Factor Xa Inhibition by Rivaroxaban Modified Mitochondrial-Associated Proteins in Human Abdominal Aortic Aneurysms.

BACKGROUND: The presence of intraluminal thrombus and mitochondrial dysfunction in human abdominal aortic aneurysms (AAAs) have been associated with aneurysmal growth and rupture. The objective of the study was to study if endogenous factor Xa (FXa) may modulate mitochondrial functionality and expression of proteins associated with mitophagy in human AAAs. METHODS: AAA sites with intraluminal thrombus were obtained from 6 patients undergoing elective AAA surgery repair. Control samples were collected from 6 organ donors. The effect of FXa was analyzed by in vitro incubation of AAA with 50 nmol/L rivaroxaban, an oral FXa inhibitor. RESULTS: The enzymatic activities of citrate synthase, a biomarker of mitochondrial density, and cytochrome C oxidase, a biomarker of mitochondrial respiratory chain functionality, were significantly reduced in the AAA sites with respect to the healthy aorta (citrate synthase activity in µU/min/µg protein: control: 3.51 ± 0.22 vs. AAA: 0.37 ± 0.15.; P < 0.01; cytochrome C oxidase activity in µOD/min/µg protein: control: 8.05 ± 1.57 vs. AAA: 3.29 ± 1.05; P < 0.05). The addition of rivaroxaban to AAA reverted the activity of both citrate synthase and cytochrome C oxidase to similar values to control. Mitochondrial Drp-1 expression was higher in AAA sites than in either control aortas or rivaroxaban-incubated AAA sites. Cytosolic content of Drp-1 phosphorylated at Ser637, mitochondrial Parkin, and mitochondrial PINK1-Parkin interaction were significantly reduced in the AAA sites with respect to control aortas. For all these parameters, rivaroxaban-incubated AAA showed similar values compared with control aortas. CONCLUSIONS: In human AAA, rivaroxaban improved mitochondrial functionality that was associated with changes in proteins related to mitophagy. Its opens possible new effects of endogenous FXa on the mitochondria in the human AAA site.

Free skin micrografts with cyanoacrylate as outpatient treatment for venous leg ulcers.

OBJECTIVE: The present study describes an ambulatory, free skin micrograft technique with cyanoacrylate as a coadjuvant venous leg ulcer (VLU) healing strategy and its outcomes after one month. METHODS: This prospective study involved Comprehensive Classification System for Chronic Venous Disorders (CEAP) stage C6 patients with good granulation tissue and negative culture results, consecutively recruited in January 2017 in the Hospital Clinico San Carlos. A skin micrograft was harvested from the anterior surface of the patient's thigh with a 0.4cm punch (0.12cm2). The graft was adhered to the ulcer bed with cyanoacrylate. Anti-adherent dressing and double-layer bandaging was applied, with weekly replacements. Measurements were obtained of the surface of the VLU and graft progression (in cm2) using a photographic grid. RESULTS: A total of 12 VLUs in 12 patients were included, with a mean treated surface of 20.32±13.9cm2. A total of 18 grafts were placed and all were found to be viable after one week. Average graft growth was not noticeable after one week but was found to be 0.25±0.08cm2 after week two, 0.41±0.98cm2 after week three, and 0.70±0.15cm2 after week four (p<0.001). There were no complications in the donor zone. CONCLUSION: The findings of this study show that free skin micrografting with cyanoacrylate as outpatient treatment for VLUs was simple, rapid and without complication in this study, and may contribute to its wider application in clinical use.

Endovascular treatment of abdominal aortic aneurysms with narrow aortic bifurcation using Excluder bifurcated stent grafts.

OBJECTIVE: This study investigated the influence of the aortic bifurcation anatomy on the endovascular treatment of abdominal aortic aneurysms using Excluder (W. L. Gore & Associates, Flagstaff, Ariz) bifurcated stent grafts. METHODS: This was a retrospective single-center study of patients treated with the Excluder stent graft. Analysis included anatomical factors of the aortic bifurcation (aortic bifurcation diameter [ABD], calcification, thrombus), characteristics of the stent graft limbs (sum of stent graft limbs diameters [SLD]), and the SLD/ABD ratio. Narrow bifurcation was defined as ABD <20 mm. Primary outcomes were intraoperative stenosis, need for additional intraoperative measures, limb stenosis, and occlusion during follow-up. RESULTS: The study included 232 patients. Mean ABD was 24.6 ± 6 mm, with 53 patients (23%) presenting with narrow bifurcation (range, 12.5-19.5 mm). Median SLD in these patients was 28 mm, and the SLD/ABD ratio was 1.64. Calcification involving >50% of the bifurcation circumference was present in 32% of the patients, with 17% presenting thrombus in this area. Of 53 patients with narrow bifurcation, intraoperative stenosis >50% occurred in three (5.7%), which required adjunctive treatment. Computed tomography at 1 month showed limb stenosis >50% in nine patients (17%). No limb occlusions were recorded with a median follow-up of 34 months. Multivariate analysis of the overall series showed a higher risk of limb stenosis on the computed tomography at 1 month in patients with peripheral artery disease (hazard ratio [HR], 5.3; 95% confidence interval [CI], 1.2-24.4; P = .032), narrow bifurcation (HR, 5.7; 95% CI, 2-15.8; P = .001), higher SLD/ABD ratio (HR, 29.3; 95% CI, 4-215.2; P = .001), and calcium >50% (HR, 3; 95% CI, 1.1-8; P = .03), and lower in bifurcations with thrombus (HR, 0.3; 95% CI, 0.1-0.8; P = .017). CONCLUSIONS: Abdominal aortic aneurysms with narrow bifurcation can be treated with the bifurcated Excluder device without additional adjunctive measures. The presence of limb stenosis during follow-up is not associated with occlusion. Long-term follow-up studies are needed to confirm these results.

Impact of the Repositionable C3 Excluder System on the Endovascular Treatment of Abdominal Aortic Aneurysms With Unfavorable Neck Anatomy.

PURPOSE: To analyze the midterm clinical outcomes among patients with favorable and unfavorable neck morphology for endovascular aneurysm repair (EVAR), specifically the impact of the repositionable C3 Excluder stent-graft on type I endoleak in patients with unfavorable neck. METHODS: A retrospective review was conducted of 249 patients (mean age 74.3 years; 241 men) who underwent successful EVAR from January 2000 to December 2014 using either the traditional Excluder (n=140) or the C3 repositionable system (n=109). Unfavorable proximal aortic neck anatomy was defined by length <15 mm, angulation >60°, >50% circumferential thrombus, or >50% neck calcification. By these criteria, unfavorable neck anatomy was present in 71 (28.5%) patients (41 traditional Excluder and 30 C3 Excluder). The main endpoint was the incidence of type Ia endoleak and the need for a proximal cuff according to the type of neck anatomy. Comparisons between groups are reported as the odds ratio (OR) and 95% confidence interval (CI). RESULTS: A proximal extension cuff for type Ia endoleak was needed in 4 (2.2%) patients with favorable neck anatomy compared to 7 (9.9%) patients with unfavorable neck (OR 4.76, 95% CI 1.3 to 16.8, p=0.014). Among the patients with unfavorable neck, a proximal cuff was implanted in 6/41 (14.6%) traditional Excluder stent-grafts vs 1/30 (3.3%) in the C3 Excluder group (OR 4.39, 95% CI 0.55 to 34.58, p=0.23). Median follow-up was 30.5 and 38 months for favorable vs unfavorable neck groups, respectively (p=0.29). Only 1 case of type Ia endoleak was registered at 6.5 years' follow-up (traditional Excluder), with no device migration. CONCLUSION: Both Excluder stent-grafts provide good midterm clinical outcomes after EVAR in patients with unfavorable neck anatomy. Investigation of a larger cohort will be needed to identify if the C3 Excluder device offers any improvement over the traditional Excluder in terms of freedom from endoleaks.

Outcomes of the Endovascular Treatment of Stenotic Lesions versus Chronic Total Occlusions in the Iliac Sector.

BACKGROUND: This study compares outcomes of the endovascular treatment (EVT) of iliac artery occlusive disease according to whether the treated lesion is a stenosis or a chronic total occlusion (CTO). METHODS: Patients undergoing EVT from 2003 to 2013 for iliac artery occlusive disease were identified and the lesions treated stratified into stenotic (Group 1, n = 375) or CTO (Group 2, n = 87). Patients were followed clinically and hemodynamically (thigh-brachial index, TBI). Comorbidities, procedural factors, and outcomes were compared between the 2 groups using Kaplan-Meier, Breslow, and Cox models. RESULTS: Four hundred sixty-two iliac endovascular procedures in 378 patients were included in a retrospective study. The 2 groups only differed in preprocedural TBI [0.77 (Group 1) vs. 0.67 (Group 2), P < 0.001], lesion length [39.7 mm (Group 1) vs. 49.9 mm (Group 2), P < 0.001], and the use of a covered stent [11.6% (Group 1) vs. 46.2% (Group 2), P < 0.001]. The technical success rate was higher in Group 1 (99.2% vs. 89.7%, P < 0.001). Five early occlusions were recorded in Group 1 and 3 in Group 2 (1.3% vs. 3.8%, P = 0.146). Median follow-up was 34 months (1-113). At 12 and 36 months, stenotic lesions showed better primary (P1) and secondary (P2) patency rates [P1 93.0% and 85.8% vs. 83.1% and 74.7%, hazard ratio (HR) 1.90 (1.15-3.14), P = 0.018; P2 97.8% and 96.8% vs. 93.0% and 87.4%, HR 2.86 (1.39-5.90), P = 0.007] and freedom from reintervention (FFR) rates [91.6% and 83.5% vs. 84.1% and 78.9%, HR 1.51 (0.90-2.53), P = 0.132]. In a multivariate analysis, CTO showed a worse P2 than stenotic lesions [HR 2.81 (1.17-6.76), P = 0.021], yet no differences emerged in P1 [HR 1.41 (0.76-2.63), P = 0.277] or FFR [HR 1.43 (0.79-2.57), P = 0.237]. A lower preprocedural TBI was correlated with a greater risk of EVT failure in terms of patency and FFR (P < 0.05). The use of a stent shorter than 40 mm emerged as a protective factor with an HR for P1 of 3.68 (1.53-8.87) (P = 0.004). CONCLUSIONS: EVT for iliac artery disease offers good outcomes in terms of long-term patency, although improved results were observed here for the treatment of stenotic lesions over CTO. Procedures performed in patients with a lower TBI and the use of a stent >40 mm were related to a worse stent patency.

Open Versus Endovascular Treatment for Patients with Post-Carotid Endarterectomy Restenosis: Early and Long-term Results.

BACKGROUND: The aim of this study is to assess and compare the short- and long-term results of carotid artery stenting (CAS) and redo surgery in patients with restenosis after carotid endarterectomy (CEA). METHODS: From January 1988 to December 2014, 44 consecutive patients were treated for carotid restenosis (CR): 23 redo-CEA (52.3%) and 21 CAS (47.7%). Data from these patients were prospectively collected in a dedicated database. Early results and 3-year end points were analyzed and compared between groups with χ2 test, Kaplan-Meier curves, and Breslow test. RESULTS: Demographic characteristics and comorbidity were similar in both groups, except for arterial hypertension and chronic renal insufficiency which were higher in the CAS group. CR was symptomatic in 7 patients in the redo-CEA group (30.4%) and 1 (4.8%) in CAS (P = 0.04). No differences were found in the time period between primary CEA and reintervention, critical carotid stenosis, or contralateral carotid occlusion. Median follow-up was 61.5 months. In the redo-CEA group, 1 patient (4.3%) had a perioperative transient ischemic attack and 3 (13%) experienced cranial nerve injury with complete regression at 30 days. No differences were found between groups in terms of early and long-term mortality, neurologic morbidity, and overall morbidity. The rate of secondary restenosis and freedom from reintervention was similar in both groups during follow-up. CONCLUSIONS: Both CAS and redo-CEA are suitable options for patients with CR. CAS might be the treatment of choice due to the risk of cranial nerve injuries in redo-CEA. When CAS is contraindicated, redo-CEA remains a safe and effective treatment option.

Clinical Outcomes after Endovascular Treatment Failure in Patients with Femoropopliteal Occlusive Disease.

BACKGROUND: To analyze the clinical impact derived from endovascular treatment failure on patients with femoropopliteal occlusive disease (FPOD) regarding their preoperative clinical stage. METHODS: Retrospective review for primary endovascular procedures for FPOD from 2008 to 2013. Primary end point included clinical deterioration defined as acute limb ischemia (ALI) or clinical worsening by, at least, one Rutherford's classification category, related to procedure's failure (restenosis >70% or occlusion). RESULTS: Ninety procedures were analyzed in 85 patients, 87.8% operated due to critical limb ischemia. The lesion treated was classified as Trans-Atlantic Inter-Society Consensus (TASC)-A/B in 76.7%, with a mean length of 98.5 ± 54 mm. Covered stent graft (SG) was used in 31.1% of the cases. Median follow-up was 14.5 months and treatment failure occurred in 33.3% of cases (n = 30, 9 restenosis and 21 occlusions). Clinical worsening was assessed in 40% of treatment failures and 6 of 21 (28.6%) presented as ALI. Twenty-two major adverse limb events (MALEs) were recorded and 8 major amputations. Regarding the type of stent, more occlusions were recorded on patients treated with SG compared with bare metal stent (39.3% vs. 16%; P = 0.02). However, no differences were found between groups regarding clinical worsening attributable to treatment failure (HR, 1.33; CI 95%, 0.5-3.5; P = 0.5). On multivariate analysis, TASC-C/D lesions (HR, 5.5; CI 95%, 2.3-13.3; P < 0.001) and female sex (HR, 4.9; CI 95%, 1.9-12.5; P = 0.001) behaved as significant predictors for failure and dual-antiplatelet therapy as a protective factor (HR, 0.3; CI 95%, 0.3-0.13; P = 0.03). No predictors were obtained regarding clinical worsening and occurrence of MALEs in our series. CONCLUSIONS: Patients with failure of endovascular procedures on FPOD appeared with clinical worsening in a no negligible number of cases in our sample regarding their preoperative clinical situation. Thus, we believe that endovascular treatment should be carefully deliberated.

Renal function after abdominal aortic aneurysm repair in patients with baseline chronic renal insufficiency: open vs. endovascular repair.

BACKGROUND: The aim of this study is to analyze renal function impairment (RFI) after abdominal aortic aneurysm (AAA) repair in patients with preoperative chronic kidney disease (CKD). METHODS: Retrospective cohort study of patients with CKD undergoing elective AAA repair between 2008-2015, dividing the sample into two groups: open repair (OR) and endovascular repair (EVAR). The primary outcome was RFI defined by the RIFLE scale, studying Risk (1.5-fold increase in Cr or GFR decline >25% compared to baseline) and kidney injury (doubling of Cr or GFR decline >50%). RESULTS: Seventy-five patients (OR=29, EVAR=46). Baseline characteristics for OR and EVAR were similar except for age (70.4 vs. 77.2 years; P<0.001), coronary artery disease (31% vs. 56.5%; P=0.04), neck length (12.3 vs. 22.7 mm; P=0.001) and baseline GFR (40.6 vs. 36.9 mL/min; P=0.03). There were no inter-group differences in postoperative RFI: Risk of RFI 13.8% OR vs. 13% EVAR and kidney Injury 6.9% vs. 0% (P=0.19). There were also no differences in RFI at one year. Comparing GFR and Cr after surgery and at 12 months to baseline values, the OR group presented a significant postoperative decline in GFR compared to EVAR group (-3.8% vs. 11.1%; P=0.03), which had recovered at one-year follow-up (16.6% vs. 9.5%; P=0.43), while EVAR group presented with a tendency toward increased Cr during follow-up (-9.2% vs. 2.2%; P=0.08). Multivariate analysis did not identify independent RFI prognostic factors. CONCLUSIONS: Both techniques can be used safely in patients with CKD and baseline CKD is not a limiting factor for either technique. RFI is rare and transient in both groups.

Prospective study of safety and effectiveness in the use of radiofrequency ablation for incompetent great saphenous vein ≥12 mm.

OBJECTIVE: The objective of this study was to assess the outcomes of radiofrequency ablation (RFA) in incompetent great saphenous vein (GSV) according to its diameter. METHODS: This was a prospective single-center study including all patients treated with RFA from September 2014 to December 2015. The sample was divided according to the maximum GSV diameter measured on duplex ultrasound scan (A, <12 mm; B, ≥12 mm). Second-generation catheters (ClosureFast; Covidien, Mansfield, Mass) and tumescent anesthesia were used. Clinical stage (according to Clinical, Etiology, Anatomy, and Pathophysiology [CEAP] classification), quality of life (measured by the 14-item Chronic Venous Insufficiency Questionnaire), and pain on visual analog scale were recorded before the procedure and during follow-up. Technical success was defined as GSV occlusion on duplex ultrasound scan. Safety was defined as incidence and type of adverse events at 10 days, 1 month, 6 months, and 12 months. RESULTS: There were 257 patients included, 183 (71%) with GSV diameter <12 mm and 74 (29%) with GSV diameter ≥12 mm. Mean GSV diameter was 8 ± 2 mm (4-11 mm) and 14 ± 2 mm (12-21 mm), respectively. Before the procedure, although a tendency toward greater clinical severity was observed in group B, no significant differences were found in the percentage of patients in C4 and C5 categories (A, 10%; B, 22%), median pain perception (A, 40; B, 39), or median quality of life value on the 14-item Chronic Venous Insufficiency Questionnaire scale (A, 27; B, 27). The rate of GSV occlusion at 1 month (n = 221) was 97% in group A and 100% in group B (P = .325); at 6 months (n = 158), it was 97% and 98%, respectively (P > .999); and at 12 months (n = 90), it was 99% and 96% (P = .481). There was a significant improvement in pain and quality of life in both groups, without differences between them. Finally, no differences between groups were found in terms of adverse events. Paresthesias were the most frequent event (A, 4%; B, 5%; P = NS), which disappeared during follow-up in half of the cases. Regarding major adverse events, there was only one case of deep venous thrombosis in group B. CONCLUSIONS: RFA is safe and effective for the treatment of GSV ≥12 mm at midterm.