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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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Catheterization of target vessels (TV) represented by renal visceral vessels are the crucial aspect during fenestrated and branched endovascular repair. This study aims to assess the efficacy and complications associated with upper limb catheterization during complex aneurysm endovascular surgery repair., Methods: A systematic review was conducted after Preferred Reporting Items for a Systematic Review and Meta-analysis (PRISMA) guidelines, involving a search across PubMed, Cochrane CENTRAL, and Web of Science. Primary endpoint was represented by 30-day stroke. Secondary endpoints were target vessels' (TVs) technical success, 30-day mortality, and local access-related complications. Meta-analyses were performed using a random-effects model., Results: Sixteen observational studies encompassing 4,137 patients were included. The 30-day stroke incidence for upper limb access was 1.4% (95% CI 1.0-1.8%), which was slightly higher than lower limb, despite not statistically significant. Mortality varied between 0 and 6.8%, and local access-related complications occurred in 3.2% (95% CI 1.9-4.4%). Technical success in TV catheterization was 99.2% (95% CI 98.4-100.0%)., Conclusions: This systematic review and meta-analysis demonstrate the safety and efficacy of upper limb access for Fenestrated and Branched Endovascular Aortic Repair (f/b-EVAR), with low stroke risk, mortality rates, and minimal local complications. Despite the risk of bias, the findings suggest that upper limb access may be beneficial, especially in bailout situations when femoral access fails, offering valuable insights for clinical decision-making., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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 (> 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., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

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) log e 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., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Frozen elephant trunk (FET) technique was developed as an alternative to the conventional elephant trunk (cET) procedure for the repair of complex aortic arch pathology. However, short term results between these different procedures are sparsely described. This systematic review with meta-analysis aimed to compare short term outcomes between FET and cET in the repair of aortic arch pathology., Evidence Acquisition: PubMed, Web of Science and Scopus electronic databases were searched for studies comparing performance of FET and cET procedures in patients with aortic arch pathology. The primary outcome of interest was early mortality, defined as 30-day or in-hospital mortality. Secondary outcomes were stroke, and spinal cord ischemia (SCI). Meta-analysis utilizing the random-effects model was performed using Review Manager (RevMan) software, version 5.4., Evidence Synthesis: Ten studies, comprising 1481 patients with aortic arch pathology, were included. Meta-analysis demonstrated statistically significant reduction of early mortality (odds ratio [OR], 0.63; 95% CI, 0.41-0.97) in the FET group. For neurologic outcomes, no significant differences were noted in stroke risk between both groups (OR, 1.21; 95% CI, 0.83-1.75), but an increased risk of SCI was present in FET patients (OR, 2.07; 95% CI, 1.05-4.10)., Conclusions: FET appears to be associated with a significant lower early mortality, at costs of greater SCI risk. Larger studies are needed to provide confident recommendations towards preferential use of either procedure.

Introduction: Hyperbaric oxygen therapy (HBOT) is increasingly being used in the treatment of as diabetic foot ulcers (DFU). However, definitive evidence regarding its beneficial effects is still scarce. The present systematic review aims to analyze the role of HBOT in the prevention of limb amputation along with improvement of ulcer healing in patients with lower limbs DFU., Evidence Acquisition: Three databases were searched: PubMed, Scopus, and ISI Web of Knowledge. The search was enrolled during October 2020. Both titles and abstracts were examined by two independent reviewers. Only randomized controlled trials (RCTs) reporting a comparison between standard DFU treatment and standard treatment associated with HBOT were included. In all studies eligibility was assessed and data regarding studies characteristics, methods and considered outcomes was obtained. Odds ratio (OR) was used to evaluate amputation and complete ulcer healing rates. Percentage of ulcer reduction at two weeks was evaluated using the inverse variance method, and the values were compared using mean difference values. Meta-analysis was done using a fixed-effect model if I 2 values were under 50%, and a random-effects model if not., Evidence Synthesis: Eleven RCTs were included, with a total of 668 patients studied. Patients undergoing HBOT had lower risk of amputation (OR 0.53 95% CI 0.32-0.90, I 2 =31%). No difference was found in minor amputations (OR 0.89 95% CI 0.35-2.24, I 2 =69%). Regarding, healing rates, HBOT patients had greater chances of ulcer healing (OR 4,00 95% CI 1.54-10.44, I 2 =70%). It has also shown higher percentage of ulcer area reduction after two weeks of treatment in the HBOT group (mean difference 23.19%; 95% CI 14.86-31.52; I 2 =0%)., Conclusions: The present review offers evidence that adjuvant HBOT decreases risk of major amputation while promoting wound healing when combined to standard treatment in the management of DFU. These findings may have clinical relevance in a selected group of patients, yet further larger studies are still needed.

Objective: The aim of this study was to investigate the association between post-implantation syndrome (PIS) and long term outcomes, with emphasis on cardiovascular prognosis., Methods: One hundred and forty-nine consecutive patients undergoing EVAR in a tertiary institution were previously included in a study investigating the risk factors and short term consequences of PIS (defined as tympanic temperature ≥ 38°C and CRP > 10 mg/L, after excluding complications with an effect on inflammatory markers). This study was based on a prospectively maintained database. Survival status was derived from inquiry of civil registry database information and causes of death from the Dutch Central Bureau of Statistics. The primary endpoint was cardiovascular events. Secondary endpoints were overall and specific cause mortality (cardiovascular, ischaemic heart disease, AAA, and cancer related mortality). Aneurysm sac dynamics and occurrence of endoleaks were also analysed. Survival estimates were obtained using Kaplan-Meier plots and a multivariable model was constructed to correct for confounders., Results: The PIS incidence was 39% (58/149). At the time of surgery, patients had a mean age of 73 ± 7 years and were predominantly male. There were no baseline differences between the PIS and non-PIS groups. The median follow up was 6.4 years (3.2 - 8.3), similar in both groups (p = .81). There was no difference in cardiovascular events for PIS and non-PIS patients (p = .63). However, Kaplan-Meier plots suggest a trend towards a higher rate of cardiovascular events in PIS patients during the first years: freedom from cardiovascular events at one year was 94% vs. 89% and at three years 90% vs. 82%. No differences were found in overall and specific cause mortality. There was a higher rate of type II endoleaks for non-PIS patients (28% vs. 9%, p = .005). Sac dynamics were similar in both groups., Conclusion: The results suggest that PIS is not associated with a statistically significantly higher risk of cardiovascular events. PIS had no impact on mortality. Lastly, PIS patients had fewer type II endoleaks, but sac dynamics were analogous., (Copyright © 2021 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Objective: Aortic neck dilatation (AND) occurs after endovascular aneurysm repair (EVAR) with self expanding stent grafts (SESs). Whether it continues, ultimately exceeding the endograft diameter leading to abdominal aortic aneurysm (AAA) rupture, remains uncertain. Dynamics, risk factors, and clinical relevance of AND were investigated after EVAR with standard SESs., Methods: All intact EVAR patients treated from 2000 to 2015 at a tertiary institution were included. Demographic, anatomical, and device related characteristics were investigated as risk factors for AND. Outer to outer diameters were measured at a single standardised aortic level on reconstructed computed tomography (CT) images., Results: A total of 460 patients were included (median follow up 5.2 years, interquartile range [IQR] 3.0, 7.7 years; CT imaging follow up 3.3 years, IQR 1.3, 5.4). Baseline neck diameter was 24 mm (IQR 22, 26) and increased 11.1% (IQR 1.5%, 21.9%) at last CT imaging. Endograft oversizing was 20.0% (IQR 13.6, 28.0). AND was greater during the first year (5.2% [IQR 0, 11.7]) decreasing subsequently (two to four years to 1.4%/year [IQR 0.0, 4.5%], p ≤ .001) and was associated with suprarenal fixation endografts (t value = 7.9, p < .001) and oversizing (t value = 4.4, p < .001). AND exceeding the endograft was 3.5% (95% CI 2.2% - 4.8%) and 14.4% (95% CI 11.0% - 17.8%) at five and eight years, respectively. Excessive AND was associated with baseline neck diameter (OR 1.2/mm, 95% CI 1.05 - 1.41) while the Excluder endograft had a protective effect (OR 0.15, 95% CI 0.04 - 0.58). Excessive AND was associated with type 1A endoleak (HR 3.3, 95% CI 1.1 - 9.7) and endograft migration > 5 mm (HR 3.1, 95% CI 1.4 - 6.9)., Conclusion: AND after EVAR with SES is associated with endograft oversizing and radial force but decelerates after the first post-operative year. Baseline aortic neck diameter and suprarenal stent bearing endografts were associated with an increased risk of AND beyond nominal stent graft diameter. However, it remains unclear whether patient selection, differences in endograft radial force or the suprarenal stent are accountable for this difference., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Post-thrombotic syndrome (PTS) is the most common chronic complication of deep vein thrombosis. Recent studies suggested that iliac stenting in chronic obstructive venous disease is safe and effective. However, systematic reviews focusing on mid-term efficacy of iliac stenting in post-thrombotic syndrome are lacking. This systematic review aimed to analyze mid-term stent patency rates and clinical outcomes of iliac stenting in post-thrombotic syndrome., Evidence Acquisition: Two databases were searched: Pubmed/Medline and Scopus. Articles published between January 2000 and July 2020 were selected and titles and abstracts were independently reviewed. Eighteen articles were included for the qualitative analysis. From this initial set of articles, fourteen articles were included for the quantitative analysis., Evidence Synthesis: Overall, 1008 patients were included in this study. The pooled technical success rate was 96%. The pooled primary and secondary patency rates were 98.2% and 100% at 30 days, 78.1% and 94.5% at 12 months and 66.3% and 89.4% at 36 months, respectively. The rates of ulcer healing, pain and edema relief were 78.1%, 53.4% and 48.8%, respectively. The pooled rate of complications including intraoperative venous injury, back pain and stent fracture were 28%, 57.1%, and 5.9%, respectively., Conclusions: Iliac venous stenting in PTS presents durable mid-term patency rates, as well as significant symptomatic improvement. Therefore, endovascular treatment should be considered in symptomatic patients with PTS.

Introduction: Inflammation is a common underlying feature of atherosclerosis. Several inflammatory biomarkers have been reported to have prognostic value, in several areas, including in vascular surgery. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) may permit to identify patients at greater risk for cerebrovascular events, tailor patient management, improve preoperative status and possibly develop target anti-atherosclerotic therapy. However, studies reporting usefulness of these hematological biomarkers in the context of carotid artery disease are still scarce. The aim of this study was to review the literature concerning the prognostic ability of NLR and PLR in the subpopulation of vascular patients with carotid artery disease., Methods: A Medline search was performed in order to identify publications focused on the physiopathology of NLR and PLR and their impact in the management of patients with carotid artery disease., Results: The study identified 18 articles with a total of 5339 patients. NLR is associated with carotid intima-media thickness, carotid plaques, carotid stenosis, symptomatic stenosis and intra-stent restenosis after carotid artery stenting and cognitive dysfunction after carotid endarterectomy. PLR is associated with carotid stenosis, symptomatic stenosis and predicts post-operative outcomes after carotid artery revascularization, including post-operative stroke, acute coronary syndrome and all-cause mortality., Conclusions: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have the ability to predict sub-clinic atherosclerosis, atherosclerosis progression in carotid artery disease and propensity for carotid stenosis to become symptomatic along with morbidity following CEA and carotid stenting. Consequently, these parameters may be considered to tailored therapy and improve patient management.

Background: Myocardial injury after non-cardiac surgery (MINS) stands for myocardial injury due to ischemia that occurs during or within 30-days after non-cardiac surgery. Although MINS is known to be independently associated with 30-day mortality after intervention, little is described about the impact of MINS after vascular procedures, particularly after endovascular aneurysm repair (EVAR)., Methods: This is an observational, retrospective, single-centered study. All patients underwent elective standard EVAR between January 2008 and June 2017, and them with at least one postoperative measurement of troponin I in the first 48 h after surgery, were retrospectively included. MINS was defined as the value exceeding the 99 th percentile of a normal reference population with a coefficient of variation <10%. Primary outcomes include the prevalence of MINS in this subset of EVAR patients, as well as its impact in mid-term all-cause mortality. As secondary aim, the preoperative predictors of MINS were also assessed., Results: One-hundred and thirty-six patients with postoperative troponin measurements were included (95.6% male; mean age 75.51years). MINS was diagnosed in 16.2% (N.=22) of the patients, and in 86.4% of the cases (N.=19) it was completely asymptomatic. Heart failure (31.8% vs. 10.5%, P=0.016), ASA Score ≥3 (95.5% vs. 67.5%, P=0.004), pre-operative (P=0.036) and postoperative (P=0.04) hemoglobin concentrations ≤12 g/dL were found to be significantly associated with MINS. Regarding remaining baseline characteristics, anesthesia and femoral access, no further differences were observed. Survival at 1, 3 and 5 years was 92% (95% CI: 4.6-6.9, standard error [SE] 0.023), 81% (95% CI: 5.6-7.6, SE=0.034) and 71% (95% CI: 6.9-8.7, SE=0.04), with two deaths reported at 30 days follow-up. MINS was found to be significantly associated with increased mid-term all-cause mortality after EVAR at 24 months follow-up (84.2±3.4% vs. 63.6±10.3%, P=0.001), with a 2.12-fold risk increase of death., Conclusions: MINS is a common complication after EVAR and negatively impacts the mid-term prognosis of such interventions. In the majority of cases, it is asymptomatic and, therefore, not detectable unless routine postoperative troponin measurements are performed.

Purpose: To compare changes in abdominal aortic aneurysm (AAA) sac volume between endovascular aneurysm repairs (EVAR) performed for ruptured (rEVAR) vs intact (iEVAR) AAAs and to determine the impact of early volume shrinkage on future complications., Materials and Methods: A retrospective analysis was performed of all patients undergoing standard infrarenal EVAR from 2002 to 2016 at a tertiary referral institution. Only patients with degenerative AAAs and with 30-day and 1-year computed tomography angiography (CTA) imaging were included. Early sac shrinkage was defined as a volume sac reduction >10% between the first (<30-day) and the 1-year CTA. The primary endpoint was to compare AAA sac volume changes between patients undergoing rEVAR (n=51; mean age 71.0±8.5 years; 46 men) vs iEVAR (n=393; mean age 72.3±7.5 years; 350 men). Results are reported as the mean difference with the interquartile range (IQR Q1, Q3). The secondary endpoint was freedom from aneurysm-related complications after 1 year as determined by regression analysis; the results are presented as the hazard ratio (HR) and 95% confidence interval (CI)., Results: At baseline, the rEVAR group had larger aneurysms (p<0.001) and shorter (p<0.001) and more angulated (p=0.028) necks. Aneurysm sac volume decreased more in the rEVAR group during the first year [-26.3% (IQR -38.8%, -12.5%)] vs the iEVAR group [-11.9% (IQR -27.5%, 0); p<0.001]. However, after the first year, the change in sac volume was similar between the groups [-3.8% (IQR -32.9%, 31.9%) for rEVAR and -1.5% (IQR -20.9%, 13.6%) for iEVAR, p=0.74]. Endoleak occurrence during follow-up was similar between the groups. In the overall population, patients with early sac shrinkage had a lower incidence of complications after the 1-year examination (adjusted HR 0.59, 95% CI 0.39 to 0.89, p=0.01)., Conclusion: EVAR patients treated for rupture have more pronounced aneurysm sac shrinkage compared with iEVAR patients during the first year after EVAR. Patients presenting with early shrinkage are less likely to encounter late complications. These parameters may be considered when tailoring surveillance protocols.

Vascular injuries following anterior shoulder dislocations are rare, with an estimated incidence of 1-2%. The formation of an axillary artery pseudoaneurysm secondary to vascular trauma is a possible late complication and frequently underdiagnosed since it may remain asymptomatic for many years. A rupture of a pseudoaneurysm may occur either from the dislocation itself or after forceful reduction attempts. A ruptured pseudoaneurysm of the axillary artery is a medical emergency and may result in significative upper-limb morbidity or even patient mortality. Nowadays, endovascular techniques have progressively gained ground for the treatment of such lesion, especially in an emergency context. In the present article, the authors present the case of a 77-years-old male patient with a rupture of a pseudoaneurysm of the left axillary artery after repeated forceful reductions of an anterior glenohumeral dislocation and its treatment with percutaneous endovascular stenting., (©Copyright: the Author(s).)

Introduction: Open repair remains the gold standard technique for popliteal aneurysm repair. However, the endovascular approach has gained increased popularity. Comparison between these techniques remain crucial to aid the physician choice, yet, data on mid-term outcomes lack in the literature. The present review aims to compare the limb salvage and reintervention rates in these different approaches., Evidence Acquisition: A comprehensive literature review was conducted to identify publications on endovascular treatment or open repair of popliteal artery aneurysms (PAAs). Primary endpoints were reintervention and limb salvage., Evidence Synthesis: Twenty-seven studies were selected for analysis describing a total of 5425 patients: 1651 PAAs underwent endovascular repair and 4166 PAAs were treated with open surgery. The technical success rates varied between 83.3% to 100% in the endovascular group and 79% to 100% in the open repair. For endovascular repair, the limb salvage at 1 year ranged between 84.2% and 100%, at 3 years between 88.9% and 100%; and at 5 years between 64.7% and 100%. The reintervention rate at 1 year ranged between 3.7% and 21%, at 3 years between 18.9% and 28%, and at 5 years between 34.5% and 38%. For open repair, the limb salvage varied between 94.3% and 100% at 1 year, 94.5% and 99% at 3 years, and 86.4% to 97% at 5 years. Regarding the reintervention rate, at 1 year was 12.8% and 13%, at 3 years 3.6% and 12%, and at 5 years varied between 15.7% and 30%., Conclusions: Both endovascular and open repair of popliteal aneurysms represent safe options for popliteal aneurysm repair. Yet, on mid-term, open repair is associated with greater limb salvage and fewer reintervention rates. Still, further studies are needed to access the long-term durability of this technique and its suitability in emergency settings.

Introduction: Endovascular aneurysm repair for ruptured abdominal aortic aneurysms (r-EVAR) sometimes complicates with abdominal compartment syndrome (ACS) due to extensive retroperitoneal hematoma, with significant prognostic implications. This systematic review aimed to analyze the incidence of the syndrome and assess the impact of ACS on mortality. Mortality after decompressive laparotomy was also assessed., Evidence Acquisition: Two databases were searched: Medline and Web of Science. The search was conducted through October 2019. The titles and abstracts of the retrieved articles were independently reviewed. All studies reporting on the ACS incidence after r-EVAR were initially included. From each study, eligibility was determined and descriptive, methodological, and outcome data was extracted. The incidence was calculated with summary proportion. Odds ratio was used to compare the mortality rate. Meta-analysis was performed with fixed effect model when calculating the ACS incidence in r-EVAR patients and when assessing the impacts of ACS and DL in the mortality rate., Evidence Synthesis: A total of 46 studies were included, with a cumulative cohort of 3064 patients. Two hundred and fifty-two (8.2%) patients developed ACS. The ACS pooled incidence was 9% with a 95% confidence interval of [0.08; 0.11]. Among the 46 included studies, 19 studies reported data on the mortality rate, corresponding to 1825 of the 3064 patients. Of these, 169 (9.3%) had developed ACS and 94 (55.6%) of them died by multi organ failure. Among the 1656 patients without ACS, 328 died (19.8%). The mortality odds ratio meta-analysis was 6.25 with a 95% confidence interval of [4.44, 8.80]. Decompressive laparotomy was performed in 41 patients, decreasing mortality in 47%., Conclusions: ACS affects approximately 9% of patients submitted to r-EVAR, and significantly increases perioperative mortality. Close postoperative surveillance to clinical signs of ACS is vital in these patients.

Introduction: A paradoxical negative association between diabetes mellitus and abdominal aortic aneurysm (AAA) prevalence and growth is established. However, so far is not possible to determine whether this protection comes from the disease itself or the medication for Diabetes. The aim of this manuscript is to review the association between oral antidiabetic drugs and AAA incidence and growth., Evidence Acquisition: A search was conducted on PubMed and Scopus databases until December 2019 to identify publications reporting on the association between oral antidiabetic drugs (biguanides/metformin, sulfonylureas(SU), thiazolidinediones(TZD), dipeptidyl-peptidase 4(DPP-4) inhibitors, glucagon-like peptide 1(GLP-1) agonists, sodium-glucose transporter protein-2(SGLT2) inhibitors) and the outcomes AAA incidence and growth. Only data from human studies were considered, with a minimum of 3 months follow-up., Evidence Synthesis: Six studies enrolling 25,810 patients were included: one reporting on the AAA risk and five reporting on AAA growth. Metformin prescription was associated with a 28% reduction in AAA occurrence, while SU and TZD were associated with a 18% decrease in AAA risk. Regarding AAA enlargement, results were concordant for a slower expansion rate associated with metformin, with a decrease ranging from -0.30 mm/y to -1.30 mm/y, but not consistent for other antidiabetic drugs., Conclusions: Metformin seems to be associated with a decrease in AAA risk and enlargement rate. Evidence for the other classes is lacking. Studies evaluating the association between oral antidiabetic drugs and AAA progression, independently of the diabetic status, are needed.

Background: This study aims to evaluate the incidence of myocardial injury after non-cardiac surgery for an extensive disease pattern (TASC II type D) and to examine its prognostic value., Methods: This prospective study included a total of 66 consecutive patients (62 males, 4 females; mean age 62.5±8.2 years) who underwent elective revascularization for aortoiliac TASC II type D lesions in the tertiary setting between January 2013 and March 2019. The patients were scheduled for revascularization either by open surgery or endovascular approach. Cardiac troponins were routinely measured in the postoperative period. Myocardial injury after non-cardiac surgery was defined as the elevation of cardiac troponin for at least one value above the 99th percentile upper reference limit. Myocardial infarction, acute heart failure, stroke, major adverse cardiovascular events, major adverse limb events, and all-cause mortality were assessed both postoperatively and during follow-up., Results: The incidence of myocardial injury after non-cardiac surgery was 25.8%. In the multivariate analysis, chronic heart failure was found to be a significant risk factor for myocardial injury after non-cardiac surgery (odds ratio: 10.3; 95% confidence interval 1.00-106.8, p=0.018). At 12 months after revascularization, the diagnosis of myocardial injury after non-cardiac surgery was significantly associated with myocardial infarction, stroke, major adverse cardiovascular events, major adverse limb events, and all-cause mortality. At 12 months after revascularization, the diagnosis of myocardial injury after non-cardiac surgery was significantly associated with myocardial infarction (log-rank p=0.002), stroke (log-rank p=0.007), major adverse cardiovascular events (log-rank p=0.000), major adverse limb events (log-rank p=0.007), and all-causemortality (log-rank p=0.000)., Conclusion: Our study results suggest that myocardial injury after non-cardiac surgery plays a role as a predictor of significant cardiovascular comorbidities and mortality after complex aortoiliac revascularization. The presence of chronic heart failure is also associated with a higher incidence of myocardial injury after aortoiliac TASC II type D revascularization. Therefore, preemptive strategies should be adopted to identify and treat these patients., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2020, Turkish Society of Cardiovascular Surgery.)

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 cm 3 ). 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 freedom from AAA related complications was 79%, 66%, 58% and 56%, respectively (p = .007). At five years, freedom from neck related events was 86%, 84%, 73%, and 71%, respectively, for the four groups (p = .009), and freedom from iliac related events was 96%, 91%, 88%, and 88%, respectively (p = .335). On multivariable analysis, luminal volume was an independent predictor of late complications (Q4 vs. Q1 - hazard ratio: 1.91, 95% confidence interval 1.01-3.6, p = .046). Overall survival at five years was not affected by lumen volume (p = .75)., Conclusion: AAA luminal volume represents an important risk factor for AAA related complications. This information may be considered when deciding tailoring surveillance protocols after EVAR. However, larger studies are needed to validate this hypothesis., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

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 outside the IFU are at greater risk for late complications. Surveillance protocols may be tailored according to individual anatomy and IFU compliance rather than timing of repair., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Many endografts are currently available for standard endovascular repair of infrarenal abdominal aortic aneurysms. Comparison of long-term outcomes between devices might aid in this decision process, but comparative data are scarce. The purpose of this study was to report long-term clinical outcomes of two commercially available endoprosthesis, the Endurant (Medtronic Vascular, Inc, Minneapolis, Minn) and the Excluder (W. L. Gore & Associates, Flagstaff, Ariz) stent grafts., Methods: Patients undergoing standard endovascular repair from July 2004 to December 2011 in a single institution with the Endurant or the Low-Porosity Excluder endografts were eligible. Only patients treated for intact degenerative abdominal infrarenal aneurysms were included. All measurements were performed on center-lumen line reconstructions obtained on dedicated software. The primary end point was primary clinical success, defined as clinical success without the need for an additional or secondary surgical or endovascular procedure. Neck-related events (a composite of type IA endoleak, neck-related secondary intervention, or migration of >5 mm), neck morphology changes, renal function, and overall survival were secondary end points., Results: The study included 277 patients (156 Endurants; 121 Excluders). The median follow-up was 5.8 years (range, 0.1-12.4 years) and did not differ between groups (P = .18). Patients treated with the Endurant stent graft had wider (neck diameter of >28 mm, 27.3% vs 1.7% [P < .001]; neck diameter of 27 mm, [interquartile range (IQR), 24-29 mm] for Endurant and 24 mm [IQR, 22-25 mm] for Excluder; P < .001) and more angulated necks (β-angle of >60°, 26.7% vs 12.5%; P = .004). Oversizing was greater in the Endurant group (16% [IQR, 12%-22%] vs 13% [IQR, 8%-17%], respectively; P < .001). Patients were treated outside device instructions for use regarding proximal neck: 16.7% in the Endurant and 17.3% in the Excluder group (P = .720). The 7-year primary clinical success was 54.7% for the Endurant and 58.1% for the Excluder groups (P = .53). Freedom from neck-related events at 7 years was 76.7% for the Endurant and 78.8% for Excluder group (P = .94). The Endurant stent graft (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.3-5.8; P = .009) was an independent predictor of significant renal function decline. Neck dilatation was greater in Endurant-implanted patients (13% [95% CI, 2%-22%] vs 4% [95% CI, 0%-10%]; P < .001). Overall survival at 7 years was 61.4% in the Endurant and 50.3% (n = 50; standard error, 0.047) in the Excluder group (P = .39)., Conclusions: This study reveals that durable and sustainable results can be obtained with either of these late generation devices. This finding suggests that careful planning and a tailored device selection taking into account the patient's anatomy are more relevant determinants than the graft model itself to obtain clinical success. The Endurant endoprosthesis seems to be associated with a higher rate of neck dilatation and faster decrease in the estimated glomerular filtration rate, but further studies with longer follow-up are necessary to determine the clinical relevance of these findings., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: The feasibility of endovascular aneurysm repair (EVAR) is often challenged by the concurrent presence of common iliac artery aneurysms, which prevent the attainment of a successful distal sealing. The present review aims to portray the safety and efficacy of two internal iliac artery (IIA) preservation strategies in the endovascular treatment of aortoiliac aneurysms: the iliac branch extension device (IBED) and the parallel graft - "sandwich" technique (PG-ST)., Evidence Acquisition: A comprehensive literature review was conducted to identify publications on endovascular treatment of iliac aneurysmal disease using IBED or PG-ST. Primary endpoints were freedom from endoleak, IIA branch occlusion and secondary interventions., Evidence Synthesis: Twenty-eight studies were selected for analysis describing a total of 1316 patients, 1169 in the IBED group and 147 in the PG-ST group. The technical success rates were akin for IBED and PG-ST (83.9-100% versus 81.3-100%). The defined primary endpoints were reported by fourteen articles. Freedom from endoleak, IIA branch occlusion and reintervention, at 6 months, were as follows: 82-100% versus 86%, 90-94% versus 88%, and 90-98% versus 87%, respectively for IBED and PG-ST. Later outcomes were only recorded in the IBED group, and freedom from endoleak, IIA branch occlusion and reintervention, at 9 years, were 83%, 81-90%, and 64-75%, respectively., Conclusions: Both IBED and PG-ST have proven to be safe and valid approaches. However, while IBED has established as a durable procedure, mid-term data lacks on PGs performance and further studies are required to attest durability of the latter procedure.

Introduction: Thoracic endovascular aortic repair (TEVAR) has been increasingly adopted in the treatment of intact thoracic aorta aneurysms (iTAA), offering a less invasive approach with good effectiveness. Women usually present with smaller aortas, while having greater aneurysm growth rates. How sex can affect mortality and re-interventions after TEVAR for iTAA is the aim of this review., Evidence Acquisition: A search was conducted on PubMed databases to identify studies with gender-specific data on outcomes after TEVAR for iTAA. Primary endpoints were 30-day (or in-hospital) and mid-term mortality. Secondary endpoints were 30-day and mid-term secondary interventions., Evidence Synthesis: Nine studies were included with a total of 4484 patients (2707 men and 1777 women). Thirty-day mortality ranged from 0% to 6% in female and from 1.1% to 5.3% for male patients. Three studies reported gender-specific mortality one year after TEVAR, ranging from 12% to 15.2% for female and from 8% to 16.8% in male patients. Six studies were found describing gender-related secondary intervention data., Conclusions: Mortality after TEVAR for iTAA seems to be similar between genders. While there was a tendency for higher mortality in women, specially at 30-days, statistically significant differences were reported in only two studies. Re-interventions rates were higher in men in 4 of 6 studies, probably due to increased rates of endoleak in men, but no statically significant difference was found. Further studies with larger female population and longer follow-up are needed to firmly confirm differences among genders.

Introduction: Endovascular aneurysm repair (EVAR) became the preferred modality for abdominal aortic aneurysm (AAA) repair. However, long term survival benefit may sometimes be questionable as many patients would die from other causes rather than aneurysm rupture. It is paramount to identify critical risk factors for late mortality after EVAR to understand its real benefit. The aim of this review is to identify most clinically relevant determinants of late mortality after elective EVAR., Evidence Acquisition: English literature was searched to identify publications on long-term predictors of mortality following elective EVAR. A follow-up extending for at least 5 years was the minimum required as inclusion criteria. Primary endpoint was all-cause mortality. We addressed clinical and demographic variables and observe if they had any associations with long-term all-cause mortality following EVAR., Evidence Synthesis: Twelve studies were included describing more than 82306 patients, exploring at least one predictor of long-term mortality. All-cause mortality was associated to age (Hazard ratio [HR] 1.06-3.34), gender (HR: 1.07), aneurysm diameter (HR: 1.09-1.64), smoking habits (HR: 1.51-1.73), heart failure (HR: 1.60-7.34), ischemic heart disease (HR: 1.60), peripheral vascular disease (HR: 1.30), cerebrovascular disease (HR: 1.55), diabetes mellitus (HR: 6.35), chronic obstructive pulmonary disease (HR: 1.50-2.06) and chronic renal disease (HR: 1.90-3.08)., Conclusions: Risk factors associated with long-term mortality following elective EVAR remain scarcely published. Several demographic, anatomical, cardiovascular, pulmonary and renal comorbidities seem to have an association with long-term mortality. Critical scrutiny of clinical patient status remains fundamental for a fair health resources allocation.

Introduction: Endovascular aneurysm repair for ruptured abdominal aortic aneurysm has been increasingly advocated due to short term benefits. Most observational studies point towards survival advantage for endovascular aneurysm repair over open repair. However, randomized clinical trials already performed did not support this data. The aim of this review is to compare post-operative outcomes between endovascular aneurysm repair and open surgery for the treatment of ruptured abdominal aortic aneurysms., Materials and Methods: MEDLINE databases were searched to access outcomes after endovascular aneurysm repair for ruptured abdominal aortic aneurysm and open repair for ruptured abdominal aneurysm repair. All the randomized controlled trials were included. Large and contemporary observational studies were also considered., Results: Thirty day mortality ranged between 18% - 53% for endovascular aneurysm repair for ruptured abdominal aortic aneurysm and between 24% - 53% for open repair. Post-operative complications ranged between 33% - 77% for endovascular aneurysm repair for ruptured abdominal aortic aneurysm and 37% - 80% for open repair. In hospital stay ranged between 8.5 and 14.3 days for endovascular aneurysm repair for ruptured abdominal aortic aneurysm and between 12.2 and 20.5 days for open repair. Intensive care unit days ranged between 1.75 - 4.2 days for endovascular aneurysm repair for ruptured abdominal aortic aneurysm and 2.5 - 6.3 days for open repair., Discussion: Survival benefit is found for endovascular aneurysm repair for ruptured abdominal aortic aneurysm in most observational studies, but those are not reproduced by randomized controlled trials data. However, endovascular aneurysm repair for ruptured abdominal aortic aneurysm showed less post-operative complications and hospitalization days., Conclusion: Endovascular aneurysm repair for ruptured abdominal aortic aneurysm should be considered as first line of treatment in centers with expertise and proper facilities.

Vascular procedures in general, and specifically abdominal aortic aneurysm (AAA) repair, are associated with worse outcomes in female patients. However, how female gender influences outcomes in the setting of aneurysm-rupture remains unclear and may be even more pronounced when compared to elective operations. In this report, the authors aim to review the literature regarding ruptured AAA repair in women. Using the traditional threshold for AAA of 30 mm of maximum diameter, the prevalence in women is lesser than in men. However, the true prevalence may be underestimated due to gender discrepancies in normal aortic diameter. For females, aneurysmal disease seems to manifest later, have more associated comorbidities, and rupture occurs at smaller aortic diameters. This has obvious implications for management. There is still no consensus over the optimal treatment for ruptured AAA in women. They are less frequently treated by endovascular aneurysm repair, possibly due to anatomical restrains. When feasible, endovascular repair shows better outcomes, at least in the short-term, and there is new evidence suggesting a lasting benefit as well. For open repair the results are consensually worse when compared to male counterparts. Finally, despite benefitting of apparently similar healthcare, women have a lower relative survival after rAAA repair when compared to men. Further investigation to determine the reasons of these discrepancies is warranted.

Supersaturating drug delivery systems (SDDS), as solid dispersions (SDs), stand out among strategies to enhance bioavailability of poorly soluble drugs. After oral administration, their dissolution in gastrointestinal fluids often leads to supersaturation, which drives to a rapid and sustained absorption. Polymers and surfactants play important roles in SDs through inhibiting precipitation caused by transitions from amorphous into crystalline form, in supersaturated solutions, and also through improving SDs physical stability. Novel chlorthalidone SDs, a BCS IV drug, were developed using polymeric and non-polymeric carriers, specially a polymer-surfactant complex. SDs drug releases were evaluated using sink and non-sink conditions in water and biorelevant medium. Their physical stability was also monitored under different storage conditions. Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SOL), sodium lauryl sulfate (SLS) and a combination of both showed promising results in apparent solubility studies, and therefore they were selected to compose the spray dried SDs. Dissolution studies demonstrated the SOL-SLS complex potential for providing chlorthalidone fast release (>80% in 15min), producing and maintaining in vitro supersaturation. This formulation comprising high drug loading (75%) reached a high supersaturation degree under non-sink condition (up to 6-fold the equilibrium solubility) once maintained for 6h in biorelevant medium. In addition, this SD presented better physical stability when compared to the chlorthalidone neat amorphous. The SOL-SLS complex impacts positively on chlorthalidone release and physical stability, highlighting its potential as carrier in SDDS of a poorly soluble drug., (Copyright © 2017. Published by Elsevier B.V.)

The choice of inodilator drug in the acute management of patients with pulmonary hypertension (PH) having right ventricular (RV) failure remains unsettled and challenging. Comprehensive experimental evaluations may provide further insight and fundamental translational research clues to support inodilator selection and clinical trial design. Our aim was to compare acute dose-response hemodynamic effects of inodilators dobutamine (DOB), milrinone (MIL), and levosimendan (LEV) in chronic experimental PH. Seven-week-old male Wistar rats were randomly injected with 60 mg·kg -1 monocrotaline (MCT) or vehicle (Ctrl, n = 7) and underwent systemic and pulmonary artery (PA) pressure and RV pressure-volume (PV) hemodynamic evaluation under halogenate anesthesia 24 to 30 days after injection. The MCT-injected animals (n = 7 each) randomly received dose-response infusions of DOB (1, 3, 6 and 12 μg·kg -1 ·min -1 ), MIL (MIL: 1, 3, 6 and 12 μg·kg -1 ·min -1 ), or LEV (0.3, 0.6, 1.2 and 2.4 μg·kg -1 ·min -1 ). Load-independent indexes were obtained by inferior vena cava occlusion at baseline and after the last dose. All inodilators increased RV ejection fraction, preload recruitable stroke work, and ventricular-vascular coupling without jeopardizing perfusion pressure. Dobutamine raised heart rate and PA pressure. Only LEV increased cardiac index and decreased PA elastance and pulmonary vascular resistance (PVR). Moreover, only LEV downward-shifted the end-diastolic PV relationship, thereby improving RV compliance. Adding sildenafil to LEV further decreased PVR. Levosimendan had beneficial acute systolic and diastolic functional effects in experimental chronic PH and RV afterload compared to DOB and MIL. It should be further tested in clinical trials enrolling patients with PH in the perioperative and critical care settings.

Introduction: The suitability of the proximal and distal landing zones remains one of the main limitations to thoracic endovascular aortic repair. The advent of custom-made scalloped stent grafts widened the endovascular options in some challenging anatomies., Methods: The authors present three cases of thoracic aortic aneurysm (TAA), with three different hostile anatomies, successfully treated with custom-made scalloped stent grafts., Results: Case1: Male patient, 47 years old, no relevant medical history. Angio-CT revealed a 54mm post- traumatic TAA, extending distally from the origin of the left subclavian artery. Inadequate sealing in Ishimaru zone 2 was evident. The patient was sequentially treated by means of a carotid-subclavian bypass followed by TEVAR with proximal scallop to the left common carotid artery. Proper proximal sealing was obtained. Case2: Male patient, 76 years old, diagnosed with a 65mm diameter TAA, involving the origin of the left subclavian artery. Presence of a bovine trunk, and inadequate landing zone distally to it, were noted. The patient was sequentially treated by means of a carotid-subclavian bypass followed by TEVAR with proximal scallop to the bovine trunk. Proper sealing in Ishimaru zone 2 was granted. Case3: Male patient, 77 years old, multiple comorbidities. Angio-CT revealed a 59,3mm saccular aneurysm of the distal thoracic descending aorta, extending proximally from the origin of the celiac trunk. Good collateralization was observed after celiac trunk occlusion test. Proper distal seal was obtained by means of selective embolization of the celiac trunk followed by TEVAR with distal scallop to the superior mesenteric artery. All procedures were uneventful, with no reported endoleaks, birdbeaks, migrations or re- interventions. There are no reported complications at 1-year follow-up., Conclusion: Custom-made scalloped thoracic stentgrafts are an accessible, reproducible and safe therapeutic option when dealing with hostile descending thoracic anatomies, and should be considered as a minimally-invasive effective solution in selected cases.

Introduction: Endovascular aneurysm repair (EVAR) has progressively expanded to more complex anatomies, frequently outside manufacturer's instructions for use (IFU). However, the long term results of off-label use of EVAR remain largely undocumented. The aim of this paper is to examine the long term results of outside IFU EVAR., Evidence Acquisition: English literature was searched to identify publications on long term results for outside IFU EVAR. A follow-up extending for at least 5 years was the minimum required as inclusion criteria. The outcomes measured were: overall mortality, aneurysm-related mortality (ARM), freedom from postimplant aneurysm rupture, aneurysm sac enlargement, type I endoleaks and secondary interventions. Results were compared to randomized clinical trials (RCTs) with long term results published (EVAR-1, DREAM, OVER and ACE Trial)., Evidence Synthesis: Thirteen studies were included. 7 studies described outcomes associated to a specific breached IFU, while 6 studies presented general outside IFU results. In patients outside IFU, 3 to 8 years estimates of overall mortality ranged from 21.5% to 40% (RCTs:13.7-46%) and ARM from 0-11% (RCTs: 1.2-7%). Five-year estimates of sac enlargement was approximately 43%. Type I endoleak rates for outside IFU (follow-up 5-12 years) ranged from 3.8-15%, which is higher than found in RCT-derived data (6.6-6.9%). Comparable results are seen for postimplant rupture and secondary interventions., Conclusions: The long term results of off-label use of EVAR are scarcely published. Although overall mortality and ARM does not seem to differ significantly at long-term, higher rates of type I endoleaks may be expected, mainly in short necks. However, for patients with severe angulation or high thrombus load in the proximal neck, results of outside IFU EVAR seem to match the results of inside IFU.

Recent studies suggest right ventricular (RV) stiffness is important in pulmonary hypertension (PH) prognosis. Smaller stroke volume (SV) variation after a certain RV end-diastolic pressure (EDP) respiratory variation as assessed by spectral transfer function (STF) may identify RV stiffness. Our aim was to evaluate RV stiffness in monocrotaline (MCT)-induced PH progression and to validate STF gain between EDP and SV as marker of stiffness. Seven-week-old male Wistar rats randomly injected with 60 mg/kg MCT or vehicle were divided into three groups (n = 12 each) according to cardiac index (CI): controls (Ctrl), preserved CI (MCT pCI), and reduced CI (MCT rCI). All underwent RV pressure-volume (PV) evaluation 24-34 days after MCT, under halogenate anesthesia and constant positive-pressure ventilation. End-diastolic stiffness (β i ), end-systolic elastance (Ees i ), arterial elastance for indexed volumes (Ea i ), and preload recruitable stroke work (PRSW) were obtained and beat-to-beat fluctuations during ventilation assessed by STF. Ea i was the strongest determinant of CI, alongside β i but not PRSW. MCT rCI showed impaired ventricular-vascular coupling (VVC) and higher β i , along with low end-diastolic pressure (EDP) and stroke volume index (SV i ) STF gain, denoting impaired preload reserve. On multivariate analysis β i and not Ees i correlated with EDP-SV i STF gain (P < 0.001). Receiver-operating characteristics (ROC) curve analysis of EDP-SV i STF gain showed an area under curve of 0.84 for β i prediction (P = 0.002). Afterload, impaired VVC and RV stiffness are major players in RV failure. RV stiffness can be assessed by STF gain analysis of respiratory fluctuations between EDP and SV i , which may constitute a prognostic tool in PH., (Copyright © 2016 the American Physiological Society.)

Preserved ejection fraction heart failure (HFpEF) diagnosis remains controversial, and invasive left ventricular (LV) hemodynamic evaluation and/or exercise testing is advocated by many. The stiffer HFpEF myocardium may show impaired stroke volume (SV) variation induced by fluctuating LV filling pressure during ventilation. Our aim was to investigate spectral transfer function (STF) gain from end-diastolic pressure (EDP) to indexed SV (SVi) in experimental HFpEF. Eighteen-week-old Wistar-Kyoto (WKY) and ZSF1 lean (ZSF1 Ln) and obese rats (ZSF1 Ob) randomly underwent LV open-chest (OC, n = 8 each group) or closed-chest hemodynamic evaluation (CC, n = 6 each group) under halogenate anesthesia and positive-pressure ventilation at constant inspiratory pressure. Beat-to-beat fluctuations in hemodynamic parameters during ventilation were assessed by STF. End-diastolic stiffness (βi) and end-systolic elastance (Eesi) for indexed volumes were obtained by inferior vena cava occlusion in OC (multibeat) or single-beat method estimates in CC. ZSF1 Ob showed higher EDP spectrum (P < 0.001), higher STF gain between end-diastolic volume and EDP, and impaired STF gain between EDP and SVi compared with both hypertensive ZSF1 Ln and normotensive WKY controls (P < 0.001). Likewise βi was only higher in ZSF1 Ob while Eesi was raised in both ZSF1 groups. On multivariate analysis βi and not Eesi correlated with impaired STF gain from EDP to SVi (P < 0.001), and receiver-operating characteristics analysis showed an area under curve of 0.89 for higher βi prediction (P < 0.001). Results support further clinical testing of STF analysis from right heart catheterization-derived EDP surrogates to noninvasively determined SV as screening/diagnostic tool to assess myocardial stiffness in HFpEF., (Copyright © 2016 the American Physiological Society.)

Myocardial stiffness and upward-shifted end-diastolic pressure-volume (P-V) relationship (EDPVR) are the key to high filling pressures in heart failure with preserved ejection fraction (HFpEF). Nevertheless, many patients may remain asymptomatic unless hemodynamic stress is imposed on the myocardium. Whether delayed relaxation induced by pressure challenge may contribute to high end-diastolic pressure (EDP) remains unsettled. Our aim was to assess the effect of suddenly imposed isovolumic afterload on relaxation and EDP, exploiting a highly controlled P-V experimental evaluation setup in the ZSF1 obese rat (ZSF1 Ob) model of HFpEF. Twenty-week-old ZSF1 Ob (n = 12), healthy Wistar-Kyoto rats (WKY, n = 11), and hypertensive ZSF1 lean control rats (ZSF1 Ln, n = 10) underwent open-thorax left ventricular (LV) P-V hemodynamic evaluation under anesthesia with sevoflurane. EDPVR was obtained by inferior vena cava occlusions to assess LV ED chamber stiffness constant β, and single-beat isovolumic afterload acquisitions were obtained by swift occlusions of the ascending aorta. ZSF1 Ob showed increased ED stiffness, delayed relaxation, as assessed by time constant of isovolumic relaxation (τ), and elevated EDP with normal ejection fraction. Isovolumic afterload increased EDP without concomitant changes in ED volume or heart rate. In isovolumic beats, relaxation was delayed to the extent that time for complete relaxation as predicted by 3.5 × monoexponentially derived τ (τexp) exceeded effective filling time. EDP elevation correlated with reduced time available to relax, which was the only independent predictor of EDP rise in multiple linear regression. Our results suggest that delayed relaxation during pressure challenge is an important contributor to lung congestion and effort intolerance in HFpEF., (Copyright © 2015 the American Physiological Society.)

Both NMDA receptor blockade and GABAA receptor overactivation during the brain growth spurt may contribute to the hyperactivity phenotype reminiscent of attention-deficit/hyperactivity disorder. Here, we evaluated the effects of exposure to MK801 (a NMDA antagonist) and/or to muscimol (a GABAA agonist) during the brain growth spurt on locomotor activity of juvenile Swiss mice. This study was carried out in two separate experiments. In the first experiment, pups received a single i.p. injection of either saline solution (SAL), MK801 (MK, 0.1, 0.3 or 0.5 mg/kg) or muscimol (MU, 0.02, 0.1 or 0.5 mg/kg) at the second postnatal day (PND2), and PNDs 4, 6 and 8. In the second experiment, we investigated the effects of a combined injection of MK (0.1 mg/kg) and MU (doses: 0.02, 0.1 or 0.5 mg/kg) following the same injection schedule of the first experiment. In both experiments, locomotor activity was assessed for 15 min at PND25. While MK promoted a dose-dependent increase in locomotor activity, exposure to MU failed to elicit significant effects. The combined exposure to the highest dose of MU and the lowest dose of MK induced marked hyperactivity. Moreover, the combination of the low dose of MK and the high dose of MU resulted in a reduced activity in the center of the open field, suggesting an increased anxiety-like behavior. These findings suggest that, during the brain growth spurt, the blockade of NMDA receptors induces juvenile locomotor hyperactivity whereas hyperactivation of GABAA receptors does not. However, GABAA overactivation during this period potentiates the effects of NMDA blockade in inducing locomotor hyperactivity., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Inclusion of exercise testing in diagnostic guidelines for heart failure with preserved ejection fraction (HFpEF) has been advocated, but the target population, technical challenges, and underlying pathophysiological complexity raise difficulties to implementation. Hemodynamic stress tests may be feasible alternatives. Our aim was to test Trendelenburg positioning, phenylephrine, and dobutamine in the ZSF1 obese rat model to find echocardiographic surrogates for end-diastolic pressure (EDP) elevation and HFpEF. Seventeen-week-old Wistar-Kyoto, ZSF1 lean, and obese rats (n = 7 each) randomly and sequentially underwent (crossover) Trendelenburg (30°), 5 μg·Kg(-1)·min(-1) dobutamine, and 7.5 μg·Kg(-1)·min(-1) phenylephrine with simultaneous left ventricular (LV) pressure-volume loop and echocardiography evaluation under halogenate anesthesia. Effort testing with maximum O2 consumption (V̇o 2 max) determination was performed 1 wk later. Obese ZSF1 showed lower effort tolerance and V̇o 2 max along with higher resting EDP. Both Trendelenburg and phenylephrine increased EDP, whereas dobutamine decreased it. Significant correlations were found between EDP and 1) peak early filling Doppler velocity of transmitral flow (E) to corresponding myocardial tissue Doppler velocity (E') ratio, 2) E to E-wave deceleration time (E/DT) ratio, and 3) left atrial area (LAA). Diagnostic efficiency of E/DT*LAA by receiver-operating characteristic curve analysis for elevation of EDP above a cut-off of 13 mmHg during hemodynamic stress was high (area under curve, AUC = 0.95) but not higher than that of E/E' (AUC = 0.77, P = 0.15). Results in ZSF1 obese rats suggest that noninvasive echocardiography after hemodynamic stress induced by phenylephrine or Trendelenburg can enhance diagnosis of stable HFpEF and constitute an alternative to effort testing., (Copyright © 2015 the American Physiological Society.)

Levosimendan is a pyridazinone-dinitrile derivative with positive inotropic and vasodilatory effects that has beneficial effects on myocardial performance. In previous randomized studies levosimendan improved hemodynamics and clinical course, but its effect on prognosis is still unclear. This important issue has limited its use. Although primarily used in the management of acute heart failure syndromes, this new inotropic agent may play a role in other clinical conditions. This review aims to summarize current knowledge on levosimendan and to present future prospects for the use of this drug., (Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.)