Four-Dimensional Flow MRI-Derived Hemodynamics in Abdominal Aortic Aneurysms: Reproducibility and Associations With Diameter, Intraluminal Thrombus Volume, and Vorticity.

BACKGROUND: Maximum diameter measurements are used to assess the rupture risk of abdominal aortic aneurysms (AAAs); however, these are not precise enough to predict all ruptures. Four-dimensional (4D) flow MRI-derived parameters provide additional information by visualizing hemodynamics in AAAs but merit further investigation before they are clinically applicable. PURPOSE: To assess the reproducibility of 4D flow MRI-derived hemodynamics, to investigate possible correlations with lumen and maximum diameter, and to explore potential relationships with vorticity and aneurysm growth. STUDY TYPE: Prospective single-arm study. POPULATION: A total of 22 (71.5 ± 6.1 years, 20 male) asymptomatic AAA patients with a maximum diameter of at least 30 mm. FIELD STRENGTH/SEQUENCE: A 3.0 T/Free-breathing 4D flow MRI phase-contrast acquisition with retrospective ECG-gating. ASSESSMENT: Patients underwent two consecutive 4D flow MRI scans 1-week apart. Aortic volumes were segmented from time-averaged phase contrast magnetic resonance angiographies. Reproducibility was assessed by voxelwise analysis after registration. Mean flow velocity, mean wall shear stress (WSS), mean lumen diameter, and qualitative vorticity scores were assessed. In addition, Dixon MRI and retrospective surveillance data were used to study maximum diameter (including thrombus), intraluminal thrombus volume (ILT), and growth rate. STATISTICAL TESTS: For reproducibility assessment, Bland-Altman analyses, Pearson correlation, Spearman's correlation, and orthogonal regression were conducted. Potential correlations between hemodynamics and vorticity scores were assessed using linear regression. P < 0.05 was considered statistically significant. RESULTS: Test-retest median Pearson correlation coefficients for flow velocity and WSS were 0.85 (IQR = 0.08) m/sec and 0.82 (IQR = 0.10) Pa, respectively. Mean WSS significantly correlated with mean flow velocity (R = 0.75) and inversely correlated with mean lumen diameter (R = -0.73). No significant associations were found between 4D flow MRI-derived hemodynamic parameters and maximum diameter (flow velocity: P = 0.98, WSS: P = 0.22). DATA CONCLUSION: A 4D flow MRI is robust for assessing the hemodynamics within AAAs. No correlations were found between hemodynamic parameters and maximum diameter, ILT volume and growth rate. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

A Statistical Shape Model of Infrarenal Aortic Necks in Patients With and Without Late Type Ia Endoleak After Endovascular Aneurysm Repair.

PURPOSE: Hostile aortic neck characteristics, including short length, severe suprarenal and infrarenal angulation, conicity, and large diameter, have been associated with increased risk for type Ia endoleak (T1aEL) after endovascular aneurysm repair (EVAR). This study investigates the mid-term discriminative ability of a statistical shape model (SSM) of the infrarenal aortic neck morphology compared with or in combination with conventional measurements in patients who developed T1aEL post-EVAR. MATERIALS AND METHODS: The dataset composed of EVAR patients who developed a T1aEL during follow-up and a control group without T1aEL. Principal component (PC) analysis was performed using a parametrization to create an SSM. Three logistic regression models were created. To discriminate between patients with and without T1aEL, sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve (AUC) were calculated. RESULTS: In total, 126 patients (84% male) were included. Median follow-up time in T1aEl group and control group was 52 (31, 78.5) and 51 (40, 62.5) months, respectively. Median follow-up time was not statistically different between the groups (p=0.72). A statistically significant difference between the median PC scores of the T1aEL and control groups was found for the first, eighth, and ninth PC. Sensitivity, specificity, and AUC values for the SSM-based versus the conventional measurements-based logistic regression models were 79%, 70%, and 0.82 versus 74%, 73%, and 0.85, respectively. The model of the SSM and conventional measurements combined resulted in sensitivity, specificity, and AUC of 81%, 81%, and 0.92. CONCLUSION: An SSM of the infrarenal aortic neck determines its 3-dimensional geometry. The SSM is a potential valuable tool for risk stratification and T1aEL prediction in EVAR. The SSM complements the conventional measurements of the individual preoperative infrarenal aortic neck geometry by increasing the predictive value for late type Ia endoleak after standard EVAR. CLINICAL IMPACT: A statistical shape model (SSM) determines the 3-dimensional geometry of the infrarenal aortic neck. The SSM complements the conventional measurements of the individual pre-operative infrarenal aortic neck geometry by increasing the predictive value for late type Ia endoleaks post-EVAR. The SSM is a potential valuable tool for risk stratification and late T1aEL prediction in EVAR and it is a first step toward implementation of a treatment planning support tool in daily clinical practice.

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.

Shortest Apposition Length at the First Postoperative Computed Tomography Angiography Identifies Patients at Risk for Developing a Late Type Ia Endoleak After Endovascular Aneurysm Repair.

PURPOSE: Imaging surveillance following endovascular aneurysm repair (EVAR) is strictly recommended. This study investigates the value of endograft apposition and position relative to the aortic neck on the first postoperative computed tomography angiography (CTA) in determining patients at risk for a late type Ia endoleak (T1aEL). MATERIALS AND METHODS: Patients with a T1aEL after the first postoperative CTA were selected from a consecutive database and matched with uncomplicated controls. Endograft apposition and position, including the shortest apposition length (SAL), were determined on the first postoperative CTA. The SAL is the shortest distance between the proximal endograft fabric and the first slice where circumferential apposition with the aortic wall is lost. Differences in endograft apposition at the first postoperative CTA were compared between groups. Logistic regression analysis identified independent predictors for late T1aEL. RESULTS: A total of 32 patients with a late T1aEL were included and matched with 32 uncomplicated controls. Median follow-up after primary EVAR was 62.0 (interquartile range [IQR]: 36.8, 83.5) months in the T1aEL group compared with 47.5 (IQR: 34.0, 79.3) months in the control group; p=0.265. Median preoperative neck diameter was significantly larger in the T1aEL group than in the control group (26.6 [IQR: 24.9, 29.6] mm versus 23.4 [IQR: 22.5, 25.3] mm); p<0.001. Patients in the T1aEL group had a median SAL of 11.6 (IQR: 4.3, 20.5) mm compared with 20.7 (IQR: 13.1, 24.9) mm in the control group; p=0.002. SAL <10mm on the first postoperative CTA (odds ratio [OR]: 9.63, 95% confidence interval [CI]: 1.60-57.99) and larger neck diameter (OR: 1.80, 95% CI: 1.26-2.57) were independent predictors for developing a late T1aEL. CONCLUSION: Preoperative neck diameter and SAL on the first postoperative CTA following EVAR are important predictors for the development of a late T1aEL. Patients with a SAL of <10mm had a significantly higher risk of developing a late T1aEL. Future research should determine whether these patients would benefit from reintervention before an actual T1aEL is present. CLINICAL IMPACT: Understanding the mechanisms of endovascular aneurysm repair failure is essential to further enhance clinical outcomes. Adequate proximal sealing is necessary to foster freedom from type 1a endoleak. This study demonstrates that the shortest apposition length (SAL) at the first postoperative computed tomography angiography (CTA) is able to identify patients at risk for a late type 1a endoleak. Especially patients with a SAL <10mm are at high risk. Currently, the guidelines advice repeated imaging with CTA in patients with a seal <10mm. Future research should determine whether these patients would benefit from re-intervention before an actual type 1a endoleak is present.

Predictors of the Level of Shared Decision Making in Vascular Surgery: A Cross Sectional Study.

OBJECTIVE: Although patients with vascular diseases often face multiple treatment options with different risks and benefits, the application of shared decision making (SDM) remains low. In SDM, clinicians and their patients work together to decide upon the treatment option that best fits the patient's situation and preference. This study aimed to reveal predictors of the extent to which the SDM process occurs in vascular surgery. METHODS: This was a cross sectional cohort substudy of the OVIDIUS trial, a multicentre, randomised, stepped wedge trial on the effect of implementing SDM supporting tools. The data of outpatients visiting university and general hospitals and suffering from abdominal aortic aneurysms (AAAs), intermittent claudication (IC), or varicose veins (VV) were used. Consultations were audio recorded. SDM levels were scored independently by two evaluators, using the OPTION-5 instrument, on a scale from 0% (no SDM effort) to 100% (exemplary SDM effort). Possible associations between the OPTION-5 scores and patient, clinician, and consultation characteristics were investigated using multivariable linear regression analysis. RESULTS: Of the 342 patients included (AAA, n = 87; VV, n = 143; IC, n = 112), 60% were male and mean age was 64 years. Overall, the SDM score was relatively low; mean ± SD 33.8% ± 13.2%, mainly due to insufficient support for the patient in deliberating their options. Regression analysis showed that the mean SDM scores in consultation with patients with IC and patients with VV were -9.9 (95% confidence interval [CI] -13.2 - -6.5; p < .001) and -12.7 (95% CI -17.3 - -8.0; p < .001) points lower than in patients with AAA, respectively. Consultations by a resident in training or nurse practitioner resulted in a -8.6 (95% CI -13.1 - -4.0; p < .001) and -4.2 (95% CI -7.9 - -0.42; p = .029) point lower SDM score than by a surgeon, respectively. A consultation longer than 30 minutes resulted in a 5.8 (95% CI 1.3 - 10.3; p = .011) point higher SDM score than consultations lasting fewer than 10 minutes. CONCLUSION: In this study, it was found that SDM can still be improved, especially by helping patients understand and deliberate about their options. Spending time weighing up the options, notably with patients with IC and VV, will help improve the SDM process. Training in SDM consultations is important, particularly for junior clinicians.

Cost of Follow Up After Endovascular Abdominal Aortic Aneurysm Repair in Patients With an Initial Post-Operative Computed Tomography Angiogram Without Abnormalities.

OBJECTIVE: The Observing a Decade of Yearly Standardised Surveillance in EVAR patients with Ultrasound or CT Scan (ODYSSEUS) study was conducted to assess differences in outcomes of patients with continued or discontinued yearly follow up after endovascular abdominal aortic aneurysm repair (EVAR). Earlier results of this study showed that discontinued follow up was not associated with poor outcomes. Therefore, an incremental cost analysis and budget impact analysis of de-implementation of yearly imaging following EVAR was performed. METHODS: In total, 1 596 patients from the ODYSSEUS study were included. The expected cost savings were assessed if yearly imaging was reduced in patients with a post-operative computed tomography angiogram without abnormalities made around 30 days after EVAR. Costs were derived from the Dutch costs manual, benchmark cost prices, and literature review. Costs were expressed in euros (€) and displayed at 2019 prices. Sensitivity analysis was performed by varying costs. RESULTS: A difference of 24% in cost was found between patients with continued and discontinued imaging follow up. The cost per patient was €1 935 in the continued group vs. €1 603 per patient in the discontinued group at five years post-EVAR, with a mean difference of €332 (95% bias corrected and accelerated bootstrap confidence interval -741 to 114). De-implementation of yearly imaging would result in an annual nationwide cost saving of €678 471. Sensitivity analysis with variation in adherence rates, imaging, or secondary intervention costs resulted in a saving of at least €271 388 per year. CONCLUSION: This study provided an in depth analysis of hospital costs for post-EVAR patients in the Netherlands with a modest impact on the Dutch healthcare budget.

Improving Shared Decision Making in Vascular Surgery: A Stepped Wedge Cluster Randomised Trial.

OBJECTIVE: Different treatment options are available and feasible for various vascular surgical disorders. Hence, vascular surgery seems an area par excellence for shared decision making (SDM), in which clinicians incorporate the patient's preferences into the final treatment decision. However, current SDM levels in vascular surgical outpatient clinics are below expectations. To improve this, different decision support tools (DSTs) have been developed: online patient decision aids, consultation cards, and decision cards. METHODS: This stepped wedge cluster randomised trial was conducted in 13 Dutch hospitals. Besides the developed DSTs, training on how to apply SDM during the clinician patient encounter was used in this study. Data were obtained via questionnaires and audio recordings. The primary outcome was the OPTION-5 score, an objective tool to assess the level of SDM, expressed as a percentage of exemplary performance. Main secondary outcomes were patients' disease specific knowledge, consultation duration, and treatment choice. Factors influencing OPTION-5 scores were studied using linear regression analysis. RESULTS: Included in the study were 342 patients with an abdominal aortic aneurysm (AAA; n = 87), intermittent claudication (IC; n = 143), or varicose veins (VV; n = 112). Audiotapes of 395 consultations were analysed. Overall the mean OPTION-5 score significantly improved from 28.7% to 37.8% (mean difference 9.1%, 95% CI 6.5% - 11.8%) after implementation of the DSTs. Also, patient knowledge increased significantly (median increase: 13%, effect size: 0.13, p = .025). The number of patients choosing non-surgical treatment choices increased, with 21.4% to 28.8% for patients with AAA and doubled (16.0% to 32.0%) among patients with IC. For surgeons, the SDM training and for patients the decision aid significantly and independently increased OPTION-5 scores (p < .001 and p = .047, respectively). CONCLUSION: Introducing DSTs improves the level of shared decision making in vascular surgery, improves patient knowledge, and shifts their preference towards more non-surgical treatments. The SDM training for clinicians and the decision aid for patients appeared the most effective means of improving SDM. TRIAL REGISTRATION: NTR6487.

Editor's Choice - Post-operative Surveillance and Long Term Outcome after Endovascular Aortic Aneurysm Repair in Patients with an Initial Post-operative Computed Tomography Angiogram Without Abnormalities: the Multicentre Retrospective ODYSSEUS Study.

OBJECTIVE: Lifelong imaging surveillance is recommended following endovascular aneurysm repair (EVAR). This study aimed to examine the association between adherence to post-operative surveillance and survival and secondary interventions in patients with an initial post-operative computed tomography angiogram (CTA) without abnormalities. METHODS: All consecutive patients undergoing EVAR for intact abdominal aortic aneurysm (AAA) in 16 hospitals between 2007 and 2012 were identified retrospectively, with follow up until December 2018. Patients were included if the initial post-operative CTA showed no types I - III endoleak, kinking, infection, or limb occlusion. Discontinued follow up was defined as at least one 16 month period in which no imaging surveillance was performed. Primary outcomes were aneurysm related mortality and secondary interventions, and secondary outcome all cause mortality. Kaplan-Meier analysis was used to estimate survival, and Cox regression analyses to identify the association between independent variables and outcome. Sensitivity analyses were performed by varying the definition of continued yearly follow up. The study protocol was published (bmjopen-2019-033584). RESULTS: 1 596 patients (552 continued, 1 044 discontinued follow up) were included with a median (interquartile range) follow up of 89.1 months (52.6). Cumulative aneurysm related, overall, and intervention free survival was 99.4/94.8/96.1%, 98.5/72.9/85.9%, and 96.3/45.4/71.1% at 1, 5, and 10 years, respectively. American Society of Anesthesiologists (ASA) classification (ASA IV hazard ratio [HR] 3.810, 95% confidence interval [CI] 1.296 - 11.198), increase in AAA diameter (HR 3.299, 95% CI 1.408 - 7.729), and continued follow up (HR 3.611, 95% CI 1.780 - 7.323) were independently associated with aneurysm related mortality. The same variables and age (HR 1.063 per year, 95% CI 1.052 - 1.074) were significantly associated with all cause mortality. No difference in secondary interventions was observed between patients with continued vs. discontinued follow up (89/552; 16% vs. 136/1044; 13%; p = .091). Sensitivity analyses showed worse aneurysm related and overall survival in patients with continued follow up. CONCLUSION: Discontinued follow up is not associated with poor outcomes. Future prospective studies are indicated to determine in which patients imaging follow up can be safely reduced.

Analysis of Outcomes After Endovascular Abdominal Aortic Aneurysm Repair in Patients With Abnormal Findings on the First Postoperative Computed Tomography Angiography.

PURPOSE: Lifelong follow-up after endovascular abdominal aortic aneurysm repair (EVAR) is recommended due to a continued risk of complications, especially if the first postoperative imaging shows abnormal findings. We studied the long-term outcomes in patients with abnormalities on the first postoperative computed tomography angiography (CTA) following EVAR. MATERIALS AND METHODS: This is a retrospective study of all consecutive patients who underwent elective EVAR for nonruptured abdominal aortic aneurysm (AAA) between January 2007 and January 2012 in 16 Dutch hospitals with follow-up until December 2018. Patients were included if the first postoperative CTA showed one of the following abnormal findings: endoleak type I-IV, endograft kinking, infection, or limb occlusion. AAA diameter, complications, and secondary interventions during follow-up were registered. Primary endpoint was overall survival, and other endpoints were secondary interventions and intervention-free survival. Kaplan-Meier analyses were used to estimate overall and intervention-free survival. Cox regression analyses were used to identify the association of independent determinants with survival and secondary interventions. RESULTS: A total of 502 patients had abnormal findings on the first postoperative CTA after EVAR and had a median follow-up (interquartile range IQR) of 83.0 months (59.0). The estimated overall survival rate at 1, 5, and 10 years was 84.7%, 51.0%, and 30.8%, respectively. Age [hazard ratio (HR) 1.06, 95% confidence interval (CI) 1.05 to 1.10] and American Society of Anesthesiologists (ASA) classification (ASA IV HR 3.20, 95% CI 1.99 to 5.15) were significantly associated with all-cause mortality. Overall, 167 of the 502 patients (33.3%) underwent 238 secondary interventions in total. Fifty-eight patients (12%) underwent an intervention based on a finding on the first postoperative CTA. Overall survival was 38.4% for patients with secondary interventions and 44.5% for patients without (log rank; p=0.166). The intervention-free survival rate at 1, 5, and 10 years was 82.9%, 61.3%, and 45.6%, respectively. CONCLUSIONS: Patients with abnormalities on the first postoperative CTA after elective EVAR for infrarenal AAA cannot be discharged from regular imaging follow-up due to a high risk of secondary interventions. Patients who had a secondary intervention had similar overall survival as those without secondary interventions.

Type 2 Endoleak With or Without Intervention and Survival After Endovascular Aneurysm Repair.

OBJECTIVE: The aims of the present study were to examine the impact of type 2 endoleaks (T2EL) on overall survival and to determine the need for secondary intervention after endovascular aneurysm repair (EVAR). METHODS: A multicentre retrospective cohort study in the Netherlands was conducted among patients with an infrarenal abdominal aortic aneurysm (AAA) who underwent EVAR between 2007 and 2012. The primary endpoint was overall survival for patients with (T2EL+) or without (T2EL-) a T2EL. Secondary endpoints were sac growth, AAA rupture, and secondary intervention. Kaplan-Meier survival and multivariable Cox regression analysis were used. RESULTS: A total of 2 018 patients were included. The median follow up was 62.1 (range 0.1 - 146.2) months. No difference in overall survival was found between T2EL+ (n = 388) and T2EL- patients (n = 1630) (p = .54). The overall survival estimates at five and 10 years were 73.3%/69.4% and 45.9%/44.1% for T2EL+/T2EL- patients, respectively. Eighty-five of 388 (21.9%) T2EL+ patients underwent a secondary intervention. There was no difference in overall survival between T2EL+ patients who underwent a secondary intervention and those who were treated conservatively (p = .081). Sac growth was observed in 89 T2EL+ patients and 44/89 patients (49.4%) underwent a secondary intervention. In 41/44 cases (93.1%), sac growth was still observed after the intervention, but was left untreated. Aneurysm rupture occurred in 4/388 T2EL patients. In Cox regression analysis, higher age, ASA classification, and maximum iliac diameter were significantly associated with worse overall survival. CONCLUSION: No difference in overall survival was found between T2EL+ and T2EL- patients. Also, patients who underwent a secondary intervention did not have better survival compared with those who did not undergo a secondary intervention. This study reinforces the need for conservative treatment of an isolated T2EL and the importance of a prospective study to determine possible advantages of the intervention.

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.

Secondary Interventions and Long-term Follow-up after Endovascular Abdominal Aortic Aneurysm Repair.

BACKGROUND: Early morbidity and mortality are low after endovascular abdominal aneurysm repair (EVAR), but secondary interventions and late complications are common. The aim of the present multicenter cohort study is to detail the frequency and indication for interventions after EVAR and the impact on long-term survival. METHODS: A retrospective multicenter cohort study of secondary interventions after elective EVAR for an infrarenal abdominal aortic aneurysm was conducted. Consecutive patients (n = 349) undergoing EVAR between January 2007 and January 2012 were analyzed, with long-term follow-up until December 2018. Those requiring intervention were classified in accordance with the indications and specific nature of the intervention and treatment. The primary study end point was overall survival classified for patients with and without intervention. Kaplan-Meier analysis was used to estimate overall survival for those who did and who did not undergo secondary interventions. Univariable and multivariable Cox regression were performed to identify independent variables associated with mortality. RESULTS: Some 56 patients (16%) underwent 72 secondary interventions after EVAR during a median (interquartile range) follow-up period of 53.2 months (60.1). Some 45 patients (80.4%) underwent one intervention. Indications for intervention included mainly endograft kinking/outflow obstruction and type II endoleak. An endovascular technique was used in 40.3% of interventions. Median time to secondary intervention was 24.1 months. In 93 patients with abnormalities on imaging, no intervention was performed mainly because the abnormality had disappeared on follow-up imaging (43%). Kaplan-Meier curves showed no difference in survival for patients with and without secondary interventions (P = 0.153). Age (hazard ratio [HR]: 1.089, 95% confidence interval [CI]: 1.063-1.116), ASA classification (ASA III, IV HR: 1.517, 95% CI: 1.056-2.178) were significantly related to mortality. CONCLUSIONS: Secondary intervention rates are still considerable after EVAR. Endograft kinking/outflow obstruction and endoleak type II are the most common indications for a secondary intervention. Secondary interventions did not adversely affect long-term overall survival after EVAR.

Long-term clinical outcomes of losartan in patients with Marfan syndrome: follow-up of the multicentre randomized controlled COMPARE trial.

AIMS: The COMPARE trial showed a small but significant beneficial effect of 3-year losartan treatment on aortic root dilatation rate in adults with Marfan syndrome (MFS). However, no significant effect was found on clinical endpoints, possibly due to a short follow-up period. The aim of the current study was therefore to investigate the long-term clinical outcomes after losartan treatment. METHODS AND RESULTS: In the original COMPARE study (inclusion 2008-2009), adult patients with MFS (n = 233) were randomly allocated to either the angiotensin-II receptor blocker losartan® on top of regular treatment (ß-blockers in 71% of the patients) or no additional medication. After the COMPARE trial period of 3 years, study subjects chose to continue their losartan medication or not. In a median follow-up period of 8 years, 75 patients continued losartan medication, whereas 78 patients, originally allocated to the control group, never used losartan after inclusion. No differences existed between baseline characteristics of the two groups except for age at inclusion [losartan 34 (interquartile range, IQR 26-43) years, control 41 (IQR 30-52) years; P = 0.031], and ß-blocker use (losartan 81%, control 64%; P = 0.022). A pathological FBN1 mutation was present in 76% of patients and 58% of the patients were male. Clinical endpoints, defined as all-cause mortality, aortic dissection/rupture, elective aortic root replacement, reoperation, and vascular graft implantation beyond the aortic root, were compared between the two groups. A per-patient composite endpoint was also analysed. Five deaths, 14 aortic dissections, 23 aortic root replacements, 3 reoperations, and 3 vascular graft implantations beyond the aortic root occurred during follow-up. Except for aortic root replacement, all endpoints occurred in patients with an operated aortic root. Patients who used losartan during the entire follow-up period showed a reduced number of events compared to the control group (death: 0 vs. 5, P = 0.014; aortic dissection: 3 vs. 11, P = 0.013; elective aortic root replacement: 10 vs. 13, P = 0.264; reoperation: 1 vs. 2, P = 0.463; vascular graft implantations beyond the aortic root 0 vs. 3, P = 0.071; and composite endpoint: 14 vs. 26, P = 0.019). These results remained similar when corrected for age and ß-blocker use in a multivariate analysis. CONCLUSION: These results suggest a clinical benefit of combined losartan and ß-blocker treatment in patients with MFS.

Glycoproteomic Analysis of the Aortic Extracellular Matrix in Marfan Patients.

OBJECTIVE: Marfan syndrome (MFS) is caused by mutations in FBN1 (fibrillin-1), an extracellular matrix (ECM) component, which is modified post-translationally by glycosylation. This study aimed to characterize the glycoproteome of the aortic ECM from patients with MFS and relate it to aortopathy. Approach and Results: ECM extracts of aneurysmal ascending aortic tissue from patients with and without MFS were enriched for glycopeptides. Direct N-glycopeptide analysis by mass spectrometry identified 141 glycoforms from 47 glycosites within 35 glycoproteins in the human aortic ECM. Notably, MFAP4 (microfibril-associated glycoprotein 4) showed increased and more diverse N-glycosylation in patients with MFS compared with control patients. MFAP4 mRNA levels were markedly higher in MFS aortic tissue. MFAP4 protein levels were also increased at the predilection (convexity) site for ascending aorta aneurysm in bicuspid aortic valve patients, preceding aortic dilatation. In human aortic smooth muscle cells, MFAP4 mRNA expression was induced by TGF (transforming growth factor)-ß1 whereas siRNA knockdown of MFAP4 decreased FBN1 but increased elastin expression. These ECM changes were accompanied by differential gene expression and protein abundance of proteases from ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family and their proteoglycan substrates, respectively. Finally, high plasma MFAP4 concentrations in patients with MFS were associated with a lower thoracic descending aorta distensibility and greater incidence of type B aortic dissection during 68 months follow-up. CONCLUSIONS: Our glycoproteomics analysis revealed that MFAP4 glycosylation is enhanced, as well as its expression during the advanced, aneurysmal stages of MFS compared with control aneurysms from patients without MFS.

Editor's Choice - Nationwide Analysis of Patients Undergoing Iliac Artery Aneurysm Repair in the Netherlands.

OBJECTIVE: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR). METHODS: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests. RESULTS: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively). CONCLUSION: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.

Effect of Imaging Surveillance After Endovascular Aneurysm Repair on Reinterventions and Mortality: A Systematic Review and Meta-analysis.

Purpose: To study the effects of imaging surveillance after endovascular aortic repair (EVAR) on reintervention and mortality. Materials and Methods: A systematic review was conducted comparing complication rates in EVAR patients compliant with the imaging surveillance protocol vs partially or noncompliant patients. Two authors independently selected articles and performed quality assessment and data extraction. Risk differences for reintervention and mortality between compliant and partially/noncompliant patients were meta-analyzed. The pooled risk difference (RD) is reported with the 95% confidence interval (CI). The review protocol is registered at Prospero (CRD42017080494). Results: A total of 11 cohort studies involving 21,838 patients were included. Studies differed in imaging, their surveillance protocols, and definitions of compliance subgroups. Median follow-up was 31.7 months (interquartile range 29.8, 49.3). The overall reintervention rate was 5%, while the overall mortality was 31%. The RD for the reintervention rate was 4% (95% CI 1% to 7%) in favor of partial/noncompliance [number needed to harm 25 (95% CI 14 to 100)], while mortality showed a nonsignificant RD of 12% (95% CI -2% to 26%) in favor of partial/noncompliance. Two studies reported that 41% to 53% of reinterventions were performed for complications detected through imaging surveillance; the other events were detected through patient symptoms. Conclusion: Patients who are compliant with imaging surveillance appear to undergo more reinterventions than those who are partially or noncompliant. However, imaging surveillance does not seem to protect against mortality. This suggests that the recommended yearly imaging surveillance may not be beneficial for all EVAR patients.

A Comparative Cost-Effectiveness Analysis of Percutaneous Transluminal Angioplasty With Optional Stenting and Femoropopliteal Bypass Surgery for Medium-Length TASC II B and C Femoropopliteal Lesions.

PURPOSE: To evaluate the total midterm costs and cost-effectiveness of percutaneous transluminal angioplasty with optional stenting (PTA/S) as initial treatment compared with femoropopliteal bypass (FPB) surgery in patients with medium-length TransAtlantic Inter-Society Consensus II (TASC) B and C femoropopliteal lesions. MATERIALS AND METHODS: Over a period of 3 years, all hospital health care costs for 226 consecutive patients were calculated: 170 patients with a TASC B lesion and 56 patients with a TASC C lesion. In the 135-patient PTA/S group (mean age 69.9±10.9 years; 83 men), 108 (63.5%) patients had TASC B lesions and 27 (48.2%) patients had TASC C lesions. Ninety-one patients (mean age 68.4±10.9 years; 60 men) were treated with FPB for 62 TASC B and 29 TASC C femoropopliteal lesions. The main outcome measure was the primary patency rate at 3-year follow-up. Multiple imputation and bootstrapping techniques were used to analyze the data. The adjusted incremental cost-effectiveness ratios (ICERs) were calculated by dividing the difference in total costs by the difference in 3-year primary patency rate. Costs were expressed in euros (€), and cost differences are presented with the 95% confidence interval (CI). RESULTS: Mean total costs per patient were €29,058 in the PTA/S treatment group vs €42,437 in the FPB group (mean adjusted difference -€14,820, 95% CI -€29,044 to -€5976). Differences in 3-year primary patency between PTA/S and FPB were small and nonsignificant (68.9% and 70.3%, respectively). An ICER of 563,716 was found, indicating that FPB costs €563,716 more per one extra patient reaching 3-year primary patency in comparison with PTA/S treatment. CONCLUSION: FPB in medium-length femoropopliteal lesions involved higher total costs when evaluated over a 3-year follow-up period. An endovascular-first approach is recommended, as this will result in cost minimization for patients with medium-length femoropopliteal disease.

Estimation of Abdominal Aortic Aneurysm Rupture Risk with Biomechanical Imaging Markers.

PURPOSE: To evaluate whether the biomechanical marker known as rupture risk equivalent diameter (RRED) was superior to the actual abdominal aortic aneurysm (AAA) diameter in estimating future rupture risk in patients who had undergone pre-rupture computed tomography (CT) angiography. MATERIALS AND METHODS: A retrospective study was conducted in 13 patients with ruptured AAAs who had undergone CT angiography before and after rupture between 2001 and 2015. The median time between the 2 scans was 731 days. Biomechanical and geometrical markers such as maximal AAA diameter, peak wall stress (PWS), and RRED were calculated with AAA-dedicated software. The main analyses determined whether RRED was higher than the actual diameter and the threshold diameter for elective surgery (55 mm for men, 50 mm for women) in AAAs before and after rupture. Differences between diameter and biomechanical markers before and after rupture were tested with appropriate statistical tests. RESULTS: RRED before and after rupture was smaller than the actual diameter in 7 of 13 cases. Post-rupture RRED was estimated to be smaller than the threshold diameter for elective repair in 4 cases, again suggesting a low rupture risk. The median PWS before and after rupture was 181.7 kPa (interquartile range [IQR], 152.1-244.2 kPa) and 274.1 kPa (IQR, 172.2-377.2 kPa), respectively. CONCLUSIONS: RRED was smaller than the actual diameter in more than half of pre-rupture AAAs, suggesting a lower rupture risk than estimated with the actual diameter. The results suggest that the currently available biomechanical imaging markers might not be ready for use in clinical practice.

Editor's Choice - Sex Related Differences in Peri-operative Mortality after Elective Repair of an Asymptomatic Abdominal Aortic Aneurysm in the Netherlands: a Retrospective Analysis of 2013 to 2018.

OBJECTIVE: The aim was to compare peri-operative (30 day and/or in hospital) mortality between women and men in the Netherlands after elective repair of an asymptomatic abdominal aortic aneurysm (AAA). METHODS: This was a retrospective study using data from the Dutch Surgical Aneurysm Audit (DSAA), a mandatory nationwide registry of patients undergoing AAA repair in the Netherlands. Patients who underwent elective open surgical (OSR) or endovascular aneurysm repair (EVAR) of an asymptomatic abdominal aortic aneurysm (AAA) between 2013 and 2018 were included. Absolute risk differences (ARDs) with 95% confidence intervals (CIs) in peri-operative mortality between women and men were estimated. Logistic regression analyses were performed to estimate adjusted odds ratios (ORs) for mortality. Confounders included pre-operative cardiac and pulmonary comorbidity, serum haemoglobin, serum creatinine, type of AAA repair, and AAA diameter. RESULTS: Some 1662 women and 9637 men were included, of whom 507 (30.5%) women and 2056 (21.3%) men underwent OSR (p < .001). Crude peri-operative mortality was 3.01% in women and 1.60% in men (ARD = 1.41%, 95% CI 0.64-2.37). This significant difference was also observed for OSR (ARD = 2.63%, 95% CI 0.43-5.36), but not for EVAR (ARD = 0.36%, 95% CI -0.16 to 1.17). Female sex remained associated with peri-operative mortality after adjusting for confounders (OR = 1.79, 95% CI 1.20-2.65, p = .004), which was similarly observed for OSR (OR = 1.85, 95% CI 1.16-2.94, p = .01), but not for EVAR (OR = 1.46, 95% CI 0.72-2.95, p = .29). CONCLUSIONS: Peri-operative mortality after elective repair of an asymptomatic AAA in the Netherlands is higher in women than in men. This disparity might be explained by the higher peri-operative mortality in women undergoing OSR, because no such difference was found in patients undergoing EVAR. Yet, it is likely that there are unaccounted factors at play since female sex remained significantly associated with mortality after adjusting for type of repair.

Reporting of Complications and Mortality in Relation to Risk Communication in Patients with an Abdominal Aortic Aneurysm: A Systematic Review.

OBJECTIVES: High-quality reporting of surgical risks is necessary for evidence-based risk communication in clinical practice. Risk communication is defined as the process of discussing benefits and harms of treatment options with patients. This review addressed the current quality of reporting of complications and mortality in publications on abdominal aortic aneurysm treatment, with a focus on items relevant to risk communication. DESIGN: A systematic review. MATERIALS: Randomised clinical trials, comparative observational studies and registries from 2010 onwards were eligible if they reported complications and/or mortality in patients with an asymptomatic abdominal aortic aneurysms who received primary treatment. METHODS: Quality of reporting was assessed by scoring items relevant to risk communication from the reporting standards of the Society for Vascular Surgery (SVS) and the Consolidated Standards of Reporting Trials (CONSORT) statement. Screening, quality assessment and data extraction were independently undertaken by two authors. RESULTS: Forty-seven publications were included. Nine of 47 publications (19%) provided no definition of complications. In 14 of 47 publications (30%), it was unclear whether the number of adverse events or the number of patients with adverse events were presented. Absolute risk differences were provided in 1 of 32 publications (3.1%) that compared complications between two treatment options. Forty-six of 47 publications reported mortality, of which 42 reported overall mortality rates (91%). Absolute risk differences were given in 2 of the 31 publications (6.5%) that compared mortality between two treatment options. CONCLUSIONS: The quality of reporting of complications and mortality following primary abdominal aortic aneurysm treatment varied considerably. Better adherence to the SVS reporting standards and the CONSORT statement, as well as stating absolute risk differences may improve the quality of reporting and facilitate evidence-based risk communication.