Low Progesterone and Low Estradiol Levels Associate with Abdominal Aortic Aneurysms in Men

Context Male sex is a major risk factor for abdominal aortic aneurysms (AAA) but few studies have addressed associations between sex hormone levels and AAA. Objective To describe the associations between serum sex steroids and early, screening-detected AAA in men. Design, Setting and Participants We validated a high-sensitivity liquid chromatography-tandem mass spectrometry assay for comprehensive serum sex hormone profiling. This assay was then employed in a case-control study including 147 men with AAA (infrarenal aorta ≥30 mm) and 251 AAA-free controls recruited at the general population-based ultrasound screening for AAA in 65-year-old Swedish men. Main Outcome Measures Associations between dehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, androstenedione, estrone, testosterone, dihydrotestosterone, and estradiol and AAA presence. Results Dehydroepiandrosterone, progesterone, 17α-hydroxyprogesterone, testosterone, and estradiol, but not the other hormones, were lower in men with AAA. In models with adjustments for known AAA risk factors and comorbidity, only progesterone (odds ratio per SD decrease 1.62 [95% CI 1.18-2.22]) and estradiol (1.40 [95% CI 1.04-1.87]) remained inversely associated with the presence of AAA. Progesterone and estradiol contributed with independent additive information for prediction of AAA presence; compared with men with high (above median) levels, men with low (below median) levels of both hormones had a 4-fold increased odds ratio for AAA (4.06 [95% CI 2.25-7.31]). Conclusions Measured by a high-performance sex steroid assay, progesterone and estradiol are inversely associated with AAA in men, independently of known risk factors. Future studies should explore whether progesterone and estradiol, which are important reproductive hormones in women, are protective in human AAA.

Endovascular Reconstruction for Total Aorto–Iliac Occlusion

Objectives: To analyze outcomes following endovascular treatment of total occlusion of the infrarenal aorta and aorto–iliac bifurcation in a multicenter Italian registry. Methods: It is a multicenter, retrospective, observational cohort study. From January 2015 to December 2018, 1306 endovascular interventions for aorto–iliac occlusive disease were recorded in the vascular registry. For this analysis, only patients treated for total occlusion of the infrarenal aorta and aorto–iliac bifurcation were included. Early (<30 days) primary outcomes of interest were technical success and mortality. Late major outcomes were primary and secondary patency and freedom from conversion to open aortic surgery. Results: A total of 54 (4.1%) patients met the inclusion criteria. Total percutaneous revascularization was possible in 41 (75.9%) patients and hybrid (endo plus open) intervention in 13 (24.1%) patients. The kissing-stent-graft technique was used in 45 (83.3%) cases, covered endovascular reconstruction of the aortic bifurcation (CERAB) in 5 (9.2%), and a unibody endograft deployed in 4 (7.4%). Technical success was 98.1% (n = 53). There were no episodes of intraoperative or perioperative vessel rupture. Conversion to open surgery was not necessary, and there were no in-hospital deaths. The median patient follow-up time was 16 months (interquartrile range [IQR], 6-27). The estimated primary patency rate was 95.8% ± 0.03 (95% confidence interval [CI]: 85.5-98.9) at 1 year, 91.4% ± 0.05 (95% CI: 76.2-97.2) at 2 years, and 85 ± 0.08 (95% CI: 64.5-94.6) at 3 years. Cox regression analysis demonstrated that sex (hazard ratio [HR]: 0.96; 95% CI: 0.15-6.23, p = 0.963), extent of the occlusion (HR: 0.28; 95% CI: 0.05-1.46, p = 0.130), calcium score (HR: 1.88; 95% CI: 0.31-11.27, p = 0.490), or type of endovascular reconstruction (HR: 0.80; 95% CI: 0.13-5.15, p = 0.804) did not affect primary patency. Secondary patency was 95.5% ± 0.04 (95% CI: 78.4-99.2) at 3 years. No patients required late conversion to open surgical bypass. Conclusions: Endovascular reconstruction for total occlusion of the infrarenal aorta and aorto–iliac bifurcation was successful using a combination of percutaneous and hybrid revascularization techniques. Estimated patency rates at 3 years of follow-up are promising and are unaffected by the extent of occlusion or type of revascularization.

Treatment of patients with occlusive-stenotic diseases of the arteries of the infrarenal aorta by the hybrid method

Annotation. The treatment results of patients with arterial occlusive-stenotic diseases of the lower extremities as a result of obliterating atherosclerosis were analyzed. 79 patients underwent hybrid surgery. Most patients were ranged in age from 46 to 86 years. There were 175 men (72.0%) and 68 women (28.0%). The right lower extremity was affected more often – 148(60.9%) patients than the left ones – 95(39.1%). Of the 20 patients with stenosis of the iliac-femoral segment, 14 hybrid surgeries were completed with stenting. Endarterectomy or profundoplasty with different angioplasty options were mainly performed. Endarterectomy or thrombectomy with various angioplasty options was mainly performed in the occlusion of the femoral-popliteal segment. The main hybrid type of operation in the popliteal segment was thrombectomy of the popliteal segment and balloon angioplasty of the tibial segment. In occlusive stenotic lesions of the arteries of the tibial-foot segment in the vast majority of cases, autovenous plastics of the tibioperoneal trunk with balloon angioplasty of distal arteries were performed. The thrombosis was diagnosed in 8(10,12%) individuals as the most common complication in the early postoperative period. Limb amputation was performed in 3 patients. Mortality rate in the early postoperative period was 4,76%(2 patients died in the comparison group), in the main group there was no mortality. Acute myocardial infarction and stroke are among the most common causes of death.

Treatment of Aortic and Iliac Artery Occlusion by Catheter Thrombolysis Combined with Catheter Thrombectomy and Aortic Bifurcation Endovascular Stent Reconstruction

Aortoiliac occlusive disease (AIOD) is an occlusive disease of the infrarenal aorta and iliac arteries usually caused by stenosis or occlusion at the end of the abdominal aorta-common iliac artery. Herein, we reported a case of Trans-Atlantic Inter-Society Consensus- (TASC-) D AIOD with pale, cool, and intangible dorsalis pedis artery treated with catheter thrombolysis combined with catheter thrombectomy and aortic bifurcation endovascular stent reconstruction, which proved to be safe, effective, and minimally invasive approach. In the present paper, we discussed the physical and imaging manifestations, as well as treatments.

High Pulsatile Load Decreases Arterial Stiffness: An ex vivo Study

Measuring arterial stiffness has recently gained a lot of interest because it is a strong predictor for cardiovascular events and all-cause mortality. However, assessing blood vessel stiffness is not easy and the in vivo measurements currently used provide only limited information. Ex vivo experiments allow for a more thorough investigation of (altered) arterial biomechanical properties. Such experiments can be performed either statically or dynamically, where the latter better corresponds to physiological conditions. In a dynamic setup, arterial segments oscillate between two predefined forces, mimicking the diastolic and systolic pressures from an in vivo setting. Consequently, these oscillations result in a pulsatile load (i.e., the pulse pressure). The importance of pulse pressure on the ex vivo measurement of arterial stiffness is not completely understood. Here, we demonstrate that pulsatile load modulates the overall stiffness of the aortic tissue in an ex vivo setup. More specifically, increasing pulsatile load softens the aortic tissue. Moreover, vascular smooth muscle cell (VSMC) function was affected by pulse pressure. VSMC contraction and basal tonus showed a dependence on the amplitude of the applied pulse pressure. In addition, two distinct regions of the aorta, namely the thoracic descending aorta (TDA) and the abdominal infrarenal aorta (AIA), responded differently to changes in pulse pressure. Our data indicate that pulse pressure alters ex vivo measurements of arterial stiffness and should be considered as an important variable in future experiments. More research should be conducted in order to determine which biomechanical properties are affected due to changes in pulse pressure. The elucidation of the underlying pulse pressure-sensitive properties would improve our understanding of blood vessel biomechanics and could potentially yield new therapeutic insights.

PI 3-kinase isoform PI3Kalpha controls smooth muscle cell functionality and protects against aortic aneurysm formation

Background Class I PI 3-kinase isoform PI3Kα is a lipid kinase and signals downstream of receptor tyrosine kinases. Smooth muscle cells (SMCs) lacking PI3Kα are characterized by impaired proliferation, migration and survival. Mice, harbouring a smooth muscle specific PI3Kα deficiency (SM-PI3Kα−/−), display reduced vascular wall thickness and impaired vascular remodeling in response to vessel injury. We hypothesize that SM-PI3Kα−/− mice are prone to aortic aneurysm (AA) formation due to impaired SMC functions. Herein, we investigated, how PI3Kα-dependent signaling in SMCs affect aortic aneurysm (AA) formation, aortic wall structure, and expression of extracellular matrix (ECM) components. Methods and results AA formation in SM-PI3Kα−/− mice and wild-type littermates was examined by means of the “porcine pancreatic elastase” (PPE) AA model. PPE was infused into the infrarenal aorta to induce AA formation. Ultrasound examination revealed a significantly increased aortic diameter in SM-PI3Kα−/− mice (1.22±0.12 mm) compared to wild-type animals (0.96±0.02 mm, p=0.014). These data indicate a protective function of SM-PI3Kα in AA formation. In addition, the media thickness in the abdominal aorta was significantly reduced in SM-PI3Kα−/− mice (29.0±3.1 vs. 42.5±4.1 μm). Ultrastructural analysis of aortic wall morphology in SM-PI3Kα−/−mice using transmission electron microscopy (TEM) showed a deranged tunica media with detached SMCs and increased apoptotic cell death. Consequently, SM-PI3Kα deficiency significantly diminished responsiveness of aortic rings to vasodilator acetylcholine and NO-donor nitroglycerin, further indicating impaired aortic wall structure. Western blots demonstrated a reduced elastin and fibrillin expression in SMCs from SM-PI3Kα−/− mice. Furthermore, immunofluorescence stainings of PI3Kα−/− and wild-type SMCs, cultured for seven days under 10% fetal calf serum containing DMEM medium, showed significantly disturbed structures of elastin-, fibrillin-1- and collagen-1-fibers. These data indicate that PI3Kα signaling contributes to elastic fiber homeostasis thus affecting SMC phenotypic modulation. Immunoblots demonstrated that PDGF and insulin induced phosphorylation and inactivation of key regulators of SMC differentiation and dedifferentiation including FoxO1, FoxO3a, Foxo4, and GSK3b, respectively, were reduced or even abrogated in PI3Kα−/− SMCs. Conclusion These data show that deficiency of PI3Kα in SMCs promotes the formation and progression of AA. Causative is a deranged aortic structure of SM-PI3Kα−/− aortae which can likely be attributed to an impaired production of elastic fiber components by PI3Kα−/− SMCs. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft

Endovascular recanalization of chronic infrarenal aortic occlusion in a patient with two-vessel coronary artery disease: a case report

A case report on endovascular treatment of occlusion of the infrarenal aorta and iliac arteries in a patient with hemodynamically significant two-vessel coronary artery disease is presented. After a thorough examination and assessment of surgical risks, a multidisciplinary team meeting chose a staged revascularization strategy: stage 1 — percutaneous coronary intervention in the left anterior descending artery and right coronary artery; stage 2 — endovascular recanalization of aorto-iliac segment occlusion using the kissing stents technique. There were no perioperative complications and the patient was discharged on the 4th day after surgery in a satisfactory condition. The choice in favor of these types of reconstruction and staged revascularization strategy was substantiated. A conclusion was made about the effectiveness and safety of implemented measures.

AbsorbaSeal™ 5.6.7F vascular closure device: A good laboratory practice chronic study evaluating safety and efficacy in a healthy porcine model

Objectives Vascular closure devices (VCDs) are widely used for arteriotomy closure after percutaneous catheter–based procedures. In comparison to manual compression, VCDs have been associated with shorter time to hemostasis, shorter time to ambulation, and also decreased length of stay. Complexity of deployment, lack of immediate hemostasis, and residual deformity of the arterial wall remain as limitations of current VCDs. The aim of this study was to investigate the AbsorbaSeal™ 5.6.7F vascular closure device, a novel, completely bioabsorbable, intuitive, and easy to use VCD which uses a compressive, “sandwich”-type design comprising a low profile intravascular distal seal and gasket and an extravascular floating foot and proximal seal, in an open infrarenal aortic swine model. Methods Eight fully heparinized swine at a good laboratory practices facility underwent AbsorbaSeal™ 5.6.7F VCD closure of three 6F arteriotomies each in the proximal, mid, and distal infrarenal aorta. Two swine underwent harvest at each of four time cohorts: 30, 60, 90, and 120 days. Acute and chronic procedural safety and efficacy, as well as target site vascular remodeling over time, were the primary outcomes evaluated. Secondary outcome measures included local and systemic inflammatory responses, end-organ tissue analysis, and device-related complications through the follow-up periods. Histopathological evaluation was performed by a blinded pathologist. Standard statistical methods were used. Results In deployment of 24 AbsorbaSeal™ 5.6.7F VCDs, there were no device-related complications or mortalities. All deployments resulted in rapid arteriotomy seal (100% deployment success), with a mean time to hemostasis (cessation of arterial flow) of 21.5 s (median: 6.5 s) across a mean activated clotting time (ACT) of 356 s. Twenty of the 24 implant sites (83%) attained complete hemostasis within 20 s. Immediate post-implant and pre-termination angiographies at all time points were performed of all swine which demonstrated normal aortic appearance and tissue structure and normal downstream vascular beds. At 30 days, each implant’s intravascular distal seal and gasket were removed from the circulation and completely covered with a smooth neointimal layer. Minimal inflammation and no intimal or luminal thrombus were observed at any site at every time point. Conclusions AbsorbaSeal™ 5.6.7F is a safe, effective, and secure VCD that demonstrates rapid hemostasis in a fully heparinized open aortic porcine model. Removal from circulation and complete coverage of the intravascular distal seal and gasket with neointima occurred within 30 days post-implant. Natural transmural vessel healing from the arteriotomy itself with minimal inflammation was noted for each implant at every time point.

Fatal Case of a Contained Ruptured of the Infrarenal Aorta due to Simultaneous Primary Aortocaval Fistula and Aortoenteric Fistula

We report an extremely rare case of primary aortocaval fistula with simultaneous development of an aortoenteric fistula in a 68-year-old man. The patient developed under oral anticoagulation a spontaneous intracaval aortic rupture. An emergency intervention was performed with a covering of the fistula with an aorto-uniiliac stent graft and a femoro-femoral crossover bypass. One week later, the patient was transferred to our institution with the diagnosis of a psoas abscess and a suspected concomitant aortoenteric fistula. We performed a complete explantation of the endograft and implanted it after extensive debridement an aortobiiliac bypass, made of bovine pericardium. The postoperative course was complicated, first by bleeding from the left iliac anastomosis, and then by bleeding from the proximal aortic anastomosis. The entire graft was explanted and an axillo-femoral bypass was implanted. The patient then developed a multi-organ failure and died 3 months later. If possible, an extended surgical debridement and resection of all infected tissue with in situ reconstruction is the gold standard. However, with this therapy, there is still a high risk of reinfection. Long-term antibiotic management is mandatory.

Numerical Study of the Unsteady Flow in Simplified and Realistic Iliac Bifurcation Models

Cardiovascular diseases are a major cause of death and disability worldwide and they are commonly associated with the occurrence of atherosclerotic plaque deposition in the vessel walls, a process denoted as atherosclerosis. This is a chronic and progressive inflammatory disease of large-/medium-sized blood vessels that affects blood flow profiles, with the abdominal aorta and its branches being one of the locations prone to the development of this pathology, due to their curvatures and bifurcations. In this regard, the effect of flow patterns was studied and compared for both a simplified three-dimensional model of aorta bifurcation on the iliac arteries and a realistic model of iliac bifurcation, which was constructed from a computational tomography medical image. The flow patterns were analyzed in terms of velocity and wall shear stress distribution, but a special focus was given to the size and location of the recirculation zone. The simulations were performed using the Computational Fluid Dynamics software, FLUENT, taking into account the cardiac cycle profile at the infrarenal aorta. The shear stress and the velocity distribution observed for both models indicated that higher shear stress occurred along the flow divider wall (inner wall) and low shear stress occurred along the outer walls. In addition, the results demonstrated that the wall shear stress profiles were deeply affected by the transient profile of the cardiac cycle, with the deceleration phase being the most critical phase to the occurrence of backflow.