Methods, design, and initial results of an angiographic core lab from VOYAGER-PAD.

Background: Anatomy is critical in risk stratification and therapeutic decision making in coronary disease. The relationship between anatomy and outcomes is not well described in PAD. We sought to develop an angiographic core lab within the VOYAGER-PAD trial. The current report describes the methods of creating this core lab, its study population, and baseline anatomic variables. Methods: Patients undergoing lower-extremity revascularization for symptomatic PAD were randomized in VOYAGER-PAD. The median follow up was 2.25 years. Events were adjudicated by a blinded Clinical Endpoint Committee. Angiograms were collected from study participants; those with available angiograms formed this core lab cohort. Angiograms were scored for anatomic and flow characteristics by trained reviewers blinded to treatment. Ten percent of angiograms were evaluated independently by two reviewers; inter-rater agreement was assessed. Clinical characteristics and the treatment effect of rivaroxaban were compared between the core lab cohort and noncore lab participants. Anatomic data by segment were analyzed. Results: Of 6564 participants randomized in VOYAGER-PAD, catheter-based angiograms from 1666 patients were obtained for this core lab. Anatomic and flow characteristics were collected across 16 anatomic segments by 15 reviewers. Concordance between reviewers for anatomic and flow variables across segments was 90.5% (24,417/26,968). Clinical characteristics were similar between patients in the core lab and those not included. The effect of rivaroxaban on the primary efficacy and safety outcomes was also similar. Conclusions: The VOYAGER-PAD angiographic core lab provides an opportunity to correlate PAD anatomy with independently adjudicated outcomes and provide insights into therapy for PAD. (ClinicalTrials.gov Identifier: NCT02504216).

Rivaroxaban in Peripheral Artery Disease after Revascularization.

BACKGROUND: Patients with peripheral artery disease who have undergone lower-extremity revascularization are at high risk for major adverse limb and cardiovascular events. The efficacy and safety of rivaroxaban in this context are uncertain. METHODS: In a double-blind trial, patients with peripheral artery disease who had undergone revascularization were randomly assigned to receive rivaroxaban (2.5 mg twice daily) plus aspirin or placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes. The principal safety outcome was major bleeding, defined according to the Thrombolysis in Myocardial Infarction (TIMI) classification; major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH) was a secondary safety outcome. RESULTS: A total of 6564 patients underwent randomization; 3286 were assigned to the rivaroxaban group, and 3278 were assigned to the placebo group. The primary efficacy outcome occurred in 508 patients in the rivaroxaban group and in 584 in the placebo group; the Kaplan-Meier estimates of the incidence at 3 years were 17.3% and 19.9%, respectively (hazard ratio, 0.85, 95% confidence interval [CI], 0.76 to 0.96; P = 0.009). TIMI major bleeding occurred in 62 patients in the rivaroxaban group and in 44 patients in the placebo group (2.65% and 1.87%; hazard ratio, 1.43; 95% CI, 0.97 to 2.10; P = 0.07). ISTH major bleeding occurred in 140 patients in the rivaroxaban group, as compared with 100 patients in the placebo group (5.94% and 4.06%; hazard ratio, 1.42; 95% CI, 1.10 to 1.84; P = 0.007). CONCLUSIONS: In patients with peripheral artery disease who had undergone lower-extremity revascularization, rivaroxaban at a dose of 2.5 mg twice daily plus aspirin was associated with a significantly lower incidence of the composite outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes than aspirin alone. The incidence of TIMI major bleeding did not differ significantly between the groups. The incidence of ISTH major bleeding was significantly higher with rivaroxaban and aspirin than with aspirin alone. (Funded by Bayer and Janssen Pharmaceuticals; VOYAGER PAD ClinicalTrials.gov number, NCT02504216.).

Reduction in Acute Limb Ischemia With Rivaroxaban Versus Placebo in Peripheral Artery Disease After Lower Extremity Revascularization: Insights From VOYAGER PAD.

BACKGROUND: Patients with peripheral artery disease (PAD) are at heightened risk of acute limb ischemia (ALI), a thrombotic event associated with amputation, disability, and mortality. Previous lower extremity revascularization (LER) is associated with increased ALI risk in chronic PAD. However, the pattern of risk, clinical correlates, and outcomes after ALI early after LER are not well-studied, and effective therapies to reduce ALI post-LER are lacking. METHODS: The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD; rNCT02504216) randomized patients with PAD undergoing LER to rivaroxaban 2.5 mg twice daily or placebo on a background of low-dose aspirin. The primary outcome was a composite of ALI, major amputation of vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. ALI was prospectively ascertained and adjudicated by a blinded committee. The cumulative incidence of ALI was calculated using Kaplan-Meier estimates, and Cox proportional hazards models were used to generate hazard ratios and associated CIs. Analyses were performed as intention-to-treat. RESULTS: Among 6564 patients followed for a median of 2.3 years, 382 (5.8%) had a total of 508 ALI events. In placebo patients, the 3-year cumulative incidence of ALI was 7.8%. After multivariable modeling, previous LER, baseline ankle-brachial index <0.50, surgical LER, and longer target lesion length were associated with increased risk of ALI. Incident ALI was associated with subsequent all-cause mortality (hazard ratio [HR], 2.59 [95% CI, 1.98-3.39]) and major amputation (HR, 24.87 [95% CI, 18.68-33.12]). Rivaroxaban reduced ALI relative to placebo by 33% (absolute risk reduction, 2.6% at 3 years; HR, 0.67 [95% CI, 0.55-0.82]; P=0.0001), with benefit starting early (HR, 0.45 [95% CI, 0.24-0.85]; P=0.0068 at 30 days). Benefit was present for severe ALI (associated with death, amputation, or prolonged hospitalization and intensive care unit stay, HR, 0.58 [95% CI, 0.40-0.83]; P=0.003) and regardless of LER type (surgical versus endovascular revascularization, P interaction=0.42) or clopidogrel use (P interaction=0.59). CONCLUSIONS: After LER for symptomatic PAD, ALI is frequent, particularly early after LER, and is associated with poor prognosis. Low-dose rivaroxaban plus aspirin reduces ALI after LER, including ALI events associated with the most severe outcomes. The benefit of rivaroxaban for ALI appears early, continues over time, and is consistent regardless of revascularization approach or clopidogrel use.

Effect of Rivaroxaban and Aspirin in Patients With Peripheral Artery Disease Undergoing Surgical Revascularization: Insights From the VOYAGER PAD Trial.

BACKGROUND: Patients with peripheral artery disease requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. The VOYAGER PAD trial (Vascular Outcomes Study of ASA [Acetylsalicylic Acid] Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) demonstrated that rivaroxaban significantly reduced this risk. The efficacy and safety of rivaroxaban has not been described in patients who underwent surgical LER. METHODS: The VOYAGER PAD trial randomized patients with peripheral artery disease after surgical and endovascular LER to rivaroxaban 2.5 mg twice daily plus aspirin or matching placebo plus aspirin and followed for a median of 28 months. The primary end point was a composite of acute limb ischemia, major vascular amputation, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction major bleeding. International Society on Thrombosis and Haemostasis bleeding was a secondary safety outcome. All efficacy and safety outcomes were adjudicated by a blinded independent committee. RESULTS: Of the 6564 randomized, 2185 (33%) underwent surgical LER and 4379 (67%) endovascular. Compared with placebo, rivaroxaban reduced the primary end point consistently regardless of LER method (P-interaction, 0.43). After surgical LER, the primary efficacy outcome occurred in 199 (18.4%) patients in the rivaroxaban group and 242 (22.0%) patients in the placebo group with a cumulative incidence at 3 years of 19.7% and 23.9%, respectively (hazard ratio, 0.81 [95% CI, 0.67-0.98]; P=0.026). In the overall trial, Thrombolysis in Myocardial Infarction major bleeding and International Society on Thrombosis and Haemostasis major bleeding were increased with rivaroxaban. There was no heterogeneity for Thrombolysis in Myocardial Infarction major bleeding (P-interaction, 0.17) or International Society on Thrombosis and Haemostasis major bleeding (P-interaction, 0.73) on the basis of the LER approach. After surgical LER, the principal safety outcome occurred in 11 (1.0%) patients in the rivaroxaban group and 13 (1.2%) patients in the placebo group; 3-year cumulative incidence was 1.3% and 1.4%, respectively (hazard ratio, 0.88 [95% CI, 0.39-1.95]; P=0.75) Among surgical patients, the composite of fatal bleeding or intracranial hemorrhage (P=0.95) and postprocedural bleeding requiring intervention (P=0.93) was not significantly increased. CONCLUSIONS: The efficacy of rivaroxaban is associated with a benefit in patients who underwent surgical LER. Although bleeding was increased with rivaroxaban plus aspirin, the incidence was low, with no significant increase in fatal bleeding, intracranial hemorrhage, or postprocedural bleeds requiring intervention. Registration: URL: http://www.clinicaltrials.gov; Unique Identifier: NCT02504216.

Early outcomes of t-Branch off-the-shelf multibranched stent graft in urgent and emergent repair of thoracoabdominal aortic aneurysms.

OBJECTIVE: We compared the outcomes between elective, urgent, and emergent treatment of thoracoabdominal aortic aneurysms (TAAAs) using the t-Branch off-the-shelf multibranched stent graft (Cook Medical, Bloomington, Ind). METHODS: All consecutive patients treated for TAAAs using the t-Branch between September 2012 and June 2019 were included in the present study. The patients were divided into three groups according to the urgency of repair: (1) elective, (2) urgent, and (3) emergent. The periprocedural details and 30-day outcomes were analyzed. Survival and reinterventions were analyzed using Kaplan-Meier curves and log-rank tests. RESULTS: The t-Branch stent graft was used for 100 patients during the study period. Of the 100 patients, 30 (73% male; mean age, 65 ± 10 years) were treated electively, 49 (54% male; mean age, 72 ± 7 years) urgently, and 21 (81% male; mean age, 75 ± 9 years) emergently. Transfemoral access with a steerable sheath was used more frequently for target vessel catheterization in the elective group (57%) than in the urgent (8%) and emergent (5%) groups (P = .021). The total number of targeted vessels was 111 of 120 (93%) in the elective group vs 185 of 196 (94%) in the urgent group and 82 of 84 (98%) in the emergent group. The corresponding technical success rates were 97% (29 of 30), 98% (48 of 49), and 95% (20 of 21). The median intensive care unit stay was shorter in the elective group (3 days; range, 1-41 days) than in the urgent group (5 days; range, 1-41 days) and emergent group (11 days; range, 3-37 days; P = .004). The 30-day mortality rate was lower in the elective group (2 of 30; 7%) than in the urgent group (8 of 49; 16%) and emergent group (5 of 21; 24%; P = .049). The acute kidney injury rate was lower in the elective group (2 of 30; 7%) than in the urgent group (11 of 49; 22%) and emergent group (8 of 21; 38%; P = .002). The spinal cord ischemia rate was also lower in the elective group (5 of 30; 17%) than in the urgent group (5 of 49; 10%) and emergent group (8 of 21; 38%; P = .051). The median follow-up was 8 months (interquartile range, 3.2-18.5 months). The cumulative survival rate was 95%, 87%, and 87% at 6, 12, and 24 months, respectively. The cumulative freedom from reintervention during follow-up was 92%, 86%, and 77% at 6, 12, and 24 months, respectively. CONCLUSIONS: The technical success of TAAA repair using t-Branch stent graft was not affected by an urgent or emergent presentation. However, the occurrence of worse periprocedural morbidity and mortality was significantly associated with an urgent or emergent presentation.

Effects of fluids vs. vasopressors on spinal cord microperfusion in hemorrhagic shock induced ischemia/reperfusion.

OBJECTIVE: Spinal cord injury induced by ischemia/reperfusion is a devastating complication of aortic repair. Despite developments for prevention and treatment of spinal cord injury, incidence is still considerably high majorly impacting patient outcome. Microcirculation is paramount for tissue perfusion and oxygen supply and often dissociated from macrohemodynamic parameters used to guide resuscitation. Effects of fluids vs. vasopressors in the setting of hemodynamic resuscitation on spinal cord microperfusion are unknown. Aim of this study was to compare the effects of vasopressor and fluid resuscitation on spinal cord microperfusion in a translational acute pig model of hemorrhagic shock induced ischemia/reperfusion injury. METHODS: We designed this study as prospective randomized explorative large animal study. We induced hemorrhagic shock in 20 pigs as a model of global ischemia/reperfusion injury. We randomized animals to receive either fluid or vasopressor resuscitation. We measured spinal cord microperfusion using fluorescent microspheres as well as laser-Doppler probes. We monitored and analyzed macrohemodynamic parameters and cerebrospinal fluid pressure. RESULTS: Spinal cord microperfusion decreased following hemorrhagic shock induced ischemia/reperfusion injury. Both fluids and vasopressors sufficiently restored spinal cord microperfusion. There were no important changes between groups (percentage changes compared to baseline: fluids 14.0 (0.31-27.6) vs. vasopressors 24.3 (8.12-40.4), p = .340). However, cerebrospinal fluid pressure was higher in animals receiving fluid resuscitation (percentage changes compared to baseline: fluids 27.7 (12.6-42.8) vs. vasopressors -5.56 ((-19.8)-8.72), p = .003). Microcirculatory resuscitation was in line with improvements of macrohemodynamic parameters. CONCLUSIONS: Both, fluids and vasopressors, equally restored spinal cord microperfusion in a porcine acute model of hemorrhagic shock induced ischemia/reperfusion injury. However, significant differences in cerebrospinal fluid pressure following resuscitation were present. Future studies should evaluate these effects in perfusion disruption induced ischemia/reperfusion conditions of microcirculatory deterioration.

Editor's Choice - Update of the European Society for Vascular Surgery (ESVS) 2020 Clinical Practice Guidelines on the Management of Acute Limb Ischaemia in Light of the COVID-19 Pandemic, Based on a Scoping Review of the Literature.

OBJECTIVE: To perform a scoping review of how patients with COVID-19 are affected by acute limb ischaemia (ALI) and evaluate the recommendations of the 2020 ESVS ALI Guidelines for these patients. METHODS: Research questions were defined, and a systematic literature search was performed following the PRISMA guidelines. Abstracts and unpublished literature were not included. The definition of ALI in this review is in accordance with the ESVS guidelines. RESULTS: Most identified papers were case reports or case series, although population based data and data from randomised controlled trials were also identified. In total, 114 unique and relevant papers were retrieved. Data were conflicting concerning whether the incidence of ALI increased, or remained unchanged, during the pandemic. Case reports and series reported ALI in patients who were younger and healthier than usual, with a greater proportion affecting the upper limb. Whether or not this is coincidental remains uncertain. The proportion of men/women affected seems unchanged. Most reported cases were in hospitalised patients with severe COVID-19. Patients with ALI as their first manifestation of COVID-19 were reported. Patients with ALI have a worse outcome if they have a simultaneous COVID-19 infection. High levels of D-dimer may predict the occurrence of arterial thromboembolic events in patients with COVID-19. Heparin resistance was observed. Anticoagulation should be given to hospitalised COVID-19 patients in prophylactic dosage. Most of the treatment recommendations from the ESVS Guidelines remained relevant, but the following were modified regarding patients with COVID-19 and ALI: 1) CTA imaging before revascularisation should include the entire aorta and iliac arteries; 2) there should be a high index of suspicion, early testing for COVID-19 infection and protective measures are advised; and 3) there should be preferential use of local or locoregional anaesthesia during revascularisation. CONCLUSION: Although the epidemiology of ALI has changed during the pandemic, the recommendations of the ESVS ALI Guidelines remain valid. The above mentioned minor modifications should be considered in patients with COVID-19 and ALI.

Early and Mid-Term Durability of Surgeon-Modified and Custom-Made Fenestrated Devices for the Treatment of Complex Aortic Pathology.

BACKGROUND: Fenestrated endovascular aneurysm repair (F-EVAR) has allowed successful treatment of patients with complex aortic aneurysms. Custom-made devices (CMDs) are manufactured by companies and tailored to the patient's anatomy to incorporate target vessels, while there is also the "off label" alternative with the devices modified by a surgeon in the operating room: surgeon-modified FEVAR (sm-FEVAR). This study aims to present and compare technical durability of CMDs- and sm-FEVAR for complex abdominal and thoracoabdominal aortic pathologies. METHODS: A retrospective cohort study was undertaken including all consecutive patients treated with sm- or CMD-FEVAR during a 3-year period in a single center. Only cases with at least 3 reno-visceral target vessels were included. Primary outcomes were technical success, and freedom from endoleak (EL) (Ia or III; all branch related) and re-intervention during follow-up period. Mortality and morbidity were also recorded. RESULTS: Thirty-two sm-FEVAR patients (81,3% male) and 79 CMD-FEVAR patients (77,2% male) were included. Indication for sm-FEVAR was exclusively urgent, while all CMD- FEVAR were elective. Technical success was similar in sm-FEVAR (100%) and CMD-FEVAR (98,7%) (P = 0.523). Mean follow-up was 16.3 ± 13 and 20 ± 17.3 months for sm-FEVAR and CMD- FEVAR, respectively (P = 0.28). The freedom from EL Ia rate was 91.7% [standard error (SE) 5.7%] at 12 months in sm-FEVAR, while it was 97.7% (SE 2.2%) and 92.3% (SE 4.3%) at 12 and 24 months, respectively in CMD-FEVAR (P = 0.69). The freedom from EL III rate was 95.5% (SE 4.4%) and 88% (SE 8.2%) at 12 and 24 months, respectively in sm-FEVAR, while it was 92.1% (SE 3.8%) and 89.2% (SE 4.7%) at 12 and 24 months, respectively in CMD-FEVAR (P = 0.68). The freedom from re-intervention rate was 91.6% (SE 5.7%) and 84.6% (SE 8.6%) at 12 and 24 months, respectively in sm-FEVAR, while it was 91.7% (SE 4%) and 83.4% (SE 5.9%) at 12 and 24 months, respectively in CMD-FEVAR (P = 0.90). The survival rate was 87.5% (5.8%) and 76.3% (7.9%) at 1 and 12 months, respectively in sm-FEVAR, while it was 93.7% (2.7%) at 1 month in CMD-FEVAR without any other death during FU period. No bridging stent occlusions were noted during follow-up period in any patient. CONCLUSION: Sm-FEVAR offers good technical success and mid-term clinical outcomes in urgent cases of complex aortic pathologies. Its durability is acceptable and comparable to CMD-FEVAR with a relatively low re-intervention rate.

A cross-sectional survey study on the nutrition patterns of patients with peripheral artery disease.

Background: Even though nutrition was demonstrated to have an impact on chronic atherosclerotic disease, there is a paucity of corresponding recommendations for patients with peripheral artery disease (PAD). A Mediterranean Diet based on daily intake of fruits and vegetables with high fibre, vegetable oil, and unsalted nuts including fish several times a week may have protective effects. This cross-sectional survey aimed to determine nutritional patterns amongst inpatients with PAD. Methods: All inpatients with symptomatic PAD who underwent revascularisation at a single centre between 1st May 2018 and 31st December 2021 were asked to fill out a questionnaire on nutritional intake. An 8-item frequency rating scale (from never to three times a day) was used for 15 food groups. For 11 of them, an adapted Mediterranean Diet score was calculated using the answers. The descriptive results were stratified by sex and disease stage (intermittent claudication vs. chronic limb-threatening ischaemia). Results: A total of 319 patients (31.7% female, 69.4 years in mean) were included. Thereof, 71.8% reported they did never receive any nutritional information considering their PAD disease. The mean adapted Mediterranean Diet score was 2.7 points (of maximum 11) with most patients not achieving the recommended servings per week for fruits (1.6%), vegetables (1.0%), and unsalted nuts (12.2%). The intake of cereals was sufficient (43.3%). When compared with men, women consumed more fruits and less meat. Conclusions: This survey demonstrated that although healthy nutrition may have a positive impact on patients with PAD, the education and adherence to a Mediterranean Diet was inappropriate. Nutritional patterns should be more focused in future PAD studies to derive specific recommendations and nutritional programmes as well as patient education in clinical practice.

Transcaval embolization for type II endoleak after endovascular aortic repair of infrarenal, juxtarenal, and type IV thoracoabdominal aortic aneurysm.

OBJECTIVE: This study aims to determine the outcomes of transcaval embolization (TCE) for type II endoleak after infrarenal endovascular aortic repair (EVAR) and fenestrated/branched EVAR (F/BEVAR). METHODS: A retrospective single-center cohort study of all consecutive TCE procedures between August 2015 and August 2019 was performed to investigate technical success, in-hospital morbidity, and 30-day mortality as well as clinical success during follow-up. The indication for TCE was an aneurysm sac growth of 5 mm or more owing to a type II endoleak after EVAR for infrarenal or F/BEVAR for juxtarenal and type IV thoracoabdominal aortic aneurysm. RESULTS: A total 25 TCE procedures in 24 patients (95.8% male) were included. Technical success was 96.0% (24/25); selective and nonselective TCE were performed in 48% of patients. The in-hospital morbidity and 30-day mortality were 0%. The median follow-up was 23.1 months (interquartile range, 10.9-40.1 months). Freedom from type II endoleak-related reintervention was 84.6% at 12 months. Comparing clinical success after TCE, reintervention was necessary in 16.7% of patients after nonselective and 20% of patients after selective TCE. Regarding TCE after EVAR vs F/BEVAR, reintervention was performed in 12.5% of EVAR and 33.3% of F/BEVAR patients during follow-up. CONCLUSIONS: TCE is an acceptable treatment alternative for type II endoleak with aneurysm sac enlargement and can be used after EVAR for infrarenal abdominal aortic aneurysms and F/BEVAR for juxtarenal abdominal aortic aneurysms and type IV thoracoabdominal aortic aneurysms.

Management of Descending Thoracic Aortic Diseases: Similarities and Differences Among Cardiovascular Guidelines.

Cardiovascular societies have developed recommendations regarding the management of thoracic aortic diseases. While improvements in treatment have been observed during the past decade in regard to patient selection, thoracic endovascular aortic repair (TEVAR) and associated techniques, and high-volume centralization, the broad expansion of TEVAR has raised considerations about its indications, appropriateness, limitations, and application. The aim of this systematic review was to assess the similarities and differences among current cardiovascular societies' guidelines for the management of thoracic aortic diseases. The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched from January 2009 to May 2020. The initial search identified 990 articles. After exclusion of duplicate or inappropriate articles, the final analysis included 5 articles from cardiovascular societies published between 2010 and 2020. Selected controversial topics were analyzed, including diagnosis, imaging, spinal cord ischemia prevention, and management of the most important thoracic aortic pathologies. The analysis included data concerning the therapeutic approach in acute and chronic type B aortic dissection, penetrating aortic ulcer, intramural hematoma, thoracic aortic aneurysm, and traumatic aortic injury, as well a discussion of inflammatory aneurysms, aortitis, and genetic syndromes. The review presents consistent and controversial recommendations, as well as "gray zone" issues that need further investigation. There was significant overlap and agreement among the 5 societies regarding the management of thoracic aortic diseases. Especially in dissection and aneurysm management, TEVAR has established its role as the treatment of choice. However, robust evidence is still needed in many aspects of the management of thoracic aortic pathologies.

How Does Female Sex Affect Complex Endovascular Aortic Repair? A Single Centre Cohort Study.

OBJECTIVE: There is growing evidence of a female patient disadvantage in complex endovascular aortic repair using fenestrated and branched endografts (FB-EVAR) primarily related to peri-procedural events including ischaemic and access vessel complications. This study aimed to determine the impact of sex differences on treatment patterns, and in hospital outcomes in a single centre cohort. METHODS: This was a retrospective cross sectional single centre cohort study of all consecutive FB-EVAR procedures provided to patients with asymptomatic pararenal and thoraco-abdominal aortic aneurysm (TAAA) between 1 January 2010 and 28 February 2021. Adjusted multivariable logistic regression models were developed using backward (Wald) elimination of variables to determine the independent impact of female sex on short term outcomes. RESULTS: In total, 445 patients (24.3% females, median age 73.0 years, IQR 66, 78) were included. Female patients had a smaller aneurysm diameter, less frequent coronary artery disease (29.6% vs. 44.8%, p = .007) and history of myocardial infarction (2.8% vs. 15.4%, p < .001) when compared with males. Females were more frequently treated for TAAA than males (49.1% vs. 25.2%, p < .001). The median length of post-procedural hospital stay was 10 days in females and 9 in males. In adjusted analyses, female sex was independently associated with higher mortality (odds ratio [OR] 10.135, 95% CI 2.264 - 45.369), post-procedural complications (OR 2.500, 95% CI 1.329 - 4.702), spinal cord ischaemia (OR 4.488, 95% CI 1.610 - 12.509), sepsis (OR 4.940, 95% CI 1.379 - 17.702), and acute respiratory insufficiency (OR 3.283, 95% CI 1.015 - 10.622) after pararenal aortic aneurysm repair during the hospital stay. CONCLUSION: In this analysis of consecutively treated patients, female sex was associated with increased in hospital mortality, peri-procedural complications, and spinal cord ischaemia after elective complex endovascular repair of pararenal aortic aneurysm, while no differences were revealed in the TAAA subgroup. These results suggest that sex related patient selection and peri-procedural management should be studied in future research.

Editor's Choice - The GermanVasc Score: A Pragmatic Risk Score Predicts Five Year Amputation Free Survival in Patients with Peripheral Arterial Occlusive Disease.

OBJECTIVE: Patients with peripheral arterial occlusive disease (PAOD) face an increased risk of both lower limb amputation and death. To date, it has been challenging to predict the long term outcomes for PAOD. The aim was to develop a risk score to predict worse five year amputation free survival (AFS). METHODS: In this retrospective analysis of claims data, symptomatic PAOD patients were split into training and validation sets. Variables in the model were patient age and sex, Elixhauser comorbidities, and the 190 most common secondary diagnoses. Penalised Cox regression (least absolute shrinkage and selection operator [LASSO]) with tenfold cross validation for variable selection was performed and patients were categorised into five risk groups using the ten most important variables. All analyses were stratified by intermittent claudication (IC) and chronic limb threatening ischaemia (CLTI). RESULTS: In total, 87 293 patients with PAOD (female 45.3%, mean age 71.4 ± 11.1 years) were included in the analysis. The most important variable predicting worse five year AFS was patient age >80 years. The GermanVasc score exhibited good predictive accuracy both for IC (c statistic = 0.70, 95% confidence interval [CI] 0.69-0.71) and CLTI (c statistic = 0.69, 95% CI 0.68-0.70) with adequate calibration due largely to alignment of observed and expected risk. Depending on the cumulative point score, the five year risk of amputation or death ranged from 9% (low risk) to 48% (high risk) for IC, and from 25% to 88% for CLTI. CONCLUSION: The GermanVasc score predicts worse five year AFS stratified for inpatients suffering from IC and CLTI, with good predictive accuracy. By separating low from high risk patients, the GermanVasc score may support patient centred consent.

Contralateral Stenosis and Echolucent Plaque Morphology are Associated with Elevated Stroke Risk in Patients Treated with Asymptomatic Carotid Artery Stenosis within a Controlled Clinical Trial (SPACE-2).

BACKGROUND: Asymptomatic carotid artery stenosis (ACS) has a low risk of stroke. To achieve an advantage over noninterventional best medical treatment (BMT), carotid endarterectomy (CEA) or carotid artery stenting (CAS) must be performed with the lowest possible risk of stroke. Therefore, an analysis of risk-elevating factors is essential. Grade of ipsilateral and contralateral stenosis as well as plaque morphology are known risk factors in ACS. METHODS: The randomized, controlled, multicenter SPACE-2 trial had to be stopped prematurely after recruiting 513 patients. 203 patients were randomized to CEA, 197 to CAS, and 113 to BMT. Within one year, risk factors such as grade of stenosis and plaque morphology were analyzed. RESULTS: Grade of contralateral stenosis (GCS) was higher in patients with any stroke (50%ECST vs. 20%ECST; p=0.012). Echolucent plaque morphology was associated with any stroke on the day of intervention (OR 5.23; p=0.041). In the periprocedural period, any stroke was correlated with GCS in the CEA group (70%ECST vs. 20%ECST; p=0.026) and with echolucent plaque morphology in the CAS group (6% vs. 1%; p=0.048). In multivariate analysis, occlusion of the contralateral carotid artery (CCO) was associated with risk of any stroke (OR 7.00; p=0.006), without heterogeneity between CEA and CAS. CONCLUSION: In patients with asymptomatic carotid artery stenosis, GCS, CCO, as well as echolucent plaque morphology were associated with a higher risk of cerebrovascular events. The risk of stroke in the periprocedural period was increased by GCS in CEA and by echolucent plaque in CAS. Due to small sample size, results must be interpreted carefully.

Xarelto plus Acetylsalicylic acid: Treatment patterns and Outcomes in patients with Atherosclerosis (XATOA): Rationale and design of a prospective registry study to assess rivaroxaban 2.5 mg twice daily plus aspirin for prevention of atherothrombotic events in coronary artery disease, peripheral artery disease, or both.

Patients with coronary artery disease (CAD), peripheral artery disease (PAD), or both remain at risk of cardiovascular events (including peripheral ischemic events), even when they receive the current guideline-recommended treatment. The phase III COMPASS trial demonstrated that treatment with rivaroxaban vascular dose 2.5 mg twice daily plus aspirin (dual pathway inhibition [DPI] regimen) significantly reduced the risk of major adverse cardiovascular events (including peripheral ischemic events) and increased the risk of major bleeding, but not fatal bleeding or intracranial hemorrhage, versus aspirin alone in patients with CAD, PAD, or both. The results of the COMPASS trial supported the regulatory approval of the DPI regimen in several geographic regions. However, it is unclear whether the patients selected for treatment with the DPI regimen in clinical practice will have a similar risk profile and event rates compared with the COMPASS trial population. The prospective post-approval XATOA registry study aims to assess treatment patterns, as well as ischemic and bleeding outcomes in patients with CAD, PAD, or both, who receive DPI therapy in routine clinical practice. Up to 10,000 patients from at least 400 centers in 22 countries will be enrolled and followed up for a minimum of 12 months, and all treatment will be at the discretion of the prescribing physician. The primary objective of the XATOA study will be to describe early treatment patterns, while ischemic and bleeding outcomes will be described as a secondary objective. TRIAL REGISTRATION NUMBER: NCT03746275.

Time trends of international English language publication activity by vascular surgeons.

OBJECTIVE: Vascular surgical publication activity in the English-language literature during a 10-year interval could have changed. The present study sought to identify which countries have made the most contributions and whether significant shifts have occurred during a 10-year period. METHODS: The study design was a retrospective study. Screening of 15 international journals in PubMed was performed for the 2006 to 2007 and 2016 to 2017 for studies reported by a first author belonging to a vascular surgery department. Data were collected by country regarding the total number of publications, cumulative impact factors (IFs), publications per inhabitant, IFs per inhabitant, and number of randomized controlled trials, meta-analyses, and systematic reviews per country in both periods. RESULTS: A total of 975 and 1459 reports were found for 2006 to 2007 and 2016 to 2017, respectively. For 2006 to 2007, most reports (n = 400; 41.0%; 1308.3 IFs) had come from the United States, followed by the United Kingdom (n = 168; 17.2%; 462.3 IFs) and The Netherlands (n = 74; 7.6%; 182.6 IFs). For 2016 to 2017, the United States led again with 607 articles (41.6%; 1968.0 IFs), followed by the United Kingdom (n = 119; 8.2%; 640.5 IFs) and The Netherlands (n = 107; 7.3%; 355.6 IFs). Of the top 15 countries, The Netherlands and Sweden contributed the most articles per inhabitant during both periods. During both periods, the United Kingdom reported the most randomized controlled trials, meta-analyses, and systematic reviews. CONCLUSIONS: Vascular surgeons from the United States and United Kingdom were the most productive in terms of the total numbers of English language publications during both periods. However, The Netherlands and Sweden were more active in relation to their population size.

Incidence, predictors, and outcomes of spinal cord ischemia in elective complex endovascular aortic repair: An analysis of health insurance claims.

OBJECTIVE: This study aimed to determine predictors and outcomes associated with spinal cord ischemia (SCI) after elective fenestrated or branched endovascular aneurysm repair (F/BEVAR) of thoracoabdominal aortic aneurysm (TAAA), abdominal aortic aneurysm (AAA), or aortic dissection. METHODS: Health insurance claims data of Germany's third largest insurance provider, DAK-Gesundheit, were used to investigate SCI in elective F/BEVAR performed between 2008 and 2017. The International Classification of Diseases and German Operation and Procedure Classification System were used. We stratified the results into F/BEVAR with one or two (AAA) vs three or more (TAAA) fenestrations or branches. RESULTS: A total of 877 patients (18.9% female; 5.8% with SCI) matching the inclusion criteria were identified during the study period. SCI occurred more often after F/BEVAR of TAAA vs AAA (10.7% vs 3.0%; P < .001). SCI was associated with female sex in the AAA group (odds ratio, 3.87; 95% confidence interval [CI], 1.25-11.15; P = .014) and with cardiac arrhythmias in the TAAA group (odds ratio, 2.98; 95% CI, 1.24-7.06; P = .013). Compared with patients without SCI, SCI patients were more likely to suffer from drug use disorders (eg, opioids, cannabinoids, sedatives) in the TAAA group (17.6% vs 2.1%; P < .05). After F/BEVAR of TAAA, the occurrence of SCI was associated with higher 90-day mortality (14.7% vs 1.1%; P < .05), longer postoperative hospital stay (22 vs 9 days; P < .05), and severe adverse events, such as acute respiratory insufficiency (44.1% vs 12.7%), acute renal failure (35.3% vs 11.3%), and pneumonia (29.4% vs 4.9%; all P < .05). In adjusted analyses, SCI was associated with worse long-term survival after F/BEVAR for TAAA (hazard ratio, 2.54; 95% CI, 1.37-4.73; P < .003). CONCLUSIONS: Female AAA patients and TAAA patients with cardiac arrhythmias are at highest risk for development of SCI after F/BEVAR. The occurrence of this event was strongly associated with higher major complication rates and worse short-term and long-term survival. This emphasizes a need to further illuminate the value of spinal cord protection protocols in F/BEVAR.

Predictors of bleeding or anemia requiring transfusion in complex endovascular aortic repair and its impact on outcomes in health insurance claims.

OBJECTIVE: This study aimed to determine predictors and outcomes associated with bleeding or anemia requiring transfusion (BAT) after fenestrated or branched endovascular aneurysm repair (FB-EVAR). METHODS: Health insurance claims data of Germany's third largest insurance provider, DAK-Gesundheit, were used to investigate BAT in elective FB-EVAR performed between 2008 and 2017. International Classification of Diseases and German Operations and Procedure Key codes were used. RESULTS: A total of 959 patients (24.8% with BAT) matching the inclusion criteria were identified during the study period. Compared with patients without BAT, patients with BAT were older (74.4 vs 73.0 years; P = .015) and suffered more frequently from congestive heart failure (18.5% vs 9.4%), cardiac arrhythmias (26.9% vs 14.7%), and hereditary or acquired coagulopathy (31.9% vs 6.2%; all P < .001). Coagulopathy (odds ratio [OR], 3.65; 95% confidence interval [CI], 2.29-5.84), female sex (OR, 2.67; 95% CI, 1.78-4.00), and multiple comorbidities (OR, 1.10; 95% CI, 1.07-1.14) were independent predictors of BAT (all P < .001). BAT was associated with higher in-hospital (11.3% vs 2.6%), 30-day (12.2% vs 3.1%), and 90-day (18.5% vs 4.4%) mortality (all P < .001). Furthermore, myocardial infarction (23.9% vs 2.8%) and paraplegia (9.7% vs 0.7%) were more frequent in the BAT group (all P < .001). In multivariable analyses, BAT was associated with worse short-term (OR, 3.19; 95% CI, 1.63-6.33; P = .001) and long-term survival (hazard ratio, 1.62; 95% CI, 1.24-2.11; P < .001). CONCLUSIONS: Patients with hereditary or acquired coagulopathy, patients with multiple comorbidities, and women are at higher risk for development of BAT after FB-EVAR. The occurrence of this event was strongly associated with higher major complication rates and worse short-term and long-term survival. This emphasizes a need to further illuminate the value of patient blood management in FB-EVAR.

A multi-institutional experience in vascular Ehlers-Danlos syndrome diagnosis.

OBJECTIVE: Vascular Ehlers-Danlos syndrome (vEDS) is a rare disorder and 1 of 13 types of EDS. The syndrome results in aortic and arterial aneurysms and dissections at a young age. Diagnosis is confirmed with molecular testing via skin biopsy or genetic testing for COL3A1 pathogenic variants. We describe a multi-institutional experience in the diagnosis of vEDS from 2000 to 2015. METHODS: This is a multi-institutional cross-sectional retrospective study of individuals with vEDS. The institutions were recruited through the Vascular Low Frequency Disease Consortium. Individuals were identified using the International Classification of Diseases-9 and 10-CM codes for EDS (756.83 and Q79.6). A review of records was then performed to select individuals with vEDS. Data abstraction included demographics, family history, clinical features, major and minor diagnostic criteria, and molecular testing results. Individuals were classified into two cohorts and then compared: those with pathogenic COL3A1 variants and those diagnosed by clinical criteria alone without molecular confirmation. RESULTS: Eleven institutions identified 173 individuals (35.3% male, 56.6% Caucasian) with vEDS. Of those, 11 (9.8%) had nonpathogenic alterations in COL3A1 and were excluded from the analysis. Among the remaining individuals, 86 (47.7% male, 68% Caucasian, 48.8% positive family history) had pathogenic COL3A1 variants and 76 (19.7% male, 19.7% Caucasian, 43.4% positive family history) were diagnosed by clinical criteria alone without molecular confirmation. Compared with the cohort with pathogenic COL3A1 variants, the clinical diagnosis only cohort had a higher number of females (80.3% vs 52.3%; P < .001), mitral valve prolapse (10.5% vs 1.2%; P = .009), and joint hypermobility (68.4% vs 40.7%; P < .001). Additionally, they had a lower frequency of easy bruising (23.7% vs 64%; P < .001), thin translucent skin (17.1% vs 48.8%; P < .001), intestinal perforation (3.9% vs 16.3%; P = .01), spontaneous pneumothorax/hemothorax (3.9% vs 14%, P.03), and arterial rupture (9.2% vs 17.4%; P = .13). There were no differences in mortality or age of mortality between the two cohorts. CONCLUSIONS: This study highlights the importance of confirming vEDS diagnosis by testing for pathogenic COL3A1 variants rather than relying on clinical diagnostic criteria alone given the high degree of overlap with other forms genetically triggered arteriopathies. Because not all COL3A1 variants are pathogenic, the interpretation of the genetic testing results by an individual trained in variant assessment is essential to confirm the diagnosis. An accurate diagnosis is critical and has serious implications for lifelong screening and treatment strategies for the affected individual and family members.

Use of a Steerable Sheath for Antegrade Catheterization of a Supra-aortic Branch of an Inner-Branched Arch Endograft via a Percutaneous Femoral Access.

Purpose: To describe the use of a steerable sheath from a femoral access for antegrade catheterization of the left common carotid artery (LCCA) in an inner-branched arch endograft. Technique: This technique is demonstrated in a patient with residual aortic dissection after replacement of the ascending aorta for acute type A aortic dissection. He presented 4 years later with aneurysmal degeneration of the thoracoabdominal aorta and a proximal tear located in the aortic arch. A 2-stage hybrid approach was devised to treat the patient. An axilloaxillary crossover graft (left to right) with plug occlusion of the innominate artery was performed initially. Later, a dual-branched custom-made device was implanted. To avoid an additional LCCA cutdown for retrograde branch access, an 18-F steerable sheath was used through a percutaneous femoral access. Two wires were delivered within the steerable sheath: the first one was directed into the left subclavian artery to stabilize the sheath position in the ascending aorta; the second wire was used to catheterize the first inner branch and the LCCA to deploy the covered bridging stent. Conclusion: Transfemoral access to catheterize antegrade branches for supra-aortic vessels is feasible using a large steerable sheath in branched endovascular arch repair.