Clinical Outcomes of 5000 IU Heparin Versus Activated Clotting Time-Guided Heparinization During Noncardiac Arterial Procedures: A Propensity Score Matched Analysis.

PURPOSE: Previous studies have shown that activated clotting time (ACT)-guided heparinization leads to better anticoagulation levels during noncardiac arterial procedures (NCAP) than a standardized bolus of 5000 IU. Better anticoagulation should potentially result in lower incidence of thrombo-embolic complications (TEC). Comparative investigations on clinical outcomes of these heparinization strategies are scarce. This study investigated clinical outcomes of ACT-guided heparinization with a starting dose of 100 IU/kg in comparison with a single standardized bolus of 5000 IU heparin during NCAP. MATERIALS AND METHODS: Analysis from a prospectively collected database of patients undergoing NCAP in 2 vascular centers was performed. Patients receiving ACT-guided heparinization were matched 1:1 with patients receiving 5000 IU heparin using propensity score matching (PSM). Primary outcomes were TEC, bleeding complications, and mortality within 30 days of procedure or during the same admission. RESULTS: A total of 759 patients (5000 IU heparin: 213 patients, ACT-guided heparinization: 546 patients) were included. Propensity score matching resulted in 209 patients in each treatment group. After PSM, the groups were comparable, with the exception of a higher prevalence of peripheral arterial disease in the ACT-guided heparinization group (103 patients, 49% vs 82 patients, 39%, p=0.039). The target ACT (>200 seconds) was reached in 198 patients (95%) of the ACT-guided group versus 71 patients (34%) of the 5000 IU group (p<0.001), indicating successful execution of the ACT-guided protocol. Incidence of TEC (13 patients, 6.2% vs 10 patients, 4.8%, p=0.52), mortality (3 patients, 1.4% vs 0 patients, p=0.25), and bleeding complications (32 patients, 15% vs 25 patients, 12%, p=0.32) did not differ between patients receiving ACT-guided heparinization and 5000 IU heparin. Protamine was administered in 118 patients (57%) in the ACT group versus 11 patients (5.3%) in the 5000 IU group (p<0.001), but did not influence incidence of TEC (17 patients, 5.9% vs 6 patients, 4.7%, p=0.61) or bleeding complications (34 patients, 12% vs 22 patients, 17%, p=0.14). CONCLUSION: No difference in TEC, bleeding complications, or mortality was found between ACT-guided heparinization and a single bolus of 5000 IU heparin during NCAP. CLINICAL IMPACT: Previous studies have shown that activated clotting time (ACT)-guided heparinization leads to better anticoagulation levels during non-cardiac arterial procedures (NCAP) then a standardized bolus of 5000 IU. Comparative investigations on clinical outcomes are scarce. This study focussed on clinical outcomes of both protocols in NCAP in a propensity score matched cohort. Thrombo-embolic complications (TEC), bleeding complications and mortality within 30 days after NCAP or during the same admission were comparable between groups. Future studies should focus on optimizing ACT-guided protocols, specifically in patients with a high risk of TEC and bleeding complications.

Systematic review of clinical guidelines and consensus statements concerning heparin and protamine dosing and monitoring of anticoagulation levels for non-cardiac arterial procedures.

OBJECTIVES: This systematic review was performed to examine all published practice Guidelines and Consensus Statements (together: GCS) on heparin dosing and monitoring during non-cardiac arterial procedures (NCAP). The objective was to scrutinize the recommendations and advice outlined within these GCS documents and to evaluate the supporting evidence for these recommendations. Additionally, the use of the activated clotting time (ACT) and target ACT values were explored. METHODS: This systematic review was performed in accordance with the PRISMA Guidelines. Medline and Embase databases were searched to identify all GCSs in the English language on NCAP. The final literature search was performed in January 2023. This search was supplemented by searching websites of relevant professional vascular surgical organizations for GCSs. Titles and abstracts were assessed by two independent reviewers. RESULTS: Of 9716 titles identified, 27 GCSs met the predefined inclusion criteria: six GCSs regarding carotid intervention, seven regarding procedures for aneurysmal disease of the abdominal aorta and iliac arteries, 12 regarding interventions for acute and chronic peripheral arterial occlusive disease and two regarding open and endovascular interventions of thoraco-abdominal aortic aneurysms. Administration of heparin is advised for al NCAP. There was high variability concerning heparin dose: both standard dose as weight based dosing (30-150 IU/kg) was advised. Recommendations on repeated doses, ACT monitoring and heparin reversal using protamine also varied widely. In none of the GCSs, the type of the ACT measuring device or used cartridges were specified. CONCLUSIONS: Large variability was found between the included GCSs with regard to the recommendations on heparin dose and target ACT values during NCAP. Advice and recommendations in GCSs were based on low-quality studies or without providing any reference at all. The described variability in recommendations emphasizes the need for large prospective (randomized) studies or the incorporation of data on heparin and the use of ACT monitoring into verified vascular surgery registries, to develop evidence-based, practical and uniform applicable recommendations.

Open E-survey on the Use and Perception of Chatbots in Vascular Surgery.

Objective: Large language models and artificial intelligence (AI) based chatbots have brought new insights in healthcare, but they also raise major concerns. Their applications in vascular surgery have scarcely been investigated to date. This international survey aimed to evaluate the perceptions and feedback from vascular surgeons on the use of AI chatbots in vascular surgery. Methods: This international open e-survey comprised 50 items that covered participant characteristics, their perceptions on the use of AI chatbots in vascular surgery, and their user experience. The study was designed in accordance with the Checklist for reporting Results of Internet E-Surveys and was critically reviewed and approved by international members of the European Vascular Research Collaborative (EVRC) prior to distribution. Participation was open to self reported health professionals specialised (or specialising) in vascular surgery, including residents or fellows. Results: Of the 342 individuals who visited the survey page, 318 (93%) agreed to participate; 262 (82.4%) finished the survey and were included in the analysis. Most were consultants or attending physicians (64.1%), most declared not having any training or education related to AI in healthcare (221; 84.4%), and 198 (75.6%) rated their knowledge about the abilities of AI chatbots between average to very poor. Interestingly, 95 participants (36.3%) found that AI chatbots were very useful or somewhat useful in clinical practice at this stage and 229 (87.4%) agreed that they should be systematically validated prior to being used. Eighty participants (30.5%) had specifically tested it for questions related to clinical practice and 59 (73.8%) of them experienced issues or limitations. Conclusion: This international survey provides an overview of perceptions of AI chatbots by vascular surgeons and highlights the need to improve knowledge and training of health professionals to better evaluate, define, and implement their use in vascular surgery.

Systematic Review of Outcome Reporting for Interventions to Treat Patients with Acute Lower Limb Ischaemia.

OBJECTIVE: Inconsistencies in outcome data of therapeutic strategies for acute lower limb ischaemia (ALI) have hindered the synthesis of findings. A core outcome set (COS) may offer a solution to this problem by defining a minimum set of outcomes that are considered essential to all stakeholders involved. The first step in developing a COS is to review the previously reported outcomes on various treatment strategies for ALI. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched from inception to August 2023. REVIEW METHODS: This systematic review was conducted in accordance with the Core Outcome Measures in Effectiveness Trials (COMET) initiative framework, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and was pre-registered with PROSPERO (CRD42022320073). Abstracts were independently screened by two authors for full text review. All outcomes and their definitions were extracted from selected papers. Outcomes with different terminologies were then categorised into an agreed outcome term. The list of agreed outcomes was given a standardised outcome domain and core area using a 38 item standardised taxonomy. RESULTS: Of 6 184 articles identified, 176 relevant studies were included, yielding 1 325 verbatim outcomes. After deduplication, 72 unique verbatim outcomes were categorised into five broad outcome domains. Outcomes considered key to the evaluation of treatment of ALI were further categorised as delivery of care (19.4%), vascular outcomes (13.8%), and adverse events (12.5%). The three most frequently reported agreed outcomes were amputation (14.1%), death (12.3%), and general bleeding (11.6%). CONCLUSION: This systematic review provides an overview of currently reported outcomes in the literature of interventions for ALI. After categorisation into agreed outcome terms, 72 outcomes were identified that can be used in the development of a COS.

Activated clotting time-guided heparinization during open AAA surgery: a pilot study.

BACKGROUND: Arterial thrombo-embolic complications (TEC) are still common during and after non-cardiac arterial procedures (NCAP). While unfractionated heparin has been used during NCAP for more than 70 years to prevent TEC, there is no consensus regarding the optimal dosing strategy. The aim of this pilot study was to test the effectiveness and feasibility of an activated clotting time (ACT)-guided heparinization protocol during open abdominal aortic aneurysm (AAA) surgery, in anticipation of a randomized controlled trial (RCT) investigating if ACT-guided heparinization leads to better clinical outcomes compared to a single bolus of 5000 IU of heparin. METHODS: A prospective multicentre pilot study was performed. All patients undergoing elective open repair for an AAA (distal of the superior mesenteric artery) between March 2017 and January 2020 were included. Two heparin dosage protocols were compared: ACT-guided heparinization with an initial dose of 100 IU/kg versus a bolus of 5000 IU. The primary outcome was the effectiveness and feasibility of an ACT-guided heparinization protocol with an initial heparin dose of 100 IU/kg during open AAA surgery. Bleeding complications, TEC, and mortality were investigated for safety purposes. RESULTS: A total of 50 patients were included in the current study. Eighteen patients received a single dose of 5000 IU of heparin and 32 patients received 100 IU/kg of heparin with additional doses based on the ACT. All patients who received the 100 IU/kg dosing protocol reached the target ACT of > 200 s. In the 5000 IU group, TEC occurred in three patients (17%), versus three patients (9.4%) in the 100 IU/kg group. Bleeding complications were found in six patients (33%) in the 5000 IU group and in 9 patients (28%) in the 100 IU/kg group. No mortality occurred in either group. CONCLUSIONS: This pilot study demonstrated that ACT-guided heparinization with an initial dose of 100 IU/kg appears to be feasible and leads to adequate anticoagulation levels. Further randomized studies seem feasible and warranted to determine whether ACT-guided heparinization results in better outcomes after open AAA repair.

Editor's Choice - International Perspective on Extremity Vascular Trauma in Children: A Scoping Review.

OBJECTIVE: Extremity vascular trauma in children can result in significant morbidity and mortality. Most published studies have focused on supracondylar humeral fracture related injuries, with little focus on other injuries. This scoping review describes the current state of knowledge on paediatric vascular injuries in the upper and lower limbs, excluding injuries related to supracondylar humeral fractures. METHODS: MEDLINE, PubMed, Web of Science, and Cochrane databases were searched for relevant studies evaluating the epidemiology, diagnosis, management, and outcomes of upper and lower limb vascular trauma in those aged under 18 years. Studies related to supracondylar humeral fractures were excluded. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for Scoping Reviews was used. RESULTS: A total of 39 studies was included, all of which were retrospective, and 74% of which were based in North America or Europe. Extremity vascular trauma was reported to cause 0.6 - 4.4% of all paediatric trauma admissions, with penetrating mechanisms and upper limb injuries being the most common. Operative intervention was reported in 80 - 100% of children in the included studies. Primary repair was the most commonly reported operative intervention, followed by interposition graft and bypass graft. Synthetic graft use was less commonly reported (incidence range 0.5 - 33%). Lower limb fasciotomies and amputations were not commonly reported (incidence range 0 - 23% and 0 - 13%, respectively). The mortality rate appeared low, with 23 studies reporting no deaths (incidence range 0 - 4%). Complications were reported inconsistently, with no uniform outcome or follow up measures used. CONCLUSION: The incidence of extremity vascular trauma appears low in children, with penetrating mechanisms and upper extremity injuries appearing to dominate. Most studies are from high income countries, with probable selection bias towards those treated by operative intervention. Prospective studies are required focusing on patterns of injury, rates of operative and endovascular intervention, and long term outcomes.

Acute kidney injury in patients undergoing endovascular or open repair of juxtarenal or pararenal aortic aneurysms.

BACKGROUND: The aim of this cohort study was to report the proportion of patients who develop periprocedural acute kidney injury (AKI) after endovascular repair (ER) and open surgery (OS) in patients with juxta/pararenal abdominal aortic aneurysm and to assess potential risk factors for AKI. The study also aimed to report the short- and long-term outcomes of patients with and without AKI. METHODS: This was a multicenter cohort study of five European academic high-volume centers (>50 OS or 50 ER infrarenal AAA repairs, plus >15 complex AAA repairs per year). All consecutively treated patients were extracted from a prospective vascular surgical registry and the data were scrutinized retrospectively. The primary end point for this study was the development of AKI. AKI was diagnosed when there is a two-fold increase of serum creatinine or decrease of glomerular filtration rate of >50% within 1 week of AAA repair. Secondary end points included long-term mortality and end-stage renal disease (ESRD). RESULTS: AKI occurred in 16.6% of patients in the ER group vs 30.3% in the OS group (P < .001). The 30-day mortality rate was higher among patients with AKI in both ER (15.4% vs 3.1%; P = .006) and OS (13.2% vs 5.3%; P = .001) groups. Age, chronic kidney disease, presence of significant thrombus burden in the pararenal region, >1000 mL blood loss in ER group were associated with development of AKI. Age, diabetes mellitus, chronic kidney disease, presence of significant thrombus burden in the pararenal region, and a proximal clamping time of >30 minutes in the OS group were associated with the development of AKI, whereas renal perfusion during clamping was the protective factor against AKI development. After a median follow-up of 91 months, AKI was associated with higher mortality rates in both the ER group (58.9% vs 29.7%; P < .001) and the OS group (61.5% vs 27.3%; P < .001). After the same follow-up period, AKI was associated with a higher incidence of ESRD in both the ER group (12.8% vs 3.6%; P = .009) and the OS group (9.9% vs 2.9%; P < .001). CONCLUSIONS: The current study identified important pre and postoperative factors associated with AKI after juxta/pararenal abdominal aortic aneurysm repair. Patients with postoperative AKI had significantly higher short- and long term mortality and higher incidence of ESRD than patients without AKI.

The Additional Value of Activated Clotting Time-Guided Heparinization During Interventions for Peripheral Arterial Disease.

PURPOSE: Unfractionated heparin is widely used to lower the risk of arterial thromboembolic complications (ATECs) during interventions for peripheral arterial disease (PAD), but it is still unknown which heparin dose is the safest in terms of preventing ATECs and bleeding complications. This study aims to evaluate the incidence of complications during interventions for PAD and the relation between this incidence and different heparinization protocols. MATERIALS AND METHODS: A retrospective analysis of a prospective multicenter cohort study was performed. Between June 2015 and September 2022, 355 patients who underwent peripheral interventions for PAD were included. All patients who were included before July 2018 received 5000 international units (IU) of heparin (group 1). Starting from July 2018, all included patients received an initial dose of 100 IU/kg, with potential additional heparin doses based on activated clotting time (ACT) values (group 2). Data on ACT values and complications within 30 days post-procedurally were collected. RESULTS: In total, 24 ATECs and 48 bleeding complications occurred. In group 1, 8.7% (n=11) of patients suffered from ATEC, compared with 5.7% (n=13) in group 2. Thirteen percent of patients (n=17) in group 1 had a bleeding complication, compared with 14% (n=31) in group 2. Arterial thromboembolic complications were more often found in patients with peak ACT values of <200 seconds, compared with ACT values between 200 and 250 seconds, 15% (n=6) versus 5.9% (n=9), respectively, p=0.048. Patients with peak ACT values >250 seconds had a higher incidence of bleeding complications compared with an ACT between 200 and 250 seconds, 24% (n=21) versus 9.8% (n=15), respectively, p=0.003. Forty-four percent of patients (n=23) in group 1 reached a peak ACT of >200 seconds, compared with 95% (n=218) of patients in group 2 (p=0.001). CONCLUSION: ATEC was found in 6.8% (n=24) and bleeding complications in 14% (n=48) of patients who underwent a procedure for PAD. There was a significantly higher incidence of ATECs in patients with a peak ACT value <200 seconds, and a higher incidence of bleeding complications in patients with a peak ACT value >250 seconds. The findings obtained from this study may serve as a basis for conducting future research on heparinization during procedures for PAD, with a larger sample size. CLINICAL IMPACT: Heparin is administered during arterial interventions for peripheral arterial disease (PAD) to decrease the risk of arterial (thrombo)embolic complications (ATEC) during or shortly following surgery. The effect of heparin is unpredictable in the individual patient, and the optimal dosage of this anticoagulant has not yet been established. Using the activated clotting time (ACT), the anticoagulatory effect of heparin can be monitored periprocedurally. Previous research on the incidence of both ATEC and bleeding complications, or on the optimal dosage of heparin administration, is scarce. This study aims to investigate the incidence of ATEC and bleeding complications between 2 different dosage protocols of heparin-a standard bolus of 5000 IU or ACT-guided heparinization-and thereby provide clarity on the optimal dose of heparin during peripheral arterial interventions for PAD.

The Effect of Smoking on the Activated Clotting Time and the Incidence of Complications in Noncardiac Arterial Procedures.

PURPOSE: Smoking is a well-known risk factor for developing arterial diseases and for an increase of complications during and after vascular procedures. Although smoking has a proven effect on hemostasis, no literature is available on the effect of smoking on the activated clotting time (ACT), which is used to monitor the effect of heparin during noncardiac arterial procedures (NCAP). The aim of this study was to examine the effect of smoking on ACT values and the incidence of complications during the same admission or 30 day follow-up of NCAP. MATERIALS AND METHODS: A post hoc analysis of a prospective multicenter cohort study was performed. Patients older than 18 years, who underwent NCAP between December 2016 and April 2021, were enrolled. Patients were divided into 2 groups based on smoking status: never/former smokers and current smokers. Two heparin dosing protocols were used: an initial bolus of 5000 IU or 100 IU/kg bodyweight. RESULTS: In total, 773 patients met the inclusion criteria. Five minutes after administration of 5000 IU of heparin, mean ACT values were 190 and 196 seconds for nonsmokers and smokers, respectively (p=0.078). After 100 IU/kg of heparin, mean ACT values were 229 and 226 seconds for nonsmokers and smokers, respectively (p=0.37). Incidence of complications in the whole study cohort was not significantly different for nonsmokers compared with smokers (arterial thrombo-embolic complication [ATEC] 4.7% vs 5.7% p=0.55; hemorrhagic complications 15% vs 18% p=0.29). In subgroup-analysis, a significant difference between smoking groups was found for hemorrhagic complications after open aneurysm repair (p=0.024). However, after adjusting for confounders, the difference between the smoking groups annulled. CONCLUSION: The results of this study suggest that smoking does not have a significant effect on ACT values or on the incidence of complications in NCAP. Large-scale studies are required to further analyze potential factors having an effect on the ACT and perioperative and postoperative complications, which could help individualize heparinization strategy. CLINICAL IMPACT: There is high variance between patients in their response on administration of heparin, this is not yet fully understood. This study investigated the effect of smoking in a large prospective multicentre cohort. The results suggests that active smoking does not have an effect on the activated clotting time after administration of heparin. Also no significant effect of smoking could be found on the incidence of all registered complications. Monitoring of the effect of heparin remains important to provide patients with safe anticoagulation during vascular procedures.

Management of Paget-Schroetter Syndrome: a Systematic Review and Meta-Analysis.

OBJECTIVE: Currently, there is no consensus on the optimal management of Paget-Schroetter syndrome (PSS). The objective was to summarise the current evidence for management of PSS with explicit attention to the clinical outcomes of different management strategies. DATA SOURCES: The Cochrane, PubMed, and Embase databases were searched for reports published between January 1990 and December 2021. REVIEW METHODS: A systematic review and meta-analysis was conducted following PRISMA 2020 guidelines. The primary endpoint was the proportion of symptom free patients at last follow up. Secondary outcomes were success of initial treatment, recurrence of thrombosis or persistent occlusion, and patency at last follow up. Meta-analyses of the primary endpoint were performed for non-comparative and comparative reports. The quality of evidence was assessed using the GRADE approach. RESULTS: Sixty reports were included (2 653 patients), with overall moderate quality. The proportions of symptom free patients in non-comparative analysis were: anticoagulation (AC), 0.54; catheter directed thrombolysis (CDT) + AC, 0.71; AC + first rib resection (FRR), 0.80; and CDT + FRR, 0.96. Pooled analysis of comparative reports confirmed the superiority of CDT + FRR compared with AC (OR 13.89, 95% CI 1.08 - 179.04; p = .040, I2 87%, very low certainty of evidence), AC + FRR (OR 2.29, 95% CI 1.21 - 4.35; p = .010, I2 0%, very low certainty of evidence), and CDT + AC (OR 8.44, 95% CI 1.12 - 59.53; p = .030, I2 63%, very low certainty of evidence). Secondary endpoints were in favour of CDT + FRR. CONCLUSION: Non-operative management of PSS with AC alone results in persistent symptoms in 46% of patients, while 96% of patients managed with CDT + FFR were symptom free at end of follow up. Superiority of CDT + FRR compared with AC, CDT + AC, and AC + FRR was confirmed by meta-analysis. The overall quality of included reports was moderate, and the level of certainty was very low.

Unfractionated heparin and the activated clotting time in non-cardiac arterial procedures.

INTRODUCTION: Unfractionated heparin is administered during non-cardiac arterial procedures (NCAP) to prevent thromboembolic complications. In order to achieve a safe level of anticoagulation, the effect of heparin can be measured. The aim of this review was to provide an overview on what is known about heparin, suggested tests to monitor the effect of heparin, including the activated clotting time (ACT), and the factors that could influence that ACT. EVIDENCE ACQUISITION: A literature search in PubMed was performed. Articles reporting on heparin, clotting time tests (including thrombin time, activated partial thromboplastin time, anti-activated factor X and ACT), and ACT measurement devices were selected. EVIDENCE SYNTHESIS: Heparin has a non-predictable effect in the individual patient, which could be measured using the ACT. However, ACT values can be influenced by many factors, such as hemodilution, hypothermia and thrombocytopenia. In addition, a high variation in ACT outcomes is found between measurement devices of different brands. In the sparse literature on the role of ACT during NCAP, no consensus has been reached on optimal target ACT values. An ACT >250 seconds leads to more bleeding complications. Females have a longer ACT after heparin administration, with a higher risk of bleeding complications. CONCLUSIONS: The effect of heparin is unpredictable. ACT can be used to monitor the effect of heparin and achieve individualized anticoagulation, tailored to the patient and the specifics of the operative procedure. However, the ACT itself can be affected by several factors and caution must be present, as measured ACT values differ between measurement devices.

Sex Related Outcomes Following Thoracic Endovascular Aortic Repair for Blunt Thoracic Aortic Injury.

OBJECTIVE: Current literature suggests that thoracic endovascular aortic repair (TEVAR) in older patients with aortic aneurysms results in higher peri-operative mortality and lower long term survival in females compared with males. However, sex related outcomes in younger patients with blunt thoracic aortic injury (BTAI) undergoing TEVAR remain unknown. This study examined the association between sex and outcomes after TEVAR for BTAI. METHODS: A retrospective cohort study was performed of all patients who underwent TEVAR for BTAI in the American College of Surgeons Trauma Quality Improvement Program (ACS-TQIP) between 2016 and 2019. The primary outcome was in hospital death. Secondary outcomes were peri-operative complications. Multivariable logistic regression was used to adjust for demographics, comorbidities, injury severity score, and aortic injury grade. RESULTS: Two thousand and twenty-two patients were included; 26% were female. Compared with males, females were older (46 [IQR 30, 62] vs. 39 [IQR 28, 56] years; p < .001), more often obese (41% vs. 33%; p = .005), had lower rates of alcohol use disorder (4.1% vs. 8.9%; p < .001) and a higher prevalence of hypertension (29% vs. 22%; p = .001). The injury severity was comparable between females and males (Injury Severity Score ≥ 25; 84% vs. 80%; p = .11) and there was no difference in aortic injury grades when comparing females with males (grade 1, 33% vs. 33%; grade 2, 24% vs. 25%; grade 3, 43% vs. 40%; grade 4, 0.8% vs. 1.3%; p = .53). Multivariable logistic regression demonstrated no difference for in hospital mortality between females and males (OR 1.02; 95% CI 0.67 - 1.53, p = .93). Compared with males, females were at lower risk of acute kidney injury (AKI) (OR 0.33; 95% CI 0.17 - 0.64; p = .001) and ventilator associated pneumonia (VAP) (OR 0.50; 95% CI 0.28 - 0.91; p = .023). CONCLUSION: This study did not demonstrate a sex related in hospital mortality difference following TEVAR for BTAI. However, female sex was associated with a lower risk of AKI and VAP. Future studies should evaluate sex differences and long term outcomes following TEVAR in patients with BTAI.

Short Term and Long Term Clinical Outcomes of Endovascular versus Open Repair for Juxtarenal and Pararenal Abdominal Aortic Aneurysms Using Propensity Score Matching: Results from Juxta- and pararenal aortic Aneurysm Multicentre European Study (JAMES).

OBJECTIVE: The aim of this study was to compare the short and long term clinical outcomes of endovascular (EVAR) vs. open surgical repair (OSR) of juxtarenal (JAAAs) and pararenal abdominal aortic aneurysms (PAAAs) in five high volume European academic centres. METHODS: This was a retrospective multicentre cohort study of five high volume European academic centres (> 50 open or 50 endovascular abdominal aortic aneurysm repairs annually) including 834 consecutive patients who were operated on and prospectively followed. Using propensity score matching (PSM) each patient who underwent OSR was matched with one patient who underwent EVAR in a 1:1 ratio (145 patients per group). The primary endpoint was long term all cause mortality, while the secondary endpoint was freedom from aortic related re-intervention. RESULTS: After a follow up of 87 months, no difference in overall survival between the two groups was observed (38.6% for EVAR vs. 42.1% for OSR; p = .88). Patients undergoing EVAR underwent aortic related re-interventions more frequently (24.1% vs. 6.9%; p < .001). Acute kidney injury (AKI) occurred more frequently in patients in the OSR group (40.7% vs. 24.8%; p = .006). However, most patients who suffered from AKI recovered without further progression to renal failure. In hospital (3.4% for EVAR vs. 4.1% for OSR; p = 1.0) and 30 day (4.1% for EVAR vs. 5.5% for OSR; p = .80) mortality rates did not differ between groups. CONCLUSION: Both open and endovascular treatment can be performed in high volume aortic centres with low short term mortality and morbidity rates, and good long term outcomes. These data provide useful information to help patients choose between the two procedures when both are feasible.

Early Versus Delayed Thoracic Endovascular Aortic Repair for Blunt Thoracic Aortic Injury: A Propensity Score-Matched Analysis.

OBJECTIVE: We examined early (≤24 h) versus delayed (>24 h) thoracic endovascular aortic repair (TEVAR) for blunt thoracic aortic injury (BTAI), taking the aortic injury severity into consideration. BACKGROUND: Current trauma surgery guidelines recommend delayed TEVAR following BTAI. However, this recommendation was based on small studies, and specifics regarding recommendation strategies based on aortic injury grades are lacking. METHODS: Patients undergoing TEVAR for BTAI in the American College of Surgeons Trauma Quality Improvement Program between 2016 and 2019 were included and then stratified into 2 groups (early: ≤24 h vs. delayed: >24 h). In-hospital outcomes were compared after creating 1:1 propensity score-matched cohorts, matching for demographics, comorbidities, concomitant injuries, additional procedures, and aortic injury severity based on the acute aortic syndrome (AAS) classification. RESULTS: Overall, 1339 patients were included, of whom 1054(79%) underwent early TEVAR. Compared with the delayed group, the early group had significantly less severe head injuries (early vs delayed; 25% vs 32%; P =0.014), fewer early interventions for AAS grade 1 occurred, and AAS grade 3 aortic injuries often were intervened upon within 24 hours (grade 1: 28% vs 47%; grade 3: 49% vs 23%; P <0.001). After matching, the final sample included 548 matched patients. Compared with the delayed group, the early group had a significantly higher in-hospital mortality (8.8% vs 4.4%, relative risk: 2.2, 95% CI: 1.1-4.4; P =0.028), alongside a shorter length of hospital stay (5.0 vs 10 days; P =0.028), a shorter intensive care unit length of stay (4.0 vs 11 days; P <0.001) and fewer days on the ventilator (4.0 vs 6.5 days; P =0.036). Furthermore, regardless of the higher risk of acute kidney injury in the delayed group (3.3% vs 7.7%, relative risk: 0.43, 95% CI: 0.20-0.92; P =0.029), no other differences in in-hospital complications were observed between the early and delayed group. CONCLUSION: In this propensity score-matched analysis, delayed TEVAR was associated with lower mortality risk, even after adjusting for aortic injury grade.

Catheter Directed Thrombolysis for Not Immediately Threatening Acute Limb Ischaemia: Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis reports the outcomes of catheter directed thrombolysis (CDT) in patients with not immediately threatening (Rutherford I) acute lower limb ischaemia (ALI). DATA SOURCES: PubMed, Embase, and the Cochrane Library. REVIEW METHODS: A systematic search of PubMed, Embase, and the Cochrane Library was performed to identify observational studies and trials published between 1990 and 2022 reporting on the results of CDT in patients with Rutherford I ALI. A meta-analysis was performed using a random effects model with 95% confidence intervals (CIs). The outcomes of interests were treatment duration, angiographic success, bleeding complications, amputation and mortality rates, primary and secondary patency, and functional outcome expressed as pain free walking distance. RESULTS: Thirty-nine studies were included, comprising 1 861 patients who received CDT for not immediately threatening ALI. Funnel plots showed an indication of publication bias, and heterogeneity was substantial. Data from 5 to 13 studies were included in the meta-analysis. The pooled treatment duration was 2 days (95% CI 1 - 2), with an angiographic success rate of 80% (95% CI 73 - 86) and a 30 day freedom of amputation rate of 98% (95% CI 92 - 100). The major bleeding rate was 5% (95% CI 2 - 14), with a 30 day mortality rate of 3% (95% CI 1 - 5). The amputation free survival rate was 71% (95% CI 62 - 80) at the one year and 63% (95% CI 51 - 73) at the three year follow up. Long term patency rates were retrieved from four studies: 48% at one year (95% CI 27 - 70). No data could be retrieved on patient walking distance. CONCLUSION: Although CDT in the treatment of not immediately threatening ALI showed high angiographic success, the long term outcomes were relatively poor, with low patency and a substantial risk of major amputation. Further research is required to interpret the outcome of CDT in the context of potential confounders such as age and comorbidities.

Major Bleeding During Thrombolytic Therapy for Acute Lower Limb Ischaemia: Value of Laboratory Tests for Clinical Decision Making, 17 Years of Experience.

OBJECTIVE: Regular measurement of fibrinogen as dose guidance in catheter directed thrombolysis (CDT) for acute limb ischaemia (ALI) has recently been dropped from European guidelines based on inconsistent literature. This study aimed to determine whether low fibrinogen levels and high activated partial thromboplastin time (APTT) are associated with an increased major bleeding risk during CDT. METHODS: All consecutive patients treated with CDT for ALI in two Dutch hospitals between January 2004 and April 2021 were analysed retrospectively. Patients were treated with two dosing regimens (low dose: 50 000 IU/hour; high dose: 100 000 IU/hour) of urokinase and, after 2018, with a single low dose regimen of alteplase (rtPA) due to urokinase manufacturing problems. The incidence of major bleeding and associated APTT and fibrinogen levels were reviewed from patient charts. RESULTS: Of the 443 included cases, 277 underwent CDT with urokinase and 166 with rtPA. The incidence of major bleeding in the whole cohort was 7%. Patients with a fibrinogen levels < 1.0 g/L developed more major bleeding than those in whom the fibrinogen level did not drop below 1.0 g/L (15% vs. 6%; p = .041). Systemic heparinisation during CDT or high (> 80 seconds) APTT were not significantly associated with major bleeding. Angiographic success (47% vs. 72%; p = .003) and 30 day amputation free survival (53% vs. 82%; p < .001) were lower for cases with major bleeding. Older age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02 - 1.11), cardiac history (OR 3.35, 95% CI 1.39 - 8.06), high dose regimens (≥ 75 000 IU/hour urokinase; OR 2.67, 95% CI 1.18 - 6.04), and fibrinogen values < 1.0 g/L (OR 5.59, 95% CI 1.98 - 15.77) were independent predictors for major bleeding during CDT. CONCLUSION: High dose thrombolytic regimens and fibrinogen levels of ≤ 1.0 g/L are associated with more major bleeding during thrombolytic therapy. Major bleeding significantly worsened the clinical outcome. A prospective comparative study is needed to assess the benefit of monitoring fibrinogen levels.

Males and females have similar mortality after thoracic endovascular aortic repair for blunt thoracic aortic injury.

OBJECTIVE: Prior literature has demonstrated worse outcomes for female patients after abdominal aortic aneurysm repair. Also, prior studies in the context of thoracic endovascular aneurysm repair (TEVAR) for thoracic aortic aneurysms have reported conflicting results regarding sex-related outcomes. Because the influence of sex on the outcomes after TEVAR for blunt thoracic aortic injuries (BTAIs) remains understudied, we evaluated the association between sex and outcomes after TEVAR for BTAI. METHODS: We identified patients who had undergone TEVAR for BTAIs in the Vascular Quality Initiative registry from 2013 to 2022 and included those who had undergone TEVAR within zones 2 to 5 of the thoracic aorta. Patients with missing information regarding the aortic injury grade (Society for Vascular Surgery aortic injury grading system) were excluded. We performed multivariable logistic regression and Cox regression to determine the influence of sex on the perioperative outcomes and long-term mortality, respectively. RESULTS: We identified 1311 patients, of whom 27% were female. The female patients were significantly older (female, 47 years [interquartile range (IQR), 30-63 years]; male, 38 years [IQR, 28-55 years]; P < .001) with higher rates of comorbidities. Although the female patients had had higher Glasgow coma scale scores (median, 15 [IQR, 11-15]; vs 14 [IQR, 8-15]; P = .028), no differences were found in the aortic injury grade or other coexisting traumatic injuries between the sexes. Apart from the longer procedure duration for the female patients (median, 79 minutes [IQR, 52-119 minutes]; vs 69 minutes [IQR, 48-106 minutes]; P = .008), the procedural characteristics were comparable. After adjustment, no significant association was found between female sex and perioperative mortality (7.1% vs 8.1%; odds ratio, 0.76; 95% confidence interval [CI], 0.43-1.3; P = .34). The male and female patients had had comparable rates of postoperative complications (26% vs 29%; odds ratio, 0.89; 95% CI: 0.52-1.5]; P = .26) including access-related complications (0.5% vs 0.8%; P=.83). However, females had a significantly higher risk for reintervention during the index admission (odds ratio, 2.5; 95% CI, 1.1-5.5; P = .024). No significant difference was found between the male and female patients with respect to 5-year mortality (hazard ratio, 0.87; 95% CI, 0.57-1.35; P = .50). CONCLUSIONS: Unlike the sex-based outcome disparities observed after thoracic aortic aneurysm repair, we found no significant association between sex and perioperative outcomes or long-term mortality after TEVAR for BTAIs. This contrast in the sex-related outcomes after other vascular pathologies might be explained by differences in the pathology, demographics, and anatomic factors in these patients.

Feasibility of Microbubble-Accelerated Low-Dose Thrombolysis of Peripheral Arterial Occlusions Using an Ultrasound Catheter.

PURPOSE: Intra-arterial administration of microbubbles (MBs) through an ultrasound (US) catheter increases the local concentration of MBs into the thrombus and may further enhance outcomes of contrast-enhanced sonothrombolysis (CEST). The objective of this study was to evaluate the feasibility and lytic efficacy of intra-arterial infusion of MBs during US-enhanced thrombolysis in both in vitro and in vivo peripheral arterial occluded models. MATERIALS AND METHODS: SonoVue and Luminity MBs were infused at a flow rate of 20 mL/h through either the drug delivery lumen of the US catheter (DDC, n=20) or through the tube lumen of the vascular phantom (systematic infusion, n=20) during thrombolysis with a low-dose urokinase (UK) protocol (50 000 IU/h) with(out) US application to assess MB survivability and size by pre-treatment and post-treatment measurements. A human thrombus was placed into a vascular phantom of the flow system to examine the lytic effects of CEST by post-treatment D-dimer concentrations measurements of 5 treatment conditions (saline, UK, UK+US, UK+US+SonoVue, and UK+US+Luminity). Thrombolytic efficacy of localized MBs and US delivery was then investigated in vivo in 5 porcine models by arterial blood flow, microcirculation, and postmortem determined thrombus weight and remaining length. RESULTS: US exposure significantly decreased SonoVue (p=0.000) and Luminity (p=0.000) survivability by 37% and 62%, respectively. In vitro CEST treatment resulted in higher median D-dimer concentrations for the SonoVue (0.94 [0.07-7.59] mg/mL, p=0.025) and Luminity (0.83 [0.09-2.53] mg/mL, p=0.048) subgroups when compared with thrombolysis alone (0.36 [0.02-1.00] mg/mL). The lytic efficacy of CEST examined in the porcine model showed an improved median arterial blood flow of 21% (7%-79%), and a median thrombus weight and length of 1.02 (0.96-1.43) g and 2.25 (1.5-4.0) cm, respectively. One allergic reaction and 2 arrhythmias were observed due to the known allergic reaction on lipids in the porcine model. CONCLUSION: SonoVue and Luminity can be combined with an US catheter and could potentially accelerate thrombolytic treatment of peripheral arterial occlusions. CLINICAL IMPACT: Catheter-directed thrombolysis showed to be an effective alternative to surgery for acute peripheral arterial occlusions, but this technique is still associated with several limb and life-threatening complications. The effects of thrombolysis on clot dissolution may be further enhanced by intra-arterial administration of microbubbles through an ultrasound catheter. This study demonstrates the feasibility and lytic efficacy of intra-arterial infusion of microbubbles during US-enhanced thrombolysis in both in vitro and in vivo peripheral arterial occluded models.

Editor's Choice - Sex Differences in Response to Administration of Heparin During Non-Cardiac Arterial Procedures.

OBJECTIVE: Females are more prone to complications during non-cardiac arterial procedures (NCAPs) than males. The current study investigated the difference in the effect of peri-procedural prophylactic heparin in males and females, using the activated clotting time (ACT). This was a retrospective analysis of a prospective multicentre cohort study. METHODS: All patients undergoing elective NCAP using heparin and ACT measurements between January 2016 and March 2020 were included. Two heparin dosage protocols were used: weight based dosing of 100 IU/kg (international units per kilogram) or a bolus of 5 000 IU. The primary outcome was the anticoagulatory effect of heparin after five minutes, measured by ACT. Secondary outcomes were the effect of heparin after 30 minutes, bleeding complications, and arterial thromboembolic complications (ATECs). RESULTS: A total of 778 patients were included; 26% were female. After 100 IU/kg (n = 300), females more often reached longer ACT (< 200 seconds: 22% vs. 25%, p = .62; 200 - 250 seconds: 41% vs. 53%, p = .058; 251 - 280 seconds, 26% vs. 15%, p = .030). The mean ACT after 100 IU/kg heparin was 233 seconds (95% confidence interval [CI] 224 - 243) for females and 226 seconds (95% CI 221 - 231) for males (p = .057). After a bolus of 5 000 IU of heparin (n = 411), females reached significantly higher levels of anticoagulation than males (mean ACT 204 seconds vs. 190 seconds: p ≤ .001; ACT < 200 seconds: 44% vs. 66%; p < .001; ACT 200 - 250 seconds: 47% vs. 30%, p = .001; ACT 251 - 280 seconds: 7.8% vs. 2.3%, p = .009). Thirty minutes after heparin administration, 58% of all patients had an ACT < 200 seconds. ATECs did not differ between females and males (6.9% vs. 5.1%, p = .33) but bleeding complications were higher in females (27% vs. 16%, p = .001). CONCLUSION: Heparin leads to significantly longer ACT in females during NCAP. Further research is needed to investigate whether individually based heparin protocols lead to fewer bleeding complications and lower incidence of ATECs.