascular repair. Despite these results, wound complications from large harvest site incisions remain a significant barrier preventing surgical bypass as being the preferred initial treatment. To mitigate wound complications, our practice has adopted EVH as the standard approach for harvesting bypass conduit. Here, we report our recent 5-year experience using EVH for LE bypass. MethodsOne hundred sixty-eight LE bypasses with EVH were evaluated from 2017 to 2022. The cohort included 14 vascular surgeons in 8 hospitals. The primary end point was 30-day surgical wound complications. Secondary end points included bypass patency, need for major amputation, 30-day morbidity and mortality, length of operation, and length of hospitalization. Wound complications were measured using Szilagyi's method, with class I characterized by erythema necessitating antibiotics, class II having drainage or superficial dehiscence, and class III threatening graft integrity and requiring surgical intervention. ResultsA total of 168 LE bypasses with EVH were performed on 166 patients. Of these, 65.48% were male with a median age of 68.4 ± 9.7 years. There were no wound complications related to saphenectomy. Surgical site infections occurred in 22 patients (13.10%). Seven patients (4.17%) had class I complications, 12 (7.14%) had class II complications, and 3 (1.79%) had class III complications. Primary patency at 30 days was 96.10% and 86.84% at 1 year). Seven patients (4.17%) required major amputation at 30 days. The 1-year amputation-free survival was 89.39%. The 30-day postoperative stroke, myocardial infarction, and death rates were 0.60%, 0.60%, and 2.38%, respectively. The median operative time was 3.30 ± 1.18 hours. The median length of hospitalization was 3.00 ± 3.56 days. ConclusionsEVH minimizes saphenectomy wound complications without compromising patency and limb salvage rates. Older studies suggesting lower patency rates after EVH may have been limited by older technology and inexperienced operators. Whether EVH should be the standard of care for LE bypass warrants further investigation.

Proprotein convertase subtilisin/kexin type 9 inhibitors in peripheral artery disease: A review of efficacy, safety, and outcomes.

Peripheral artery disease (PAD) is a common condition characterized by atherosclerosis in the peripheral arteries, associated with concomitant coronary and cerebrovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a class of drugs that have shown potential in hypercholesterolemic patients. This review focuses on the efficacy, safety, and clinical outcomes of PCSK9 inhibitors in PAD based on the literature indexed by PubMed. Trials such as FOURIER and ODYSSEY demonstrate the efficacy of evolocumab and alirocumab in reducing cardiovascular events, offering a potential treatment option for PAD patients. Safety evaluations from trials show few adverse events, most of which are injection-site reactions, indicating the overall safety profile of PCSK9 inhibitors. Clinical outcomes show a reduction in cardiovascular events, ischemic strokes, and major adverse limb events. However, despite these positive findings, PCSK9 inhibitors are still underutilized in clinical practice, possibly due to a lack of awareness among care providers and cost concerns. Further research is needed to establish the long-term effects and cost-effectiveness of PCSK9 inhibitors in PAD patients.

The Association Between Completion of Supervised Exercise Therapy and Long-Term Outcomes in Patients with Intermittent Claudication, Concomitant Sarcopenia, and Cardiometabolic Multimorbidity

The combination of intermittent claudication (IC), cardiometabolic multimorbidity (CMM) and sarcopenia is associated with worse outcomes than IC alone. This study aimed to identify whether the completion of Supervised exercise therapy(SET) attenuates these adverse outcomes in patients with combined IC, sarcopenia and CMM. This registry review included consecutive IC patients with concomitant CMM and sarcopenia, who were referred for SET from 2014 to 2017. CMM was defined as two or more comorbidities (diabetes, heart disease, stroke, or chronic kidney disease). Sarcopenia was assessed using the L3-skeletal muscle index (L3SMI) from CT scans in the preceding 18 months. Outcomes of interest were progression to chronic limb-threatening ischemia (CLTI), major adverse cardiovascular events (MACE), and major adverse limb events (MALE). Survival and Cox regression analyses were performed. Eighty-two patients with a combination of IC, CMM and sarcopenia were included. Of these, 56 declined or prematurely discontinued SET and 26 completed SET. Baseline characteristics and L3SMI did not significantly differ between groups. Completion of SET was associated with slower progression to CLTI (HR: 0.23; 95% CI: 0.07-0.69; p = 0.02) and a reduced risk of MALE (HR: 0.21; 95%CI: 0.057-0.775;p=0.02). However, there was no reduction in the risk of MACE (HR: 0.88; 95%CI: 0.423-1.629; p=0.73). Models demonstrated good predictive accuracy (Harrell's C-index>0.6). Completion of SET was associated with significant improvements in adverse limb outcomes in patients with IC, concomitant sarcopenia and CMM.

Clinical evolution of patients with lower extremity peripheral artery disease during the COVID-19 pandemic (the COVID-PAD study).

Background: The COVID-19 pandemic has led to significant disruptions in chronic disease care and forced people to stay at home. The effects of such issues on outpatients with lower extremity peripheral artery disease (PAD) remain unknown. Patients and methods: Single-centre, retrospective-prospective study conducted in a Swiss University Hospital. Patients with PAD were included between May 1 and July 31, 2020, with a follow-up visit at 12 months. Upon both visits, the Leriche-Fontaine PAD stage was recorded, and study participants underwent ankle-brachial index (ABI) calculation to assess limb perfusion. Functional capacities were assessed through the 6-minute walking and treadmill tests. Major adverse cardiovascular (MACE) and limb events (MALE) were recorded. Data collected during the pandemic were compared with the pre-pandemic period (January 1, 2019-April 30, 2020). Results: Overall, 259 patients were included. Mean age was 69 years and male sex was prevalent (69.1%). Odds of experiencing a degradation in PAD stage were lower during the pandemic than before (odds ratio [OR]: 0.43; 95% confidence interval [CI]: 0.21-0.87; p = 0.018). No significant difference was found between periods in terms of ABI trends. Both pain-free walking time at treadmill test (p = 0.003) and maximal pain intensity at 6-minute walking test (p = 0.001) significantly improved during the pandemic. Compared with the pre-pandemic period, during the pandemic patients were hospitalized less frequently (p = 0.028) and were less likely to undergo elective limb revascularization (p<0.001). No significant difference was found between periods in terms of MALE (p = 0.311), whereas non-fatal strokes were less frequently reported during the pandemic (p = 0.043). Conclusion: In a cohort of outpatients with PAD, we found no evidence of clinical deterioration during the pandemic compared with the pre-pandemic period, though rates of adverse events were nonnegligible in both periods. In case of future pandemics, patients with PAD should be encouraged to maintain an active lifestyle while being closely monitored to avoid clinical worsening.

Staged versus nonstaged elective hybrid iliofemoral revascularization – analysis of ten years of prospective data

Reports of large series of hybrid iliofemoral revascularization for chronic lower limb ischemia are scarce. The aims of this study were to evaluate outcomes for staged and non-staged procedures, and to evaluate risk factors for outcomes at 90 days. Patients were consecutively included between 2013 and 2023. Surgical site infection (SSI) was defined by the ASEPSIS criteria and major adverse limb events (MALE) as onset of acute or continuing or worsening chronic limb ischemia or major amputation. Factors associated with outcomes were tested in a multivariable logistic regression analysis and expressed in Odds ratios (OR) with 95% confidence intervals (CI). Patients undergoing non-staged procedures (n=124) had higher TASC (Trans-Atlantic Inter-Society Consensus) class representing anatomical occlusive complexity, more often through-and through femoral guidewire access, more endoprosthesis, more covered stents, longer procedure time with open groin wounds, and less contralateral femoral access, than those undergoing staged procedures (n=31). The median time interval between the staged procedures was one day, and iliac stenting was done first in 77%. The median in-hospital stay was non-significantly longer in staged procedure (8 versus 6 days, p=0.053). The overall SSI and MALE rates were 25.8% and 20.0%, respectively, without differences between groups. Diabetes mellitus (OR 3.7, 95% CI 1.2 - 7.2]) and presence of a foot ulcer (OR 3.7, 95% CI [1.5 - 9.4]) were independently associated with MALE at 90 days. Postoperative hyperglycemia was non-significantly associated with SSI (OR 2.1 [95% CI 1.0 - 4.5], p=0.066) in multivariable analysis. The risks of SSI and MALE after elective hybrid iliofemoral revascularization were high. There appears to be no benefit in performing staged as opposed to non-staged procedures. The extent of iliofemoral occlusive disease according to the TASC classification had little influence on outcomes whereas diabetes mellitus and presence of a foot ulcer had greater impact on MALE.

Colchicine for cardiovascular and limb risk reduction in Medicare beneficiaries with peripheral artery disease: emulation of target trials.

Recent evidence from randomized trials demonstrates that colchicine can reduce the risk of major adverse cardiovascular events (MACE) in patients with coronary artery disease. Colchicine's effect on lower-extremity peripheral artery disease (PAD) is not known. To make inferences about the real-world effectiveness of colchicine in PAD, we emulated two target trials leveraging the variable prescribing practice of adding colchicine vs. a non-steroidal anti-inflammatory drug (NSAID) to urate-lowering therapy in patients with gout and PAD. Emulated Trial 1 compared colchicine initiators with NSAID initiators. Emulated Trial 2 compared long-term (indefinite) and short-term (3 months) treatment strategies after initiating colchicine. Eligible individuals were those continuously enrolled in Medicare receiving care at a multicentre academic health system between July 2007 and December 2019. The primary outcome for both trials was a 2 year composite of major adverse limb events (MALE), MACE, and all-cause mortality. Secondary outcomes included MALE and death, MACE and death, and individual components of the primary outcome. Inverse probability weighting was used to adjust for confounding. Percentile-based 95% confidence intervals (CIs) were estimated using non-parametric bootstrapping. A total of 1820 eligible patients were included; the mean age was 77 years [standard deviation (SD) 7], 32% were female, and 9% were non-White. The mean (SD) duration of colchicine and NSAID therapy was 247 (345) and 137 (237) days, respectively. In the emulation of Trial 1, the risk of the primary composite outcome of MALE, MACE, and death at 2 years was 29.9% (95% CI 27.2%, 32.3%) in the colchicine group and 31.5% (28.3%, 34.6%) in the NSAID group, with a risk difference of -1.7% (95% CI -6.5%, 3.1%) and a risk ratio of 0.95 (95% CI 0.83, 1.07). Similar findings were noted in the emulation of Trial 2, with a risk of the primary composite outcome at 2 years of 30.7% (95% CI 23.7%, 38.1%) in the long-term colchicine group and 33.4% (95% CI 29.4%, 37.7%) in the short-term group, with a risk difference of -2.7% (95% CI -10.3%, 5.4%) and risk ratio of 0.92 (95% CI 0.70, 1.16). In a real-world sample of patients with PAD and gout, estimates of the effect of colchicine were consistent across two analyses and provided no conclusive evidence that colchicine decreased the risk of adverse cardiovascular or limb events and death. The cardiovascular and limb benefits of colchicine in older, comorbid populations with PAD and advanced systematic atherosclerosis remain uncertain.

Presentation and patterns of reinterventions after revascularization in patients with premature peripheral arterial disease

ObjectivePremature peripheral arterial disease (PAD) (age ≤50 years) has been shown to negatively impact the outcomes of lower extremity revascularization (LER). Patients with premature PAD have an increased risk of major amputation compared with older patients. The primary goal of this study is to compare the frequency of reinterventions after LER in patients with premature PAD to their older counterparts with common age of presentation (ie, 60-80 years). MethodsA retrospective review of consecutive patients undergoing LER for PAD in a single center was performed. Clinical, procedural, and socioeconomic characteristics were compared between patients with premature PAD and the older group. Perioperative and long-term outcomes were captured and compared including mortality, major amputation, reintervention rate and frequency, as well as major adverse limb events. ResultsThere were 1274 patients who underwent LER (4.3% premature, 61.8% age 60-80). Patients with premature PAD were more likely to be females of racial minorities. Notably, the mean Distressed Communities Index score was significantly higher in the premature PAD group compared with the older patients. Patients with premature PAD were significantly more likely to have end-stage renal disease but less likely to have hypertension, hyperlipidemia, and coronary artery disease compared with older patients. There was no significant difference in perioperative complications. After a mean follow-up of 5 years, patients with premature PAD were significantly more likely to undergo more frequent reinterventions compared with older patients. Kaplan-Meier curves showed similar overall survival and major adverse limb event-free survival between the two groups. ConclusionsPatients with premature PAD are likely to undergo more frequent reinterventions after initial LER and have similar 5-year survival curves compared with patients at least 20 years older. Demographic and socioeconomic differences impacting patients with premature PAD, even in this relatively underpowered institutional experience, are striking and warrant further investigation.

The Impact of Small Artery Disease (SAD) and Medial Arterial Calcification (MAC) Scores on Chronic Wound and Amputation Healing: Can It Tell Us More?

In 2021, Ferraresi etal. created a novel scoring system based on the impact of small artery disease (SAD) and medial arterial calcification (MAC) on wound healing. SAD and MAC scores functioned similar to Wound, Ischemia, and foot Infection (WIfI) but with minimal resource expenditure. Despite its potential, few studies have expanded on the original dataset. We aim to validate SAD's impact and MAC's impact on wound healing outcomes and determine their utility in relation to current predictive models. Single-institution retrospective review was used to identify amputations for chronic (>1month) podiatric wounds between 2015 and 2020. Foot X-ray (MAC) or angiography (SAD)<6months of index procedure was required. Primary outcomes included major amputation, wound healing, major adverse limb events, and amputation-free survival (AFS). Statistical analysis included chi-squared, 1-way analysis of variance, nonparametric correlation, Kaplan-Meier, Cox regression, and Akaike/Bayesian Inclusion Criteria model comparison. Of 136 limbs, 67 received SAD scores (0-2) and 128 received MAC scores (0-2). SAD cohorts exhibited similar comorbidity profiles with exception of coronary disease, heart failure, and chronic kidney disease. MAC cohorts were notably disparate in prevalence of multiple conditions. High mean SAD/MAC scores were seen in severe (3-vessel) below-ankle disease (P=0.001∗ [SAD], P=0.041∗ [MAC]). Both SAD and MAC correlated with lower mean toe pressure (P=0.043∗ [SAD], P ≤ 0.001∗ [MAC]), while only MAC correlated with higher overall WIfI score (P=0.029∗). No significant procedural differences were noted. However, higher readmission rates (73.9% [2] vs. 46.9% [0], P=0.014∗) and all-cause mortality (65.2% [2] vs. 26.0% [0], P=0.002∗) were noted with higher MAC. Survival analysis revealed higher 1-year major amputation rates (P=0.036∗), impaired wound healing (P<0.001∗), and lower AFS (P=0.001∗) with increasing MAC severity. Additionally, MAC-2 patients underwent amputation at faster rates than MAC-0 patients (hazard ratio 5.25, 95% confidence interval [1.82, 9.77]) with longer times to wound healing (hazard ratio 0.21, 95% confidence interval [0.08, 0.53]). Model comparison suggested a combination of WIfI and MAC could improve accuracy of predicted time to major amputation, wound healing, and AFS. MAC scoring showed significant promise both as individual predictor and adjunct to current predictive models of long-term wound healing outcomes. Routine use of MAC scoring in chronic limb-threatening ischemia evaluation, especially when noninvasive testing is unavailable, could promote timely referral for intervention and efficient resource utilization in limited-resource or critical care settings. Furthermore investigation is necessary to determine MAC's impact on revascularization and how scoring can be used to guide surgical decision-making.

Prediction of Peripheral Artery Disease Prognosis Using Clinical and Inflammatory Biomarker Data.

Inflammatory biomarkers associated with peripheral artery disease (PAD) have been examined separately; however, an algorithm that includes a panel of inflammatory proteins to inform prognosis of PAD could improve predictive accuracy. We developed predictive models for 2-year PAD-related major adverse limb events (MALE) using clinical/inflammatory biomarker data. We conducted a prognostic study using 2 phases (discovery/validation models). The discovery cohort included 100 PAD patients that were propensity-score matched to 100 non-PAD patients. The validation cohort included 365 patients with PAD and 144 patients without PAD (non-matched). Plasma concentrations of 29 inflammatory proteins were determined at recruitment and the cohorts were followed for 2 years. The outcome of interest was 2-year MALE (composite of major amputation, vascular intervention, or acute limb ischemia). A random forest model was trained with 10-fold cross-validation to predict 2-year MALE using the following input features: 1) clinical characteristics, 2) inflammatory biomarkers that were expressed differentially in PAD vs non-PAD patients, and 3) clinical characteristics and inflammatory biomarkers. The model discovery cohort was well-matched on age, sex, and comorbidities. Of the 29 proteins tested, 5 were elevated in PAD vs non-PAD patients (MMP-7, MMP-10, IL-6, CCL2/MCP-1, and TFPI). For prognosis of 2-year MALE on the validation cohort, our model achieved AUROC 0.63 using clinical features alone and adding inflammatory biomarker levels improved performance to AUROC 0.84. Using clinical characteristics and inflammatory biomarker data, we developed an accurate predictive model for PAD prognosis.

Prevent III score as a predictor of limb salvage and mortality after aortoiliac revascularization.

This prospective study aimed to validate the prognostic value of Prevent III (PIII) risk score in patients undergoing aortoiliac revascularization, both in limb-related outcomes and cardiovascular risk. The prospective cohort study included 130 consecutive patients (122 males, 8 females; mean age: 62.1±9.2 years; range, 53 to 71 years) undergoing elective aortoiliac revascularization between January 2013 and September 2022. Patients' demographic and clinical characteristics were retrieved and PIII scores were calculated. A risk category was assigned according to the total points: low-risk (score ≤3), medium-risk (score 4-7), or high-risk (score ≥8). The median follow-up period was 55 months (interquartile range, 39 to 70 months). Twenty-four (18.5%) patients had a PIII score ≥4. Regarding short-term outcomes, patients with PIII scores ≥4 exhibited lower ankle-brachial index changes at 30 days and more extended hospital stays. There were no significant associations between PIII scores and major adverse events at 30 days. However, during follow-up, a PIII score ≥4 was associated with increased major adverse limb events (p=0.036) and all-cause mortality (p=0.007). The PIII score is a reliable predictor of long-term limb and mortality risk in patients undergoing aortoiliac revascularization procedures, leveraging five user-friendly clinical parameters. More research with larger cohorts and studies comparing PIII with other validated scores should be performed in the future.

Effect of Peripheral Interventions in Patients with Peripheral Artery Disease Receiving Rivaroxaban and Aspirin: Analyses from the XATOA Registry

To assess the characteristics and clinical outcomes of patients with lower extremity peripheral artery disease (PAD) in XATOA receiving dual pathway inhibition (DPI) with rivaroxaban 2.5 mg twice daily plus aspirin according to lower extremity revascularisation (LER) history. XATOA is an international, multicentre, prospective, single arm registry study. This subanalysis investigated patients with lower extremity PAD according to LER history. Patients with coronary artery disease, PAD, or both, receiving DPI were followed for 12 or more months. Baseline characteristics and clinical outcomes were assessed according to LER history. A time dependency analysis assessed outcomes by time between the most recent LER procedure and the start of DPI. A multivariate analysis assessed the influence of patient characteristics on clinical outcomes. In XATOA (n = 5 532), 2 820 (51.0%) patients had lower extremity PAD, of whom 1 736 (61.6%) had prior LER and 1 084 (38.4%) had no prior LER. Baseline characteristics were generally similar between patients with or without prior LER. A higher proportion of patients with prior LER experienced any treatment emergent clinical events compared with those without prior LER (15.0% vs. 9.4%, respectively), with greater differences observed between incidence rates of limb events, including major adverse limb events (9.06 vs. 4.09 events per 100 patient years, respectively). Similar rates of myocardial infarction, stroke, and major bleeding were observed in both subgroups. Clinical event rates were generally higher in patients who had previous LER for six months or less compared with patients who had previous LET for more than six months before starting DPI, regardless of LER type. Multivariate analyses showed that prior LER was predictive of limb events. This subanalysis of XATOA found that prior LER was associated with increased rates of limb events, consistent with results of COMPASS and VOYAGER PAD. Rates of bleeding were also low regardless of LER history and consistent with the findings from these trials.

Short-term efficacy of endovascular procedures for lower extremity thromboangiitis obliterans (Buerger’s disease)

ABSTRACT Purpose Although thrombolysis obliterans (TAO) has been recognized for more than a century, there is no optimal treatment for this disease. The aim of this report was to compare the short-term efficacies of catheter-directed thrombolysis (CDT), percutaneous transluminal angioplasty (PTA) and CDT+PTA in treating TAO disease. Method Consecutive patients with TAO treated at Ganzhou People’s Hospital between 2012 and 2022 were included in this retrospective study. According to the information provided in the medical records, endovascular procedures included CDT, PTA or CDT+PTA. One-year follow-up outcomes of the patients with TAO who underwent endovascular procedures were compared. The primary outcome was major adverse limb event (MALE) and the secondary outcomes were the technical success, complications, ABI at 1 week after surgery and minor amputation. Results Sixty-nine patients with TAO were assessed for inclusion in our single-center study from 2012 to 2022 and received endovascular procedures. Among them, 22 patients underwent CDT, 21 patients underwent PTA, and 26 patients underwent PTA+CDT. The one-year follow-up revealed significant differences in the MALE-free survival rates among the three groups, particularly between the CDT group and the PTA+CDT group (the hazard ratio (HR) for MALE-free survival was 0.173, 95% CI [0.050–0.599], p = 0.006). The technical success rates of the three groups were 63.6%, 90.5%, and 92.3%, respectively. There were differences in the ABI at one week after surgery among the three groups. Conclusions Endovascular procedures are effective for TAO in the short term. The effectiveness of CDT alone is suboptimal; combining CDT with PTA achieves the most favorable endovascular treatment outcome; while the effectiveness of PTA falls in between these two procedures.

Supra-Inguinal Inflow for Distal Bypasses Have Acceptable Patency and Limb Salvage Rates

There is a paucity of data evaluating outcomes of lower extremity bypass (LEB) using supra-inguinal inflow for revascularization of infra-inguinal vessels. The purpose of this study is to report outcomes after LEB originating from aortoiliac arteries to infra-femoral targets. The Vascular Quality Initiative database (2003-2020) was queried for patients undergoing LEB from the aortoiliac arteries to the popliteal and tibial arteries. Patients were stratified into 3 cohorts based on outflow targets (above-knee [AK] popliteal, below-knee [BK] popliteal, and tibial arteries). Perioperative and 1-year outcomes including primary patency, amputation-free survival (AFS), and major adverse limb events (MALEs) were compared. A Cox proportional hazards model was used to estimate the independent prognostic factors of outcomes. Of 403 LEBs, 389 (96.5%) originated from the external iliac artery, while the remaining used the aorta or common iliac artery as inflow. In terms of the distal target, the AK popliteal was used in 116 (28.8%), the BK popliteal in 151 (27.5%), and tibial vessels in 136 (43.7%) cases. BK popliteal and tibial bypasses, compared to AK popliteal bypasses, were more commonly performed in patients with chronic limb-threatening ischemia (69.5% and 69.9% vs. 48.3%; P<0.001). Vein conduit was more often used for tibial bypass than for AK and BK popliteal bypasses (46.3% vs. 21.9% and 16.3%; P<0.001). In the perioperative period, BK popliteal and tibial bypass patients had higher reoperation rates (16.9% and 13.2% vs. 5.2%; P=0.02) and lower primary patency (89.4% and 89% vs. 95.7%; P=0.04) than AK bypass patients. At 1year, compared with AK popliteal bypasses, BK and tibial bypasses demonstrated lower primary patency (81.9% vs. 56.7% vs. 52.4%, P<0.001) and freedom from MALE (77.6% vs. 70.2% vs. 63.1%, P=0.04), although AFS was not significantly different (89.7% vs. 90.6% vs. 83.8%, P=0.19).On multivariable analysis, compared with AK popliteal bypasses, tibial bypasses were independently associated with increased loss of primary patency (hazard ratio 1.9, 95% confidence interval, 1.03-3.51, P=0.04). Subanalysis of patients with chronic limb-threatening ischemia demonstrated significantly higher primary patency in the AK popliteal cohort at discharge and 1 year, but no difference in AFS or freedom from MALE between the cohorts at follow-up. LEB with supra-inguinal inflow appear to have acceptable rates of 1-year patency and limb salvage in patients at high risk of bypass failure. Tibial outflow target was independently associated with worse primary patency but not with MALE or AFS.

Associations between lipoprotein(a), oxidized phospholipids, and extracoronary vascular disease

The roles of lipoprotein(a) [Lp(a)] and related oxidized phospholipids (OxPLs) in the development and progression of coronary disease is known, but their influence on extracoronary vascular disease is not well-established. We sought to evaluate associations between Lp(a), OxPL apolipoprotein B (OxPL-apoB), and apolipoprotein(a) (OxPL-apo(a)) with angiographic extracoronary vascular disease and incident major adverse limb events (MALEs). Four hundred forty-six participants who underwent coronary and/or peripheral angiography were followed up for a median of 3.7 years. Lp(a) and OxPLs were measured before angiography. Elevated Lp(a) was defined as ≥150 nmol/L. Elevated OxPL-apoB and OxPL-apo(a) were defined as greater than or equal to the 75th percentile (OxPL-apoB ≥8.2 nmol/L and OxPL-apo(a) ≥35.8 nmol/L, respectively). Elevated Lp(a) had a stronger association with the presence of extracoronary vascular disease compared to OxPLs and was minimally improved with the addition of OxPLs in multivariable models. Compared to participants with normal Lp(a) and OxPL concentrations, participants with elevated Lp(a) levels were twice as likely to experience a MALE (odds ratio: 2.14, 95% confidence interval: 1.03, 4.44), and the strength of the association as well as the C statistic of 0.82 was largely unchanged with the addition of OxPL-apoB and OxPL-apo(a). Elevated Lp(a) and OxPLs are risk factors for progression and complications of extracoronary vascular disease. However, the addition of OxPLs to Lp(a) does not provide additional information about risk of extracoronary vascular disease. Therefore, Lp(a) alone captures the risk profile of Lp(a), OxPL-apoB, and OxPL-apo(a) in the development and progression of atherosclerotic plaque in peripheral arteries.