Efficiency and safety of dual pathway inhibition for the prevention of femoropopliteal artery restenosis in repeated endovascular interventions.

OBJECTIVE: There is a lack of consensus regarding the optimal strategy for evaluating the efficiency and safety of dual-pathway inhibition (DPI) in preventing femoropopliteal restenosis in patients undergoing repeated endovascular interventions. Despite several therapeutic interventions available for preventing femoropopliteal restenosis post repeated endovascular interventions, the ideal strategy, particularly evaluating the efficacy and safety of DPI, remains a matter of debate. METHODS: From January 2015 to September 2021, patients who underwent repeated endovascular interventions for femoropopliteal restenosis were compared with those who underwent DPI or dual antiplatelet therapy (DAPT) after surgery using a propensity score-matched analysis. The primary outcome was clinically driven target lesion revascularization (CD-TLR). The principal safety outcome was a composite of major bleeding and clinically relevant non-major (CRNM) bleeding. To further enhance the rigor, Kaplan-Meier plots, Cox proportional hazards modeling, and sensitivity analyses, as well as subgroup analyses were employed, reducing potential confounders. RESULTS: A total of 441 patients were included in our study, of whom 294 (66.7%) received DAPT and 147 (33.1%) received DPI, with 114 matched pairs (mean age, 72.21 years; 84.2% male). Cumulative probability of CD-TLR at 36 months in the DPI group (17%) trended lower than that in the DAPT group (32%) (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.26-0.78; P =.004). The cumulative probability of freedom from CD-TLR at 36 months in the DPI group was 83%. No significant difference was observed in the composite outcome of major or CRNM bleeding between the DPI and DAPT groups (HR, 1.26; 95% CI, 0.34 to 4.69; P = .730). The DPI group was associated with significantly lower rates of CD-TLR in the main subgroup analyses of diabetes (P = .001), previous smoking history (P = .008), longer lesion length (>10 cm) (P = .003), and treatment with debulking strategy (P = .003). CONCLUSIONS: In our investigation focused on CD-TLR, we found that DPI exhibited a significant reduction in the risk of reintervention compared with other treatment modalities. This underscores the potential of DPI as a viable therapeutic strategy in preventing reinterventions. Moreover, our assessment of safety outcomes revealed that the bleeding risks associated with DPI were on par with DAPT, thereby not compromising patient safety. These findings pave the way for potential broader clinical implications, emphasizing the effectiveness and safety of DPI in the context of reducing reintervention risks.

Endovascular revascularization vs open surgical revascularization as the first strategy for arterial acute mesenteric ischemia: A systematic review and meta-analysis.

OBJECTIVE: This paired meta-analysis aimed to compare the mortality and morbidity of endovascular revascularization (EVR) and open surgical revascularization (OSR) as the first strategy for arterial acute mesenteric ischemia (AMI). METHODS: This systematic review and meta-analysis were performed in accordance with the PRISMA statement. A systematic search strategy was performed to identify eligible studies using the following databases: PubMed, Embase, and Cochrane Library database from inception to December 31, 2023, with restriction to the English language. The end search date was January 2, 2024. The primary outcome was short-term mortality. Secondary outcomes included bowel resection, second-look laparotomy, and short bowel syndrome. The counterenhanced funnel plot and the Peters' test were used to assess bias. Outcomes were reported as odds ratio (OR) with a 95% confidence interval (CI) using the Mantel-Haenszel method. The GRADE classification was used to estimate the certainty of evidence. RESULTS: A total of 11 studies (1141 patients) comparing EVR vs OSR for arterial AMI were identified and analyzed. The mean patient age was 61.9 to 73.6 years and 45.1% of the patients were male. Compared with OSR, EVR as the first treatment may not decrease short-term mortality (OR, 0.79; 95% CI, 0.50-1.25; P = .31; very low certainty) and second-look laparotomy (OR, 1.00; 95% CI, 0.30-3.36; P = .99; very low certainty). However, EVR may be associated with decreased bowel resection (OR, 0.42; 95% CI, 0.20-0.88; P = .022; very low certainty) and short bowel syndrome (OR, 0.39; 95% CI, 0.21-0.75; P = .005; very low certainty). The metaregression revealed that the mortality regarding EVR vs OSR was not impacted significantly by thrombotic etiology (-0.002; 95% CI, -0.027 to 0.022; P = .85), whereas it was impacted significantly by publication year (0.076; 95% CI, 0.069-0.145; P = .031). CONCLUSIONS: Compared with OSR, EVR as the first treatment for arterial AMI may not decrease short-term mortality or second-look laparotomy. Future multicenter randomized controlled trials are needed urgently to confirm these results.

Patient-specific risk factors for reintervention following primary endovascular treatment of iliac artery disease.

OBJECTIVE: Predictive models for reintervention may guide clinicians to optimize selection, education, and follow-up of patients undergoing endovascular iliac revascularization. Although the impact of lesion- and device-related characteristics on iliac restenosis and reintervention risk is well-defined, data on patient-specific risk factors are scarce and conflicting. This study aimed to explore the value of patient-related factors in predicting the need for clinically driven target-vessel revascularization (CD-TVR) in patients undergoing primary endovascular treatment of iliac artery disease. METHODS: Consecutively enrolled patients undergoing endovascular revascularization for symptomatic iliac artery disease at a tertiary vascular referral center between January 2008 and June 2020 were retrospectively analyzed. Primary and secondary outcomes were CD-TVR occurrence within 24 months and time to CD-TVR, respectively. Patients who died or did not require CD-TVR within 24 months were censored at the date of death or at 730 days, respectively. Multiple imputation was used to account for missing data in primary analyses. RESULTS: A total of 1538 iliac interventions were performed in 1113 patients (26% females; 68 years). CD-TVR occurred in 108 limbs (74 patients; 7.0%) with a median time to CD-TVR of 246 days. On multivariable analysis, increasing age was associated with lower likelihood of CD-TVR (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.50-0.83; P = .001) and decreased risk of CD-TVR at any given time (hazard ratio [HR], 0.66; 95% CI, 0.52-0.84; P = .001). Similarly, a lower likelihood of CD-TVR (OR, 0.75; 95% CI, 0.59-0.95; P = .017) and decreased risk of CD-TVR at any given time (HR, 0.73; 95% CI, 0.58-0.93; P = .009) were observed with higher glomerular filtration rates. Lastly, revascularization of common vs external iliac artery disease was associated with lower likelihood of CD-TVR (OR, 0.48; 95% CI, 0.24-0.93; P = .030) and decreased risk of CD-TVR at any given time (HR, 0.48; 95% CI, 0.25-0.92; P = .027). No associations were observed between traditional cardiovascular risk factors (sex, hypertension, higher low-density lipoprotein cholesterol, higher hemoglobin A1c, smoking) and CD-TVR. CONCLUSIONS: In this retrospective cohort study, younger age, impaired kidney function, and external iliac artery disease were associated with CD-TVR. Traditional markers of cardiovascular risk were not seen to predict reintervention.

Sarcopenia is a possible risk factor for amputation after peripheral arterial interventions.

OBJECTIVES: Sarcopenia has been demonstrated to be related to unfavorable clinical outcomes in patients with vascular diseases. The purpose of this study is to evaluate the relationship between sarcopenia and clinical results in patients with peripheral arterial disease who underwent endovascular therapy (EVT). METHODS: This single-center retrospective study involved patients with PAD who underwent peripheral EVT at Ankara City Hospital, between January 2018 and December 2021. Two groups of patients were created: sarcopenic and non-sarcopenic patients according to computed tomography angiography muscle measurements. Primary outcome measures were major and minor amputation and survival. Mortality, amputation, and clinical characteristics were compared between the two patient groups. Hazard ratios (HRs) for amputation were calculated for each risk factor via univariate and multivariate analyses. Secondary outcomes included length of hospital stay and post-procedural complications. RESULTS: The mean follow-up period was 29.9 ± 9 months for all patients. A total number of 100 patients (mean age 63.5 ± 9.2 years) were involved in the study cohort. A significant association was identified between mortality and sarcopenia (p < .001). The mortality rate in the group with sarcopenia was significantly higher than the other group; 65.7% (23 patients) versus (20%, 13 patients) (p < .001). The major amputation rate in the group with sarcopenia was 57.1%, the major amputation rate in the group without sarcopenia was calculated as 15.4%, revealing that the major amputation rate was detected to be significantly higher in the sarcopenia group (p < .001). Multivariate regression analyses showed that only sarcopenia (HR, 0.52; 95% CI, 0.21-1.27; p = 0.15) was independently associated with major amputation in patients with PAD after EVT. Kaplan-Meier analysis revealed a statistically significant difference between the survival curves of sarcopenia and non-sarcopenia patients (p < .001). CONCLUSIONS: Sarcopenia seems to be a possible risk factor associated with amputation in patients with PAD who undergo EVT. The results of this study imply that sarcopenia is a possible risk factor for overall survival in patients with PAD.

Endovascular revascularization strategies for aortoiliac and femoropopliteal artery disease: a meta-analysis.

AIMS: Optimal endovascular management of intermittent claudication (IC) remains disputed. This systematic review and meta-analysis compares efficacy and safety outcomes for balloon angioplasty (BA), bare-metal stents (BMS), drug-coated balloons (DCB), drug-eluting stents (DES), covered stents, and atherectomy. METHODS AND RESULTS: Electronic databases were searched for randomized, controlled trials (RCT) from inception through November 2021. Efficacy outcomes were primary patency, target-lesion revascularization (TLR), and quality-of-life (QoL). Safety endpoints were all-cause mortality and major amputation. Outcomes were evaluated at short-term (<1 year), mid-term (1-2 years), and long-term (≥2 years) follow-up. The study was registered on PROSPERO (CRD42021292639). Fifty-one RCTs enrolling 8430 patients/lesions were included. In femoropopliteal disease of low-to-intermediate complexity, DCBs were associated with higher likelihood of primary patency [short-term: odds ratio (OR) 3.21, 95% confidence interval (CI) 2.44-4.24; long-term: OR 2.47, 95% CI 1.93-3.16], lower TLR (short-term: OR 0.33, 95% CI 0.22-0.49; long-term: OR 0.42, 95% CI 0.29-0.60) and similar all-cause mortality risk, compared with BA. Primary stenting using BMS was associated with improved short-to-mid-term patency and TLR, but similar long-term efficacy compared with provisional stenting. Mid-term patency (OR 1.64, 95% CI 0.89-3.03) and TLR (OR 0.50, 95% CI 0.22-1.11) estimates were comparable for DES vs. BMS. Atherectomy, used independently or adjunctively, was not associated with efficacy benefits compared with drug-coated and uncoated angioplasty, or stenting approaches. Paucity and heterogeneity of data precluded pooled analysis for aortoiliac disease and QoL endpoints. CONCLUSION: Certain devices may provide benefits in femoropopliteal disease, but comparative data in aortoiliac arteries is lacking. Gaps in evidence quantity and quality impede identification of the optimal endovascular approach to IC.

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

OBJECTIVE: In 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). METHODS: Patients 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. RESULTS: The 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. CONCLUSIONS: Severe 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.

Carbon dioxide angiography during peripheral vascular interventions is associated with decreased cardiac and renal complications in patients with chronic kidney disease.

OBJECTIVE: Patients with chronic kidney disease (CKD) who undergo peripheral vascular interventions (PVI) with iodinated contrast are at higher risk of post-contrast acute kidney injury (PC-AKI). Carbon dioxide (CO2) angiography can reduce iodinated contrast volume usage in this patient population, but its impact on PC-AKI has not been studied. We hypothesize that CO2 angiography is associated with a decrease in PC-AKI in patients with advanced CKD. METHODS: The Vascular Quality Initiative PVI dataset from 2010 to 2021 was reviewed. Only patients with advanced CKD (estimated glomular filtration rate <45 ml/min/1.73 m2) treated for peripheral arterial disease were included. Propensity matching and multivariate logistic regression based on demographics, comorbidities, CKD stage, and indications were used to compare the outcomes of patients treated with and without CO2. RESULTS: There were 20,706 PVIs performed in patients with advanced CKD, and only 22% utilized CO2 angiography. Compared with patients treated without CO2, patients who underwent CO2 angiography were younger and less likely to be women or White, and more likely to have poor renal function, diabetes, cardiac comorbidities, and present with tissue loss. Propensity matching yielded well-matched groups with 4472 patients in each group. The procedural details after matching demonstrated 50% reduction in the volume of contrast used (32±33 vs 65±48 mL; P < .01). PVI with CO2 angiography was associated with lower rates of PC-AKI (3.9% vs 4.8%; P = .03) and cardiac complications (2.1% vs 2.9%; P = .03) without a significant difference in technical failure or major/minor amputations. Low contrast volumes (≤50 mL for CKD3, ≤20 mL for CKD4, and ≤9 mL for CKD5) are associated with reduced risk of PC-AKI (hazard ratio, 0.59; P < .01). CONCLUSIONS: CO2 angiography reduces iodinated contrast volume usage during PVI and is associated with decreased cardiac complications and PC-AKI. CO2 angiography is underutilized and should be considered for patients with advanced CKD who require endovascular therapy.

Association of Sarcopenia With Mortality in Patients With Chronic Limb-Threatening Ischemia Undergoing Endovascular Revascularization.

INTRODUCTION: Chronic limb-threatening ischemia (CLTI) is the most severe form of peripheral artery disease and leads high mortality. Sarcopenia, characterized by the loss of muscle mass or poor muscle quality, is associated with adverse clinical outcomes. This study aimed to investigate the association between sarcopenia and the long-term outcomes in patients with CLTI after endovascular revascularization. METHODS: We retrospectively reviewed the medical records of all patients with CLTI who underwent endovascular revascularization between January 2015, and December 2021. The skeletal muscle area was calculated at the third lumbar vertebra from computed tomography images using the manual trace method and normalized to patient height. Sarcopenia was defined as a third lumbar skeletal muscle index of <40.8 cm2/m2 in males and <34.9 cm2/m2 in females. The Kaplan-Meier and Cox proportional hazards regression analyses were used for survival analysis and to evaluate the association between sarcopenia and mortality. RESULTS: A total of 137 patients (90 men; mean age 71.7 ± 9.6 y) were enrolled for the study, of whom 56 (40.8%) had sarcopenia. The 3-year overall survival rate in patients with CLTI who underwent endovascular revascularization was 71.2%. The sarcopenic group had a significantly worse 3-year overall survival rate than the nonsarcopenic group (55.3% versus 78.6%, P = 0.001). Multivariate Cox proportional hazard regression analyses revealed that sarcopenia (hazard ratio, 2.262; 95% confidence interval, 1.132-4.518; P = 0.021) and dialysis (hazard ratio, 3.021; 95% confidence interval, 1.337-6.823; P = 0.008) were independently associated with increased risk of all-cause mortality, whereas technical success had significantly opposing correlation with mortality. (hazard ratio, 0.400, 95% confidence interval, 0.194-0.826, P = 0.013). CONCLUSIONS: Sarcopenia can be highly prevalent in patients with CLTI who undergo endovascular revascularization, and is independently associated with long-term mortality. These results may help risk stratification to assist in personalized assessment and clinical decision-making.

Acute Kidney Injury Following Revascularization in Patients With Chronic Limb-Threatening Ischemia and Non-Dialysis-Dependent Chronic Kidney Disease: Insights From the NSQIP Database at 30-Day Follow-Up.

BACKGROUND: Patients with chronic limb-threatening ischemia (CLTI) and chronic kidney disease (CKD) are at risk of developing renal injury following revascularization. We aimed to compare the risk of adverse renal events following endovascular revascularization (ER) or open surgery (OS) in patients with CLTI and CKD. METHODS: A retrospective analysis of the National Surgical Quality Improvement Program (NSQIP) databases (2011-2017) was performed including patients with CLTI and non-dialysis-dependent CKD, comparing ER to OS. The primary outcome was a composite of postprocedural kidney injury or failure within 30 days. Thirty-day mortality, major adverse cardiac and cerebrovascular events (MACCE), amputation, readmission or target lesion revascularization (TLR) were compared using multivariate logistic regression and propensity-score matched analysis. RESULTS: A total of 5009 patients were included (ER: 2361; OS: 3409). The risk for the composite primary outcome was comparable between groups (odds ratio [OR]: 0.78, 95% confidence interval (CI): 0.53-1.17) as for kidney injury (n=54, OR: 0.97, 95% CI: 0.39-1.19) or failure (n=55, OR: 0.68, 95% CI: 0.39-1.19). In the adjusted regression, a significant benefit was observed with ER for the primary outcome (OR: 0.60, p=0.018) and renal failure (OR: 0.50, p=0.025), but not for renal injury (OR: 0.76, p=0.34). Lower rates of MACCE, TLR, and readmissions were observed after ER. Thirty-day mortality and major amputation rates did not differ. In the propensity score analysis, revascularization strategy was not associated with renal injury or failure. CONCLUSIONS: In this cohort, the incidence of renal events within 30 days of revascularization in CLTI was low and comparable between ER and OR. CLINICAL IMPACT: In a cohort of 5009 patients with chronic limb-threatening ischemia and non-end-stage chronic kidney disease (CKD), postprocedural kidney injury or failure within 30 days was comparable between patients submitted to open or endovascular revascularization (ER). Lower rates of major adverse cardiac and cerebrovascular events, target lesion revascularization, and readmissions were observed after endovascular revascularization. Based on these findings, ER should not be avoided due to fear of worsening renal function in CKD patients with chronic limb-threatening ischemia. In fact, these patients benefit more from ER regarding cardiovascular outcomes with no increased risk of kidney injury.

Outcomes of Covered Endovascular Reconstruction of the Aortic Bifurcation (CERAB) Procedure for the Treatment of Extensive Aortoiliac Occlusive Disease Using the BeGraft Balloon-Expandable Covered Stent: A Multicenter Observational Study.

PURPOSE: The covered endovascular reconstruction of the aortic bifurcation (CERAB) technique offers an alternative for Trans-Atlantic Inter-Society Consensus (TASC) C/D lesions involving the aortic bifurcation. The study aims to evaluate the outcomes of the CERAB technique for extensive aortoiliac occlusive disease (AIOD) using the BeGraft balloon-expandable covered stent (BECS). MATERIALS AND METHODS: This is a physician-initiated, multicenter, retrospective, observational study. Between June 2017 and June 2021, all consecutive patients who underwent the CERAB procedure using the BeGraft stent (Bentley InnoMed, Hechingen, Germany) in 3 clinics were enrolled. Patients' demographics, lesion characteristics, and procedural results were collected and retrospectively analyzed. Follow-up was done at 1, 6, and 12 months and then annually with clinical examination, ankle-brachial index (ABI), and duplex ultrasound. The primary endpoint was the patency at 12 months. Secondary endpoints included procedural-related complications, secondary patency, freedom from target lesion revascularization (TLR), and clinical improvement. RESULTS: In all, 120 patients (64 men) with a median age of 65 years (range: 34-84 years) were analyzed. Most patients had extensive AIOD classified as TASC II C (n=32; 26.7%) or TASC II D (n=81; 67.5%). The median duration of the procedure was 120 minutes (interquartile range [IQR]: 80-180 minutes). All 454 BeGraft stents (137 aortic and 317 peripheral) were successfully delivered and deployed. The overall procedural complication rate was 14 (11.7%). The median hospital length of stay was 5 days (IQR: 3-6 days). All patients improved clinically, and the ABI increased significantly (p<0.05). The median follow-up was 19 months (range: 6-56 months). The primary patency rate, secondary patency rate, and freedom from TLR at 12 months were 94.5%, 97.3%, and 93.5%, respectively. CONCLUSIONS: The CERAB procedure with BeGraft BECSs has a high technical success rate, favorable patency outcomes, and low morbidity, even in relatively ill patients with extensive AIOD. Prospective randomized studies on the CERAB technique are definitely recommended. CLINICAL IMPACT: This study evaluates the outcomes of BeGraft stents used during the covered endovascular reconstruction of the aortic bifurcation (CERAB) procedure. To date, several balloon-expandable covered stents have been used for this technique with satisfactory results. This study showed the safety and excellent patency of the CERAB technique in extensive AIOD using BeGraft balloon-expandable covered stents.

Endovascular treatment of re-stenotic iliac artery stents with drug-eluting balloons.

AIM: To evaluate the results of revascularization of stenotic iliac stents using drug-eluting balloons (DEBs). MATERIAL AND METHODS: Seventy-four patients with various levels of iliac stent restenosis were enrolled to study. All restenotic stents were treated using paclitaxel-coated balloons. RESULTS: Through a follow-up median period of 24 months (4-24 months), there were no in-stent re-restenosis in 55 patients (74.3%) and there was one in class 1 (1.4%), four in class 2 (5.4%), and fourteen in class 3 (18.9%). CONCLUSION: We conclude that; DEBs can be used for restenotic iliac artery stents for some Type C and D lesions, in addition to Types A and B with satisfacting results.

Comparison Between the Efficacy of Spinal Cord Stimulation and of Endovascular Revascularization in the Treatment of Diabetic Foot Ulcers: A Retrospective Observational Study.

OBJECTIVE: We aimed to compare the effects of spinal cord stimulation (SCS) with those of endovascular revascularization on the treatment of diabetic foot ulcers. MATERIALS AND METHODS: A total of 104 patients with diabetic foot ulcers who met the inclusion criteria were retrospectively analyzed and classified to the SCS treatment group (n = 46) and endovascular revascularization treatment group (n = 46). The quality-of-life scores (Quality of Life Scale for Patients with Liver Cancer v2.0), visual pain analog scale score, lower limb skin temperature, lower limb arterial ultrasound results, and lower extremity electromyography results were analyzed to compare the efficacy of the two treatments for diabetic foot ulcers in the two groups before surgery and six months after surgery. RESULTS: A total of 92 patients (men: 73.9%, mean age: 66.51 ± 11.67 years) completed the six-month postoperative follow-up period. The patients in the SCS treatment group had a higher quality-of-life score (25.54% vs 13.77%, p < 0.05), a larger reduction in pain scores (69.18% vs 37.21%, p < 0.05), and a larger reduction in foot temperature (18.56% vs 7.24%, p < 0.05) than those of the endovascular revascularization treatment group at six months after surgery. The degree of vasodilation in the lower limbs on color Doppler arterial ultrasound and the nerve conduction velocity were higher in the SCS treatment group than in the endovascular revascularization treatment group at six months after surgery (p < 0.05). CONCLUSION: SCS was more effective than endovascular revascularization in improving quality of life, relieving pain, improving lower limb skin temperature, increasing lower limb blood flow, and improving nerve conduction in patients with diabetic foot ulcers at six months after surgery.

Serum high mobility group box-1 levels associated with cardiovascular events after lower extremity revascularization: a prospective study of a diabetic population.

BACKGROUND: Peripheral arterial disease (PAD) is one of the most disabling cardiovascular complications of type 2 diabetes mellitus and is indeed associated with a high risk of cardiovascular and limb adverse events. High mobility group box-1 (HMGB-1) is a nuclear protein involved in the inflammatory response that acts as a pro-inflammatory cytokine when released into the extracellular space. HMBG-1 is associated with PAD in diabetic patients. The aim of this study was to evaluate the association between serum HMGB-1 levels and major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after lower-extremity endovascular revascularization (LER) in a group of diabetic patients with chronic limb-threatening ischemia (CLTI). METHODS: We conducted a prospective observational study of 201 diabetic patients with PAD and CLTI requiring LER. Baseline serum HMGB-1 levels were determined before endovascular procedure. Data on cardiovascular and limb outcomes were collected in a 12-month follow-up. RESULTS: During the follow-up period, 81 cases of MACE and 93 cases of MALE occurred. Patients who subsequently developed MACE and MALE had higher serum HMGB-1 levels. Specifically, 7.5 ng/mL vs 4.9 ng/mL (p < 0.01) for MACE and 7.2 ng/mL vs 4.8 ng/mL (p < 0.01) for MALE. After adjusting for traditional cardiovascular risk factors, the association between serum HMGB-1 levels and cardiovascular outcomes remained significant in multivariable analysis. In our receiver operating characteristic (ROC) curve analysis, serum HMGB-1 levels were a good predictor of MACE incidence (area under the curve [AUC] = 0.78) and MALE incidence (AUC = 0.75). CONCLUSIONS: This study demonstrates that serum HMGB-1 levels are associated with the incidence of MACE and MALE after LER in diabetic populations with PAD and CLTI.

Contemporary outcomes of concomitant suprainguinal bypass with infrainguinal revascularization procedures in patients with chronic limb-threatening ischemia.

OBJECTIVE: Combined suprainguinal and infrainguinal revascularization is sometimes necessary in the treatment of patients with chronic limb-threatening ischemia (CLTI). However, data on outcomes of concomitant revascularization procedures are lacking. We studied the outcomes of patients with CLTI who underwent suprainguinal bypass (SIB) alone, SIB with concomitant infrainguinal bypass (IIB), and SIB with concomitant infrainguinal peripheral endovascular intervention (IIPVI). METHODS: We reviewed all patients in the Vascular Quality Initiative with CLTI who underwent SIB from January 2010 to June 2020. Logistic regression, Kaplan-Meier survival estimates, log-rank tests, and Cox regression were used to analyze outcomes. Outcomes were 30-day mortality, perioperative myocardial infarction, perioperative major amputation, 1-year amputation-free survival, and 5-year survival. RESULTS: Of 8037 patients included, 81.3% (n = 6537) underwent SIB alone, 9.7% (n = 783) underwent SIB+IIB, and 8.9% (n = 717) underwent SIB+IIPVI. The indication for surgery was rest pain in 5040 (62.5%) and tissue loss in 3031 (37.6%). There were no significant differences in 30-day mortality and perioperative myocardial infarction rates. However, there was 2.8-fold increased odds of perioperative major amputation in both SIB+IIPVI (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.30-5.88; P = .008) and SIB+IIB (OR, 2.79; 95% CI, 1.38-5.54; P = .004) among patients with rest pain as compared with SIB alone. Comparing SIB+IIPVI with SIB alone, there were no significant differences in 1-year freedom from amputation and amputation-free survival. SIB+IIPVI was associated with a 27% increased risk of 5-year mortality (hazard ratio [HR], 1.27; 95% CI, 1.03-1.55; P = .035). Compared with SIB alone, SIB+IIB was associated with 97% increased risk of 1-year major amputation among patients with rest pain (HR, 1.97; 95% CI, 1.06-3.69; P = .033), but a 47% decreased risk of 1-year major amputation or death for patients with tissue loss (HR, 0.53; 95% CI, 0.37-0.78; P = .001). SIB+IIPVI, compared with SIB+IIB, was associated with a two-fold increased risk of 1-year major amputation or death (HR, 2.04; 95% CI, 1.04-2.23), P = .003) and a 52% increased risk of 5-year mortality (HR,1.52; 95% CI, 1.04-2.24; P = .032) among patients with tissue loss. CONCLUSIONS: This study shows that SIB with concomitant infrainguinal revascularization in patients with rest pain is associated with an increased risk of amputation, whereas SIB+IIB in patients with tissue loss is associated with decreased risk of amputation or death. SIB+IIB outperformed SIB+IIPVI in patients with tissue loss. SIB with infrainguinal revascularization should be limited in patients with rest pain in line with current guidelines, but SIB+IIB may be preferred in patients with tissue loss.

Toward a Better Understanding of Muscle Microvascular Perfusion During Exercise in Patients With Peripheral Artery Disease: The Effect of Lower-Limb Revascularization.

PURPOSE: Leg muscle microvascular blood flow (perfusion) is impaired in response to maximal exercise in patients with peripheral artery disease (PAD); however, during submaximal exercise, microvascular perfusion is maintained due to a greater increase in microvascular blood volume compared with that seen in healthy adults. It is unclear whether this submaximal exercise response reflects a microvascular impairment, or whether it is a compensatory response for the limited conduit artery flow in PAD. Therefore, to clarify the role of conduit artery blood flow, we compared whole-limb blood flow and skeletal muscle microvascular perfusion responses with exercise in patients with PAD (n=9; 60±7 years) prior to, and following, lower-limb endovascular revascularization. MATERIALS AND METHODS: Microvascular perfusion (microvascular volume × flow velocity) of the medial gastrocnemius muscle was measured before and immediately after a 5 minute bout of submaximal intermittent isometric plantar-flexion exercise using contrast-enhanced ultrasound imaging. Exercise contraction-by-contraction whole-leg blood flow and vascular conductance were measured using strain-gauge plethysmography. RESULTS: With revascularization there was a significant increase in whole-leg blood flow and conductance during exercise (p<0.05). Exercise-induced muscle microvascular perfusion response did not change with revascularization (pre-revascularization: 3.19±2.32; post-revascularization: 3.89±1.67 aU.s-1; p=0.38). However, the parameters that determine microvascular perfusion changed, with a reduction in the microvascular volume response to exercise (pre-revascularization: 6.76±3.56; post-revascularization: 2.42±0.69 aU; p<0.01) and an increase in microvascular flow velocity (pre-revascularization: 0.25±0.13; post-revascularization: 0.59±0.25 s-1; p=0.02). CONCLUSION: These findings suggest that patients with PAD compensate for the conduit artery blood flow impairment with an increase in microvascular blood volume to maintain muscle perfusion during submaximal exercise. CLINICAL IMPACT: The findings from this study support the notion that the impairment in conduit artery blood flow in patients with PAD leads to compensatory changes in microvascular blood volume and flow velocity to maintain muscle microvascular perfusion during submaximal leg exercise. Moreover, this study demonstrates that these microvascular changes are reversed and become normalized with successful lower-limb endovascular revascularization.

Retrograde endovascular revascularization for chronic total occlusion of the internal carotid artery: a case report.

Endovascular revascularization of a chronically occluded internal carotid artery (ICA) is challenging because the occlusive segment can be long and tortuous. A case is presented of a successful recanalization of a chronically occluded ICA by retrograde passing of a guidewire from the intracranial ICA to the cervical ICA via the posterior communicating artery. This case suggests that a retrograde approach for reopening an occluded artery may be useful during neurovascular interventions, similar to percutaneous coronary interventions. In this patient, daily transient ischemic attacks disappeared after successful recanalization of the ICA.

Sex-related differences in outcome after endovascular revascularization for lower extremity artery disease.

Background: Sex-related differences may influence the outcome of endovascular revascularization (EVR) in patients with lower extremity arterial disease (LEAD) even under optimized healthcare supply. Patients and methods: LEAD patients who underwent EVR at the Department of Cardiology I - Coronary and Peripheral Vascular Disease, Heart Failure, University Hospital Muenster, Germany between 2014 and 2016 were included into the retrospective study. Detailed information on risk factors and co-morbidities, medication, LEAD related measures, and interventional parameters were assessed. Outcome defined as technical success rate, complications, and mortality was analyzed up to 12 months follow-up. Results: In total, 165 female and 437 male LEAD patients were included. Women and men presented with comparable severity of LEAD in terms of critical limb threatening ischemia (46.2%), wound status (34.9%), and amputation rate (9.6%, all n.s.) at index. Intake of platelet inhibitors (65.8% female vs. 70.0% male), oral anticoagulants (21.3% vs. 25.4%), and statins (65.6% vs. 76.0%) was observed less frequently in female patients. Against the background of high technical success (85%), in-hospital death (0.8%), severe adverse cardiac (MCE; 1.7%), and limb events (MALE; 6.1%) occurred at low rates in either sex. Adjusted long-term mortality was not affected by patients' sex (female HR 0.755; p=0.312). Conclusions: Despite critical LEAD stages in every second patient, EVR was performed safe with high technical success rates in female and male patients. Long-term outcomes were observed at comparatively low rates in both sexes at the specialized vascular center. During aftercare, supply with statin therapy turned out improvable particularly in female LEAD patients.

Revascularization of multiple tibial arteries is not associated with improved limb salvage.

OBJECTIVE: We sought to determine the benefit of performing multiple tibial artery revascularization compared with single vessel revascularization for patients with chronic limb-threatening ischemia (CLTI). METHODS: We performed a single-center, retrospective cohort study of all patients with CLTI treated with below-the-knee endovascular intervention from 2012 to 2019. Group 1 included patients who had undergone single tibial artery revascularization. Group 2 included patients who had undergone multiple (two or more) tibial artery revascularization. More proximal disease, if present, was treated, in addition to the tibial disease. The primary endpoint was freedom from amputation. The secondary endpoints included the reintervention rates and all-cause mortality. RESULTS: A total of 527 limbs in 470 patients with CLTI (nonhealing ulcers, 62%; gangrene, 33%; and ischemic rest pain, 5%) were included in the present study. Of the 527 limbs, 245 (46%) had undergone single vessel revascularization and 282 (54%) had undergone multiple vessel revascularization. The mean follow-up was 19 ± 18 months. No difference was found in freedom from amputation between the two groups (68% vs 63%; P = .109). On multivariable analysis, the factors associated with amputation included dialysis (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.16-2.45), dyslipidemia (OR, 1.37; 95% CI, 0.96-1.94), and gangrene (OR, 2.08; 95% CI, 1.50-2.98). No differences were found in the reintervention rates between the two groups (21.2% vs 16.7%; P = .13). The overall survival rate was 73% in both study groups. CONCLUSIONS: The results from the present large, single-center study have demonstrated that multiple below-the-knee vessel revascularization is not associated with improved limb salvage compared with single vessel revascularization.

Smaller Superficial Femoral Artery is Associated with Worse Outcomes after Percutaneous Transluminal Angioplasty for De Novo Atherosclerotic Disease.

BACKGROUND: With the exponential increase in the use of endovascular techniques in the treatment of peripheral artery disease, our understanding of factors that affect intervention failures continues to grow. We sought to assess the outcomes of percutaneous transluminal angioplasty for isolated de novo superficial femoral artery (SFA) disease based on balloon diameter. METHODS: The Vascular Quality Initiative database was queried for patients undergoing percutaneous balloon angioplasty for isolated de novo atherosclerotic SFA disease. Based on the diameter of the angioplasty balloon as a surrogate measure of arterial diameter, patients were stratified into 2 groups: group 1, balloon diameter <5 mm (354 patients) and group 2, balloon diameter ≥5 mm (1,550 patients). The primary patency and major adverse limb event (MALE) were estimated by the Kaplan-Meier method and compared with the log-rank test, based on vessel diameter. Multivariable Cox regression analysis was used to determine factors associated with the primary patency. RESULTS: From January 2010 through December 2018, a total of 1,904 patients met criteria for analysis, with a mean follow-up of 13.3 ± 4.5 months. The mean balloon diameters were 3.92 ± 0.26 mm and 5.47 ± 0.55 mm in group 1 and 2, respectively (P < 0.001). The mean length of treatment and distribution of TASC lesions were not statistically different between the groups. Primary patency at 18 months was significantly lower in group 1, compared with group 2 (55% vs. 67%; log-rank P < 0.001). The MALE rate was higher in group 1 than group 2 (33% vs. 26%; log-rank P < 0.001). Among patients with claudication, there was no significant difference in the primary patency (61% vs 68%; log-rank P = 0.073) and MALE (27% vs. 22%; log-rank P = 0.176) at 18 months between groups 1 and 2, respectively. However, in patients with CLTI, group 1 had significantly lower 18-month primary patency (47% vs. 64%; log-rank P < 0.014) and higher MALE rates (41% vs. 35%; log-rank P = 0.012) than group 2. Cox proportional hazard analysis confirmed that balloon diameter < 5 mm was independently associated with increased risks of primary patency loss (HR 1.35; 95% CI, 1.04-1.72; P = 0.021) and MALE (HR 1.29; 95% CI, 1-1.67; P = 0.048) at 18-months. CONCLUSIONS: In patients undergoing isolated SFA balloon angioplasty for CLTI, smaller SFA (<5 mm) was associated with worse primary patency and MALE. Using balloon size as a surrogate, our findings suggest that patients with a smaller SFA diameter appear to be at increased risk for treatment failure and warrant closer surveillance. Furthermore, these patients may also be considered for alternative approaches, including open revascularization.

Hypoperfusion Intensity Ratio Predicts Malignant Edema and Functional Outcome in Large-Vessel Occlusive Stroke with Poor Revascularization.

BACKGROUND AND OBJECTIVE: Malignant cerebral edema (MCE) is a well-known complication in patients with acute ischemic stroke with core infarcts ≥ 80 mL caused by large-vessel occlusions. MCE can also develop in patients with smaller infarcts with moderate -to-large volume of tissue at risk who do not achieve successful revascularization with endovascular thrombectomy (ET). Features that predict the development of MCE in this population are not well-described. We aim to identify predictors of MCE and 90-day functional outcome in stroke patients with an anterior circulation large vessel occlusion (LVO) and a < 80 mL ischemic core who do not achieve complete reperfusion. METHODS: We reviewed our institutional stroke registry and included patients who achieved unsuccessful revascularization, mTICI 0-2a, after ET and whose baseline imaging was notable for a core infarct < 80 mL, a Tmax > 6 s volume ≥ 80 mL, and a mismatch ratio ≥ 1.8. MCE was defined as ≥ 5 mm of midline shift on follow-up imaging, obtained 6-48 h after the pre-ET perfusion scan. RESULTS: Thirty-six patients met inclusion criteria. Unadjusted analysis demonstrated that younger age, higher systolic blood pressure, larger core volume, and higher hypoperfusion intensity ratio (HIR) were associated with MCE (all p < 0.02). In multivariate logistic regression analysis, age, HIR, and core infarct volume were independent predictors of MCE. The optimal HIR threshold to predict MCE was ≥ 0.54 (OR 14.7, 95% CI 2.4-78.0, p = 0.003). HIR was also associated with 3-month mRS (HIR ≥ 0.54 for mRS of 3-6: OR 10.8, 95% CI 1.9-44.0, p = 0.02). CONCLUSIONS: Younger age, larger core infarct volume, and higher HIR are predictive of MCE in patients with anterior circulation LVO, moderate-to-large tissue at risk, and suboptimal revascularization. HIR is correlated with three-month functional outcomes.