Prevalence of type II endoleak after elective endovascular aneurysm repair with polytetrafluoroethylene- or polyester-based endografts.

OBJECTIVE: Type II endoleak is the most frequent complication after endovascular abdominal aneurysm repair. Polytetrafluoroethylene and polyester (PE) are the two most commonly used graft materials in endovascular aneurysm repair (EVAR) devices. Biological properties of the material might influence the appearance and persistence of type II endoleak (T2EL). Therefore, the aim of this study was to evaluate potential differences in the prevalence of T2EL after EVAR between polytetrafluoroethylene (PTFE) and PE endografts in patients electively treated for an infrarenal abdominal aortic aneurysm. METHODS: A single-center, retrospective, observational study was conducted between January 2011 and January 2022. Preoperative, procedural, and follow-up data were derived from electronic health records. Imaging included computed tomography scans, and/or duplex ultrasound examination. The primary end point was the prevalence of T2EL diagnosed within 1 year after EVAR. Secondary end points included the prevalence of T2EL throughout follow-up, early (≤30 days) and late (>30 days) T2EL, the rate of T2EL disappearance during the follow-up period, the prevalence of type I and III endoleak, and T2EL-related reinterventions. RESULTS: Follow-up was available for 394 patients, 245 in the PE and 149 in the PTFE group. The prevalence of T2EL diagnosed within 1 year after endovascular repair was 11.8% in the PE group and 21.5% in the PTFE group (P = .010). There was no significant difference in early (≤30 days) and late (>30 days) T2EL between groups (P = .270 and P = .311). There was no difference in the freedom from endoleak type II reinterventions between groups (P = .877). CONCLUSIONS: The prevalence of T2EL after elective EVAR is significantly higher with the use of PTFE-based endografts compared with PE-based endografts. This difference is mostly based on T2EL diagnosed after 30 days of follow-up.

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.

Perprocedural Heparinization in Non-cardiac Arterial Procedures: The Current Practice in the Netherlands.

PURPOSE: Heparin is the most widely-used anticoagulant to prevent thrombo-embolic complications during non-cardiac arterial procedures (NCAP). Unfortunately, there is a lack of evidence and consequently non-uniformity in guidelines on perprocedural heparin management. Detailed insight into the current practice of antithrombotic strategies during NCAP in the Netherlands is important, aiming to identify potential optimal protocols and local differences concerning perprocedural heparinization. MATERIALS AND METHODS: A comprehensive online survey was distributed electronically to vascular surgeons of every hospital in the Netherlands in which NCAP were performed. Data were collected from September 2020 to October 2021. RESULTS: The response rate was 90% (53/59 hospitals). During NCAP, all surgeons generally administered heparin before arterial clamping. In 74% (39/54) of hospitals, a single heparin dosing protocol was used for all types of patients and vascular procedures. In 40%, there was no uniformity in heparin dosing between vascular surgeons. Depending on the procedure, a fixed bolus heparin, predominantly 5000 IU, was administered in 73% to 93%. In the remaining hospitals (7%-27%), a bodyweight-based heparin protocol was used, with an initial dose of 70 or 100 IU/kg. A minority (28%) monitored the effect of heparin in patients using the activated clotting time add (ACT) after activated clotting time. Target values varied between 180 and 250 seconds or 2 times the baseline ACT. CONCLUSION: This survey demonstrates considerable variability in perprocedural heparinization during NCAP in the Netherlands. Future research on heparin dosing is needed to harmonize and optimize heparin dosage protocols and contemporary guidelines during NCAP, and thereby improve vascular surgical care and patient safety. CLINICAL IMPACT: This survey demonstrated persisting intra- and inter-hospital variability in perprocedural heparinization during non-cardiac arterial procedures (NCAP) in the Netherlands. The observed variability in heparinization strategies highlights the need for high quality evidence on perprocedural anticoagulation strategies. This is needed in order to harmonize and optimize heparin dosage protocols and contemporary guidelines and thereby improve vascular surgical patient care. Based on the current results, an international survey will be conducted by the authors to gain additional insight into the antithrombotic strategies used during NCAP, aiming to harmonize anticoagulation protocols worldwide.

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.

Identifying high risk for proximal endograft failure after endovascular aneurysm repair in patients suitable for both open and endovascular elective aneurysm repair.

OBJECTIVE: Proximal endograft failure (type Ia endoleak or migration) after endovascular aneurysm repair (EVAR) is associated with hostile aneurysm neck morphology. Neck scoring systems were developed to predict proximal endograft failure but were studied in retrospective studies, which, due to selection bias, may have led to an overestimation of bad outcomes after EVAR. To predict patients who benefit from open repair, preoperative neck morphology and occurrence of long-term proximal endograft failure were investigated in patients enrolled in the endovascular arm of the Dutch Randomized Endovascular Aneurysm Management (DREAM) trial who were suitable for open repair by definition and have long-term follow-up. METHODS: A post-hoc on-treatment analysis of patients after EVAR was performed in 171 patients. Aneurysm neck morphology was quantified using the aneurysm severity grading (ASG) neck score calculated on preoperative computed tomography angiography images. The ASG neck score was used to predict proximal endograft failure. Receiver operating characteristic analysis was performed to calculate a threshold to divide favorable and unfavorable aneurysm necks (low and high risk); positive and negative likelihood-ratios were calculated accordingly. Freedom from proximal endograft failure was compared between groups using Kaplan-Meier analysis. RESULTS: During a median follow-up of 7.6 years, 20 patients suffered proximal endograft failure. Receiver operating characteristic analysis showed an area under the curve of 0.77 (95% confidence interval [CI], 0.65-0.90; P < .001), indicating acceptable prediction. The threshold was determined at ASG neck score ≥5; 30 patients had unfavorable neck morphology, of whom 11 developed proximal endograft failure. The positive likelihood-ratio was 4.4 (95% CI, 2.5-7.8), and the negative likelihood-ratio was 0.51 (95% CI, 0.3-0.8). Twelve years postoperatively, freedom from proximal endograft failure was 91.7% in the favorable group and 53.2% in the unfavorable group, a difference of 38.5% (95% CI, 13.9-63.1; P < .001). CONCLUSIONS: In this study, the ASG neck score predicted proximal endograft failure during the entire follow-up. This exhibits the persistent risk for proximal endograft failure long after EVAR and calls for ongoing surveillance especially in patients with unfavorable aneurysm necks.

Long-term age-stratified survival following endovascular and open abdominal aortic aneurysm repair.

OBJECTIVE: The long-term survival differences between endovascular repair (EVAR) and open repair for abdominal aortic aneurysms (AAAs) and specifically the impact of age on these differences remain a topic of debate. Therefore, we compared the long-term mortality between EVARand open abdominal aneurysm repair for patients of different ages. METHODS: This was a retrospective cohort study of prospectively collected data from patients undergoing elective EVAR or open repair for infrarenal AAAs within the Vascular Quality Initiative multinational clinical registry (2003-2021). The primary outcome was long-term all-cause mortality comparing EVAR and open repair for patients aged less than 65 years, between 65 and 79 years, and those aged 80 and older. In addition, we investigated the interaction between repair modality and 10-year hazard of mortality for sex, aneurysm diameter, and several preoperative comorbid conditions within each age category. To account for the nonrandom assignment of treatment, we used propensity scores and inverse probability weighted Cox proportional hazard analysis. RESULTS: We identified 48,074 patients undergoing elective infrarenal abdominal aneurysm repair (89% EVAR) within the study period, including 7940 patients aged less than 65, 29,555 aged between 65 and 79, and 10,579 aged 80 years or more. EVAR was associated with a higher propensity score-adjusted long-term hazard of mortality compared with open repair in the cohort aged less than 65 years (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.04-1.86; P = .026). The mortality was similar in the age cohort between 65 and 79 (HR, 0.94; 95% CI, 0.79-1.10; P = .43), whereas EVAR was associated with a lower hazard of mortality in the cohort aged 80 years or more (HR, 0.63; 95% CI, 0.46-0.86; P = .004). In patients aged less than 65 years, the hazard of mortality was higher with EVAR compared with open repair in those with female sex (HR, 4.40; 95% CI, 1.75-11.0), an aneurysm diameter of more than 65 mm (HR, 2.19; 95% CI, 1.11-4.34), and an absence of coronary artery disease (HR, 1.26; 95% CI, 0.83-1.91), congestive heart failure (HR, 1.41; 95% CI, 1.03-1.92), and renal dysfunction (HR, 1.46; 95% CI, 1.04-2.05). In the patient cohort aged 80 and older, a lower hazard of mortality for EVAR versus open repair was observed for male patients or those with small aneurysms or certain comorbidities. CONCLUSIONS: In a selected group of young patients with a substantial life expectancy, the long-term mortality is higher with EVAR compared with open repair for infrarenal AAAs. Long-term mortality with EVAR is similar in the middle cohort and lower in the elderly cohort compared with open repair.

Results from a nationwide prospective registry on open surgical or endovascular repair of juxtarenal abdominal aortic aneurysms.

BACKGROUND: Juxtarenal abdominal aortic aneurysms (JRAAAs) can be treated either with open surgical repair (OSR) including suprarenal clamping or by complex endovascular aneurysm repair (cEVAR). In this study, we present the comparison between the short-term mortality and complications of the elective JRAAA treatment modalities from a national database reflecting daily practice in The Netherlands. METHODS: All patients undergoing elective JRAAA open repair or cEVAR (fenestrated EVAR or chimney EVAR) between January 2016 and December 2018 registered in the Dutch Surgical Aneurysm Audit (DSAA) were eligible for inclusion. Descriptive perioperative variables and outcomes were compared between patients treated with open surgery or endovascularly. Adjusted odds ratios for short-term outcomes were calculated by logistic regression analysis. RESULTS: In all, 455 primary treated patients with JRAAAs could be included (258 OSR, 197 cEVAR). Younger patients and female patients were treated more often with OSR vs cEVAR (72 ± 6.1 vs 76 ± 6.0; P < .001 and 22% vs 15%; P = .047, respectively). Patients treated with OSR had significantly more major and minor complications as well as a higher chance of early mortality (OSR vs cEVAR, 45% vs 21%; P < .001; 34% vs 23%; P = .011; and 6.6% vs 2.5%; P = .046, respectively). After logistic regression with adjustment for confounders, patients who were treated with OSR showed an odds ratio of 3.64 (95% confidence interval [CI], 2.25-5.89; P < .001) for major complications compared with patients treated with cEVAR, and for minor complications, the odds ratios were 2.17 (95% CI, 1.34-3.53; P = .002) higher. For early mortality, the odds ratios were 3.79 (95% CI, 1.26-11.34; P = .017) higher after OSR compared with cEVAR. CONCLUSIONS: In this study, after primary elective OSR for JRAAA, the odds for major complications, minor complications, and short-term mortality were significantly higher compared with cEVAR.

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.

Weight Based Heparin Dosage with Activated Clotting Time Monitoring Leads to Adequate and Safe Anticoagulation in Non-Cardiac Arterial Procedures.

BACKGROUND: Unfractionated heparin has an unpredictable effect in an individual patient. The activated clotting time (ACT) can be used to measure the effect of heparin in the individual patient and guide additional heparin dosages. Previous cohort studies showed that a standardized bolus of 5,000 IU during noncardiac arterial procedures (NCAP) does not lead to an adequate ACT in the vast majority of patients. The aim of this study was to investigate whether an initial heparin dose of 100 IU/kg leads to an adequate but safe ACT, from 200 to 300 s. METHODS: In this multicenter prospective study, 186 patients undergoing NCAP were enrolled and received an initial heparin dose of 100 IU/kg. Target ACT was set at ≥250 s initially; during the course of the study the target ACT was lowered to ≥200 s. After the initial heparin dose, additional heparin dosages were administered depending on the ACT values following a heparin dose protocol. ACT measurements and complications were monitored. RESULTS: The mean baseline ACT was 134 ± 17 s. The mean ACT 5 minutes after the initial heparin dose was 227 ± 37 s. After the initial dose of heparin, 78 and 46% of patients reached an ACT of 200 and 250 s, respectively. Seven patients (4%) reached an ACT of 300 s or more. Ninety-four patients (51%) received at least one additional dose of heparin. After one additional dose of heparin, 91% of patients reached an ACT of 200 s and 13 patients (7%) reached an ACT of 300 s or more. Arterial thromboembolic complications occurred in 4.3% and bleeding complications occurred in 9.7%. CONCLUSIONS: A bolus of 100 IU/kg of heparin during NCAP results in adequate coagulation in most patients. ACT measurements enable accurate additional dosing, ensuring the individual patient tailored and safe coagulation. KEY WORDS: anticoagulants; heparin; blood coagulation tests; vascular surgical procedures; peripheral vascular disease.

Systematic review of embolization of type I endoleaks using liquid embolic agents.

OBJECTIVE: The long-term success of endovascular aneurysm repair (EVAR) is limited by complications, most importantly endoleaks. In case of (persistent) type I endoleak (T1EL), secondary intervention is indicated to prevent secondary aneurysm rupture. Different treatment options are suggested for T1ELs, such as endo anchors, (fenestrated) cuffs, embolization, or open conversion. Currently, the treatment of T1EL with liquid embolic agents is available; however, results are not yet addressed. This review presents the safety and efficacy of embolization with liquid embolic agents for treatment of T1ELs after EVAR. METHODS: A systematic literature search was performed for all studies reporting the use of liquid embolic agents as monotherapy for treatment of T1ELs after EVAR. Patient numbers, technical success (successful delivery of liquid embolics in the T1EL) and clinical success (absence of aneurysm related death, endoleak recurrence or additional interventions during follow-up) were examined. RESULTS: Of 1604 articles, 10 studies met the selection criteria, including 194 patients treated with liquid embolics; 73.2% of the patients were male with a median age of 71 years. The overall technical success was 97.9%. Clinical success was 87.6%. Because the median follow-up was only 13.0 months (range, 1-89 months), data on long-term success are almost absent. Four cases (2.1%) of secondary aneurysm rupture after embolization owing to endoleak recurrence were reported. All ruptures occurred in aneurysms exceeding initial treatment diameter of 70 mm. CONCLUSIONS: Initial technical success after liquid embolization for T1EL is high, although long-term clinical success rates are lacking. Within this review, the risk of secondary rupture is comparable with untreated T1EL at 2% with a median follow-up of 13 months, regardless of the initial success of embolization. In general, no decrease in secondary aneurysm rupture after embolization of T1EL after EVAR is demonstrated, although the results of late embolization are debated.

Image Fusion During Standard and Complex Endovascular Aortic Repair, to Fuse or Not to Fuse? A Meta-analysis and Additional Data From a Single-Center Retrospective Cohort.

PURPOSE: To determine if image fusion will reduce contrast volume, radiation dose, and fluoroscopy and procedure times in standard and complex (fenestrated/branched) endovascular aneurysm repair (EVAR). MATERIALS AND METHODS: A search of the PubMed, Embase, and Cochrane databases was performed in December 2019 to identify articles describing results of standard and complex EVAR procedures using image fusion compared with a control group. Study selection, data extraction, and assessment of the methodological quality of the included publications were performed by 2 reviewers working independently. Primary outcomes of the pooled analysis were contrast volume, fluoroscopy time, radiation dose, and procedure time. Eleven articles were identified comprising 1547 patients. Data on 140 patients satisfying the study inclusion criteria were added from the authors' center. Mean differences (MDs) are presented with the 95% confidence interval (CI). RESULTS: For standard EVAR, contrast volume and procedure time showed a significant reduction with an MD of -29 mL (95% CI -40.5 to -18.5, p<0.001) and -11 minutes (95% CI -21.0 to -1.8, p<0.01), respectively. For complex EVAR, significant reductions in favor of image fusion were found for contrast volume (MD -79 mL, 95% CI -105.7 to -52.4, p<0.001), fluoroscopy time (MD -14 minutes, 95% CI -24.2 to -3.5, p<0.001), and procedure time (MD -52 minutes, 95% CI -75.7 to -27.9, p<0.001). CONCLUSION: The results of this meta-analysis confirm that image fusion significantly reduces contrast volume, fluoroscopy time, and procedure time in complex EVAR but only contrast volume and procedure time for standard EVAR. Though a reduction was suggested, the radiation dose was not significantly affected by the use of fusion imaging in either standard or complex EVAR.

Patient-Specific 3-Dimensional Model of Smooth Muscle Cell and Extracellular Matrix Dysfunction for the Study of Aortic Aneurysms.

INTRODUCTION: Abdominal aortic aneurysms (AAAs) are associated with overall high mortality in case of rupture. Since the pathophysiology is unclear, no adequate pharmacological therapy exists. Smooth muscle cells (SMCs) dysfunction and extracellular matrix (ECM) degradation have been proposed as underlying causes. We investigated SMC spatial organization and SMC-ECM interactions in our novel 3-dimensional (3D) vascular model. We validated our model for future use by comparing it to existing 2-dimensional (2D) cell culture. Our model can be used for translational studies of SMC and their role in AAA pathophysiology. MATERIALS AND METHODS: SMC isolated from the medial layer of were the aortic wall of controls and AAA patients seeded on electrospun poly-lactide-co-glycolide scaffolds and cultured for 5 weeks, after which endothelial cells (EC) are added. Cell morphology, orientation, mechanical properties and ECM production were quantified for validation and comparison between controls and patients. RESULTS: We show that cultured SMC proliferate into multiple layers after 5 weeks in culture and produce ECM proteins, mimicking their behavior in the medial aortic layer. EC attach to multilayered SMC, mimicking layer interactions. The novel SMC model exhibits viscoelastic properties comparable to biological vessels; cytoskeletal organization increases during the 5 weeks in culture; increased cytoskeletal alignment and decreased ECM production indicate different organization of AAA patients' cells compared with control. CONCLUSION: We present a valuable preclinical model of AAA constructed with patient specific cells with applications in both translational research and therapeutic developments. We observed SMC spatial reorganization in a time course of 5 weeks in our robust, patient-specific model of SMC-EC organization and ECM production.

Inflammatory Gene Expression of Human Perivascular Adipose Tissue in Abdominal Aortic Aneurysms.

OBJECTIVE: Perivascular adipose tissue (PVAT) contributes to vascular homeostasis and is increasingly linked to vascular pathology. PVAT density and volume were associated with abdominal aortic aneurysm (AAA) presence and dimensions on imaging. However, mechanisms underlying the role of PVAT in AAA have not been clarified. This study aimed to explore differences in PVAT from AAA using gene expression and functional tests. METHODS: Human aortic PVAT and control subcutaneous adipose tissue were collected during open AAA surgery. Gene analyses and functional tests were performed. The control group consisted of healthy aorta from non-living renal transplant donors. Gene expression tests were performed to study genes potentially involved in various inflammatory processes and AAA related genes. Live PVAT and subcutaneous adipose tissue (SAT) from AAA were used for ex vivo co-culture with smooth muscle cells (SMCs) retrieved from non-pathological aortas. RESULTS: Adipose tissue was harvested from 27 AAA patients (n [gene expression] = 22, n [functional tests] = 5) and five control patients. An increased inflammatory gene expression of PTPRC (p = .008), CXCL8 (p = .033), LCK (p = .003), CCL5 (p = .004) and an increase in extracellular matrix breakdown marker MMP9 (p = .016) were found in AAA compared with controls. Also, there was a decreased anti-inflammatory gene expression of PPARG in AAA compared with controls (p = .040). SMC co-cultures from non-pathological aortas with PVAT from AAA showed increased MMP9 (p = .033) and SMTN (p = .008) expression and SAT increased SMTN expression in these SMC. CONCLUSION: The data revealed that PVAT from AAA shows an increased pro-inflammatory and matrix metallopeptidase gene expression and decreased anti-inflammatory gene expression. Furthermore, increased expression of genes involved in aneurysm formation was found in healthy SMC co-culture with PVAT of AAA patients. Therefore, PVAT from AAA might contribute to inflammation of the adjacent aortic wall and thereby plays a possible role in AAA pathophysiology. These proposed pathways of inflammatory induction could reveal new therapeutic targets in AAA treatment.

More Effective Anticoagulation During Non-Cardiac Arterial Procedures Using Activated Clotting Time Guided Heparin Administration.

OBJECTIVES: Arterial thrombo-embolic complications (ATEC) are still common during and after non-cardiac arterial procedures (NCAP) despite the administration of (a fixed bolus of) heparin. These ATEC could be due to existing individual differences in heparin sensitivity. The purpose of this study was to evaluate the feasibility and safety of an ACT guided heparin dose protocol and to evaluate if a more effective target ACT can be achieved during NCAP. METHODS: In this multi-center prospective study, 194 patients undergoing elective and non-elective NCAP were enrolled and received heparin according to a heparin dose protocol which aimed to obtain a target ACT of 250 seconds (s.), measured by the Medtronic HMS Plus. Patients received a standardized bolus of 5 000 IU followed by additional boluses depending on the actual ACT. Primary outcome was the ACT value reached. Secondary outcomes were incidence of all ATEC and haemorrhagic complications. RESULTS: The mean baseline ACT was 138 ± 17 s. The mean ACT five minutes after the initial heparin bolus of 5 000 IU was 197 ± 31 s. 48% of patients reached an ACT of 200 s. and six per cent of patients reached an ACT of 250 s. Additional dosages of heparin were administered in 72% of patients. With this ACT guided heparin protocol 86% of patients reached an ACT of 200 s. and 26% of patients reached an ACT of 250 s. A negative correlation was found between body weight and the ACT at T1 (P ˂ 0.001). ATEC and haemorrhagic complications occurred in 11.3% and 16.5% of patients. The lowest incidence of ATEC was found in patients with peak ACT between 200 and 250 s, namely 6.3%. CONCLUSION: This ACT guided heparin protocol proved to be feasible, safe and more patients reached an ACT > of 200 s. compared to a standardized heparin bolus of 5 000 IU. Further research is needed to investigate if ACT guided heparin administration could be preferable over not monitoring the anticoagulant effect of peri-procedural heparin and results in a lower incidence of ATEC, without an increase in haemorrhagic complications.

A Standardized Bolus of 5 000 IU of Heparin Does not Lead to Adequate Heparinization during Non-cardiac Arterial Procedures.

BACKGROUND: In non-cardiac arterial procedures (NCAP), heparin is administered to prevent arterial thromboembolic complications (ATEC). Heparin has a nonpredictable effect in the individual patient, also known as variation in heparin sensitivity. Various dosing protocols are in use, but the optimal dose is currently still unknown. A standardized bolus of 5 000 IU heparin is most frequently used by vascular surgeons and interventional radiologists. The activated clotting time (ACT) is an established method to measure the level of anticoagulation, but has, until now, not gained widespread use in NCAP. The purpose of this study was to evaluate the anticoagulant effect during NCAP of a standardized bolus of 5 000 IU heparin by measuring the ACT. METHODS: In this prospective study, 190 patients undergoing NCAP were enrolled between December 2016 and September 2018. The ACT was measured during open and endovascular/hybrid procedures. All patients received a standardized bolus of 5 000 IU heparin. The ACT was measured by the Hemostasis Management System Plus (HMS Plus, Medtronic®), before, 5 minutes after administration of heparin, and every 30 minutes thereafter. The primary outcome was periprocedural ACT values measured. Secondary outcomes were ATEC and hemorrhagic complications. RESULTS: A large individual patient variability in the response to heparin was found. The mean baseline ACT in all patients was 129 ± 18 s., and the mean ACT 5 minutes after the initial bolus of heparin was 191 ± 36 s. After the initial dose of 5 000 IU heparin 60 (33%) and 10 (6%) patients reached an ACT of 200 and 250 s., respectively. Despite the use of heparin, ATEC occurred in 17 patients (9%). The lowest number of ATEC occurred in the group of patients with an ACT between 200 and 250 s. CONCLUSIONS: A standardized bolus of 5 000 IU heparin does not lead to adequate and safe heparinization in non-cardiac arterial procedures. Patient response to heparin shows a large individual variability. Therefore, routine ACT measurements are necessary to ascertain adequate anticoagulation. Further research is needed to investigate if heparin dosing based on the ACT could result in less arterial thromboembolic complications, without increasing hemorrhagic complications.

Gutter Characteristics and Stent Compression of Self-Expanding vs Balloon-Expandable Chimney Grafts in Juxtarenal Aneurysm Models.

Purpose: To assess in silicone juxtarenal aneurysm models the gutter characteristics and compression of different types of chimney graft (CG) configurations. Materials and Methods: Fifty-seven combinations of Excluder C3 or Conformable Excluder stent-grafts (23, 26, and 28.5 mm) were deployed in 2 silicone juxtarenal aneurysm models with 3 types of CGs: Viabahn self-expanding (VSE; 6 and 13 mm) or Viabahn balloon-expandable (VBX; 6, 10, and 12 mm) stent-grafts and Advanta V12 balloon-expandable stent-grafts (ABX; 6 and 12 mm). Setups were divided into 4 groups on the basis of increasing CG and main graft (MG) diameters. Two independent observers assessed gutter size and type as well as CG compression on computed tomography scans using postprocessing software. Results: In the smaller diameter combinations (6-mm CG and 23-, 26-, and 28.5-mm MGs), both VSE (p=0.006 to 0.050) and ABX (p=0.045 to 0.050) showed lower gutter areas and volumes compared with VBX. In turn, the VBX showed a nonsignificant tendency to decreased compression, especially compared to ABX. Use of the Excluder C3 showed a 6-fold increase in type A1 gutters (related to type Ia endoleak) as compared to the Conformable Excluder (p=0.018). Balloon-expandable stent-grafts (both ABX and VBX) showed a 3-fold increase in type A1 gutters in comparison with self-expanding stent-grafts (p=0.008). Conclusion: The current study suggests that use of the Conformable Excluder in combination with VSE chimney grafts is superior to the other tested CG/MG combinations in terms of gutter size, gutter type, and CG compression.

No Concluding Evidence on Optimal Activated Clotting Time for Non-cardiac Arterial Procedures.

OBJECTIVES: Heparin has a non-predictable effect in the individual patient. The activated clotting time (ACT) is used to measure the level of anticoagulation after administration of heparin. To date, appropriate heparin dose protocols and corresponding therapeutic ACT values have not been established in non-cardiac arterial procedures (NCAP). The aim of this review was to study the use of ACT monitoring during NCAP, and whether an optimal ACT could be determined based on the fewest arterial thrombo-embolic complications (ATEC) and bleeding complications. METHODS: This systematic review was performed in accordance with the PRISMA Guidelines. A systematic search was conducted in MEDLINE, EMBASE, and the Cochrane database. Any associations were evaluated between peri-procedural ACT levels and ATEC and bleeding complications detected during the same admission as the primary procedure or during 30 day follow up. Also, heparin dose protocols, peri-procedural target ACTs, different ACT devices, protamine use and pre-, peri-, and post-procedural anticoagulation therapy were evaluated. RESULTS: In total, 21 studies with 3982 patients were included, on both open and endovascular NCAP. Four studies were primarily designed to correlate peak peri-procedural ACT with clinical outcomes; however, the definitions of the results and the clinical outcomes were too heterogeneous for analysis. There was major variability in all studied aspects of ACT measurement, heparin and protamine use, and in the type of procedures in the included studies. Overall methodological quality of the included studies was poor. No randomised controlled trials were found. Studies were at a high risk of bias. CONCLUSIONS: This systematic review demonstrates a lack of data and no consensus in the literature concerning the optimal ACT, and the possible association with haemorrhagic complications and ATEC during NCAP.

Aortic neck dilation is not associated with adverse outcomes after fenestrated endovascular aneurysm repair.

OBJECTIVE: Long-term outcomes after endovascular aneurysm repair (EVAR) are threatened by aortic neck dilation (AND), graft migration, and subsequent endoleak development. The aim of this study was to determine the rate of AND and the occurrence of endoleaks after fenestrated EVAR of juxtarenal aneurysms with physician-modified endovascular grafts (PMEGs). METHODS: The study included 77 patients presenting with asymptomatic and ruptured juxtarenal abdominal aortic aneurysms treated with PMEGs who received radiologic follow-up. Analysis of computed tomography images took place on a three-dimensional workstation (TeraRecon, San Mateo, Calif). Aortic neck diameter was measured before and after EVAR at the lowest patent renal artery outer wall to outer wall. Significant AND was defined as >3-mm increase between baseline and follow-up, and sac regression >5 mm was considered significant. The patient's 1-month initial postoperative computed tomography measurement was considered baseline. The rate of AND was measured by comparing the baseline measurement with measurements at 6 months, 12 months, and annually thereafter up to 4 years. RESULTS: In this cohort of patients, 75% were men with a mean age of 74 ± 7.9 years. Median preoperative aneurysm size was 62 (57-73) mm, and median follow-up was 12 (3.5-30) months. Mean endograft oversizing was 17% ± 12.5%, and mean seal zone length was 41 ± 11 mm. At 1-year follow-up, the median aortic neck increase was 1.7 (0-3) mm. Maximum aneurysm size decreased dramatically during the first postoperative year, with significant sac regression in 65% of the patients. Aortic neck diameter at 1 year did correlate positively with the percentage of device oversizing. No other correlations were found. During the 4-year follow-up, there were no cases of type IA endoleaks. CONCLUSIONS: AND does not influence outcome after endovascular repair of juxtarenal aneurysms using PMEGs. These midterm results support the applicability of PMEGs in juxtarenal aneurysm repair.

Secondary Fill Minimizes Gutter Size in Chimney EVAS Configurations In Vitro.

PURPOSE: To investigate in an in vitro model if secondary endobag filling can reduce gutter size during chimney endovascular aneurysm sealing (chEVAS). MATERIALS AND METHODS: Nellix EVAS systems were deployed in 2 silicone juxtarenal aneurysm models with suprarenal aortic diameters of 19 and 24 mm. Four configurations were tested: EVAS with 6-mm balloon-expandable (BE) or self-expanding (SE) chimney grafts (CGs) in the renal branches of both models. Balloons were inflated simultaneously in the CGs and main endografts during primary and secondary endobag filling and polymer curing. Computed tomography (CT) was performed immediately after the primary and secondary fills. Cross-sectional lumen areas were measured on the CT images to calculate gutter volumes and percent change. CG compression was calculated as the reduction in lumen surface area measured perpendicular to the central lumen line. The largest gutter volume and highest compression were presented per CG configuration per model. RESULTS: Secondary endobag filling reduced the largest gutter volumes from 99.4 to 73.1 mm3 (13.2% change) and 84.2 to 72.0 mm3 (27.6% change) in the BECG configurations and from 67.2 to 44.0 mm3 (34.5% change) and 92.7 to 82.3 mm3 (11.2% change) in the SECG configurations in the 19- and 24-mm models, respectively. Secondary endobag filling increased CG compression in 6 of 8 configurations. BECG compression changed by -0.2% and 5.4% and by -1.0% and 0.4% in the 19- and 24-mm models, respectively. SECG compression changed by 10.2% and 16.0% and by 7.2% and 7.3% in the 19- and 24-mm models, respectively. CONCLUSION: Secondary endobag filling reduced paragraft gutters; however, this technique did not obliterate them. Increased CG compression and prolonged renal ischemia time should be considered if secondary endobag filling is used.

High Density of Periaortic Adipose Tissue in Abdominal Aortic Aneurysm.

OBJECTIVES: Perivascular adipose tissue (PVAT) is currently seen as a paracrine organ that produces vasoactive substances, including inflammatory agents, which may have an impact on the vasculature. In this study PVAT density was quantified in patients with an aortic aneurysm and compared with those with a non-dilated aorta. Since chronic inflammation, as the pathway to medial thinning, is a hallmark of abdominal aortic aneurysms (AAAs), it was hypothesised that PVAT density is higher in AAA patients. METHODS: In this multicentre retrospective case control study, three groups of patients were included: non-treated asymptomatic AAA (n = 140), aortoiliac occlusive disease (AIOD) (n = 104), and individuals without aortic pathology (n = 97). A Hounsfield units based analysis was performed by computed tomography (CT). As a proxy for PVAT, the density of adipose tissue 10 mm circumferential to the infrarenal aorta was analysed in each consecutive CT slice. Intra-individual PVAT differences were reported as the difference in PVAT density between the region of the maximum AAA diameter (or the mid-aortic region in patients with AIOD or controls) and the two uppermost slices of infrarenal non-dilated aorta just below the renal arteries. Furthermore, subcutaneous (SAT) and visceral (VAT) adipose tissue measurements were performed. Linear models were fitted to assess the association between the study groups, different adipose tissue compartments, and between adipose tissue compartments and aortic dimensions. RESULTS: AAA patients presented higher intra-individual PVAT differences, with higher PVAT density around the aneurysm sac than the healthy neck. This association persisted after adjustment for cardiovascular risk factors and diseases and other fat compartments (ß = 13.175, SE 4.732, p = .006). Furthermore, intra-individual PVAT differences presented the highest correlation with aortic volume that persisted after adjustment for other fat compartments, body mass index, sex, and age (ß = 0.566, 0.200, p = .005). CONCLUSION: The results suggest a relation between the deposition of PVAT and AAA pathophysiology. Further research should explore the exact underlying processes.