Unsuccessful Stent Graft Repair of a Hepatic Artery Aneurysm Presenting with Haemobilia:Case Report and Comprehensive Literature Review

AIMS: To discuss treatment strategies for non-traumatic, non-iatrogenic hepatic artery aneurysms (HAAs) in the presence of an arteriobiliary fistula, illustrated by a case and followed by a comprehensive review of the literature. METHODS: Following the PRISMA guidelines, 24 eligible HAA cases presenting with haemobilia were identified. Characteristics of patients, aneurysms, treatment strategies and their outcomes were collected. RESULTS: A 69 year old patient with no previous hepatobiliary intervention or trauma, presented with jaundice and haemobilia caused by a HAA. Initial treatment by endovascular stenting was chosen to prevent ischaemic liver complications. Unfortunately, this strategy failed because of stent migration due to ongoing infection leading to a type 1A endoleak. The patient had to be converted to open surgery with ligation of the HAA. The patient recovered uneventfully and no complications occurred during the following 12 months. COMPREHENSIVE LITERATURE REVIEW: Of the 24 cases, nine had a true HAA and 15 were pseudo/mycotic aneurysms, mainly caused by endocarditis or cholecystitis. The majority were located in the right hepatic artery. In 20 cases, an endovascular first approach was chosen with embolisation, none with covered stents. Three of these cases had to be converted to open surgery because of rebleeding. In all open (primary or secondary) cases, ligation of the HAA was performed. One patient in these series died. No liver ischaemia or abscesses were reported, although one patient developed an ischaemic gallbladder. CONCLUSIONS: Patients who present with a HAA and haemobilia may be treated safely by embolisation or open ligation. Using a covered stent graft in these patients can cause problems due to ongoing infection and should be monitored closely by imaging. Publication bias and lack of long term follow up imply cautious interpretation of these findings

Aneurysm Sac Dynamics and its Prognostic Significance Following Fenestrated and Branched Endovascular Aortic Aneurysm Repair

Objective: This study aimed to assess aneurysm sac dynamics and its prognostic significance following fenestrated and branched endovascular aneurysm repair (F/BEVAR). Methods: Patients undergoing F/BEVAR for degenerative complex aortic aneurysm from 2008 to 2020 at two large vascular centres with two imaging examinations (30 day and one year) were included. Patients were categorised as regression and non-regression, determined by the proportional volume change (&gt; 5%) at one year compared with 30 days. All cause mortality and freedom from graft related events were assessed using Kaplan–Meier methods. Factors associated with non-regression at one year and aneurysm sac volume over time were examined for FEVAR and BEVAR independently using multivariable logistic regression and linear mixed effects modelling. Results: One hundred and sixty-five patients were included: 122 FEVAR, of whom 34% did not regress at one year imaging (20% stable, 14% expansion); and 43 BEVAR, of whom 53% failed to regress (26% stable, 28% expansion). Following F/BEVAR, after risk adjusted analysis, non-regression was associated with higher risk of all cause mortality within five years (hazard ratio [HR] 2.56, 95% confidence interval [CI] 1.09 – 5.37; p = .032) and higher risk of graft related events within five years (HR 2.44, 95% CI 1.10 – 5.26; p = .029). Following multivariable logistic regression, previous aortic repair (odds ratio [OR] 2.56, 95% CI 1.11 – 5.96; p = .029) and larger baseline aneurysm diameter (OR/mm 1.04, 95% CI 1.00 – 1.09; p = .037) were associated with non-regression at one year, whereas smoking history was inversely associated with non-regression (OR 0.21, 95% CI 0.04 – 0.96; p = .045). Overall following FEVAR, aneurysm sac volume decreased significantly up to two years (baseline vs. two year, 267 [95% CI 250 – 285] cm 3 vs. 223 [95% CI 197 – 248] cm 3), remaining unchanged thereafter. Overall following BEVAR, aneurysm sac volume remained stable over time. Conclusion: Like infrarenal EVAR, non-regression at one year imaging is associated with higher five year all cause mortality and graft related events risks after F/BEVAR. Following FEVAR for juxtarenal aortic aneurysm, aneurysm sacs generally displayed regression (66% at one year), whereas after BEVAR for thoraco-abdominal aortic aneurysm, aneurysm sacs displayed a concerning proportion of growth at one year (28%), potentially suggesting a persistent risk of rupture and consequently requiring intensified surveillance following BEVAR. Future studies will have to elucidate how to improve sac regression following complex EVAR, and whether the high expansion risk after BEVAR is due to advanced disease extent.</p

Aneurysm Sac Dynamics and its Prognostic Significance Following Fenestrated and Branched Endovascular Aortic Aneurysm Repair

Objective: This study aimed to assess aneurysm sac dynamics and its prognostic significance following fenestrated and branched endovascular aneurysm repair (F/BEVAR). Methods: Patients undergoing F/BEVAR for degenerative complex aortic aneurysm from 2008 to 2020 at two large vascular centres with two imaging examinations (30 day and one year) were included. Patients were categorised as regression and non-regression, determined by the proportional volume change (&gt; 5%) at one year compared with 30 days. All cause mortality and freedom from graft related events were assessed using Kaplan–Meier methods. Factors associated with non-regression at one year and aneurysm sac volume over time were examined for FEVAR and BEVAR independently using multivariable logistic regression and linear mixed effects modelling. Results: One hundred and sixty-five patients were included: 122 FEVAR, of whom 34% did not regress at one year imaging (20% stable, 14% expansion); and 43 BEVAR, of whom 53% failed to regress (26% stable, 28% expansion). Following F/BEVAR, after risk adjusted analysis, non-regression was associated with higher risk of all cause mortality within five years (hazard ratio [HR] 2.56, 95% confidence interval [CI] 1.09 – 5.37; p = .032) and higher risk of graft related events within five years (HR 2.44, 95% CI 1.10 – 5.26; p = .029). Following multivariable logistic regression, previous aortic repair (odds ratio [OR] 2.56, 95% CI 1.11 – 5.96; p = .029) and larger baseline aneurysm diameter (OR/mm 1.04, 95% CI 1.00 – 1.09; p = .037) were associated with non-regression at one year, whereas smoking history was inversely associated with non-regression (OR 0.21, 95% CI 0.04 – 0.96; p = .045). Overall following FEVAR, aneurysm sac volume decreased significantly up to two years (baseline vs. two year, 267 [95% CI 250 – 285] cm 3 vs. 223 [95% CI 197 – 248] cm 3), remaining unchanged thereafter. Overall following BEVAR, aneurysm sac volume remained stable over time. Conclusion: Like infrarenal EVAR, non-regression at one year imaging is associated with higher five year all cause mortality and graft related events risks after F/BEVAR. Following FEVAR for juxtarenal aortic aneurysm, aneurysm sacs generally displayed regression (66% at one year), whereas after BEVAR for thoraco-abdominal aortic aneurysm, aneurysm sacs displayed a concerning proportion of growth at one year (28%), potentially suggesting a persistent risk of rupture and consequently requiring intensified surveillance following BEVAR. Future studies will have to elucidate how to improve sac regression following complex EVAR, and whether the high expansion risk after BEVAR is due to advanced disease extent.</p

MORPHOLOGIC CHANGES AND CLINICAL CONSEQUENCES OF WIDE AAA NECKS TREATED WITH 34-36MM PROXIMAL DIAMETER EVAR DEVICES

Introduction: Endovascular aneurysm repair (EVAR) became the preferred modality for infrarenal aneurysm (AAA) repair. Several available endografts have main body proximal diameters up to 36mm, allowing for treatment of proximal AAA necks up to 32 mm. However, large neck represents a predictor of proximal complications after EVAR. The purpose of this study is to evaluate mid-term outcomes of patients requiring 34-36mm main body devices. Methods: Retrospective review of a prospectively maintained database including all patients undergoing elective EVAR for degenerative AAA in a single tertiary referral hospital in The Netherlands were eligible. All measurements were performed on center-lumen line reconstructions obtained on dedicated software. Patients were classified as large diameter (LD) if the implanted device was >32mm wide. The remaining patients were classified as normal diameter (ND). Primary endpoint was neck-related events (a composite of “endoleak” (EL) 1A, neck-related secondary intervention or migration >5mm). Neck morphology changes and survival were also assessed. Differences in groups were adjusted by multivariable analysis. Results: The study included 502 patients (90 in the LD group; 412 in the ND group). Median follow-up was 3.5 years (1.5–6.2) and 4.5 years (2.1–7.3) for the LD and ND groups, respectively (P = .008). Regarding baseline characteristics, hypertension (83% vs 69.7%, P=.012) and smoking (86% vs 74.1%, P=.018) were more frequent in the LD group. Patients in the LD group had wider (Proximal neck Ø > 28 mm: 75% vs 3.3%, P45º: 21% vs 9%, P=.002), more conical (39.8% vs 20.3%, P25%: 42% vs 32.3%, P 5mm occurred similarly in both groups (7.8% vs 5.1%, P=.32). Neck-related secondary interventions were also more common among LD patients (13.3% vs 8.7%; P = .027). On multivariable regression analysis, LD group was an independent risk factor for neck-related adverse events (Hazard Ratio [HR]: 2.29; 95% confidence interval [CI], 1.37–3.83, P=0.002). Neck dilatation was greater among LD patients (median, 3 mm [IQR, 0–6] vs 2mm [IQR, 0–4]; P =.034) On multivariable analysis, LD was an independent predictor for neck dilatation > 10 % (HR: 1.61 CI 95% 1.08–2.39, P=.020). Survival at 5-years was 66.1% for LD and 71.2% for SD groups, P=.14. Conclusion: Standard EVAR in patients with large infrarenal necks requiring a 34- to 36-mm proximal endograft is independently associated to increased rate of neck related events and more neck dilatation. This subgroup of patients could be considered for more proximal seal strategies with fenestrated or branched devices, if unfit for open repair. Tighter surveillance following EVAR in these patients in the long term is also advised

Circulating biomarkers of cardiovascular disease are related to aneurysm volume in abdominal aortic aneurysm

Background: Surveillance programs in abdominal aortic aneurysms (AAA) are mainly based on imaging and leave room for improvement to timely identify patients at risk for AAA growth. Many biomarkers are dysregulated in patients with AAA, which fuels interest in biomarkers as indicators of disease progression. We examined associations of 92 cardiovascular disease (CVD)-related circulating biomarkers with AAA and sac volume. Methods: In a cross-sectional analysis, we separately investigated (1) 110 watchful waiting (WW) patients (undergoing periodic surveillance imaging without planned intervention) and (2) 203 patients after endovascular aneurysm repair (EVAR). The Cardiovascular Panel III (Olink Proteomics AB, Sweden) was used to measure 92 CVD-related circulating biomarkers. We used cluster analyses to investigate protein-based subphenotypes, and linear regression to examine associations of biomarkers with AAA and sac volume on CT scans. Results: Cluster analyses revealed two biomarker-based subgroups in both WW and EVAR patients, with higher levels of 76 and 74 proteins, respectively, in one subgroup versus the other. In WW patients, uPA showed a borderline significant association with AAA volume. Adjusting for clinical characteristics, there was a difference of −0.092 (−0.148, −0.036) loge mL in AAA volume per SD uPA. In EVAR patients, after multivariable adjustment, four biomarkers remained significantly associated with sac volume. The mean effects on sac volume per SD difference were: LDLR: −0.128 (−0.212, −0.044), TFPI: 0.139 (0.049, 0.229), TIMP4: 0.110 (0.023, 0.197), IGFBP-2: 0.103 (0.012, 0.194). Conclusion: LDLR, TFPI, TIMP4, and IGFBP-2 were independently associated with sac volume after EVAR. Subgroups of patients with high levels of the majority of CVD-related biomarkers emphasize the intertwined relationship between AAA and CVD. ClinicalTrials.gov Identifier: NCT03703947.</p

Targeted proteomics and metabolomics for biomarker discovery in abdominal aortic aneurysm and post-EVAR sac volume

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) patients undergo uniform surveillance programs both leading up to, and following surgery. Circulating biomarkers could play a pivotal role in individualizing surveillance. We applied a multi-omics approach to identify relevant biomarkers and gain pathophysiological insights. MATERIALS AND METHODS: In this cross-sectional study, 108 AAA patients and 200 post-endovascular aneurysm repair (post-EVAR) patients were separately investigated. We performed partial least squares regression and ingenuity pathway analysis on circulating concentrations of 96 proteins (92 Olink Cardiovascular-III panel, 4 ELISA-assays) and 199 metabolites (measured by LC-TQMS), and their associations with CT-based AAA/sac volume. RESULTS: The median (25th-75th percentile) maximal diameter was 50.0 mm (46.0, 53.0) in the AAA group, and 55.4 mm (45.0, 64.2) in the post-EVAR group. Correcting for clinical characteristics in AAA patients, the aneurysm volume Z-score differed 0.068 (95 %CI: (0.042, 0.093)), 0.066 (0.047, 0.085) and -0.051 (-0.064, -0.038) per Z-score valine, leucine and uPA, respectively. After correcting for clinical characteristics and orthogonalization in the post-EVAR group, the sac volume Z-score differed 0.049 (0.034, 0.063) per Z-score TIMP-4, -0.050 (-0.064, -0.037) per Z-score LDL-receptor, -0.051 (-0.062, -0.040) per Z-score 1-OG/2-OG and -0.056 (-0.066, -0.045) per Z-score 1-LG/2-LG. CONCLUSIONS: The branched-chain amino acids and uPA were related to AAA volume. For post-EVAR patients, LDL-receptor, monoacylglycerols and TIMP-4 are potential biomarkers for sac volume. Additionally, distinct markers for sac change were identified.</p

Targeted proteomics and metabolomics for biomarker discovery in abdominal aortic aneurysm and post-EVAR sac volume

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) patients undergo uniform surveillance programs both leading up to, and following surgery. Circulating biomarkers could play a pivotal role in individualizing surveillance. We applied a multi-omics approach to identify relevant biomarkers and gain pathophysiological insights. MATERIALS AND METHODS: In this cross-sectional study, 108 AAA patients and 200 post-endovascular aneurysm repair (post-EVAR) patients were separately investigated. We performed partial least squares regression and ingenuity pathway analysis on circulating concentrations of 96 proteins (92 Olink Cardiovascular-III panel, 4 ELISA-assays) and 199 metabolites (measured by LC-TQMS), and their associations with CT-based AAA/sac volume. RESULTS: The median (25th-75th percentile) maximal diameter was 50.0 mm (46.0, 53.0) in the AAA group, and 55.4 mm (45.0, 64.2) in the post-EVAR group. Correcting for clinical characteristics in AAA patients, the aneurysm volume Z-score differed 0.068 (95 %CI: (0.042, 0.093)), 0.066 (0.047, 0.085) and -0.051 (-0.064, -0.038) per Z-score valine, leucine and uPA, respectively. After correcting for clinical characteristics and orthogonalization in the post-EVAR group, the sac volume Z-score differed 0.049 (0.034, 0.063) per Z-score TIMP-4, -0.050 (-0.064, -0.037) per Z-score LDL-receptor, -0.051 (-0.062, -0.040) per Z-score 1-OG/2-OG and -0.056 (-0.066, -0.045) per Z-score 1-LG/2-LG. CONCLUSIONS: The branched-chain amino acids and uPA were related to AAA volume. For post-EVAR patients, LDL-receptor, monoacylglycerols and TIMP-4 are potential biomarkers for sac volume. Additionally, distinct markers for sac change were identified.</p

Total Luminal Volume Predicts Risk after Endovascular Aneurysm Repair

Objective: Large aneurysm diameter represents a well known predictor of late complications after endovascular aneurysm repair (EVAR). However, the role of the thrombus free lumen inside the abdominal aortic aneurysm (AAA) sac is not clear. It was hypothesised that greater luminal volume represents a relevant risk factor for late complications after EVAR. Methods: A retrospective cohort analysis was performed including all patients undergoing EVAR from 2005 to 2016 at a tertiary referral institution. Pre-operative AAA lumen volume was measured in centre lumen line reconstructions and patients were stratified into quartiles according to luminal volume. The primary endpoint was freedom from AAA related complications. Secondary endpoints were freedom from neck events (type 1A endoleak, migration >5 mm or any pre-emptive neck related intervention), iliac related events (type 1B endoleak or pre-emptive iliac related intervention), and overall survival. Results: Four hundred and four patients were included: 101 in the first quartile (Q1; <61 cm3). Patients with higher luminal volumes had wider, shorter, and more angulated proximal necks. There were more ruptured AAAs, more aorto-uni-iliac implanted devices and patients outside neck instructions for use in the 4th quartile. Five year freedo

Targeted plasma multi-omics propose glutathione, glycine and serine as biomarkers for abdominal aortic aneurysm growth on serial CT scanning

Background and aims: Abdominal aortic aneurysm (AAA) patients undergo uniform imaging surveillance until reaching the surgical threshold. In spite of the ongoing exploration of AAA pathophysiology, biomarkers for personalized surveillance are lacking. This study aims to identify potential circulating biomarkers for AAA growth on serial CT scans. Methods: Patients with an AAA (maximal diameter ≥40 mm) were included in this multicentre, prospective cohort study. Participants underwent baseline blood sampling and yearly CT-imaging to determine AAA diameter and volume. Proteins and metabolites were measured using proximity extension assay (Olink Cardiovascular III) or separate ELISA panels, and mass-spectrometry (LC-TQMS), respectively. Linear mixed-effects, orthogonal partial least squares, and Cox regression were used to explore biomarker associations with AAA volume growth rate and the risk of surpassing the surgical threshold, as formulated by current guidelines. Results: 271 biomarkers (95 proteins, 176 metabolites) were measured in 109 (90.8 % male) patients with mean age 72. Median baseline maximal AAA diameter was 47.8 mm, volume 109 mL. Mean annual AAA volume growth rate was 11.5 %, 95 % confidence interval (CI) (10.4, 12.7). Median follow-up time was 23.2 months, 49 patients reached the surgical threshold. Patients with one standard deviation (SD) higher glutathione and glycine levels at baseline had an AAA volume growth rate that respectively was 1.97 %, 95%CI (0.97, 2.97) and 1.74 %, 95%CI (0.78, 2.71) larger, relative to the actual aneurysm size. Serine was associated with the risk of reaching the surgical threshold, independent of age and baseline AAA size (cause-specific hazard ratio per SD difference 1.78, 95%CI (1.30, 2.44)). Conclusions: Among multiple intertwined biomarkers related to AAA pathophysiology and progression, glutathione, glycine and serine were most promising.</p

Comparison of midterm results of endovascular aneurysm repair for ruptured and elective abdominal aortic aneurysms

Objective: Endovascular aneurysm repair (EVAR) became an increasingly preferred modality for abdominal aortic aneurysm (AAA) repair both in elective AAA repair (el-EVAR) and EVAR of a ruptured AAA (r-EVAR) setting. Ruptured AAAs usually have more hostile anatomies and less time for planning. Consequently, more complications may arise after r-EVAR. The purpose of this study was to compare mi-term outcomes between r-EVAR and el-EVAR. Methods: A retrospective cohort analysis of patients undergoing EVAR from 2000 to 2015 at a tertiary institution was performed. Patients with previous aortic surgery, nonatherosclerotic AAA and isolated iliac aneurysms were excluded. In-hospital casualties or patients who were intraoperatively converted to open repair were also excluded. For the midterm outcome analysis, only patients with at least two postoperative examinations (a 30-day computed tomography scan and a second postoperative examination performed 6 months or later) were considered. The primary end point was freedom from aneurysm-related complications (a composite of type I or III endoleak, aneurysm sac growth, migration of more than 5 mm, device integrity failure, AAA-related death, late postimplant rupture, or AAA-related secondary intervention). Freedom from secondary interventions, neck-related events (defined as a composite of type IA endoleak, migration of more than 5 mm, or preemptive neck-related secondary intervention) and late survival were secondary end points. The impact of device instructions for use (IFU) compliance on neck events was also assessed. Results: The study included 565 patients (65 r-EVAR and 500 el-EVAR). Eighty-two patients were treated outside proximal neck IFU, 13 in the r-EVAR group (21.3%) and 69 (14.5%) in the el-EVAR (P =.16). During the index hospitalization, there were more complications (12.3% vs 3.2%; P =.001) and reinterventions (12.3% vs 2.8%; P <.001) in the r-EVAR group. After discharge, median clinical follow-up time was 4.3 years (interquartile range, 2.1-7.0 years) without differences between both groups. Five-year freedom from AAA-related complications was 53.9% in the r-EVAR group and 65.4% in the el-EVAR (P =.21). In multivariable analysis the r-EVAR group was not at increased risk for late complications (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.54-1.61; P =.81). Five-year freedom from neck-related events was 74% in r-EVAR and 82% in the el-EVAR group (P =.345). Patients treated outside neck IFU were at greater risk for neck-related events both in r-EVAR (HR, 6.5; 95% CI, 1.8-22.9; P =.004) and el-EVAR group (HR, 2.6; 95% CI, 1.5-4.5; P <.001). Freedom from secondary interventions at 5 years was 63.0% for r-EVAR and 76.9% for el-EVAR (P =.16). Survival at 5 years was 68.8% in the r-EVAR group and 73.3% in the el-EVAR group (P =.30). Conclusions: Durable and sustainable midterm outcomes were found for both r-EVAR and el-EVAR patients who survived the postoperative period. Patients treated out