Sex disparities in popliteal artery aneurysms.

OBJECTIVE: Only 5% of patients with popliteal artery aneurysms (PAAs) are female. Evidence on PAA treatment and outcomes in women is therefore scarce. The POPART Registry provides one of Europe's largest data collections regarding PAA treatment. Data on clinical presentation, aneurysm morphology, and perioperative outcomes after open surgical PAA repair in women will be presented. METHODS: POPART is a multicenter, noninterventional registry for open and endovascular PAA repair, with 42 participating centers in Germany and Luxembourg. All patients aged >18 years who have been treated for PAA since 2010 are eligible for study inclusion. Data collection is based on an online electronic case report form. RESULTS: Of the 1236 PAAs, 58 (4.8%) were in women. There were no significant differences in age or cardiopulmonary comorbidities. However, female patients had a lower prevalence of contralateral PAAs and abdominal aortic aneurysms (P < .05). PAAs in women were more likely to be symptomatic before surgery (65.5% vs 49.4%; P = .017), with 19% of women presenting with acute limb ischemia (vs 11%; P = .067). Women had smaller aneurysm diameters than men (22.5 mm vs 27 mm; P = .004) and became symptomatic at smaller diameters (20 mm vs 26 mm; P = .002). Only 8.6% of women and 11.6% of men underwent endovascular aneurysm repair (P > .05); therefore, the perioperative outcome analysis focused on open surgical repair. In total, 23.5% of women and 16.9% of men developed perioperative complications (P > .05). There were no differences in major cardiovascular events (P > .05), but women showed a higher incidence of impaired wound healing (15.7% vs 7.2%; P = .05) and major amputation (5.9% vs 1.1%; P = .027). Female sex was significantly associated with the need for nonvascular reinterventions within 30 days after surgery (odds ratio: 2.48, 95% confidence interval: 1.26-4.88), whereas no significant differences in the odds for vascular reinterventions were observed (odds ratio: 1.98, 95% confidence interval: 0.68-5.77). In the multiple logistic regression model, female sex, symptomatic PAAs, poor quality of outflow vessels, and graft material other than vein graft were independently associated with perioperative reinterventions. CONCLUSIONS: Women have smaller PAAs, are more likely to be symptomatic before treatment, and are more often affected by nonvascular reinterventions in the perioperative course. As our understanding of aneurysmatic diseases in women continues to expand, sex-specific treatment strategies and screening options for women in well-selected cohorts with modified screening protocols should be continuously re-evaluated.

Diagnosis and treatment of venous leg ulcers: S2k Guideline of the German Society of Phlebology and Lymphology (DGPL) e.V.

This S2k guideline on venous leg ulcers was created on the initiative and under the leadership of the German Society of Phlebology and Lymphology (DGPL). The guideline group also consisted of representatives from the German Society for Phlebology and Lymphology, German Dermatological Society, German Society for General Medicine, German Society for Angiology, German Society for Vascular Surgery and Vascular Medicine, German Society for Surgery, German Society for Dermatosurgery, German Society for Wound Healing and Wound Treatment, Professional Association of Phlebologists and Lymphologists and Initiative Chronische Wunden. The aim of this guideline is to combine the different approaches and levels of knowledge of the respective professional groups on the basis of consensus, so that a basic concept for the best possible treatment of patients with venous leg ulcers can be provided. A total of 70 specific recommendations were formulated and agreed upon, divided into the subject areas of diagnostics, therapy, prevention of recurrences, and everyday challenges. The guideline thus reflects the current state of scientific knowledge and is intended to be widely used as the best available document for the treatment of patients with venous leg ulcers in everyday clinical practice.

Sex difference in early mortality after abdominal aortic aneurysm repair.

OBJECTIVE: Although female patients have a lower prevalence of abdominal aortic aneurysm (AAA), they seem to have a worse treatment outcome compared with male patients. Both maximum aneurysm diameter and aortic size index (ASI) are important indicators of the risk of AAA rupture, among which ASI has been shown capable of equalizing sex-related anatomical differences. Our study aimed to investigate whether sex is an independent risk factor for early postoperative mortality and how the diameter or ASI affects the association between sex and mortality. METHODS: We performed a retrospective analysis of patients who enrolled in the AAA registry of the German Society of Vascular Surgery from 2013 to 2019. The patients were treated by either open surgical repair (OSR) or endovascular aneurysm repair (EVAR). The association between sex and 30-day mortality was investigated using logistic regression analysis. The interaction and mediating effects of maximum aneurysm diameter and ASI were investigated to verify their roles in the effect of sex on mortality. The relationships between the diameter (or ASI) and the risk of 30-day mortality in different sexes were demonstrated by the restricted cubic spline. RESULTS: Overall, 23,275 cases were included in our analysis, with 20,130 male (86.5%) and 3139 female (13.5%) patients. Female patients had a smaller maximum aneurysm diameter (OSR, 55.23 ± 10.29 mm vs 58.05 ± 11.28 mm [P < .001]; EVAR, 54.06 ± 9.08 mm vs 56.11 ± 9.38 mm [P < .001]), but a higher ASI (OSR, 3.16 ± 0.71 vs 2.92 ± 0.69 [P < .001]; EVAR, 3.05 ± 0.66 vs 2.80 ± 0.59 [P < .001]) compared with male patients. The 30-day mortality rate was higher for female patients in both OSR (6.6% vs 4.2%; P = .002) and EVAR groups (1.8% vs 0.8%; P < .001). Logistic regression confirmed a significantly higher risk of 30-day mortality for female patients compared with male patients (odds ratio, 1.55; 95% confidence interval, 1.21-1.99; P = .001). No interaction was found between sex and diameter or ASI, but there were mediating effects for diameter and ASI in the effect of sex on 30-day mortality. For female patients, the risk of 30-day mortality linearly increased with the increase of diameter (PNonlinear = .089) or ASI (PNonlinear = .888), whereas the risk for male patients was U-shaped (for diameter, PNonlinear < .001; for ASI, PNonlinear = .020). CONCLUSIONS: Sex is an independent risk factor for 30-day mortality after AAA repair. Both diameter and ASI are mediating factors for the effect of sex on 30-day mortality. The relationship between diameter or ASI and the risk of 30-day mortality is different for male and female patients.

Long-term outcome and cancer incidence after lower extremity bypass surgery in patients with critical limb threatening ischemia.

PURPOSE: The influence of cancer development on long-term outcome after lower extremity bypass surgery in patients with critical limb threatening ischemia was investigated. METHODS: Patient survival and cancer incidence were recorded for 21,082 patients with peripheral artery disease (PAD) stage III (n = 5631; 26.7%) and stage IV (n = 15,451; 73.3%) registered with the AOK health insurance company in Germany who underwent infrainguinal bypass surgery. All patients were preoperative and in their history cancer-free. RESULTS: After a median follow-up of 44 months, 25.6% of all patients developed cancer (Kaplan-Meier estimated), with no significant differences between patients with PAD stage III and IV (cancer incidence stage III 25.7%, stage IV 25.5%; p = 0.421). In the Cox regression analysis, male gender (HR 1.885; 95% CI 1.714-2.073, p < 0.001) and age over 70 years (HR 1.399; 95% CI 1.285-1.522, p < 0.001) were significant risk factors for the development of cancer. Survival was significantly lower in stage IV (23.4%) compared to stage III (44.5%) (HR 1.720; 95% CI 1.645-1.799, p < 0.001). Cancer was a significant risk factor for overall survival in PAD stage III patients (HR: 1.326; 95% CI 1.195-1.471, p < 0.001) but not in PAD stage IV (HR 0.976; 95% CI 0.919-1.037, p = 0.434). CONCLUSION: Patients with PAD stage III have significantly better survival after infrainguinal bypass surgery compared to patients with stage IV. While cancer incidence was essential for survival in stage III, it was of no importance in stage IV.

Changes in miRNA expression in patients with peripheral arterial vascular disease during moderate- and vigorous-intensity physical activity.

BACKGROUND: Walking is the preferred therapy for peripheral arterial disease in early stage. An effect of walking exercise is the increase of blood flow and fluid shear stress, leading, triggered by arteriogenesis, to the formation of collateral blood vessels. Circulating micro-RNA may act as an important information transmitter in this process. We investigated the acute effects of a single bout of 1) aerobic walking with moderate intensity; and 2) anaerobic walking with vigorous intensity on miRNA parameters related to vascular collateral formation. METHODS: Ten (10) patients with peripheral arterial disease with claudication (age 72 ± 7 years) participated in this two-armed, randomized-balanced cross-over study. The intervention arms were single bouts of supervised walking training at (1) vigorous intensity on a treadmill up to volitional exhaustion and (2) moderate intensity with individual selected speed for a duration of 20 min. One week of washout was maintained between the arms. During each intervention, heart rate was continuously monitored. Acute effects on circulating miRNAs and lactate concentration were determined using pre- and post-intervention measurement comparisons. RESULTS: Vigorous-intensity walking resulted in a higher heart rate (125 ± 21 bpm) than the moderate-intensity intervention (88 ± 9 bpm) (p < 0.05). Lactate concentration was increased after vigorous-intensity walking (p = 0.005; 3.3 ± 1.2 mmol/l), but not after moderate exercising (p > 0.05; 1.7 ± 0.6 mmol/l). The circulating levels of miR-142-5p and miR-424-5p were up-regulated after moderate-intensity (p < 0.05), but not after vigorous-intensity training (p > 0.05). CONCLUSION: Moderate-intensity walking seems to be more feasible than vigorous exercises to induce changes of blood flow and endurance training-related miRNAs in patients with peripheral arterial disease. Our data thus indicates that effect mechanisms might follow an optimal rather than a maximal dose response relation. Steady state walking without the necessity to reach exhaustion seems to be better suited as stimulus.

Changes in Aortic Diameter and Wall Strain in Progressing Abdominal Aortic Aneurysms.

OBJECTIVES: The analysis of wall strain opens new perspectives in the prediction of abdominal aortic aneurysm (AAA) rupture. This study investigates the capability of four-dimensional ultrasound (4D US) to detect and characterize changes in wall strain in the same patients during follow-up observations. METHODS: Eighteen patients were examined by 64 4D US scans during a median follow-up period of 24.5 months. After performing the 4D US and manual aneurysm segmentation, kinematic analysis was performed using a customized interface and evaluation of the mean and peak circumferential strain, as well as spatial heterogeneity. RESULTS: All aneurysms showed a continuous diameter growth with a mean rate of 4% per year (P < .001). The mean circumferential strain (MCS) tends to increase from a median 0.89% by 10.49% per year in follow-up independent of the aneurysm diameter (P = .063). The subgroup analysis reveals a cohort with increasing MCS and decreasing spatial heterogeneity, as well as a cohort with nonincreasing MCS and increasing spatial heterogeneity (P < .05). CONCLUSIONS: The 4D US is able to register the strain changes in AAA follow-up. The MCS tends to increase during the observation time in the entire cohort, but the changes were independent of the maximum aneurysm diameter. The kinematic parameters allow the entire AAA cohort to differentiate into two subgroups and provide additional information about the pathologic behavior of the aneurysm wall.

Outcomes of endovascular repair of infrarenal penetrating aortic ulcers.

Background: To report technical success as well as perioperative outcomes of patients who underwent endovascular aortic repair (EVAR) of penetrating abdominal aortic ulcers ≤35 mm in diameter (PAU). Patients and methods: The abdominal aortic aneurysm (AAA) quality registry of the German institute for vascular research (DIGG) was used to identify patients with standard EVAR for infrarenal PAU ≤35 mm between 1/1/2019 and 12/31/2021. Infectious, traumatic, inflammatory PAUs, PAUs associated with connective tissue disease, PAUs following aortic dissection as well as true aneurysms were excluded. Demographics, cardiovascular comorbidity, technical success as well as perioperative morbidity and mortality were determined. Results: Amongst 11 537 patients who underwent EVAR during the study period, 405 with PAU ≤35 mm were eligible from 95 participating hospitals across Germany (22% women, 20.5% octogenarians). The median aortic diameter was 30 mm (Interquartile range 27-33). Cardiovascular comorbidities were frequent with coronary artery disease (34.8%), chronic heart failure (30.9%), history of myocardial infarction (19.8%), hypertension (76.8%), diabetes (21.7%), smoking (20.8%), history of stroke (9.4%), symptomatic lower extremity peripheral arterial disease (20%), chronic kidney disease (10.4%) and chronic obstructive pulmonary disease (9.6%). Most patients were asymptomatic (89.9%). Among the symptomatic patients, 13 presented with distal embolization (3.2%) and 3 with contained ruptures (0.7%). Technical success of endovascular repair was 98.3%. Both, percutaneous (37.1%) or femoral cut-down access approaches (58.5%) were registered. Endoleaks of any type were present with type 1 (0.5%), type 2 (6.4%) and type 3 (0.3%) endoleaks. Overall mortality was 0.5%. Perioperative complications occurred in 12 patients (3.0%). Conclusions: According to this registry data, endovascular repair of PAU is technically feasible with acceptable perioperative outcomes, but further studies investigating mid- and long-term data are needed before invasive treatment of PAU disease in an elderly and comorbid patient population should be recommended.

Characteristics of patients with multiple arterial aneurysms.

Background: The aim of this retrospective cross-sectional observational study was to determine differences of patients with multiple arterial aneurysms to patients with single arterial aneurysms. Patients and methods: Patients with the diagnosis of an arterial aneurysm from January 2006 to January 2016 in the department of vascular surgery Heidelberg were investigated. Excluded were patients with hereditary disorders of connective tissue or systemic inflammatory disease, as well as other arterial pathologies than true aneurysms. Patients with multiple aneurysms (defined by at least four aneurysms) were compared to patients with single aneurysms concerning age at initial diagnosis, sex and affected arterial site. To verify the findings, a replication of the study was performed at a comparable institution. Results: Of 3107 patients with arterial aneurysms, 918 were excluded. Of the resulting 2189 patients, 1238 (56.6%) patients had a single, 808 (36.9%) two or three, and 143 (6.5%) at least four aneurysms (group mult-AA). Nine hundred seventy-two patients (44.4%) had a single abdominal aortic aneurysm (group sing-AAA). Age at initial diagnosis differed between mult-AA (66.7±9.5 y) and sing-AAA (69.1±8.6 y) (p=0.0338). Within mult-AA, 138 patients (96.5%) were male, compared with 865 patients (89.0%) in sing-AAA (p=0.0041). The most frequent aneurysm localization shifted from the abdominal aorta and its branches in patients with a single aneurysm (n=1029; 83.1%) to pelvic and leg arteries in patients with at least four aneurysms (n=318; 63.2%). The replication of the study at the department of vascular surgery Frankfurt confirmed the younger age at initial diagnosis in mult-AA (67.3±12.5 y) compared to sing-AAA (70.9±9.6 y) (p=0.0259) and the distribution shift toward the arteries below the aortic bifurcation in mult-AA. Conclusions: Patients with multiple aneurysms are younger at initial diagnosis and differ concerning aneurysm localization compared to patients with a single aneurysm.

[Long-term Results after Endovascular and Open Repair of Ruptured Abdominal Aortic Aneurysm - a Propensity Score Matched Analysis]. / Langzeitergebnisse nach endovaskulärer und offener Versorgung des rupturierten Bauchaortenaneurysmas ­ eine Propensity-Score-Analyse.

BACKGROUND: This retrospective propensity score matched study presents the perioperative mortality and long-term survival up to 9 years after endovascular (EVAR) and open (OAR) repair of patients with ruptured abdominal aortic aneurysm (rAAA) in Germany using health insurance data. MATERIALS AND METHODS: 2170 patients treated between January 1st, 2010 and December 31st, 2016, for rAAA within 24 hours of hospital admission and receiving blood transfusions were enrolled in the study and tracked until December 31st, 2018. For better comparability of EVAR and OAR, a 1:1 propensity score matching with 624 pairs according to patient age, sex and comorbidities was carried out using the R program (Foundation for Statistical Computing, Vienna, Austria). RESULTS: In the unadjusted groups, 29.1% (631/2170) of the patients were treated with EVAR and 70.9% (1539/2170) with OAR. EVAR patients had a significantly higher overall rate of comorbidities. After adjustment, EVAR patients showed significantly better perioperative survival (EVAR 35.7%, OAR 51.0%, p = 0.000). Perioperative complications occurred in 80.4% of EVAR patients and 80.3% of OAR patients (p = 1.000). At the end of follow-up, Kaplan-Meier estimated that 15.2% of patients survived after EVAR vs. 19.5% after OAR (p = 0.027). In the multivariate Cox regression analysis, OAR, age ≥ 80 years, diabetes mellitus type 2 and renal failure stages 3 to 5 had a negative impact on overall survival. Patients treated on weekdays had a significantly lower perioperative mortality than patients treated during the weekend (perioperative mortality on weekdays 40.6% vs. 53.4% during the weekend; p = 0.000) and a better overall survival as estimated by Kaplan-Meier. CONCLUSION: Significantly better perioperative and overall survival was observed with EVAR than with OAR in patients with rAAA. The perioperative survival benefit of EVAR was also found in patients older than 80 years. Female gender had no significant influence on perioperative mortality and overall survival. Patients treated on weekends had a significantly poorer perioperative survival than patients treated on weekdays, and this lasted through the end of follow-up. The extent to which this was dependent on hospital structure was unclear.

Real-world data of popliteal artery aneurysm treatment: Analysis of the POPART registry.

OBJECTIVE: Popliteal artery aneurysm (PAA) is a rare disease with a prevalence of 0.1% to 1%. Within previous years, endovascular repair (ER) of PAAs has been performed more frequently despite the lack of high-level evidence compared with open surgical repair (OSR). In 2014, the POPART registry was initiated to validate the current treatment options for PAA repair. METHODS: POPART is a multinational multicenter registry of the peri- and postoperative outcomes of ER and OSR for PAAs. Data sets were recorded using the online survey tool SurveyMonkey (available at: https://www.surveymonkey.com/). Regular monitoring and plausibility checks of the data sets are performed to ensure reliability. The aim of the present study was to report the findings from the POPART registry, which includes data from 41 centers. RESULTS: From June 2014 to August 2019, 794 cases had been recorded in the POPART registry. OSR had been performed in 662 patients and ER in 106 patients; 23 patients had been treated conservatively. Of the 106 patients in the primary ER group, 4 had required conversion to OSR. The ER patients were significantly older (ER, median, 71 years; OSR, median, 67 years; P < .05). No other significant differences were present in the demographic data, comorbidities, or aneurysm morphology between the two groups. Of the 662 patients in the OSR group, 50.3% were symptomatic compared with 29.2% of the 106 patients in the ER group (P < .05). Emergency treatment because of acute ischemia, critical ischemia, or rupture was necessary for 149 patients (22.5%) in the OSR group and 11 patients (10.3%) in the ER group. The most frequent postoperative complications were impaired wound healing (OSR, n = 47 [7.1%]; ER, n = 3 [2.8%]; P > .05) and major bleeding (OSR, n = 26 [3.9%]; ER, n = 3 [2.8%]; P > .05). The in-hospital length of stay was significantly longer for the OSR group than for the ER group (median, 10 days; range, 3-65 days; vs median, 7 days; range, 1-73 days). The overall patency for the OSR and ER groups after 12 and 24 months was 83.2% and 44.7% (P < .005) and 74.2% and 29.1% (P < .005), respectively. The outcomes with a prosthetic graft vs an autologous vein were significantly poorer in the OSR group (primary patency, 71.4% vs 88.1% at 12 months). CONCLUSIONS: To evaluate new treatment techniques such as ER for PAAs, real-world data are of essential importance. The present analysis of the first results for the POPART registry shows good perioperative results for endovascular treatment of PAA in asymptomatic patients with good outflow vessels. The perioperative complication rate is low and the postoperative hospital stay is shorter than after OSR. However, the patency rates after 12 and 24 months are low in the ER group compared to patients treated with open repair. More follow-up data is required for further interpretation; the completion of the data sets in the registry is ongoing.

Safety and efficacy of endovenous laser ablation (EVLA) using 1940 nm and radial emitting fiber: 3-year results of a prospective, non-randomized study and comparison with 1470 nm.

OBJECTIVES: To evaluate the safety, efficacy and ≥36 months outcomes of endovenous laser ablation (EVLA) by means of 1940 nm laser with radial fiber for the treatment of truncal vein insufficiency and compare the results to a historical cohort, obtained via reviewing the literature. METHODS: This prospective, non-randomized, single-center clinical study included 139 consecutive patients with 177 incompetent great saphenous (GSV, n = 135) and short saphenous veins (SSV, n = 42). The maximum laser power (Pmax. 10 W) and pullback velocity were adjusted individually (Vmax = 1 mm/s). The laser fiber was placed at the junction to the deep vein under duplex monitoring. Simultaneous phlebectomies were performed on all the patients. Regular follow up with clinical and duplex ultrasound examination (DUS) were carried out postoperatively at 1 month (1 M), 6 months (6 M), 12 months (12 M), 24 months (24 M), 36 months, and after that (≥36 M). The results were compared with three cohorts (total 616 EVLA procedures with 1470 nm laser and radial fiber) from literature (criteria: >100 procedures, follow-up of ≥2 years). RESULTS: The follow-up rate was 100%, 91%, 73%, 48%, and 23% of the truncal veins at 1, 6, 12, 24, and ≥36 M, respectively. In comparison to the literature using 1470, a lower average linear endovenous energy density (LEED) (53 vs. 77-82 J/cm) resulted in 100% (6 M) and 96.5% (24 M) occlusion rates, reduced local ecchymosis (2.2% vs. 3.2%-18.7%) and reduced average postoperative pain levels (1.3 vs. 2.18). Regarding adverse events, induration (1.1% vs. 1.8%), skin burns (0% vs. 0.45%), endovenous heat-induced thrombus propagation (EHIT) in the deep veins (2.3% vs. 1.8%) and laser-induced persistent paresthesia (2.2% vs. 0.5%-2.9%) were comparable. Recanalizations observed in this study (GSV 0, SSV 3) were asymptomatic and required no treatment. At ≥36 M reflux in the accessory veins was observed in 5% versus 10.5% of patients. Reintervention was required in none (0% vs. 21%). At >36 M, short average stump lengths of 1 cm (GSV) and 0.3 cm (SSV) were observed. CONCLUSION: EVLA with 1940 nm laser with radial emitting fiber is as safe and effective as 1470 nm laser for the treatment of truncal vein insufficiency. Lower postoperative pain, low analgesic requirements, short convalescence add to patients' comfort. EVLA with 1940 nm laser-guided by intraoperative DUS permits reproducible placement of the radial fiber at the saphenofemoral and saphenopopliteal junction, enabling further studies to assess the effect of shorter stump length on patterns and frequency of recurrence without increased risk of EHIT.

Quiescent-Interval Slice Selective Magnetic Resonance Angiography for Abdominal Aortic Aneurysm Treatment Planning.

PURPOSE: Diagnostic imaging of Abdominal aortic aneurysm (AAA) almost exclusively employs CT angiography (CTA) involving X-ray exposure and contrast medium that may harm some patients. Quiescent-Interval Slice Selective MR (QISS-MR) depicts vascular anatomy without radiation or contrast medium. The diagnostic quality of QISS-MRA and CTA were compared in regard to length and diameter measurements in AAA patients. Suitability of QISS-MRA for AAA treatment planning was evaluated. MATERIALS AND METHODS: The details of 30 patients with AAA who received both a QISS-MR and CTA for a known infrarenal AAA were obtained retrospectively that was approved by the local research ethics board. Two observers analyzed each dataset in terms of image quality and determined lumen diameter and length of 15 vessel segments. RESULTS: Highly accurate agreement between the diagnostic scores from the two observers was achieved. There was no significant difference between CTA and QISS-MRA for all 15 measured vessels. Although information on calcification was lacking and intraluminal thrombus was visualized in only 25 patients out of 30 patients, a founded decision to carry out OR or EVAR was possible with both imaging modalities. CONCLUSION: QISS-MRA presents a radiation and contrast free method for preoperative diagnostic AAA imaging. While QISS-MRA does not deliver exact information regarding calcification and thrombus formation, it does accurately allow measurement of vessel diameter and length. Therefore, it is potentially useful for EVAR planning in selected patients with impaired renal function.

Shear Stress-Induced miR-143-3p in Collateral Arteries Contributes to Outward Vessel Growth by Targeting Collagen V-α2.

OBJECTIVE: Arteriogenesis, describing the process of collateral artery growth, is activated by fluid shear stress (FSS). Since this vascular mechanotransduction may involve microRNAs (miRNAs), we investigated the FSS-induced expression of vascular cell miRNAs and their functional impact on collateral artery growth during arteriogenesis. Approach and Results: To this end, rats underwent femoral artery ligation and arteriovenous anastomosis to increase collateral blood flow to maximize FSS and trigger collateral vessel remodeling. Five days after surgery, a miRNA expression profile was obtained from collateral tissue, and upregulation of 4 miRNAs (miR-24-3p, miR-143-3p, miR-146a-5p, and miR-195-5p) was verified by quantitative polymerase chain reaction. Knockdown of miRNAs at the same time of the surgery in an in vivo mouse ligation and recovery model demonstrated that inhibition of miR-143-3p only severely impaired blood flow recovery due to decreased arteriogenesis. In situ hybridization revealed distinct localization of miR-143-3p in the vessel wall of growing collateral arteries predominantly in smooth muscle cells. To investigate the mechanotransduction of FSS leading to the increased miR-143-3p expression, cultured endothelial cells were exposed to FSS. This provoked the expression and release of TGF-ß (transforming growth factor-ß), which increased the expression of miR-143-3p in smooth muscle cells in the presence of SRF (serum response factor) and myocardin. COL5A2 (collagen type V-α2)-a target gene of miR-143-3p predicted by in silico analysis-was found to be downregulated in growing collaterals. CONCLUSIONS: These results indicate that the increased miR-143-3p expression in response to FSS might contribute to the reorganization of the extracellular matrix, which is important for vascular remodeling processes, by inhibiting collagen V-α2 biosynthesis.

Effects of single bouts of different endurance exercises with different intensities on microRNA biomarkers with and without blood flow restriction: a three-arm, randomized crossover trial.

PURPOSE: Physical activity is associated with altered levels of circulating microRNAs (ci-miRNAs). Changes in miRNA expression have great potential to modulate biological pathways of skeletal muscle hypertrophy and metabolism. This study was designed to determine whether the profile of ci-miRNAs is altered after different approaches of endurance exercise. METHODS: Eighteen healthy volunteers (aged 24 ± 3 years) participated this three-arm, randomized-balanced crossover study. Each arm was a single bout of treadmill-based acute endurance exercise at (1) 100% of the individual anaerobic threshold (IANS), (2) at 80% of the IANS and (3) at 80% of the IANS with blood flow restriction (BFR). Load-associated outcomes (fatigue, feeling, heart rate, and exhaustion) as well as acute effects (circulating miRNA patterns and lactate) were determined. RESULTS: All training interventions increased the lactate concentration (LC) and heart rate (HR) (p < 0.001). The high-intensity intervention (HI) resulted in a higher LC than both lower intensity protocols (p < 0.001). The low-intensity blood flow restriction (LI-BFR) protocol led to a higher HR and higher LC than the low-intensity (LI) protocol without BFR (p = 0.037 and p = 0.003). The level of miR-142-5p and miR-197-3p were up-regulated in both interventions without BFR (p < 0.05). After LI exercise, the expression of miR-342-3p was up-regulated (p = 0.038). In LI-BFR, the level of miR-342-3p and miR-424-5p was confirmed to be up-regulated (p < 0.05). Three miRNAs and LC show a significant negative correlation (miR-99a-5p, p = 0.011, r = - 0.343/miR-199a-3p, p = 0.045, r = - 0.274/miR-125b-5p, p = 0.026, r = - 0.302). Two partial correlations (intervention partialized) showed a systematic impact of the type of exercise (LI-BFR vs. HI) (miR-99a-59: r = - 0.280/miR-199a-3p: r = - 0.293). CONCLUSION: MiRNA expression patterns differ according to type of activity. We concluded that not only the intensity of the exercise (LC) is decisive for the release of circulating miRNAs-as essential is the type of training and the oxygen supply.

Intra- and Interobserver Variability of 4D Ultrasound Examination of the Infrarenal Aorta.

OBJECTIVES: The four-dimensional ultrasound (4D-US) enables imaging of the aortic segment and simultaneous determination of the wall expansion. The method shows a high spatial and temporal resolution, but its in vivo reliability is so far unknown for low-measure values. The present study determines the intraobserver repeatability and interobserver reproducibility of 4D-US in the atherosclerotic and non-atherosclerotic infrarenal aorta. METHODS: In all, 22 patients with non-aneurysmal aorta were examined by an experienced examiner and a medical student. After registration of 4D images, both the examiners marked the aortic wall manually before the commercially implemented speckle tracking algorithm was applied. The cyclic changes of the aortic diameter and circumferential strain were determined with the help of custom-made software. The reliability of 4D-US was tested by the intraclass correlation coefficient (ICC). RESULTS: The 4D-US measurements showed very good reliability for the maximum aortic diameter and the circumferential strain for all patients and for the non-atherosclerotic aortae (ICC >0.7), but low reliability for circumferential strain in calcified aortae (ICC = 0.29). The observer- and masking-related variances for both maximum diameter and circumferential strain were close to zero. CONCLUSIONS: Despite the low-measured values, the high spatial and temporal resolution of the 4D-US enables a reliable evaluation of cyclic diameter changes and circumferential strain in non-aneurysmal aortae independent from the observer experience but with some limitations for calcified aortae. The 4D-US opens up a new perspective with regard to noninvasive, in vivo assessment of kinematic properties of the vessel wall in the abdominal aorta.

Comparison of Abdominal Aortic Aneurysm Sac and Neck Wall Motion with 4D Ultrasound Imaging.

OBJECTIVE: The rupture of abdominal aortic aneurysms (AAAs) is associated with high mortality despite surgical developments. The determination of aneurysm diameter allows for follow up of aneurysm growth but fails in precisely predicting aneurysm rupture. In this study, time resolved three dimensional ultrasound (4D ultrasound) based wall motion indices (WMIs) are investigated to see if they are capable of distinguishing between uneven affected regions of the aneurysm wall. METHODS: In a prospective study, 56 patients with an AAA were examined using 4D ultrasound. Local longitudinal, circumferential, and shear strains were computed using custom methods. The deformation of the neck and sac of each aneurysm was characterised by statistical indices of the obtained distributions of local wall strains (WMIs): mean and peak strain, heterogeneity index, and local strain ratio. The locations of regions with highest local peak strain were determined. RESULTS: Compared with the aneurysm neck, the sac is characterised by low mean strain, but highly heterogeneous deformation, described by high local strain ratio and heterogeneity index. Differences were highly significant (p < .001) for all strain components. The regions with the highest circumferential peak strain were found more often in the posterior part of the aneurysm neck (p < .050) and sac (p < .001) regions, compared with other wall regions. No statistically significant correlation was found between the WMIs and maximum AAA diameter, except for longitudinal mean strain, which decreased with the increasing diameter (rho = -.42, p < .010). CONCLUSION: Characterisation of wall kinematics by 4D ultrasound based WMIs provides a new and independent criterion for the distinction of diseased tissue in the AAA sac and the less affected neck region. This is a promising step towards the establishment of new biomarkers to differentiate between the mechanical instability of the AAA and rupture risk.

Comparison of open and endovascular repair of juxtarenal abdominal aortic aneurysms.

BACKGROUND: This study compares the perioperative outcome in elective repair of the juxtarenal abdominal aortic aneurysm (AAA), depending upon whether patients received an open (OAR) or endovascular procedure (EVAR). METHODS: The database stems from the 2013-2017 AAA registry of the German Institute for Vascular Health Research (DIGG) of the German Society for Vascular Surgery and Vascular Medicine (DGG), with a total of 1603 juxtarenal AAAs. 786 patients (49.0%) were treated with an endovascular (EVAR) procedure, and 817 (51.0%) with an open (OAR) procedure. RESULTS: Patients receiving EVAR had a median age of 73 years and those receiving OAR a median age of 71 years (p < 0.001). The proportion of patients over 80 years of age was 17.0% for EVAR and 9.9% for OAR (p < 0.001). The proportion of women receiving EVAR (16.9%) was slightly lower than that receiving OAR (18.6%). Aneurysm diameter differed significantly (EVAR mean 57.80 mm, OAR 59.07 mm; p = 0.038). Preoperatively impaired renal function stages 3 to 5 were not significantly different (EVAR 12.5%, OAR 14.4%, p = 0.158). Postoperative complications were significantly less with EVAR (31%) than with OAR at 45.7% (p = 0.001). In regard to MACE (major adverse cardiac events = perioperative death, stroke, or myocardial infarction), there were no significant differences between EVAR (8.8%) and OAR (10.3%) (p = 0.191). Hospital mortality was only in trend lower with EVAR than with OAR (5.7% vs. 7.7%, respectively; p = 0.068). This held true for the hospital mortality in the group above 80 years of age as well. Inpatient stay was 9 (13.3) days for EVAR and 14 (18.8) days for OAR (p < 0.001). The hospital mortality for women receiving EVAR was 10.5%, and significantly higher (p = 0.008) than that for men (4.7%). The same held true for OAR (hospital mortality for women was 11.8%, for men 6.8%; p = 0.030). CONCLUSION: In terms of perioperative outcome, the endovascular procedure for treating juxtarenal AAA is more favorable than that documented for OAR. Further investigation is necessary to determine whether EVAR is comparable with OAR in the long term when treating juxtarenal AAA.

Pleiotropic effects of laminar flow and statins depend on the Krüppel-like factor-induced lncRNA MANTIS.

AIMS: To assess the functional relevance and therapeutic potential of the pro-angiogenic long non-coding RNA MANTIS in vascular disease development. METHODS AND RESULTS: RNA sequencing, CRISPR activation, overexpression, and RNAi demonstrated that MANTIS, especially its Alu-element, limits endothelial ICAM-1 expression in different types of endothelial cells. Loss of MANTIS increased endothelial monocyte adhesion in an ICAM-1-dependent manner. MANTIS reduced the binding of the SWI/SNF chromatin remodelling factor BRG1 at the ICAM-1 promoter. The expression of MANTIS was induced by laminar flow and HMG-CoA-reductase inhibitors (statins) through mechanisms involving epigenetic rearrangements and the transcription factors KLF2 and KLF4. Mutation of the KLF binding motifs in the MANTIS promoter blocked the flow-induced MANTIS expression. Importantly, the expression of MANTIS in human carotid artery endarterectomy material was lower compared with healthy vessels and this effect was prevented by statin therapy. Interestingly, the protective effects of statins were mediated in part through MANTIS, which was required to facilitate the atorvastatin-induced changes in endothelial gene expression. Moreover, the beneficial endothelial effects of statins in culture models (spheroid outgrowth, proliferation, telomerase activity, and vascular organ culture) were lost upon knockdown of MANTIS. CONCLUSION: MANTIS is tightly regulated by the transcription factors KLF2 and KLF4 and limits the ICAM-1 mediated monocyte adhesion to endothelial cells and thus potentially atherosclerosis development in humans. The beneficial effects of statin treatment and laminar flow are dependent on MANTIS.

IL10 Alters Peri-Collateral Macrophage Polarization and Hind-Limb Reperfusion in Mice after Femoral Artery Ligation.

Arteriogenesis is a process by which a pre-existing arterioarterial anastomosis develops into a functional collateral network following an arterial occlusion. Alternatively activated macrophages polarized by IL10 have been described to promote collateral growth. This study investigates the effect of different levels of IL10 on hind-limb reperfusion and the distribution of perivascular macrophage activation types in mice after femoral artery ligation (FAL). IL10 and anti-IL10 were administered before FAL and the arteriogenic response was measured by Laser-Doppler-Imaging perioperatively, after 3, 7, and 14 d. Reperfusion recovery was accelerated when treated with IL10 and impaired with anti-IL10. Furthermore, symptoms of ischemia on ligated hind-limbs had the highest incidence after application of anti-IL10. Perivascular macrophages were immunohistologically phenotyped using CD163 and CD68 in adductor muscle segments. The proportion of alternatively activated macrophages (CD163+/CD68+) in relation to classically activated macrophages (CD163-/CD68+) observed was the highest when treated with IL10 and suppressed with anti-IL10. This study underlines the proarteriogenic response with increased levels of IL10 and demonstrates an in-vivo alteration of macrophage activation types in the perivascular bed of growing collaterals.

The relevance of low-fidelity virtual reality simulators compared with other learning methods in basic endovascular skills training.

OBJECTIVE: The use of simulators has shown a profound impact on the development of both training and assessment of endovascular skills. Furthermore, there is evidence that simulator training is of great benefit for novice trainees. However, there are only a few simulators available geared specifically toward novice learners. Whereas research suggests that low-fidelity simulators could fill this gap, there are insufficient data available to determine the role of low-fidelity simulators in the training of endovascular skills. METHODS: Medical students in their fifth year (N = 50) with no previous endovascular experience were randomized into three groups: conventional learning through a video podcast (group V; n = 12), low-fidelity simulation training with tablet-paired touch-gesture navigation (group A; n = 12), and low-fidelity simulation training with tablet-paired physical endovascular tool navigation (group S; n = 26). Within their respective groups, all students attended a 1-day class on basic endovascular skills. Questionnaire items for self-assessment before and after the class and assessment after the class of the participant's practical skills on a high-fidelity simulator were analyzed across all three groups as well as for each group separately using nonparametric tests. RESULTS: All 50 participants completed the training. Participants in group S showed a significantly increased interest in working in interventional cardiology (P = .02) and vascular surgery (P = .03) after the class. Evaluation of the questionnaire items after the class showed that participants in group S rated their practical skills significantly higher after the class compared with those in group V and group A (P < .001 for pairwise comparison of all three groups, respectively), creating a significant trend across the three groups. However, analysis of the practical skills assessment for all three groups showed a significant difference between the groups only for choosing a guidewire (P = .045) and a significant trend in performance across the groups for choosing a guidewire and for positioning the guidewire in the vessel (P = .02 and P = .05, respectively). All other steps of the skills assessment showed no significant differences or a trend across the groups. CONCLUSIONS: Low-fidelity simulation training, particularly with physical endovascular tool navigation, led to increased motivation in novice trainees. Whereas simulator training was associated with increased confidence of trainees in their skills, assessment of their practical skills showed no actual improvement in this study. Overall, low-fidelity simulation has the potential to benefit novice trainees, but possible risks of simulation training should be further evaluated.