Impact of shaggy aorta on intraoperative cerebral embolism during carotid artery stenting.

BACKGROUND: Careful selection of patients for carotid stenting is necessary. We suggest that patients with a shaggy aorta syndrome may be at higher risk for perioperative embolic complications. METHODS: The study is a retrospective subanalysis of the SIBERIA Trial. We included 72 patients undergoing transfemoral carotid artery stenting. Patients were monitored during the procedures using multifrequency transcranial Doppler with embolus detection and differentiation. Pre- and postprocedural (2 and 30 days) cerebral diffusion-weighted cerebral MRIs were performed. RESULTS: Forty-six patients had shaggy aorta syndrome. Intraoperative embolisms were recorded in 82.6% and 46.1% of patients with and without shaggy aorta syndrome, respectively (P=0.001). New asymptomatic ischemic brain lesions in the postoperative period occurred in 78.3% and in 26.9% of patients with and without shaggy aorta syndrome, respectively (P<0.001). There were no cases of stroke within 2 days in both groups. 3 (6.5%) cases of stroke within 30 days after the procedure were observed only in patients with shaggy aorta syndrome. There were no cases of contralateral stroke. Shaggy aorta syndrome (OR 5.54 [1.83:16.7], P=0.001) and aortic arch ulceration (OR 6.67 [1.19: 37.3], P=0.02) were independently associated with cerebral embolism. Shaggy aorta syndrome (OR 9.77 [3.14-30.37], P<0.001) and aortic arch ulceration (OR 12.9 [2.3: 72.8], P=0.003) were independently associated with ipsilateral new asymptomatic ischemic brain lesions. CONCLUSIONS: Shaggy aorta syndrome and aortic arch ulceration significantly increase the odds of intraoperative embolism and new asymptomatic ischemic brain lesions. Carotid endarterectomy or transcervical carotid stent should be selected in patients with shaggy aorta syndrome.

Treatment of acute pulmonary embolism after catheter-directed thrombolysis with dabigatran vs warfarin: Results of a multicenter randomized RE-SPIRE trial.

BACKGROUND: Thrombolytic therapy is effective method in the high-risk acute pulmonary embolism (PE) treatment. Reduced-dose thrombolysis (RDT) plus oral anticoagulation therapy is effective and safe method in the moderate and severe PE treatment. It is leading to good early and intermediate-term outcomes. In the RE-COVER and RE-COVER II studies, dabigatran showed similar effectiveness as warfarin in the treatment of acute PE. Dabigatran leads to fewer hemorrhagic complications and is not inferior in efficacy to warfarin in the prevention of PE after mechanical fragmentation and RDT (catheter-directed treatment [CDT]+RDT) in patients with high and intermediate to high PE risk. We sought to evaluate the efficacy and safety (incidence of clinically significant recurrence of venous thromboembolic complications and deaths) during a 6-month course of treatment with dabigatran or warfarin in patients with high and intermediate to high acute PE risk after endovascular mechanical thrombus fragmentation procedure with RDT (CDT+RDT). METHODS: The RE-SPIRE is a prospective, multicenter randomized double-arm study. Over a 5-year period, 66 consecutive patients with symptomatic high and intermediate to high PE risk after endovascular mechanical thrombus fragmentation procedure with RDT (CDT+RDT) were randomized into two groups within the next 48 hours. The first group continued treatment with dabigatran 150 mg twice a day for 6 months; the second group continued treatment with warfarin under the control of international normalized ratio (2.0-3.0) for 6 months. Both groups received low molecular weight heparins for 2 days after surgery. Then, group 1 continued to receive low molecular-weight-heparin for 5 to 7 days, followed by a switch to dabigatran at a dosage of 150 mg two times a day. Group 2 received both low-molecular-weight heparin and warfarin up to an international normalized ratio of >2.0, followed by heparin withdrawal. The follow-up period was 6 months. RESULTS: There were 63 patients who completed the study (32 in the dabigatran group and 31 in the warfarin group). In both groups, there was a statistically significant decrease in the mean pulmonary artery pressure. The mean pulmonary artery pressure at the 6-month follow-up after surgery was 24 mm Hg (interquartile range, 20.3-29.25 mm Hg) in the dabigatran group and 23 mm Hg (interquartile range, 20.0-26.3 mm Hg) in the warfarin group. The groups did not differ statistically in the deep vein thrombosis dynamics. Partial recanalization occurred in 52.0% vs 73.1% in the dabigatran and warfarin groups, respectively (P = .15). Complete recanalization occurred in 28.0% vs 19.2% in the dabigatran and warfarin groups, respectively (P = .56). The groups did not differ in the frequency of major bleeding events according to the International Society for Thrombosis and Hemostasis (0% vs 3.2% in the dabigatran and warfarin groups, respectively; P = 1.00). However, there were more nonmajor bleeding events in the warfarin group than in the dabigatran group (16.1% vs 0%, respectively; P = .02). CONCLUSIONS: The results of the study show that dabigatran is comparable in effectiveness to warfarin. Dabigatran has greater safety in comparison with warfarin in the occurrence of all cases of bleeding in the postoperative and long-term periods. Thus, dabigatran may be recommended for the treatment and prevention of PE after CDT with RDT in patients with high and intermediate to high PE risk.

iPSC-Derived Endothelial Cells Reveal LDLR Dysfunction and Dysregulated Gene Expression Profiles in Familial Hypercholesterolemia.

Defects in the low-density lipoprotein receptor (LDLR) are associated with familial hypercholesterolemia (FH), manifested by atherosclerosis and cardiovascular disease. LDLR deficiency in hepatocytes leads to elevated blood cholesterol levels, which damage vascular cells, especially endothelial cells, through oxidative stress and inflammation. However, the distinctions between endothelial cells from individuals with normal and defective LDLR are not yet fully understood. In this study, we obtained and examined endothelial derivatives of induced pluripotent stem cells (iPSCs) generated previously from conditionally healthy donors and compound heterozygous FH patients carrying pathogenic LDLR alleles. In normal iPSC-derived endothelial cells (iPSC-ECs), we detected the LDLR protein predominantly in its mature form, whereas iPSC-ECs from FH patients have reduced levels of mature LDLR and show abolished low-density lipoprotein uptake. RNA-seq of mutant LDLR iPSC-ECs revealed a unique transcriptome profile with downregulated genes related to monocarboxylic acid transport, exocytosis, and cell adhesion, whereas upregulated signaling pathways were involved in cell secretion and leukocyte activation. Overall, these findings suggest that LDLR defects increase the susceptibility of endothelial cells to inflammation and oxidative stress. In combination with elevated extrinsic cholesterol levels, this may result in accelerated endothelial dysfunction, contributing to early progression of atherosclerosis and other cardiovascular pathologies associated with FH.

Treatment of Long Femoropopliteal Occlusive Lesions With Self-expanding Interwoven Nitinol Stent: 24 Month Outcomes of the STELLA-SUPERA-SIBERIA Register Trial.

PURPOSE: The efficacy and safety of the Supera stent in superficial femoral artery (SFA) have been reported mostly in shorter lesions with relatively low proportion of occlusions. There are little data on the effectiveness of the Supera stent in long lesions. The aim of this study was to assess the clinical safety and efficiency of the Supera stent in the treatment of long femoropopliteal occlusive lesions (Trans-Atlantic Inter-Society Consensus [TASC] C/D) in patients with symptomatic peripheral artery disease. MATERIALS AND METHODS: The STELLA-SUPERA-SIBERIA is a prospective, single-center, single-arm study. Patients with symptomatic (Rutherford stages 3-6) de novo and TASC C/D occlusive lesions of the femoropopliteal segment were treated with Supera stent. The primary endpoint was the 12 month rate of primary sustained clinical improvement (upward shift on the Rutherford classification to a one level without the need for repeated target lesion revascularization (TLR) in surviving patients without the need for unplanned amputation). Secondary endpoints were the 24 month of primary sustained clinical improvement, MALE, limb salvage, the primary patency, the secondary patency, 24 month MACE. Follow-up included clinical examination, duplex scan, and biplane x-ray up to 24 months. RESULTS: Between April 2019 and January 2020, 52 symptomatic patients with 55 long femoropopliteal occlusive lesions (52.7% TASC D lesions and 47.3% TASC C lesions) were treated. The mean target lesion length was 205±72 mm. All patients had total occlusions. The mean lesion length of the implanted Supera stents was 198±82 mm. At 12 and 24 months, the primary sustained clinical improvement rate was 80.2% and 63.6%, respectively. The Rutherford category assessment was significantly improved at 24 months compared with baseline (p=0.02). The primary patency rate at 12 and 24 months was 78.1% and 60.0%, respectively. At 12 and 24 months, freedom from TLR was 83.5% and 81.8%, respectively. There were no stent fractures at 24 months. CONCLUSION: Supera Stent implantation for TASC C/D femoropopliteal lesions revascularization appears to be a safe and efficient implant given the complexity of the treated lesions. Head-to-head studies are mandatory to establish Supera Stent as an alternative tool to open surgery for long femoropopliteal lesions. CLINICAL IMPACT: Our study indicated, that using self-expanding interwoven nitinol stent for TASC C/D femoropopliteal lesions revascularization appears to be a safe and efficient implant given the complexity of the treated lesions. Although bypass grafting is recommended for prolonged femoropopliteal lesions, open surgery is more traumatic and is associated with greater risks than endovascular procedures. Our findings suggest that the use of interwoven nitinol stents can overcome the disadvantages of traditional stents in such cases, which may help to improve patients' outcomes and reduce the risk of adverse events.

One-Year Results of Long femoropopliteal Lesions Stenting with Fasciotomy Lamina Vastoadductoria.

BACKGROUND: Fasciotomy can increase the mobility of the superficial femoral artery and decrease the incidence of stent fractures. This study aimed to compare the long-term patency of drug-eluting nitinol stents with and without fasciotomy in patients with prolonged superficial femoral artery occlusions. METHODS: A randomized clinical trial was conducted in 60 (1:1) patients with long femoropopliteal steno-occlusive lesions >200 mm. Patients in group 1 (Zilver) underwent recanalization of femoropopliteal artery occlusion with stenting. In group 2 (ZilverFas), the femoropopliteal occlusion was recanalized with stenting and fasciotomy of Gunter's canal. The follow-up assessment of the patency took place after 6-12 months. RESULTS: Twelve-month primary patency in Zilver and ZilverFas groups was 51% and 80%, respectively (P = 0.02). The freedom from target lesion revascularization in the Zilver and ZilverFas groups was 50% and 76%, respectively (P = 0.04). At 1 year, primary-assisted patency and secondary patency for the ZilverFas and Zilver groups were 83% vs. 62% (P = 0.07) and 86% vs. 65% (P = 0.05), respectively. In the Zilver and ZilverFas groups, the number of stent fractures was 14 and 7, respectively (P = 0.05). The multivariable Cox regression indicated that the stent fracture and diabetes mellitus were independent predictors of restenosis and reocclusion. Fasciotomy reduced the risk of reocclusion and restenosis by 2.94 times. CONCLUSIONS: Our study has shown that decompressing the stented segment with fasciotomy significantly improves the patency of the femoropopliteal segment and significantly reduces the number and severity of stent fractures.

Bypass Versus Interwoven Nitinol Stents for Long Femoro-Popliteal Occlusions: A Propensity Matched Analysis.

PURPOSE: To compare femoro-popliteal bypass and interwoven nitinol stenting for long occlusions of the femoro-popliteal segment. MATERIALS AND METHODS: Single center retrospective propensity matching analysis of the symptomatic patients with long occlusion of the femoro-popliteal segment (> 20 cm), who underwent stenting with interwoven nitinol stent or femoro-popliteal bypass from 2012 to 2020. PRIMARY ENDPOINTS: primary patency, primary-assisted patency, secondary patency. Secondary endpoints: major adverse cardiovascular events, major adverse limb events, primary sustained clinical improvement, survival. RESULTS: A total of 437 patients were enrolled: 294 in the bypass group and 143 in the endovascular therapy (EVT) group. After propensity score matching, 264 and 113 patients remained in the groups, respectively. A median occlusion length was 250 mm. One-year and two-year primary and secondary patency rates were comparable in both groups (two-year primary patency: 68.5% for bypass vs. 68.9% for EVT, p = 1.00). In the "above the knee" subgroup analysis, two-year secondary patency was higher in the EVT group than in the bypass group (90.9% vs. 77.5%, p = 0.048). In "below-the-knee" subgroup analysis, primary and primary assisted patency were statistically significantly higher in the EVT group than in artificial bypass subgroup (66.7% vs. 42.4%, p = .046 and 76.7% vs. 45.5%, p = .011, respectively). However, compared to autovenous bypass, the EVT group showed lower primary patency rates, although the differences are not significant. CONCLUSION: A nonselective endovascular strategy can allow for regular successful treatment of femoro-popliteal lesions longer than 25 cm.

Mitomycin-Treated Endothelial and Smooth Muscle Cells Suitable for Safe Tissue Engineering Approaches.

In our previous study, we showed that discarded cardiac tissue from the right atrial appendage and right ventricular myocardium is an available source of functional endothelial and smooth muscle cells for regenerative medicine and tissue engineering. In the study, we aimed to find out what benefits are given by vascular cells from cardiac explants used for seeding on vascular patches engrafted to repair vascular defects in vivo. Additionally, to make the application of these cells safer in regenerative medicine we tested an in vitro approach that arrested mitotic division to avoid the potential tumorigenic effect of dividing cells. A tissue-engineered construction in the form of a patch based on a polycaprolactone-gelatin scaffold and seeded with endothelial and smooth muscle cells was implanted into the abdominal aorta of immunodeficient SCID mice. Aortic patency was assessed using ultrasound, MRI, immunohistochemical and histological staining. Endothelial and smooth muscle cells were treated with mitomycin C at a therapeutic concentration of 10 µg/ml for 2 h with subsequent analysis of cell proliferation and function. The absence of the tumorigenic effect of mitomycin C-treated cells, as well as their angiogenic potential, was examined by injecting them into immunodeficient mice. Cell-containing patches engrafted in the abdominal aorta of immunodeficient mice form the vessel wall loaded with the appropriate cells and extracellular matrix, and do not interfere with normal patency. Endothelial and smooth muscle cells treated with mitomycin C show no tumorigenic effect in the SCID immunodeficient mouse model. During in vitro experiments, we have shown that treatment with mitomycin C does not lead to a decrease in cell viability. Despite the absence of proliferation, mitomycin C-treated vascular cells retain specific cell markers, produce specific extracellular matrix, and demonstrate the ability to stimulate angiogenesis in vivo. We pioneered an approach to arresting cell division with mitomycin C in endothelial and smooth muscle cells from cardiac explant, which prevents the risk of malignancy from dividing cells in vascular surgery. We believe that this approach to the fabrication of tissue-engineered constructs based on mitotically inactivated cells from waste postoperative material may be valuable to bring closer the development of safe cell products for regenerative medicine.

Influence of lamina vastoadductoria dissection on the outcomes of femoral artery extensive lesion stenting: A pilot randomised investigation.

OBJECTIVE: Aim of the study was to improve the immediate and long-term results of stenting of the superficial femoral artery in extended lesions with the changing of the biomechanics of superficial ffemoral artery and of the first portion of the popliteal artery. METHODS: Pilot randomized prospective single-center study were included 70 patients. Patients were randomized into two groups in 1 × 1 format for 35 people using the envelope method. Self-expanding bare metal stents were used in all cases. At the first group standard revascularization procedures with SFA stenting were performed; in the second group, the superficial femoral artery stenting was supplemented with fasciotomy in the Hunter's canal with the superficial femoral artery intersection. The total observation period was 2 years. During the observation period an assessment of the clinical symptoms of the lower extremities, measurement of the ankle-brachial index and ultrasound duplex scanning of the operated segment were performed. RESULTS: All procedures in both groups were successfully performed. Primary patency through 24 months was 28.5% (10 of 35) in group 1 and 60% (21 of 35) in group 2 (p = 0,015). CONCLUSIONS: Changing the biomechanical properties of the distal of the superficial femoral artery segment and of the first portion of the popliteal artery is safe and contributes to the primary patency improvement during the stenting of extended of the superficial femoral artery lesions compared to standard SFA stenting. Dissection of the lamina vastoadductoria with transection of the collateral branches of the knee joint network reduces frequent and severe damages of stents after the stenting of the superficial femoral artery extended lesion. According to the frequency of complications in the early and mid-term postoperative period, limb salvage, mortality and the secondary patency rates, the new method is comparable with standard of the superficial femoral artery stenting.

A prospective randomized trial on endovascular recanalization with stenting versus remote endarterectomy for the superficial femoral artery total occlusive lesions.

OBJECTIVE: The objective of this randomized study was to compare the short- and long-term safety and efficacy of endovascular recanalization with stenting (EI) and remote endarterectomy (RE) for patients with superficial femoral artery (SFA) total occlusive lesions (≥250 mm). METHODS: Between July 2013 and July 2017, eligible patients with SFA total occlusive lesions were randomized to EI or RE. The EI group underwent recanalization and stenting of long SFA atherosclerotic occlusive lesions. The RE group underwent semiclosed endarterectomy. Short- (30-day) and long-term (48-month) morbidity, mortality, and patency rates were compared between both groups. RESULTS: Of 400 patients assessed, 238 were ultimately randomized (119 EI and 119 RE). The cumulative primary patencies were 83% (EI) vs 82% (RE) at 12 months and 28% (EI) vs 46% (RE) at 48 months (P = .04). The limb salvage was 98% (EI) vs 95% (RE) at 12 months and 87% (EI) vs 92% (RE) at 48 months (P = .26). One-year and 4-year secondary patencies were 98% and 87% in the EI group and 100% and 90% in the RE group, respectively (P = .4). A total of 65 patients in the stenting group and 32 patients in the endarterectomy group underwent endovascular reintervention. Four-year patencies of endovascular reintervention subgroups were 37% and 60% (P = .04), respectively. CONCLUSIONS: RE shows significantly better results in the long term than primary stenting of SFA long lesions (TASC-II D lesions). In case of loss patency, a desobliterated artery can be successfully subjected to endovascular revascularization and stenting with good short- and long-term results.

Editor's Choice - Hybrid vs. Open Surgical Reconstruction for Iliofemoral Occlusive Disease: A Prospective Randomised Trial.

OBJECTIVE: The aim of this non-inferiority randomised trial was to compare the short and midterm safety and efficacy of hybrid repair (HR) and open reconstruction (OR) for patients with co-existing iliac and common femoral artery (CFA) occlusive disease. METHODS: The study was registered on the ClinicalTrials.gov register (identifier: NCT02580084). From 2015 to 2017, eligible patients presenting with combined iliac and CFA occlusive disease were randomised to either HR or OR. HR group patients underwent recanalisation and stenting of iliac arteries combined with CFA endarterectomy and patch angioplasty. The OR group underwent aortofemoral bypass with simultaneous CFA endarterectomy. Short (30 day) and midterm (36 month) outcomes including morbidity, mortality, and patency rates were compared between groups. RESULTS: Of 427 patients assessed, 202 were randomised (102 HR and 100 OR). The average hospital length of stay was shorter in the HR group (8.2 ± 4.2 days HR group vs. 15.7 ± 6.9 days OR group, p < .001); the 30 day peri-operative morbidity rate was 8.8% in the HR group vs. 21% in the OR group (p = .030). There was no significant difference in the 36 month mortality rate (p = .16). The cumulative primary patency rates were 93% (HR) vs. 93% (OR) at 12 months and 91% (HR) vs. 89% (OR) at 36 months (p = .38). The limb salvage rates were 99% (HR) vs. 99% (OR) at 12 months and 98% (HR) vs. 97% (OR) at 36 months (p = .49). CONCLUSION: The results of this first non-inferiority randomised study support the safety and midterm efficacy of hybrid procedures for patients with iliofemoral peripheral arterial disease. HR patients had a shorter length of stay with reduced peri-operative morbidity and similar medium term patency rates.

Post-Traumatic Arteriovenous Fistulas Leading to Heart Failure.

INTRODUCTION: The detection of acquired arteriovenous fistulas (AVFs) is mostly incidental. However, the modification of haemodynamic conditions secondary to AVFs can lead to dramatic systemic complications, including cardiac complications. In this report, two unusual cases of congestive heart failure secondary to acquired AVF are presented. REPORT: A 40 year old man with past history of gunshot wound of the right flank complained of severe right limb swelling and shortness of breath. An AVF between the right external iliac artery and external iliac vein responsible for the cardiac failure was diagnosed. A 40 year old woman with past history of spinal surgery complained of breathlessness and lower limb oedema. She presented with recurrent episodes of ascites and dyspnoea. An AVF between the right common iliac artery and the common iliac vein responsible for high output cardiac failure was diagnosed. Open surgery was performed in both patients and treatment of the AVFs led to the resolution of all symptoms. Follow up at four and three years, respectively, was uneventful in both cases. DISCUSSION: Although rare, heart failure secondary to an AVF can be encountered. These rare cases highlight the significance of careful inquiry into the patient's medical history and meticulous follow up physical examinations for patients with injuries in close proximity to vessels.

Cell therapy of critical limb ischemia-problems and prospects.

Cell therapy is proposed for indirect revascularization for the patient's incurable by endovascular or surgical revascularization. The therapy with stem cells (SCs) or progenitor cells is assumed to be more efficient as compared with protein or gene therapy not only because of their direct vasculogenic properties, but also thanks to their paracrine effect via secretion of manifold biologically active substances. This review gives an overview of the potential of SC-based therapy for critical limb ischemia (CLI), putative mechanism underlying cell therapy, and comparison of cell therapy to angiogenesis gene therapy in CLI treatment. Human trial data and meta-analysis, as well as some problems of clinical trials and considerations for future SC-based therapy in CLI are also discussed.