Management and outcomes of venous thoracic outlet decompression: A transition to the infraclavicular approach.

OBJECTIVE: Venous thoracic outlet syndrome (vTOS) is caused by compression of the subclavian vein at the costoclavicular space, which may lead to vein thrombosis. Current treatment includes thoracic outlet decompression with or without venolysis. However, given its relatively low prevalence, the existing literature is limited. Here, we report our single-institution experience in the treatment of vTOS. METHODS: We performed a retrospective review of all patients who underwent rib resection for vTOS at our institution from 2007 to 2022. Demographic, procedural details, and perioperative and long-term outcomes were reviewed. RESULTS: A total of 76 patients were identified. The mean age was 36 years. Swelling was the most common symptom (93%), followed by pain (6.6%). Ninety percent of patients had associated deep vein thrombosis, with 99% of these patients starting anticoagulation preoperatively. A total of 91% of patients underwent rib resection via the infraclavicular approach, 2% via the paraclavicular approach (due to a neurogenic component), and 7% via the transaxillary approach. Eighty-three percent of patients had endovascular intervention before or at the time of the rib resection, with catheter-directed thrombolysis (87%), followed by angioplasty (71%) and rheolytic thrombectomy (57%) being the most common interventions. The median time from endovascular intervention to rib resection was 14 days, with 25% at the same admission. The median postoperative stay was 3 days (2-5 days). There was no perioperative mortality or nerve injury. Fourteen percent of patients had postoperative complications, with bleeding complications (12%) being the most common. Waiting more than 30 days between initial endovascular intervention and rib resection was not associated with decreased risk of bleeding complications. Patients were seen postoperatively at 1-month (physical examination) and 6-month (duplex) intervals or for any new or recurrent symptoms. Twenty-two percent of our overall patient population underwent reintervention, most commonly angioplasty (21%). At last follow-up, 97% of subclavian veins were patent, and 93% of patients were symptom free. CONCLUSIONS: Over the last decade, we have transitioned to an infraclavicular approach for isolated vTOS, with low perioperative morbidity and good patency rates. These results support the adoption of the infraclavicular approach with adjunct endovascular techniques as a safe and efficacious treatment of vTOS.

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

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

The impact of heparin and direct thrombin inhibitors on cell-penetrating polymer siRNA transfection.

Gene therapy using siRNA has become a promising strategy to achieve targeted gene knockdown for treatment of cardiovascular pathologies. However, efficient siRNA transfection often relies on cationic delivery vectors such as synthetic cell-penetrating polymers which are susceptible to interference by negatively charged molecules. Anticoagulants such as heparin, which is negatively charged and widely used in cardiovascular applications, may pose a significant barrier to effective siRNA delivery. We therefore conducted in vitro studies utilizing human smooth muscle and endothelial cells transfected with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and ß2-microglobulin (B2M) siRNA in the presence of heparin, argatroban, and bivalirudin in order to determine which anticoagulant therapy is most compatible for siRNA delivery. We observed that while heparin, at clinical doses, decreases the efficiency of siRNA targeted mRNA knockdown, mRNA knockdown is not inhibited in the presence of either argatroban or bivalirudin. Our data suggests that heparin should be avoided during siRNA therapy with cationic transfection agents, and argatroban and bivalirudin should be used in its stead.

Early Injury Landscape in Vein Harvest by Single-Cell and Spatial Transcriptomics.

BACKGROUND: Vein graft failure following cardiovascular bypass surgery results in significant patient morbidity and cost to the healthcare system. Vein graft injury can occur during autogenous vein harvest and preparation, as well as after implantation into the arterial system, leading to the development of intimal hyperplasia, vein graft stenosis, and, ultimately, bypass graft failure. Although previous studies have identified maladaptive pathways that occur shortly after implantation, the specific signaling pathways that occur during vein graft preparation are not well defined and may result in a cumulative impact on vein graft failure. We, therefore, aimed to elucidate the response of the vein conduit wall during harvest and following implantation, probing the key maladaptive pathways driving graft failure with the overarching goal of identifying therapeutic targets for biologic intervention to minimize these natural responses to surgical vein graft injury. METHODS: Employing a novel approach to investigating vascular pathologies, we harnessed both single-nuclei RNA-sequencing and spatial transcriptomics analyses to profile the genomic effects of vein grafts after harvest and distension, then compared these findings to vein grafts obtained 24 hours after carotid-carotid vein bypass implantation in a canine model (n=4). RESULTS: Spatial transcriptomic analysis of canine cephalic vein after initial conduit harvest and distention revealed significant enrichment of pathways (P<0.05) involved in the activation of endothelial cells (ECs), fibroblasts, and vascular smooth muscle cells, namely pathways responsible for cellular proliferation and migration and platelet activation across the intimal and medial layers, cytokine signaling within the adventitial layer, and ECM (extracellular matrix) remodeling throughout the vein wall. Subsequent single-nuclei RNA-sequencing analysis supported these findings and further unveiled distinct EC and fibroblast subpopulations with significant upregulation (P<0.05) of markers related to endothelial injury response and cellular activation of ECs, fibroblasts, and vascular smooth muscle cells. Similarly, in vein grafts obtained 24 hours after arterial bypass, there was an increase in myeloid cell, protomyofibroblast, injury response EC, and mesenchymal-transitioning EC subpopulations with a concomitant decrease in homeostatic ECs and fibroblasts. Among these markers were genes previously implicated in vein graft injury, including VCAN, FBN1, and VEGFC, in addition to novel genes of interest, such as GLIS3 and EPHA3. These genes were further noted to be driving the expression of genes implicated in vascular remodeling and graft failure, such as IL-6, TGFBR1, SMAD4, and ADAMTS9. By integrating the spatial transcriptomics and single-nuclei RNA-sequencing data sets, we highlighted the spatial architecture of the vein graft following distension, wherein activated and mesenchymal-transitioning ECs, myeloid cells, and fibroblasts were notably enriched in the intima and media of distended veins. Finally, intercellular communication network analysis unveiled the critical roles of activated ECs, mesenchymal-transitioning ECs, protomyofibroblasts, and vascular smooth muscle cells in upregulating signaling pathways associated with cellular proliferation (MDK [midkine], PDGF [platelet-derived growth factor], VEGF [vascular endothelial growth factor]), transdifferentiation (Notch), migration (ephrin, semaphorin), ECM remodeling (collagen, laminin, fibronectin), and inflammation (thrombospondin), following distension. CONCLUSIONS: Vein conduit harvest and distension elicit a prompt genomic response facilitated by distinct cellular subpopulations heterogeneously distributed throughout the vein wall. This response was found to be further exacerbated following vein graft implantation, resulting in a cascade of maladaptive gene regulatory networks. Together, these results suggest that distension initiates the upregulation of pathological pathways that may ultimately contribute to bypass graft failure and presents potential early targets warranting investigation for targeted therapies. This work highlights the first applications of single-nuclei and spatial transcriptomic analyses to investigate venous pathologies, underscoring the utility of these methodologies and providing a foundation for future investigations.

Lower Extremity Bypass for Occlusive Disease: A Brief History.

BACKGROUND: This is a narrative review that aims to highlight key advancements that led to the current state of lower extremity bypass surgery. It focuses on key contributors during the last century who have driven the standardization of surgical treatment of peripheral arterial occlusive disease. METHODS: A narrative review was conducted utilizing available resources in the scientific and historical literature to track landmark achievements in the development of modern lower extremity bypass surgery for occlusive disease, focusing primarily on the last century of advancement. RESULTS: Several critical conceptual, technological, and technical landmarks were identified as critical components of modern lower extremity bypass surgery. This includes fundamental developments in the techniques of vascular anastomosis led by Carrel and others, a developing understanding of vascular occlusive disease as a localized and segmental process with broad implementation of the techniques of arteriography, and the development of safe thromboendarterectomy aided by the development and utilization of heparin for anticoagulation. These factors led to the first femoral-to-popliteal artery bypass by Jean Kunlin in 1948. From here, advances in vascular prosthetic material pioneered by Voorhees and others, alternative vascular conduits, increasing acceptance of tibial revascularization, and dispelling the myth of diabetic "small vessel" disease broadened revascularization options for patients with complex patterns of occlusive disease and those who have limited conduit availability. CONCLUSIONS: Modern lower extremity bypass surgery for occlusive disease arose steadily over a course of a century, driven by complex problem-solving in the pathophysiological understanding of atherosclerosis, technical developments in vascular anastomosis and arteriography, and evolution of conduit materials and pharmacologic therapy. Future advancements in bypass surgery are targeted at solving the complex problems of anastomotic intimal hyperplasia, expanding technology for alternative vascular conduits, ongoing optimization of risk factors, and scrutinizing of outcomes to make patient-centered, evidence-based decisions regarding revascularization strategy.

Advancements in Omics and Breakthrough Gene Therapies: A Glimpse into the Future of Peripheral Artery Disease.

Peripheral artery disease (PAD), a highly prevalent global disease, associates with significant morbidity and mortality in affected patients. Despite progress in endovascular and open revascularization techniques for advanced PAD, these interventions grapple with elevated rates of arterial restenosis and vein graft failure attributed to intimal hyperplasia (IH). Novel multiomics technologies, coupled with sophisticated analyses tools recently powered by advances in artificial intelligence, have enabled the study of atherosclerosis and IH with unprecedented single-cell and spatial precision. Numerous studies have pinpointed gene hubs regulating pivotal atherogenic and atheroprotective signaling pathways as potential therapeutic candidates. Leveraging advancements in viral and nonviral gene therapy (GT) platforms, gene editing technologies, and cutting-edge biomaterial reservoirs for delivery uniquely positions us to develop safe, efficient, and targeted GTs for PAD-related diseases. Gene therapies appear particularly fitting for ex vivo genetic engineering of IH-resistant vein grafts. This manuscript highlights currently available state-of-the-art multiomics approaches, explores promising GT-based candidates, and details GT delivery modalities employed by our laboratory and others to thwart mid-term vein graft failure caused by IH, as well as other PAD-related conditions. The potential clinical translation of these targeted GTs holds the promise to revolutionize PAD treatment, thereby enhancing patients' quality of life and life expectancy.

Bailout Distal Internal Carotid Artery Stenting after Carotid Endarterectomy: Indications, Technique, and Outcomes.

BACKGROUND: Distal internal carotid artery (ICA) stenting may be employed as a bailout maneuver when an inadequate end point or clamp injury is encountered at the time of carotid endarterectomy (CEA) in a surgically inaccessible region of the distal ICA. We sought to characterize the indications, technique, and outcomes for this infrequently encountered clinical scenario. METHODS: We performed a retrospective review of all patients who underwent distal ICA stenting at the time of CEA at our institution between September 2008 and July 2022. Procedural details and postoperative follow-up were reviewed for each patient. RESULTS: Six patients were identified during the study period. All were male with an age range of 63 to 82 years. Five underwent carotid revascularization for asymptomatic carotid artery stenosis, and one patient was treated for amaurosis fugax. Three patients were on dual antiplatelet therapy preoperatively, whereas 2 were on aspirin monotherapy, and one was on aspirin and low-dose rivaroxaban. Five patients underwent CEA with patch angioplasty, and one underwent eversion CEA. The indication for stenting was distal ICA dissection due to clamp or shunt injury in 2 patients and an inadequate distal ICA end point in 4 patients. In all cases, access for stenting was obtained under direct visualization within the common carotid artery, and a standard carotid stent was deployed with its proximal aspect landing within the endarterectomized site. Embolic protection was typically achieved via proximal common carotid artery and external carotid artery clamping for flow arrest with aspiration of debris before restoration of antegrade flow. There was 100% technical success. Postoperatively, 2 patients were found to have a cranial nerve injury, likely occurring due to the need for high ICA exposure. Median length of stay was 2 days (range 1-7 days) with no instances of perioperative stroke or myocardial infarction. All patients were discharged on dual antiplatelet therapy with no further occurrence of stroke, carotid restenosis, or reintervention through a median follow-up of 17 months. CONCLUSIONS: Distal ICA stenting is a useful adjunct in the setting of CEA complicated by inadequate end point or vessel dissection in a surgically inaccessible region of the ICA and can minimize the need for high-risk extensive distal dissection of the ICA in this situation.

A Multidisciplinary Protocolized Approach for Ruptured Abdominal Aortic Aneurysm Management: A Retrospective Before-After Study.

OBJECTIVES: To investigate whether implementation of a multidisciplinary protocol for ruptured abdominal aortic aneurysm (rAAA) management reduces rates of adverse complications. DESIGN: A retrospective before-after study. SETTING: A tertiary-care academic hospital. PARTICIPANTS: Adult patients who underwent open or endovascular rAAA repair; data were stratified into before-protocol implementation (group 1: 2015-2018) and after-protocol implementation (group 2: 2019-2022) groups. INTERVENTION: The protocol details the workflow for vascular surgery, anesthesia, emergency department, and operating room staff for a rAAA case; training was accomplished through yearly workshops. MEASUREMENTS AND MAIN RESULTS: The primary outcome was in-hospital mortality. Secondary outcomes included all-cause morbidity and other major complications. Differences in postoperative complication rates between groups were assessed using Pearson's χ2 test. Of the 77 patients included undergoing rAAA repair, 41 (53.2%) patients were in group 1, and 36 (46.8%) patients were in group 2. Patients in group 2 had a significantly shorter median time to incision (1.0 v 0.7 hours, p = 0.022) and total procedure time (180.0 v 160.5 minutes, p = 0.039) for both endovascular and open repair. After protocol implementation, patients undergoing endovascular repair exhibited significantly lower rates of mortality (46.2% v 20.0%, p = 0.048), all-cause morbidity (65.4% v 44.0%, p = 0.050), and renal complications (15.4% v 0.0%, p = 0.036); patients undergoing open repair for a rAAA exhibited significantly lower rates of mortality (53.3% v 27.3%, p = 0.018) and bowel ischemia (26.7% v 0.0%, p = 0.035). CONCLUSIONS: Implementation of a multidisciplinary protocol for the management of a rAAA may reduce rates of adverse complications and improve the quality of care.

Amputation Rates and Associated Social Determinants of Health in the Most Populous US Counties.

Importance: Social Determinants of Health (SDOH) have been found to be associated with health outcome disparities in patients with peripheral artery disease (PAD). However, the association of specific components of SDOH and amputation has not been well described. Objective: To evaluate whether individual components of SDOH and race are associated with amputation rates in the most populous counties of the US. Design, Setting, and Participants: In this population-based cross-sectional study of the 100 most populous US counties, hospital discharge rates for lower extremity amputation in 2017 were assessed using the Healthcare Cost and Utilization Project State Inpatient Database. Those data were matched with publicly available demographic, hospital, and SDOH data. Data were analyzed July 3, 2022, to March 5, 2023. Main outcome and Measures: Amputation rates were assessed across all counties. Counties were divided into quartiles based on amputation rates, and baseline characteristics were described. Unadjusted linear regression and multivariable regression analyses were performed to assess associations between county-level amputation and SDOH and demographic factors. Results: Amputation discharge data were available for 76 of the 100 most populous counties in the United States. Within these counties, 15.3% were African American, 8.6% were Asian, 24.0% were Hispanic, and 49.6% were non-Hispanic White; 13.4% of patients were 65 years or older. Amputation rates varied widely, from 5.5 per 100 000 in quartile 1 to 14.5 per 100 000 in quartile 4. Residents of quartile 4 (vs 1) counties were more likely to be African American (27.0% vs 7.9%, P < .001), have diabetes (10.6% vs 7.9%, P < .001), smoke (16.5% vs 12.5%, P < .001), be unemployed (5.8% vs 4.6%, P = .01), be in poverty (15.8% vs 10.0%, P < .001), be in a single-parent household (41.9% vs 28.6%, P < .001), experience food insecurity (16.6% vs 12.9%, P = .04), or be physically inactive (23.1% vs 17.1%, P < .001). In unadjusted linear regression, higher amputation rates were associated with the prevalence of several health problems, including mental distress (ß, 5.25 [95% CI, 3.66-6.85]; P < .001), diabetes (ß, 1.73 [95% CI, 1.33-2.15], P < .001), and physical distress (ß, 1.23 [95% CI, 0.86-1.61]; P < .001) and SDOHs, including unemployment (ß, 1.16 [95% CI, 0.59-1.73]; P = .03), physical inactivity (ß, 0.74 [95% CI, 0.57-0.90]; P < .001), smoking, (ß, 0.69 [95% CI, 0.46-0.92]; P = .002), higher homicide rate (ß, 0.61 [95% CI, 0.45-0.77]; P < .001), food insecurity (ß, 0.51 [95% CI, 0.30-0.72]; P = .04), and poverty (ß, 0.46 [95% CI, 0.32-0.60]; P < .001). Multivariable regression analysis found that county-level rates of physical distress (ß, 0.84 [95% CI, 0.16-1.53]; P = .03), Black and White racial segregation (ß, 0.12 [95% CI, 0.06-0.17]; P < .001), and population percentage of African American race (ß, 0.06 [95% CI, 0.00-0.12]; P = .03) were associated with amputation rate. Conclusions and Relevance: Social determinants of health provide a framework by which the associations of environmental factors with amputation rates can be quantified and potentially used to guide interventions at the local level.

Association of stroke or death with severity of carotid lesion calcification in patients undergoing carotid artery stenting.

OBJECTIVE: Carotid artery stenting (CAS) for heavily calcified lesions is controversial due to concern for stent failure and increased perioperative stroke risk. However, the degree to which calcification affects outcomes is poorly understood, particularly in transcarotid artery revascularization (TCAR). With the precipitous increase in TCAR use and its expansion to standard surgical-risk patients, we aimed to determine the impact of lesion calcification on CAS outcomes to ensure its safe and appropriate use. METHODS: We identified patients in the Vascular Quality Initiative who underwent first-time transfemoral CAS (tfCAS) and TCAR between 2016 and 2021. Patients were stratified into groups based on degree of lesion calcification: no calcification, 1% to 50% calcification, 51% to 99% calcification, and 100% circumferential calcification or intraluminal protrusion. Outcomes included in-hospital and 1-year composite stroke/death, as well as individual stroke, death, and myocardial infarction outcomes. Logistic regression was used to evaluate associations between degree of calcification and these outcomes. RESULTS: Among 21,860 patients undergoing CAS, 28% patients had no calcification, 34% had 1% to 50% calcification, 35% had 51% to 99% calcification, and 3% had 100% circumferential calcification/protrusion. Patients with 51% to 99% and circumferential calcification/protrusion had higher odds of in-hospital stroke/death (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.02-1.6; P = .034; OR, 1.9; 95% CI, 1.1-2.9; P = .004, respectively) compared with those with no calcification. Circumferential calcification was also associated with increased risk for in-hospital myocardial infarction (OR, 3.5; 95% CI, 1.5-8.0; P = .003). In tfCAS patients, only circumferential calcification/protrusion was associated with higher in-hospital stroke/death odds (OR, 2.0; 95% CI, 1.2-3.4; P = .013), whereas for TCAR patients, 51% to 99% calcification was associated with increased odds of in-hospital stroke/death (OR, 1.5; 95% CI, 1.1-2.2; P = .025). At 1 year, circumferential calcification/protrusion was associated with higher odds of ipsilateral stroke/death (12.4% vs 6.6%; hazard ratio, 1.64; P = .002). CONCLUSIONS: Among patients undergoing CAS, there is an increased risk of in-hospital stroke/death for lesions with >50% calcification or circumferential/protruding plaques. Increasing severity of carotid lesion calcification is a significant risk factor for stroke/death in patients undergoing CAS, regardless of approach.

Integrated single-nuclei and spatial transcriptomic analysis reveals propagation of early acute vein harvest and distension injury signaling pathways following arterial implantation.

Background: Vein graft failure (VGF) following cardiovascular bypass surgery results in significant patient morbidity and cost to the healthcare system. Vein graft injury can occur during autogenous vein harvest and preparation, as well as after implantation into the arterial system, leading to the development of intimal hyperplasia, vein graft stenosis, and, ultimately, bypass graft failure. While previous studies have identified maladaptive pathways that occur shortly after implantation, the specific signaling pathways that occur during vein graft preparation are not well defined and may result in a cumulative impact on VGF. We, therefore, aimed to elucidate the response of the vein conduit wall during harvest and following implantation, probing the key maladaptive pathways driving graft failure with the overarching goal of identifying therapeutic targets for biologic intervention to minimize these natural responses to surgical vein graft injury. Methods: Employing a novel approach to investigating vascular pathologies, we harnessed both single-nuclei RNA-sequencing (snRNA-seq) and spatial transcriptomics (ST) analyses to profile the genomic effects of vein grafts after harvest and distension, then compared these findings to vein grafts obtained 24 hours after carotid-cartoid vein bypass implantation in a canine model (n=4). Results: Spatial transcriptomic analysis of canine cephalic vein after initial conduit harvest and distention revealed significant enrichment of pathways (P < 0.05) involved in the activation of endothelial cells (ECs), fibroblasts (FBs), and vascular smooth muscle cells (VSMCs), namely pathways responsible for cellular proliferation and migration and platelet activation across the intimal and medial layers, cytokine signaling within the adventitial layer, and extracellular matrix (ECM) remodeling throughout the vein wall. Subsequent snRNA-seq analysis supported these findings and further unveiled distinct EC and FB subpopulations with significant upregulation (P < 0.00001) of markers related to endothelial injury response and cellular activation of ECs, FBs, and VSMCs. Similarly, in vein grafts obtained 24 hours after arterial bypass, there was an increase in myeloid cell, protomyofibroblast, injury-response EC, and mesenchymal-transitioning EC subpopulations with a concomitant decrease in homeostatic ECs and fibroblasts. Among these markers were genes previously implicated in vein graft injury, including VCAN (versican), FBN1 (fibrillin-1), and VEGFC (vascular endothelial growth factor C), in addition to novel genes of interest such as GLIS3 (GLIS family zinc finger 3) and EPHA3 (ephrin-A3). These genes were further noted to be driving the expression of genes implicated in vascular remodeling and graft failure, such as IL-6, TGFBR1, SMAD4, and ADAMTS9. By integrating the ST and snRNA-seq datasets, we highlighted the spatial architecture of the vein graft following distension, wherein activated and mesenchymal-transitioning ECs, myeloid cells, and FBs were notably enriched in the intima and media of distended veins. Lastly, intercellular communication network analysis unveiled the critical roles of activated ECs, mesenchymal transitioning ECs, protomyofibroblasts, and VSMCs in upregulating signaling pathways associated with cellular proliferation (MDK, PDGF, VEGF), transdifferentiation (Notch), migration (ephrin, semaphorin), ECM remodeling (collagen, laminin, fibronectin), and inflammation (thrombospondin), following distension. Conclusions: Vein conduit harvest and distension elicit a prompt genomic response facilitated by distinct cellular subpopulations heterogeneously distributed throughout the vein wall. This response was found to be further exacerbated following vein graft implantation, resulting in a cascade of maladaptive gene regulatory networks. Together, these results suggest that distension initiates the upregulation of pathological pathways that may ultimately contribute to bypass graft failure and presents potential early targets warranting investigation for targeted therapies. This work highlights the first applications of single-nuclei and spatial transcriptomic analyses to investigate venous pathologies, underscoring the utility of these methodologies and providing a foundation for future investigations.

Pedicled Flaps for High-Risk Open Vascular Procedures of the Lower Extremity: An Analysis of The National Surgical Quality Improvement Project Database.

BACKGROUND: Use of pedicled flaps in vascular procedures is associated with decreased infection and wound breakdown. We evaluated the risk profile and postoperative complications associated with lower extremity open vascular procedures with and without pedicled flaps. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database (2010-2020) was queried for Current Procedural Terminology codes representing lower extremity open vascular procedures, including trunk and lower extremity pedicled flaps. Flap patients were compared with a randomized control group without flaps (1:3 cases to controls). Univariate and multivariate analyses were performed. RESULTS: We identified 132,934 adults who underwent lower extremity open vascular procedures. Concurrent pedicled flaps were rare (0.7%), and patients undergoing bypass procedures were more likely to receive a flap than nonbypass patients (69 vs. 64%, p < 0.0001). Flap patients had greater comorbidities. On univariate analysis, flap patients were more likely to experience wound (p = 0.0026), mild systemic (p < 0.0001), severe systemic (p = 0.0452), and all-cause complications (p < 0.0001). After adjusting for factors clinically suspected to be associated with increased risk (gender, body mass index, procedure type, American Society of Anesthesiologists classification, functional status, diabetes, smoking, and albumin < 3.5 mg/dL), wound (p = 0.096) and severe systemic complications (p = 0.0719) were no longer significantly associated with flap patients. CONCLUSION: Lower extremity vascular procedures are associated with a high risk of complications. Use of pedicled flaps remains uncommon and more often performed in patients with greater comorbid disease. However, after risk adjustment, use of a pedicled flap in high-risk patients may be associated with lower than expected wound and severe systemic complications.

Perivascular CLICK-gelatin delivery of thrombospondin-2 small interfering RNA decreases development of intimal hyperplasia after arterial injury.

Bypass graft failure occurs in 20%-50% of coronary and lower extremity bypasses within the first-year due to intimal hyperplasia (IH). TSP-2 is a key regulatory protein that has been implicated in the development of IH following vessel injury. In this study, we developed a biodegradable CLICK-chemistry gelatin-based hydrogel to achieve sustained perivascular delivery of TSP-2 siRNA to rat carotid arteries following endothelial denudation injury. At 21 days, perivascular application of TSP-2 siRNA embedded hydrogels significantly downregulated TSP-2 gene expression, cellular proliferation, as well as other associated mediators of IH including MMP-9 and VEGF-R2, ultimately resulting in a significant decrease in IH. Our data illustrates the ability of perivascular CLICK-gelatin delivery of TSP-2 siRNA to mitigate IH following arterial injury.

Discrepancies in clavicle-to-carotid bifurcation length measurements for transcarotid artery revascularization using different imaging modalities.

OBJECTIVE: Transcarotid artery revascularization (TCAR) has emerged as an effective method for carotid artery stenting. However, anatomic eligibility for TCAR is most often limited by an inadequate clavicle-to-carotid bifurcation length of <5 cm. Preoperative clavicle-to-carotid bifurcation distances may be underestimated when using conventional straight-line measurements on computed tomographic angiography (CTA) imaging. We therefore compared clavicle-to-carotid bifurcation lengths as measured by straight-line CTA, center-line CTA, and intraoperative duplex ultrasound (US), to assess potential differences. METHODS: We conducted a single-center, retrospective review of consecutive TCAR procedures performed between 2016 and 2019 for atherosclerotic carotid disease. For each patient, we compared clavicle-to-carotid bifurcation lengths measured by straight-line CTA, center-line CTA using TeraRecon image reconstruction, and intraoperative duplex US with neck extension and rotation. We further assessed patient and imaging characteristics in individuals with a ≥0.5 cm difference among the measurement methods. In particular, common carotid artery (CCA) tortuosity, defined as the inability to visualize the entire CCA from clavicle to carotid bifurcation on both a single coronal and sagittal imaging cut, was examined as a contributing factor for these discrepancies. RESULTS: Of the 70 TCAR procedures identified, 46 had all three imaging modalities available for review. The median clavicle-to-carotid bifurcation length was found to be 6.4 cm (interquartile range [IQR], 5.4-6.7 cm) on straight-line CTA, 7.0 cm (IQR, 6.0-7.5 cm) on intraoperative duplex US, and 7.2 cm (IQR, 6.5-7.5 cm) on center-line CTA (P < .001). Patients with a ≥0.5 cm difference between their straight-line CTA and either their intraoperative duplex US or center-line CTA measurements were more likely to have tortuous CCAs (60.0% vs 19.1%; P = .01; 51.4% vs 0.0%; P = .01). There were no notable differences in age, gender, prior neck/cervical spine surgery, or neck immobility among these individuals. In patients with tortuous CCAs, duplex US and center-line CTA measurements added 1.0 cm (IQR, 0.6-1.5 cm) and 1.1 cm (IQR, 0.9-1.6 cm) more in length than straight-line CTA measurements, respectively. There was a strong linear correlation between the additional lengths provided by duplex US measurements and those provided by center-line CTA measurements for each individual within the tortuous CCA group (r = 0.83). CONCLUSIONS: The use of straight-line CTA during preoperative planning can underestimate the clavicle-to-carotid bifurcation lengths in patients undergoing carotid revascularization, particularly in those with tortuous CCAs. Both duplex US performed with extended-neck surgical positioning and center-line CTA provide similar and longer carotid length measurements, and should be utilized in patients with tortuous carotid vessels to better determine TCAR anatomic eligibility.

Risk of Stroke, Death, and Myocardial Infarction Following Transcarotid Artery Revascularization vs Carotid Endarterectomy in Patients With Standard Surgical Risk.

Importance: Carotid artery stenting has been limited to use in patients with high surgical risk; outcomes in patients with standard surgical risk are not well known. Objective: To compare stroke, death, and myocardial infarction outcomes following transcarotid artery revascularization vs carotid endarterectomy in patients with standard surgical risk. Design, Setting, and Participants: This retrospective propensity-matched cohort study was conducted from August 2016 to August 2019 with follow-up until August 31, 2020, using data from the multicenter Vascular Quality Initiative Carotid Artery Stent and Carotid Endarterectomy registries. Patients with standard surgical risk, defined as those lacking Medicare-defined high medical or surgical risk characteristics and undergoing transcarotid artery revascularization (n = 2962) or carotid endarterectomy (n = 35 063) for atherosclerotic carotid disease. In total, 760 patients were excluded for treatment of multiple lesions or in conjunction with other procedures. Exposures: Transcarotid artery revascularization vs carotid endarterectomy. Main Outcomes and Measures: The primary outcome was a composite end point of 30-day stroke, death, or myocardial infarction or 1-year ipsilateral stroke. Results: After 1:3 matching, 2962 patients undergoing transcarotid artery revascularization (mean [SD] age, 70.4 [6.9] years; 1910 [64.5%] male) and 8886 undergoing endarterectomy (mean [SD] age, 70.0 [6.5] years; 5777 [65.0%] male) were identified. There was no statistically significant difference in the risk of the primary composite end point between the 2 cohorts (transcarotid 3.0% vs endarterectomy 2.6%; absolute difference, 0.40% [95% CI, -0.43% to 1.24%]; relative risk [RR], 1.14 [95% CI, 0.87 to 1.50]; P = .34). Transcarotid artery revascularization was associated with a higher risk of 1-year ipsilateral stroke (1.6% vs 1.1%; absolute difference, 0.52% [95% CI, 0.03 to 1.08]; RR, 1.49 [95% CI, 1.05 to 2.11%]; P = .02) but no difference in 1-year all-cause mortality (2.6% vs 2.5%; absolute difference, -0.13% [95% CI, -0.18% to 0.33%]; RR, 1.04 [95% CI, 0.78 to 1.39]; P = .67). Conclusions and Relevance: In this study, the risk of 30-day stroke, death, or myocardial infarction or 1-year ipsilateral stroke was similar in patients undergoing transcarotid artery revascularization compared with those undergoing endarterectomy for carotid stenosis.

Impact of neighborhood social disadvantage on carotid artery disease presentation, management, and discharge outcomes.

OBJECTIVE: Recent studies have highlighted that race and socioeconomic status serve as important determinants of disease presentation and perioperative outcomes in carotid artery disease. However, these investigations only focus on individual factors of social disadvantage, and fail to account for community factors that may drive disparities. Area Deprivation Index (ADI) is a validated measure of neighborhood adversity that offers a more comprehensive assessment of social disadvantage. We examined the impact of ADI ranking on carotid artery disease severity, management, and postoperative outcomes. METHODS: We identified patients who underwent carotid endarterectomy (CEA), transfemoral carotid artery stenting (tfCAS), and transcarotid artery revascularization (TCAR) in the Vascular Quality Initiative registry between 2016 and 2020. Patients were assigned ADI scores of 1 to 100 based on zip codes and grouped into quintiles, with higher quintiles reflecting increasing adversity. Outcomes assessed included disease presentation, intervention type, and discharge patterns. Logistic regression was used to evaluate independent associations between ADI quintiles and these outcomes. RESULTS: Among 91,904 patients undergoing carotid revascularization, 9811 (10.7%) were in the lowest ADI quintile (Q1), 18,905 (20.6%) in Q2, 25,442 (27.7%) in Q3, 26,099 (28.4%) in Q4, and 11,647 (12.7%) in Q5. With increasing ADI quintiles, patients were more likely to present with symptomatic disease (Q5, 52.1% vs Q1, 46.6%; P < .001), and stroke vs transient ischemic attack (Q5, 63.1% vs Q1, 53.5%; P < .001); they also more frequently underwent CAS vs CEA (Q5, 46.4% vs Q1, 33.9%; P < .001), and specifically tfCAS vs TCAR (Q5, 54.2% vs Q1, 33.9%; P < .001). In adjusted analyses, higher ADI quintiles remained as independent risk factors for presenting with symptomatic disease and stroke and undergoing CAS and tfCAS. Across ADI quintiles, patients were more likely to experience death (Q5, 0.8% vs Q1, 0.4%; P < .001), stroke/death (Q5, 2.1% vs Q1, 1.6%; P = .001), failure to discharge home (Q5, 11.5% vs Q1, 8.0%; P < .001) and length of stay >2 days (Q5, 33.3% vs Q1, 26.3%; P < .001) following revascularization. CONCLUSIONS: Among carotid revascularization patients, those with greater neighborhood social disadvantage had greater disease severity and more frequently underwent tfCAS. These patients also had higher rates of death and stroke/death, were less frequently discharged home, and had prolonged hospital stays. Greater efforts are needed to ensure that patients in higher ADI quintiles undergo better carotid surveillance and are treated appropriately for their carotid artery disease.

Distal embolic protection use during transfemoral carotid artery stenting is associated with improved in-hospital outcomes.

OBJECTIVE: Despite current guidelines recommending the use of distal embolic protection during transfemoral carotid artery stenting (tfCAS) to prevent periprocedural stroke, there remains significant variation in the routine use of distal filters. We sought to assess in-hospital outcomes in patients undergoing tfCAS with and without embolic protection using a distal filter. METHODS: We identified all patients undergoing tfCAS in the Vascular Quality Initiative from March 2005 to December 2021 and excluded those who received proximal embolic balloon protection. We created propensity score-matched cohorts of patients who underwent tfCAS with and without attempted placement of a distal filter. Subgroup analyses of patients with failed vs successful filter placement and failed vs no attempt at filter placement were performed. In-hospital outcomes were assessed using log binomial regression, adjusted for protamine use. Outcomes of interest were composite stroke/death, stroke, death, myocardial infarction (MI), transient ischemic attack (TIA), and hyperperfusion syndrome. RESULTS: Among 29,853 patients who underwent tfCAS, 28,213 (95%) had a filter attempted for distal embolic protection and 1640 (5%) did not. After matching, 6859 patients were identified. No attempted filter was associated with significantly higher risk of in-hospital stroke/death (6.4% vs 3.8%; adjusted relative risk [aRR], 1.72; 95% confidence interval [CI], 1.32-2.23; P < .001), stroke (3.7% vs 2.5%; aRR, 1.49; 95% CI, 1.06-2.08; P = .022), and mortality (3.5% vs 1.7%; aRR, 2.07; 95% CI, 1.42-3.020; P < .001). In a secondary analysis of patients who had failed attempt at filter placement vs successful filter placement, failed filter placement was associated with worse outcomes (stroke/death: 5.8% vs 2.7%; aRR, 2.10; 95% CI, 1.38-3.21; P = .001 and stroke: 5.3% vs 1.8%; aRR, 2.87; 95% CI, 1.78-4.61; P < .001). However, there were no differences in outcomes in patients with failed vs no attempted filter placement (stroke/death: 5.4% vs 6.2%; aRR, 0.99; 95% CI, 0.61-1.63; P = .99; stroke: 4.7% vs 3.7%; aRR, 1.40; 95% CI, 0.79-2.48; P = .20; death: 0.9% vs 3.4%; aRR, 0.35; 95% CI, 0.12-1.01; P = .052). CONCLUSIONS: tfCAS performed without attempted distal embolic protection was associated with a significantly higher risk of in-hospital stroke and death. Patients undergoing tfCAS after failed attempt at filter placement have equivalent stroke/death to patients in whom no filter was attempted, but more than a two-fold higher risk of stroke/death compared with those with successfully placed filters. These findings support current Society for Vascular Surgery guidelines recommending routine use of distal embolic protection during tfCAS. If a filter cannot be placed safely, an alternative approach to carotid revascularization should be considered.

Impact of neighborhood social disadvantage on the presentation and management of peripheral artery disease.

OBJECTIVE: Studies examining the relationship between socioeconomic disparities and peripheral artery disease (PAD) often focus on individual social health determinants and fail to account for the complex interplay between factors that ultimately impact disease severity and outcomes. Area deprivation index (ADI), a validated measure of neighborhood adversity, provides a more comprehensive assessment of social disadvantage. Therefore, we examined the impact of ADI on PAD severity and its management. METHODS: We identified all patients who underwent infrainguinal revascularization (open or endovascular) or amputation for symptomatic PAD in the Vascular Quality Initiative registry between 2003 and 2020. An ADI score of 1 to 100 was assigned to each patient based on their residential zip code, with higher ADI scores corresponding with increasing adversity. Patients were categorized by ADI quintiles (Q1-Q5). The outcomes of interest included indication for procedure (claudication, rest pain, or tissue loss) and rates of revascularization (vs primary amputation). Multinomial logistic regression was used to evaluate for an independent association between ADI quintile and these outcomes. RESULTS: Among the 79,973 patients identified, 9604 (12%) were in the lowest ADI quintile (Q1), 14,961 (18.7%) in Q2, 19,800 (24.8%) in Q3, 21,735 (27.2%) in Q4, and 13,873 (17.4%) in Q5. There were significant trends toward lower rates of claudication (Q1: 39% vs Q5: 34%, P < .001), higher rates of rest pain (Q1: 12.4% vs Q5: 17.8%, P < .001) as the indication for intervention, and lower rates of revascularization (Q1: 80% vs Q5: 69%, P < .001) with increasing ADI quintiles. In adjusted analyses, there was a progressively higher likelihood of presenting with rest pain vs claudication, with patients in Q5 having the highest probability when compared with those in Q1 (relative risk: 2.0; 95% confidence interval: 1.8-2.2; P < .001). Patients in Q5, when compared with those in Q1, also had a higher likelihood of presenting with tissue loss vs claudication (relative risk: 1.4; 95% confidence interval: 1.3-1.6; P < .001). Compared with patients in Q1, patients in Q2-Q5 had a lower likelihood of undergoing any revascularization procedure. CONCLUSIONS: Among patients who underwent infrainguinal revascularization or amputation in the Vascular Quality Initiative, those with higher neighborhood adversity had more advanced disease at presentation and lower rates of revascularization. Further work is needed to better understand neighborhood factors that are contributing to these disparities in order to identify community-level targets for improvement.

Efficacy and safety of single versus dual antiplatelet therapy in carotid artery stenting.

OBJECTIVE: Current guidelines recommend dual antiplatelet (AP) therapy (DAPT) before carotid artery stenting (CAS); however, the true clinical effect of single AP therapy vs DAPT is unknown. We examined the efficacy and safety of preoperative single AP therapy vs DAPT in patients who had undergone transfemoral CAS (tfCAS) or transcarotid artery revascularization (TCAR). METHODS: We identified all patients who had undergone tfCAS or TCAR in the Vascular Quality Initiative database from 2016 to 2021. We stratified the patients by procedure and identified those who had received the following preoperative AP regimens: DAPT (acetylsalicylic acid [ASA] + P2Y12 inhibitor [P2Yi]), no AP therapy, ASA only, ASA + AP loading dose, P2Yi only, and P2Yi + AP loading dose. The AP loading dose was given within 4 hours of CAS. We generated propensity scores for each treatment regimen and assessed in-hospital outcomes using inverse probability weighted log binomial regression, with DAPT as the reference and adjusting for intraoperative protamine use. The primary efficacy outcome was a composite end point of stroke and death, and the primary safety outcome was access-related bleeding. RESULTS: Of the 18,570 tfCAS patients, 70% had received DAPT, 5.6% no AP therapy, 10% ASA only, 8.0% ASA + AP loading dose, 4.6% P2Yi only, and 2.9% P2Yi + AP loading dose. The corresponding unadjusted rates of stroke/death were 2.2%, 6.8%, 4.1%, 5.1%, 2.4%, and 2.3%. After adjustment, compared with DAPT, the incidence of stroke/death was higher with no AP therapy (relative risk [RR], 2.3; 95% confidence interval [CI], 1.7-3.2), ASA only (RR, 1.6; 95% CI, 1.2-2.1), and ASA + AP loading dose (RR, 2.0; 95% CI, 1.5-2.7) but was similar with P2Yi only (RR, 0.99; 95% CI, 0.58-1.7) and P2Yi + AP loading dose (RR, 1.1; 95% CI, 0.49-2.5). Of the 25,459 TCAR patients, 81% had received DAPT, 2.0% no AP therapy, 5.5% ASA only, 3.5% ASA + AP loading dose, 4.9% P2Yi only, and 2.4% P2Yi + AP loading dose. The corresponding unadjusted rates of stroke/death were 1.5%, 3.3%, 3.3%, 2.9%, 1.2%, and 1.1%. After adjustment, compared with DAPT, the incidence of stroke/death was higher with no AP therapy (RR, 2.0; 95% CI, 1.2-3.3) and ASA only (RR, 2.2; 95% CI, 1.5-3.1), with a trend toward a higher incidence with ASA + AP loading dose (RR, 1.6; 95% CI, 0.99-2.6), and was similar with P2Yi only (RR, 0.98; 95% CI, 0.54-1.8) and P2Yi + AP loading dose (RR, 0.66; 95% CI, 0.27-1.6). No differences were found in the incidence of access-related bleeding between the treatment groups after tfCAS or TCAR. CONCLUSIONS: Compared with DAPT, no AP therapy or ASA monotherapy was associated with higher rates of stroke/death after CAS and should be discouraged as unsafe practice. Meanwhile, P2Yi monotherapy was associated with similar rates of stroke/death. No differences were found in the incidence of bleeding complications, and adding an AP loading dose to ASA or P2Yi monotherapy within 4 hours of the procedure did not affect the outcomes. Overall, these findings support the current guidelines recommending DAPT before CAS but also suggest that P2Yi monotherapy might confer thromboembolic benefits similar to those with DAPT. However, an immediate preoperative AP loading dose might not provide additional thromboembolic benefits.