Human atherosclerotic plaque transcriptomics reveals endothelial beta-2 spectrin as a potential regulator a leaky plaque microvasculature phenotype.

The presence of atherosclerotic plaque vessels is a critical factor in plaque destabilization. This may be attributable to the leaky phenotype of these microvessels, although direct proof for this notion is lacking. In this study, we investigated molecular and cellular patterns of stable and hemorrhaged human plaque to identify novel drivers of intraplaque vessel dysfunction. From transcriptome data of a human atherosclerotic lesion cohort, we reconstructed a co-expression network, identifying a gene module strongly and selectively correlated with both plaque microvascular density and inflammation. Spectrin Beta Non-Erythrocytic 1 (sptbn1) was identified as one of the central hubs of this module (along with zeb1 and dock1) and was selected for further study based on its predominant endothelial expression. Silencing of sptbn1 enhanced leukocyte transmigration and vascular permeability in vitro, characterized by an increased number of focal adhesions and reduced junctional VE-cadherin. In vivo, sptbn1 knockdown in zebrafish impaired the development of the caudal vein plexus. Mechanistically, increased substrate stiffness was associated with sptbn1 downregulation in endothelial cells in vitro and in human vessels. Plaque SPTBN1 mRNA and protein expression were found to correlate with an enhanced presence of intraplaque hemorrhage and future cardiovascular disease (CVD) events during follow-up. In conclusion, we identify SPTBN1 as a central hub gene in a gene program correlating with plaque vascularisation. SPTBN1 was regulated by substrate stiffness in vitro while silencing blocked vascular development in vivo, and compromised barrier function in vitro. Together, SPTBN1 is identified as a new potential regulator of the leaky phenotype of atherosclerotic plaque microvessels.

Bilateral Femoral Cannulation Is Associated With Reduced Severe Limb Ischemia-Related Complications Compared With Unilateral Femoral Cannulation in Adult Peripheral Venoarterial Extracorporeal Membrane Oxygenation: Results From the Extracorporeal Life Support Registry.

OBJECTIVES: Peripheral venoarterial extracorporeal membrane oxygenation (ECMO) with femoral access is obtained through unilateral or bilateral groin cannulation. Whether one cannulation strategy is associated with a lower risk for limb ischemia remains unknown. We aim to assess if one strategy is preferable. DESIGN: A retrospective cohort study based on the Extracorporeal Life Support Organization registry. SETTING: ECMO centers worldwide included in the Extracorporeal Life Support Organization registry. PATIENTS: All adult patients (≥ 18 yr) who received peripheral venoarterial ECMO with femoral access and were included from 2014 to 2020. INTERVENTIONS: Unilateral or bilateral femoral cannulation. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the occurrence of limb ischemia defined as a composite endpoint including the need for a distal perfusion cannula (DPC) after 6 hours from implantation, compartment syndrome/fasciotomy, amputation, revascularization, and thrombectomy. Secondary endpoints included bleeding at the peripheral cannulation site, need for vessel repair, vessel repair after decannulation, and in-hospital death. Propensity score matching was performed to account for confounders. Overall, 19,093 patients underwent peripheral venoarterial ECMO through unilateral ( n = 11,965) or bilateral ( n = 7,128) femoral cannulation. Limb ischemia requiring any intervention was not different between both groups (bilateral vs unilateral: odds ratio [OR], 0.92; 95% CI, 0.82-1.02). However, there was a lower rate of compartment syndrome/fasciotomy in the bilateral group (bilateral vs unilateral: OR, 0.80; 95% CI, 0.66-0.97). Bilateral cannulation was also associated with lower odds of cannulation site bleeding (bilateral vs unilateral: OR, 0.87; 95% CI, 0.76-0.99), vessel repair (bilateral vs unilateral: OR, 0.55; 95% CI, 0.38-0.79), and in-hospital mortality (bilateral vs unilateral: OR, 0.85; 95% CI, 0.81-0.91) compared with unilateral cannulation. These findings were unchanged after propensity matching. CONCLUSIONS: This study showed no risk reduction for overall limb ischemia-related events requiring DPC after 6 hours when comparing bilateral to unilateral femoral cannulation in peripheral venoarterial ECMO. However, bilateral cannulation was associated with a reduced risk for compartment syndrome/fasciotomy, lower rates of bleeding and vessel repair during ECMO, and lower in-hospital mortality.

Surveillance After Surgical and Endovascular Treatment for Peripheral Artery Disease: a Dutch Survey.

OBJECTIVE: At present, there is no clear, optimal approach to surveillance after invasive treatment of peripheral artery disease (PAD) in terms of modality, duration, clinical benefit, and cost effectiveness. The ongoing debate on the clinical benefit and cost effectiveness of standard surveillance creates a clear knowledge gap and may result in overtreatment or undertreatment. In this study, a survey was conducted among vascular surgeons in the Netherlands to assess the currently applied surveillance programmes. METHODS: All vascular surgeons from the Dutch Society for Vascular Surgery received an online survey on follow up after open and endovascular revascularisation in patients with PAD. Surveillance was defined as at least one follow up visit after intervention with or without additional imaging or ankle brachial index (ABI) measurement. Ten types of PAD intervention were surveyed. RESULTS: Surveys were returned by 97 (46.2%) of 210 vascular surgeons, and 76% reported using a routine follow up protocol after an invasive intervention. Clinical follow up only is most commonly performed after femoral endarterectomy (53%). After peripheral bypass surgery, clinical follow up only is applied rarely (4 - 8%). In six of the 10 interventions surveyed, duplex ultrasound (DUS) was the most used imaging modality for follow up. After bypass surgery, 76 - 86% of vascular surgeons perform DUS with or without ABI measurement. After endovascular interventions, 21 - 60% performed DUS surveillance. Lifelong surveillance is most often applied after aortobifemoral bypass (57%). Surveillance frequency and duration vary greatly within the same intervention. Frequencies range from every three or six months to annually. Duration ranges from one time surveillance to lifelong follow up. CONCLUSION: There is significant practice variation in surveillance after surgical and endovascular treatment of patients with PAD in the Netherlands. Prospective studies to evaluate treatment outcomes and to define the clinical need and cost effectiveness of standardised surveillance programmes for patients with PAD are recommended.

Clinical Performance of the Low Profile Zenith Alpha Abdominal Endovascular Graft: 2 Year Results from the ZEPHYR Registry.

OBJECTIVE: The midterm outcomes of the low profile Zenith Alpha Abdominal Endovascular Graft from the ZEnith alPHa for aneurYsm Repair (ZEPHYR) registry are reported. METHODS: The ZEPHYR registry is a physician initiated, multicentre, non-randomised, core laboratory controlled, prospective registry. Inclusion criteria were patients with a non-ruptured abdominal aortic aneurysm with a maximum diameter ≥ 50 mm or enlargement > 5 mm within 6 months, with a site reported infrarenal neck length of ≥ 10 mm and with the intention to electively implant the Zenith Alpha abdominal endograft. Patients from 14 sites across Germany, Belgium, and the Netherlands were included. The primary endpoint was treatment success, defined as technical success and clinical success. Technical success was defined as successful delivery and deployment of the endograft in the planned position without unintentional coverage of internal iliac or renal arteries, with successful removal of the delivery system. Clinical success was defined as freedom from aneurysm sac expansion > 5 mm, type I or type III endoleaks, aneurysm rupture, stent graft migration > 10 mm, open conversion, and stent graft occlusion. RESULTS: Three hundred and forty-seven patients were included in the ZEPHYR registry. The median clinical follow up was 743 days (interquartile range [IQR] 657, 806) with a median imaging follow up of 725 days (IQR 408, 788). Treatment success at 6 months, 1, and 2 years was 92.5%, 90.4%, and 85.3%, respectively. Freedom from secondary intervention was 94.3%, 93.4%, and 86.9%, respectively. The predominant reason for secondary intervention was limb complications. Freedom from limb occlusion (per patient) at 6 months, 1, and 2 years was 97.2%, 95.8%, and 92.5%, respectively. Univariable and multivariable Cox regression analyses could not identify any independent predictor for limb complications. CONCLUSION: While treatment success is comparable with other commercially available grafts, the rate of limb complications at 2 years is of concern. The manufacturer's instructions for use should be followed closely. Further studies are necessary to investigate the root cause of the increased rate of limb complications with the Zenith Alpha Abdominal Endovascular Graft.

Editor's Choice -- European Society for Vascular Surgery (ESVS) 2024 Clinical Practice Guidelines on the Management of Abdominal Aorto-Iliac Artery Aneurysms.

OBJECTIVE: The European Society for Vascular Surgery (ESVS) has developed clinical practice guidelines for the care of patients with aneurysms of the abdominal aorta and iliac arteries in succession to the 2011 and 2019 versions, with the aim of assisting physicians and patients in selecting the best management strategy. METHODS: The guideline is based on scientific evidence completed with expert opinion on the matter. By summarising and evaluating the best available evidence, recommendations for the evaluation and treatment of patients have been formulated. The recommendations are graded according to a modified European Society of Cardiology grading system, where the strength (class) of each recommendation is graded from I to III and the letters A to C mark the level of evidence. RESULTS: A total of 160 recommendations have been issued on the following topics: Service standards, including surgical volume and training; Epidemiology, diagnosis, and screening; Management of patients with small abdominal aortic aneurysm (AAA), including surveillance, cardiovascular risk reduction, and indication for repair; Elective AAA repair, including operative risk assessment, open and endovascular repair, and early complications; Ruptured and symptomatic AAA, including peri-operative management, such as permissive hypotension and use of aortic occlusion balloon, open and endovascular repair, and early complications, such as abdominal compartment syndrome and colonic ischaemia; Long term outcome and follow up after AAA repair, including graft infection, endoleaks and follow up routines; Management of complex AAA, including open and endovascular repair; Management of iliac artery aneurysm, including indication for repair and open and endovascular repair; and Miscellaneous aortic problems, including mycotic, inflammatory, and saccular aortic aneurysm. In addition, Shared decision making is being addressed, with supporting information for patients, and Unresolved issues are discussed. CONCLUSION: The ESVS Clinical Practice Guidelines provide the most comprehensive, up to date, and unbiased advice to clinicians and patients on the management of abdominal aorto-iliac artery aneurysms.

End of Life Care for Unplanned Vascular Admissions.

BACKGROUND: Unplanned vascular admissions have a high mortality. Previous studies have indicated that end of life care (EoLC) among this group of patients is low but there exist limited data on EoLC in the United Kingdom. The aim of this study was to evaluate the quality and predictors of EoLC for unplanned vascular admissions to a tertiary center in the United Kingdom. METHODS: This was a retrospective single-center cohort study of unplanned vascular surgery admissions from August 1, 2019 to January 22, 2020. Data on patient demographics, markers of quality of palliative care, mortality, and cause of death of unplanned admission to the vascular surgery department were collected from hospital and general practitioner records and evaluated against EoLC to evaluate predictors and efficacy of EoLC. Quality of palliative care markers included documentation of preferred place of death and care priorities, time spent in hospital and the intensive care unit toward the end of life, and realization of documented care objectives. EoLC input was defined as a dedicated palliative care consultation (PCC) by a palliative care professional, medical doctor, surgeon, or advanced care practitioner. We also conducted a subgroup analysis of patients within this group with chronic limb-threatening ischemia (CLTI), diabetic foot, and ruptured aortic aneurysms, as all patients in this group should be offered EoLC according to international guidelines. RESULTS: One-hundred and fifty patients were included. Median age at presentation was 70.5 years, and the cohort consisted of mostly men (72%). CLTI (31%) was the most common reason for admission. Surgical intervention was carried out in 60% of patients. Two-year mortality was 36%, and pneumonia (22%) was the most common cause of death. Seven percent of patients received PCC, which occurred a median of 10 days before death. Only a minority of patients had preferred place of care/death (14%), care priorities (37%), and family involvement during advance care planning (17%) documented in their notes; 29% of patients had Recommended Summary Plan for Emergency Care and Treatment forms in place. A diagnosis of left ventricular systolic dysfunction, chronic kidney disease, and increasing age predicted Recommended Summary Plan for Emergency Care and Treatment form completion. Patients with PCC were more likely to have advance care planning, but this did not translate into improvements in the other markers of quality of palliative and, consequently, EoLC. CONCLUSIONS: EoLC was insufficient and of low quality despite a high mortality in this group. Clinical guidelines and pathways are needed to ensure these patients are considered for EoLC and those with CLTI, diabetic foot sepsis or ruptured abdominal aortic aneurysms are offered it by default. Further research is needed to help identify vascular patients who would benefit from EoLC earlier to improve quality at end of life.

Evolution of distal limb perfusion management in adult peripheral venoarterial extracorporeal membrane oxygenation with femoral artery cannulation.

Limb ischaemia is a clinically relevant complication of venoarterial extracorporeal membrane oxygenation (VA ECMO) with femoral artery cannulation. No selective distal perfusion or other advanced techniques were used in the past to maintain adequate distal limb perfusion. A more recent trend is the shift from the reactive or emergency management to the pro-active or prophylactic placement of a distal perfusion cannula to avoid or reduce limb ischaemia-related complications. Multiple alternative cannulation techniques to the distal perfusion cannula have been developed to maintain distal limb perfusion, including end-to-side grafting, external or endovascular femoro-femoral bypass, retrograde limb perfusion (e.g., via the posterior tibial, dorsalis pedis or anterior tibial artery), and, more recently, use of a bidirectional cannula. Venous congestion has also been recognized as a potential contributing factor to limb ischaemia development and specific techniques have been described with facilitated venous drainage or bilateral cannulation being the most recent, to reduce or avoid venous stasis as a contributor to impaired limb perfusion. Advances in monitoring techniques, such as near-infrared spectroscopy and duplex ultrasound analysis, have been applied to improve decision-making regarding both the monitoring and management of limb ischaemia. This narrative review describes the evolution of techniques used for distal limb perfusion during peripheral VA ECMO.

European Multicentric Experience With Fenestrated-branched ENDOvascular Stent Grafting After Previous FAILed Infrarenal Aortic Repair: The EU-FBENDO-FAIL Registry.

OBJECTIVE: To report the mid-term outcomes of fenestrated-branched endovascular aneurysm repair (F-BEVAR) following a failed previous endovascular aneurysm repair (pEVAR) or previous open aneurysm repair (pOAR). METHODS: Data from consecutive patients who underwent F-BEVAR for pEVAR or pOAR from 2006 to 2021 from 17 European vascular centers were analyzed. Endpoints included technical success, major adverse events, 30-day mortality, and 5-year estimates of survival, target vessel primary patency, freedom from reinterventions, type I/III endoleaks, and sac growth >5 mm. BACKGROUND: Treatment of a failed previous abdominal aortic aneurysm repair is a complex undertaking. F-BEVAR is becoming an increasingly attractive option, although comparative data are limited regarding associated risk factors, indications for treatment, and various outcomes. RESULTS: There were 526 patients included, 268 pOAR and 258 pEVAR. The median time from previous repair to F-BEVAR was 7 (interquartile range, 4-12) years, 5 (3-8) for pEVAR, and 10 (6-14) for pOAR, P <0.001. Predominant indication for treatment was type Ia endoleak for pEVAR and progression of the disease for pOAR. Technical success was 92.8%, pOAR (92.2%), and pEVAR (93.4%), P =0.58. The 30-day mortality was 6.5% overall, 6.7% for pOAR, and 6.2% for pEVAR, P =0.81. There were 1853 treated target vessels with 5-year estimates of primary patency of 94.4%, pEVAR (95.2%), and pOAR (94.4%), P =0.03. Five-year estimates for freedom from type I/III endoleaks were similar between groups; freedom from reintervention was lower for pEVAR (38.3%) than for pOAR (56.0%), P =0.004. The most common indication for reinterventions was for type I/III endoleaks (37.5%). CONCLUSIONS: Repair of a failed pEVAR or pOARis safe and feasible with comparable technical success and survival rates. While successful treatment can be achieved, significant rates of reintervention should be anticipated, particularly for issues related to instability of target vessels/bridging stents.

Outcomes of Elective and Non-elective Fenestrated-branched Endovascular Aortic Repair for Treatment of Thoracoabdominal Aortic Aneurysms.

OBJECTIVE: To describe outcomes after elective and non-elective fenestrated-branched endovascular aortic repair (FB-EVAR) for thoracoabdominal aortic aneurysms (TAAAs). BACKGROUND: FB-EVAR has been increasingly utilized to treat TAAAs; however, outcomes after non-elective versus elective repair are not well described. METHODS: Clinical data of consecutive patients undergoing FB-EVAR for TAAAs at 24 centers (2006-2021) were reviewed. Endpoints including early mortality and major adverse events (MAEs), all-cause mortality, and aortic-related mortality (ARM), were analyzed and compared in patients who had non-elective versus elective repair. RESULTS: A total of 2603 patients (69% males; mean age 72±10 year old) underwent FB-EVAR for TAAAs. Elective repair was performed in 2187 patients (84%) and non-elective repair in 416 patients [16%; 268 (64%) symptomatic, 148 (36%) ruptured]. Non-elective FB-EVAR was associated with higher early mortality (17% vs 5%, P <0.001) and rates of MAEs (34% vs 20%, P <0.001). Median follow-up was 15 months (interquartile range, 7-37 months). Survival and cumulative incidence of ARM at 3 years were both lower for non-elective versus elective patients (50±4% vs 70±1% and 21±3% vs 7±1%, P <0.001). On multivariable analysis, non-elective repair was associated with increased risk of all-cause mortality (hazard ratio, 1.92; 95% CI] 1.50-2.44; P <0.001) and ARM (hazard ratio, 2.43; 95% CI, 1.63-3.62; P <0.001). CONCLUSIONS: Non-elective FB-EVAR of symptomatic or ruptured TAAAs is feasible, but carries higher incidence of early MAEs and increased all-cause mortality and ARM than elective repair. Long-term follow-up is warranted to justify the treatment.

Fenestrated/branched endovascular aortic repair using unilateral femoral access in patients with iliac occlusive disease.

OBJECTIVE: Fenestrated/branched endovascular aortic repair (F/BEVAR) in patients with occluded iliac arteries is challenging owing to limited access for branch vessel catheterization and increased risk for leg and spinal ischemic complications. The aim of this study was to analyze technical strategies and outcomes of F/BEVAR in patients with unilateral iliofemoral occlusive disease. METHODS: We performed a retrospective review of all consecutive patients treated by F/BEVAR in two institutions (2003-2021). Patients with unilateral iliofemoral occlusive disease were included in the analysis. All patients had one patent iliac artery that was used for advancement of the fenestrated-branch component. Preloaded catheter/guidewire systems or steerable sheaths were used as adjuncts to facilitate catheterization. Primary endpoints were technical success, mortality, major adverse events (stroke, spinal cord injury, dialysis or decrease in the glomerular filtration rate of more than 50%, bowel ischemia, myocardial infarction, or respiratory failure), primary iliac patency, and freedom from reinterventions. RESULTS: There were 959 patients treated with F/BEVAR. Of these, 15 patients (1.56%; mean age, 74 years; 80% male) had occluded iliac arteries and 1 patent iliofemoral access and were treated for a thoracoabdominal aortic aneurysm (n = 8) or juxtarenal abdominal aortic aneurysm (n = 7). Brachial access was used in 14 of the 15 patients and preloaded systems in 7 of the 15 patients (47%). The remaining 53% had staggered deployment of stent grafts. There were seven physician-modified endovascular grafts, seven custom-made devices, and one off-the-shelf device used. Thirteen patients (87%) had distal seal using aortouni-iliac stent grafts and two (13%) had distal seal in the infrarenal aorta. Concomitant femoral crossover bypass (FCB) was performed in two patients and six patients had a prior FCB. Technical success was 100%. There were no intraoperative complications or early lower extremity ischemic complications, and all FCB were preserved. There was one mortality (7%) within 30 days owing to retrograde type A dissection. Major adverse events occurred in 20% of patients. The median follow-up was 12 months (range, 0-85 months). Two patients (13%) required three reinterventions. One patient required proximal stent graft extension for an acute type B dissection (3 months) and another required iliac extension for type Ib endoleak of an aortouni-iliac graft (21 months) and thrombolysis of that extension (50 months). At last follow-up, all patients had primary graft patency except one with secondary graft patency without new claudication. One patient had a single renal artery stent occlusion at follow-up with no r-intervention. The overall survival rate was 60%, without aortic-related deaths. CONCLUSIONS: Although challenging, F/BEVAR with unilateral femoral/brachial approach is feasible in patients with occluded iliac limbs, with an important rate of ischemic complications, but satisfactory outcomes.

End-of-life care and advance care planning for outpatients with inoperable aortic aneurysms.

OBJECTIVE: A significant proportion of patients with abdominal and thoracic aortic aneurysms (AA) do not proceed to intervention after reaching treatment threshold diameter due to a combination of poor cardiovascular reserve, frailty, and aortic morphology. This patient cohort has a high mortality; however, until this study, there exist no studies on the end-of-life care conservatively managed patients receive. METHODS: This is a retrospective multicenter cohort study of 220 conservatively managed patients with AA referred to Leeds Vascular Institute (UK) and Maastricht University Medical Centre (the Netherlands) for intervention between 2017 and 2021. Demographic details, mortality, cause of death, advance care planning and palliative care outcomes were analysed to examine predictors of palliative care referral and efficacy of palliative care consultation. RESULTS: A total of 1506 patients with AA were seen over this time period, giving a nonintervention rate of 15%. There was a 3-year mortality rate of 55%, a median survival of 364 days, and rupture was the reported cause of death in 18% of the decedents. Median follow-up was 34 months. Only 8% of all patients and 16% of decedents received a palliative care consultation, which took place a median of 3.5 days before death. Patients >81 years of age were more likely to have advance care planning. Only 5% and 23% of conservatively managed patients had documentation of preferred place of death and care priorities respectively. Patients with a palliative care consultation were more likely to have these services in place. CONCLUSIONS: Only a small proportion of conservatively treated patients had advance care planning and this was far below international guidelines on end-of-life care for adults, which recommends it for each of these patients. Pathways and guidance should be implemented to ensure patients not offered AA intervention receive end-of-life care and advance care planning.

Multicenter trans-Atlantic experience with fenestrated-branched endovascular aortic repair of chronic post-dissection thoracoabdominal aortic aneurysms.

OBJECTIVE: This multicenter international study aimed to describe outcomes of fenestrated-branched endovascular aortic repairs (FB-EVAR) in a cohort of patients treated for chronic post-dissection thoracoabdominal aortic aneurysms (PD-TAAAs). METHODS: We reviewed the clinical data of all consecutive patients treated by FB-EVAR for repair of extent I to III PD-TAAAs in 16 centers from the United States and Europe (2008-2021). Data were extracted from institutional prospectively maintained databases and electronic patient records. All patients received off-the-shelf or patient-specific manufactured fenestrated-branched stent grafts. Endpoints were any cause mortality and major adverse events at 30 days, technical success, target artery (TA) patency, freedom from TA instability, minor (endovascular with <12 Fr sheath) and major (open or ≥12 Fr sheath) secondary interventions, patient survival, and freedom from aortic-related mortality (ARM). RESULTS: A total of 246 patients (76% male; median age, 67 years [interquartile range, 61-73 years]) were treated for extent I (7%), extent II (55%), and extent III (35%) PD-TAAAs by FB-EVAR. The median aneurysm diameter was 65 mm (interquartile range, 59-73 mm). Eighteen patients (7%) were octogenarians, 212 (86%) were American Society of Anesthesiologists class ≥3, and 21 (9%) presented with contained ruptured or symptomatic aneurysms. There were 917 renal-mesenteric vessels targeted by 581 fenestrations (63%) and 336 directional branches (37%), with a mean of 3.7 vessels per patient. Technical success was 96%. Mortality and rate of major adverse events at 30 days was 3% and 28%, including disabling complications such as new onset dialysis in 1%, major stroke in 1%, and permanent paraplegia in 2%. Mean follow-up was 24 months. Kaplan-Meier (KM) estimated patient survival at 3 and 5 years was 79% ± 6% and 65% ± 10%. KM estimated freedom from ARM was 95% ± 3% and 93% ± 5% at the same intervals. Unplanned secondary interventions were needed in 94 patients (38%), including minor procedures in 64 (25%) and major procedures in 30 (12%). There was one conversion to open surgical repair (<1%). KM estimated freedom from any secondary intervention was 44% ± 9% at 5 years. KM estimated primary and secondary TA patency were 93% ± 2% and 96% ± 1% at 5 years, respectively. CONCLUSIONS: FB-EVAR for chronic PD-TAAAs was associated with high technical success and a low rate of mortality (3%) and disabling complications at 30 days. Although the procedure is effective in the prevention of ARM, patient survival was low at 5 years (65%), likely due to the significant comorbidities in this cohort of patients. Freedom from secondary interventions at 5 years was 44%, although most procedures were minor. The significant rate of reinterventions highlights the need for continued patient surveillance.

Comparison of single- and multistage strategies during fenestrated-branched endovascular aortic repair of thoracoabdominal aortic aneurysms.

OBJECTIVE: The aim of this study was to compare outcomes of single or multistage approach during fenestrated-branched endovascular aortic repair (FB-EVAR) of extensive thoracoabdominal aortic aneurysms (TAAAs). METHODS: We reviewed the clinical data of consecutive patients treated by FB-EVAR for extent I to III TAAAs in 24 centers (2006-2021). All patients received a single brand manufactured patient-specific or off-the-shelf fenestrated-branched stent grafts. Staging strategies included proximal thoracic aortic repair, minimally invasive segmental artery coil embolization, temporary aneurysm sac perfusion and combinations of these techniques. Endpoints were analyzed for elective repair in patients who had a single- or multistage approach before and after propensity score adjustment for baseline differences, including the composite 30-day/in-hospital mortality and/or permanent paraplegia, major adverse event, patient survival, and freedom from aortic-related mortality. RESULTS: A total of 1947 patients (65% male; mean age, 71 ± 8 years) underwent FB-EVAR of 155 extent I (10%), 729 extent II (46%), and 713 extent III TAAAs (44%). A single-stage approach was used in 939 patients (48%) and a multistage approach in 1008 patients (52%). A multistage approach was more frequently used in patients undergoing elective compared with non-elective repair (55% vs 35%; P < .001). Staging strategies were proximal thoracic aortic repair in 743 patients (74%), temporary aneurysm sac perfusion in 128 (13%), minimally invasive segmental artery coil embolization in 10 (1%), and combinations in 127 (12%). Among patients undergoing elective repair (n = 1597), the composite endpoint of 30-day/in-hospital mortality and/or permanent paraplegia rate occurred in 14% of single-stage and 6% of multistage approach patients (P < .001). After adjustment with a propensity score, multistage approach was associated with lower rates of 30-day/in-hospital mortality and/or permanent paraplegia (odds ratio, 0.466; 95% confidence interval, 0.271-0.801; P = .006) and higher patient survival at 1 year (86.9±1.3% vs 79.6±1.7%) and 3 years (72.7±2.1% vs 64.2±2.3%; adjusted hazard ratio, 0.714; 95% confidence interval, 0.528-0.966; P = .029), compared with a single stage approach. CONCLUSIONS: Staging elective FB-EVAR of extent I to III TAAAs was associated with decreased risk of mortality and/or permanent paraplegia at 30 days or within hospital stay, and with higher patient survival at 1 and 3 years.

Safety of Percutaneous Femoral Access for Endovascular Aortic Aneurysm Repair Through Previously Surgically Exposed or Repaired Femoral Arteries.

OBJECTIVE: Percutaneous femoral artery access is being increasingly used in endovascular aortic repair (EVAR). The technique can be challenging in patients with previously surgically exposed or repaired femoral arteries because of excessive scar tissue. However, a successful percutaneous approach may cause less morbidity than a "re-do" open femoral approach. The aim of this study was to assess the impact of prior open surgical femoral exposure on technical success and clinical outcomes of percutaneous approach. METHODS: This study retrospectively reviewed the clinical data of patients who underwent percutaneous EVAR between 2010 and 2020 at 2 major aortic centers. Patients were divided into 2 groups (with or without prior open surgical femoral access) for analysis of clinical outcomes. Only punctures with sheaths ≥12Fr were included for analysis. The access and (pre)closure techniques were similar in both institutions. Primary end points were intraoperative technical success, access-related revision, and access complications. A multivariate analysis was performed to identify determinants of conversion to open approach and femoral access complications in intact and re-do groins. RESULTS: A total of 632 patients underwent percutaneous (complex) EVAR: 98 had prior open surgical femoral access and 534 patients underwent de novo femoral percutaneous access. A total of 1099 femoral artery punctures were performed: 149 in re-do and 950 in intact groins. The extent of endovascular repair included 159 infrarenal, 82 thoracic, 368 fenestrated/branched, and 23 iliac branch devices. No significant differences were seen in technical success (re-do 93.3% vs intact 95.3%, p=0.311), access-related surgical revision (0.7% vs 0.6%, p=0.950), and access complications (2.7% vs 4.0%, p=0.443). For the whole group, significant predictors for access complications in multivariate analyses were main access site (odds ratio [OR] 2.39; 95% confidence interval [CI] 1.07%-5.35%; p=0.033) and increase of the procedure time per hour (OR 1.65; 95% CI 1.34%-2.04%; p<0.001), while increase in sheath-vessel ratio had a protective effect (OR 0.33; 95% CI 0.127%-0.85%; p=0.021). Surgical conversion was predicted by main access site (OR 2.32; 95% CI 1.28%-4.19%; p=0.007) and calcification of 50% to 75% of the circumference of the access vessel (OR 3.29; 95% CI 1.38%-7.86%; p=0.005). CONCLUSION: Within our population prior open surgical femoral artery exposure or repair had no negative impact on the technical success and clinical outcomes of percutaneous (complex) endovascular aortic aneurysm repair.

Editor's Choice - Quality of Life after Stenting for Iliofemoral Venous Obstruction: A Randomised Controlled Trial with One Year Follow Up.

OBJECTIVE: Deep venous obstruction (DVO) is a great burden on the healthcare system and patients' quality of life (QoL). Case series show stenting is safe and effective, however most studies lack control groups and QoL changes have not been compared with conventional treatment. The aim was to assess the difference in QoL changes from baseline to 12 months between stent and conventionally treated patients with DVO. METHODS: Subjects > 18 years old with DVO due to post-thrombotic (PTS) or non-thrombotic iliac vein lesions (NIVLs) in a tertiary hospital were prospectively randomised to best medical therapy (BMT) or stent placement with BMT in a ratio 2:1, stratified for PTS or NIVL. The primary outcome was the between group difference in VEINES-QoL scores change from baseline to 12 months after treatment. Secondary outcomes included the difference in score changes for EuroQoL 5-Dimension 5 Level (EQ-5D-5L), Pain Disability Index (PDI), Venous Clinical Severity Score (VCSS), and the Villalta score. RESULTS: After three years, the inclusion rate dropped to almost zero, therefore the study had to be stopped. Sixty-three patients were randomised to either the stent (n = 42) or control group (n = 21). Overall, 50 patients had available data for primary outcome analysis. The adjusted mean difference between 12 month scores for VEINES-QoL and VEINES-Sym was 8.07 (95% CI 3.04 - 13.09) and 5.99 (95% CI 0.75 - 11.24) (p = .026), respectively, in favour of the stent group. The differences were significant, but a pre-defined meaningful 14 point improvement in QoL was not reached. The mean difference between 12 month scores for VCSS was -2.93 (95% CI -5.71 - 0.16, p = .040), -11.83 (95% CI -20.81 - 2.86, p = .011) for PDI, 0.015 (95% CI -0.12 - 0.15, p = .82) for the EQ-5D index, and -2.99 (95% CI -7.28 - 1.30, p = .17) for the Villalta score. CONCLUSION: Symptomatic patients with DVO who received dedicated venous stents had significantly higher VEINES-QoL/Sym scores at 12 months compared with the control group, but the between group difference was lower than the pre-specified clinically relevant QoL difference of at least 14 points. STUDY REGISTRATION NUMBER: NCT03026049.

Systematic Review of the Effect of Cerebrospinal Fluid Drainage on Outcomes After Endovascular Descending Thoracic/Thoraco-Abdominal Aortic Aneurysm Repair.

OBJECTIVE: This study aimed to investigate whether prophylactic use of cerebrospinal fluid (CSF) drainage in endovascular descending thoracic aortic aneurysm (DTAA) and thoraco-abdominal aortic aneurysm (TAAA) repair contributes to a lower rate of post-operative spinal cord ischaemia (SCI). DATA SOURCES: MEDLINE, Embase, and CINAHL. REVIEW METHODS: A literature review was conducted in accordance with PRISMA guidelines (PROSPERO registration no. CRD42021245893). Risk of bias was assessed through the Newcastle-Ottawa scale (NOS), and the certainty of evidence was graded using the GRADE approach. A proportion meta-analysis was conducted to calculate the pooled rate and 95% confidence interval (CI) of both early and late onset SCI. Pooled outcome estimates were calculated using the odds ratio (OR) and associated 95% CI. The primary outcome was SCI, both early and lateonset. Secondary outcomes were complications of CSF drainage, length of hospital stay, and peri-operative (30 day or in hospital) mortality rates. RESULTS: Twenty-eight observational, retrospective studies were included, reporting 4 814 patients (2 599 patients with and 2 215 without CSF drainage). The NOS showed a moderate risk of bias. The incidence of SCI was similar in patients with CSF drainage (0.05, 95% CI 0.03 ‒ 0.08) and without CSF drainage (0.05, 95% CI 0.00 ‒ 0.14). No significant decrease in SCI was found when using CSF drainage (OR 0.67, 95% CI 0.29 ‒ 1.55, p = .35). The incidence rate of CSF drainage related complication was 0.10 (95% CI 0.04 ‒ 0.19). The 30 day and in hospital mortality rate with CSF drainage was 0.08 (95% CI 0.05 ‒ 0.12). The 30 day and in hospital mortality rate without CSF drainage and comparison with late mortality and length of hospital stay could not be determined due to lack of data. The quality of evidence was considered very low. CONCLUSION: Pre-operative CSF drainage placement was not related to a favourable outcome regarding SCI rate in endovascular TAAA and DTAA repair. Due to the low quality of evidence, no clear recommendation on pre-operative use of CSF drainage placement can be made.

Novel cannulation strategy with a bidirectional cannula for distal limb perfusion during peripheral veno-arterial extracorporeal life support: A preliminary, single-centre study.

INTRODUCTION: Limb ischemia is a severe complication of peripheral veno-arterial extracorporeal life support (V-A ECLS). Several techniques have been developed to prevent this, but it remains a major and frequent adverse event (incidence: 10-30%). In 2019, a new cannula with bidirectional flow (retrograde towards the heart and antegrade towards the distal limb) has been introduced. A single-centre experience with this cannula in patients undergoing peripheral V-A ECLS is herewith reported. METHODS: This prospective observational study included adults (≥18 years) undergoing V-A ECLS from January 2021 to October 2022 with the use of a bidirectional femoral artery cannula. Primary outcome was limb ischemia requiring intervention during cardio-circulatory support. Secondary outcomes were compartment syndrome, limb amputation, cannulation site bleeding, need for other surgical intervention due to cannula related complications, duplex ultrasound parameters from the femoral vessels, and in-hospital survival. RESULTS: Twenty-two consecutive patients were included. During extracorporeal life support (ECLS) support, limb ischemia requiring intervention occurred in one patient (4.5%) and no patients developed a compartment syndrome, or required a fasciotomy or amputation. Significant bleeding was reported in two patients (9%) due to slight cannula dislodgement, easily solved with cannula repositioning. In-hospital survival was 63.6%. CONCLUSIONS: The bidirectional cannula is associated with a low risk for limb ischemia-related complications compared to current literature, and apparently represents a safe alternative to dedicated distal perfusion cannula. Further studies are warranted to confirm these preliminary findings.

Perioperative and long-term outcome after ascending aortic and arch repair with elephant trunk and open thoracoabdominal aortic aneurysm repair.

OBJECTIVE: To describe the outcome of open thoracoabdominal aortic aneurysm (TAAA) repair following previous aortic arch repair including elephant trunk (ET) or frozen elephant trunk (FET) for acute and chronic pathologies. METHODS: This was a retrospective, observational, multicenter study including 32 patients treated between 2006 and 2019 in two aortic centers using identical surgical protocols. Assessment focused on perioperative and long-term outcome, namely in-hospital morbidity and mortality, as well as procedure-related reintervention rate and aortic-related mortality rate. Kaplan-Meier curves with 95% confidence intervals were used to analyze the overall survival after surgery within the cohort. RESULTS: Thirty-two patients (mean age, 45.0 ± 13.6 years; 20 males [62.5%]) were treated because of acute (34.38% [n = 11]) or chronic (65.62% [n = 21]) aortic pathologies, including residual dissection following acute, symptomatic type A dissection (n = 7) and symptomatic mega aortic syndrome (n = 4), as well as post-dissection TAAA (n = 18) and asymptomatic mega aortic syndrome (n = 3). Twenty-eight patients (87.5%) received type II repair, and 4 patients (12.5%) received type III repair after previous ascending aorta and arch repair including ET/FET. Concomitant infrarenal and iliac vessel repair was performed in 38.7% (n = 12) and 29.4% (n = 10), respectively. The in-hospital mortality rate was 18.75% (n = 6). Spinal cord ischemia occurred in two cases, both after one-stage emergency procedure with one case of permanent paraplegia. Temporary acute kidney injury occurred in 41.94% (n = 13). The estimated 1-year survival rate was 78.1% (95% confidence interval, 63.9%-95.6%), with a median follow-up time of 1.29 years (interquartile range, 0.26-3.88 years). No procedure-related reinterventions and one case of aortic-related mortality, namely sepsis because of graft infection, was observed. CONCLUSIONS: Open TAAA repair following aortic arch repair including ET or FET because of acute or chronic aortic pathologies is associated with a relevant perioperative morbidity and mortality rate. During follow-up, a low aortic-related mortality rate and procedure-related reintervention rate were observed.

Multicenter experience of upper extremity access in complex endovascular aortic aneurysm repair.

PURPOSE: Upper extremity access (UEA) for antegrade cannulation of aortic side branches is a relevant part of endovascular treatment of complex aortic aneurysms and can be achieved using several techniques, sites, and sides. The purpose of this study was to evaluate different UEA strategies in a multicenter registry of complex endovascular aortic aneurysm repair (EVAR). METHODS: In six aortic centers in the Netherlands, all endovascular aortic procedures from 2006 to 2019 were retrospectively reviewed. Patients who received UEA during complex EVAR were included. The primary outcome was a composite end point of any access complication, excluding minor hematomas. Secondary outcomes were access characteristics, access complications considered individually, access reinterventions, and incidence of ischemic cerebrovascular events. RESULTS: A total of 417 patients underwent 437 UEA for 303 fenestrated/branched EVARs and 114 chimney EVARs. Twenty patients had bilateral, 295 left-sided, and 102 right-sided UEA. A total of 413 approaches were performed surgically and 24 percutaneously. Distal brachial access (DBA) was used in 89 cases, medial brachial access (MBA) in 149, proximal brachial access (PBA) in 140, and axillary access (AA) in 59 cases. No significant differences regarding the composite end point of access complications were seen (DBA: 11.3% vs MBA: 6.7% vs PBA: 13.6% vs AA: 10.2%; P = .29). Postoperative neuropathy occurred most after PBA (DBA: 1.1% vs MBA: 1.3% vs PBA: 9.3% vs AA: 5.1%; P = .003). There were no differences in cerebrovascular complications between access sides (right: 5.9% vs left: 4.1% vs bilateral: 5%; P = .75). Significantly more overall access complications were seen after a percutaneous approach (29.2% vs 6.8%; P = .002). In multivariate analysis, the risk for access complications after an open approach was decreased by male sex (odds ratio [OR]: 0.27; 95% confidence interval [CI]: 0.10-0.72; P = .009), whereas an increase in age per year (OR: 1.08; 95% CI: 1.004-1.179; P = .039) and diabetes mellitus type 2 (OR: 3.70; 95% CI: 1.20-11.41; P = .023) increased the risk. CONCLUSIONS: Between the four access localizations, there were no differences in overall access complications. Female sex, diabetes mellitus type 2, and aging increased the risk for access complications after a surgical approach. Furthermore, a percutaneous UEA resulted in higher complication rates than a surgical approach.

Reactive Oxygen-Forming Nox5 Links Vascular Smooth Muscle Cell Phenotypic Switching and Extracellular Vesicle-Mediated Vascular Calcification.

RATIONALE: Vascular calcification, the formation of calcium phosphate crystals in the vessel wall, is mediated by vascular smooth muscle cells (VSMCs). However, the underlying molecular mechanisms remain elusive, precluding mechanism-based therapies. OBJECTIVE: Phenotypic switching denotes a loss of contractile proteins and an increase in migration and proliferation, whereby VSMCs are termed synthetic. We examined how VSMC phenotypic switching influences vascular calcification and the possible role of the uniquely calcium-dependent reactive oxygen species (ROS)-forming Nox5 (NADPH oxidase 5). METHODS AND RESULTS: In vitro cultures of synthetic VSMCs showed decreased expression of contractile markers CNN-1 (calponin 1), α-SMA (α-smooth muscle actin), and SM22-α (smooth muscle protein 22α) and an increase in synthetic marker S100A4 (S100 calcium binding protein A4) compared with contractile VSMCs. This was associated with increased calcification of synthetic cells in response to high extracellular Ca2+. Phenotypic switching was accompanied by increased levels of ROS and Ca2+-dependent Nox5 in synthetic VSMCs. Nox5 itself regulated VSMC phenotype as siRNA knockdown of Nox5 increased contractile marker expression and decreased calcification, while overexpression of Nox5 decreased contractile marker expression. ROS production in synthetic VSMCs was cytosolic Ca2+-dependent, in line with it being mediated by Nox5. Treatment of VSMCs with Ca2+ loaded extracellular vesicles (EVs) lead to an increase in cytosolic Ca2+. Inhibiting EV endocytosis with dynasore blocked the increase in cytosolic Ca2+ and VSMC calcification. Increased ROS production resulted in increased EV release and decreased phagocytosis by VSMCs. CONCLUSIONS: We show here that contractile VSMCs are resistant to calcification and identify Nox5 as a key regulator of VSMC phenotypic switching. Additionally, we describe a new mechanism of Ca2+ uptake via EVs and show that Ca2+ induces ROS production in VSMCs via Nox5. ROS production is required for release of EVs, which promote calcification. Identifying molecular pathways that control Nox5 and VSMC-derived EVs provides potential targets to modulate vascular remodeling and calcification in the context of mineral imbalance. Graphic Abstract: A graphic abstract is available for this article.