Endovascular repair of ascending aortic pathologies in patients unfit for open surgery: case series and literature review.

The number of vascular centers performing endovascular repair of ascending aortic disease is constantly increasing. Accordingly to the guidelines, open surgical repair remains the gold standard for these pathologies. However, approximately one quarter of patients are deemed unfit for open surgery. In this study, we describe three cases of ascending thoracic endovascular aortic repair (TEVAR) performed at our center. All the patients were deemed unfit for open surgery by the aortic team. Two patients had an ascending aortic pseudoaneurysm, and the third had a focal type A aortic dissection. In two cases, we used two abdominal aortic cuffs deployed from zone 0B to zone 0C, with no need for supra-aortic trunk debranching. In one case, we performed a "reverse" extrathoracic debranching, and we deployed a thoracic endograft from zone 0B to zone 2. Complications included one minor stroke and one inguinal hematoma. In one patient with an infected pseudoaneurysm, we performed ascending TEVAR as a bridge strategy for open repair. This patient developed a type Ia endoleak; however, clinical stabilization and infection control were obtained, and he was able to undergo heart surgery successfully. He underwent a second reintervention to treat superior mesenteric embolic occlusion. At 2 years of follow-up, all three patients were alive. Our preliminary experience demonstrates the technical feasibility and clinical appropriateness of ascending TEVAR using standard, commercially available endografts. However, no consensus has been reached regarding some critical aspects, such as the development of a standardized technique or the efficacy of the currently available devices. The improvements in graft design and the adoption of the "aortic team" approach could help in the near future to standardize the procedure, establish appropriate indications, and ensure good clinical outcomes.

Volumetric analysis in primary and residual type B aortic dissection treated with stented-assisted balloon-induced intimal disruption and relamination technique can predict aortic reintervention.

OBJECTIVE: The aim of this study was to investigate the mid-term results of stented-assisted balloon-induced intimal disruption and relamination (STABILISE) in patients with aortic dissection with the implementation of volumetric analysis. METHODS: This was a single-center retrospective analysis of prospectively collected data. From May 2017 to September 2022, 42 patients underwent STABILISE for acute complicated or subacute high-risk aortic dissection. STABILISE was completed with distal extended endovascular aortic repair in 24 patients. A computed tomography scan was performed at baseline, before hospital discharge, and at 1, 3, and 5 years. Perfused total aortic, true lumen, and false lumen volumes were assessed for thoracic, visceral, and aorto-iliac segment. The ratio between false lumen and total volume was named perfusion dissection index (PDI). Complete remodeling was defined as PDI = 0, and positive remodeling as PDI ≤0.1. RESULTS: Technical success was 97.6%. No 30-day deaths, spinal cord injuries, or retrograde dissections were observed. Mean follow-up was 44 ± 19.4 months. Thoracic diameter was lower at last available computed tomography scan (36.7 vs 33.0 mm; P = .01). Aortic growth >5 mm was observed in 9.5% of the patients. Thoracic and visceral aortic complete remodeling were 92.8% and 83.3%, respectively, with no difference between acute and subacute group. Distal extended endovascular aortic repair significantly increased complete remodeling in the aorto-iliac segment, compared with STABILISE alone (69.6% vs 21.4%; P < .001). Freedom from vascular reinterventions at 3 years was 83.1% (95% confidence interval, 71.5%-96.6%). Total PDI ≤0.1 at first postoperative control was a predictor of vascular reinterventions (P < .0001). CONCLUSIONS: STABILISE is a safe and feasible technique associated with high mid-term rates of complete remodeling in the thoracic and visceral aorta. Volumetric analysis allows the quantification of aortic remodeling and represents a predictor of aortic reinterventions.

Sex-Specific Morphometric Analysis of Ascending Aorta and Aortic Arch for Planning Thoracic Endovascular Aortic Repair: A Retrospective Cohort Study.

OBJECTIVE: In many studies on aortic disease, women are underrepresented. The present study aims to assess sex-specific morphometric differences and gain more insight into endovascular treatment of the ascending aorta (AA) and arch. METHODS: Electrocardiogram-gated cardiac computed tomography scans of 116 consecutive patients who were evaluated for transcatheter aortic valve replacement were retrospectively reviewed. Measurements of the AA and aortic arch were made in multiplanar views, perpendicular to the semi-automatic centerline. Multiple linear regression analysis was performed to identify predictors affecting AA and aortic arch diameter in men and women. Propensity score matching was used to investigate whether sex influences aortic morphology. RESULTS: In both sexes, body surface area (BSA) was identified as a positive predictor and diabetes as a negative predictor for aortic diameters. In men, age was identified as a positive predictor and smoking as a negative predictor for aortic diameters. Propensity score matching identified 40 pairs. Systolic and diastolic mean diameters and AA length were significantly wider in men. On average, male aortas were 7.4% wider than female aortas, both in systole and diastole. CONCLUSIONS: The present analysis demonstrates that, in women, increased BSA is associated with increased aortic arch diameters, while diabetes is associated with decreased AA and arch diameters. In men, increased BSA and age are associated with increased AA and arch diameters, while smoking and diabetes are associated with decreased AA and arch diameters. Men were confirmed to have 7.4% greater AA and arch diameters than women. CLINICAL IMPACT: Men had 7.4% greater ascending aorta and arch diameters than women in a retrospective cohort, gated computed tomography-based study of 116 patients. Sex-specific differences in ascending aortic and arch size should be considered by aortic endovascular device manufacturers and physicians when developing ascending and arch endografts and planning aortic interventions.

Experimental Analysis of Radiation Protection Offered by a Novel Exoskeleton-Based Radiation Protection System versus Conventional Lead Aprons.

PURPOSE: To evaluate the radiation protection offered by an exoskeleton-based radiation protection system (Stemrad MD) and to compare it with that offered by conventional lead aprons. METHODS: The experimental setup involved 2 anthropomorphic phantoms, an operator, a patient, and a C-arm as the x-ray radiation source. Thermoluminescent detectors were used to measure radiation doses to different radiosensitive body parts on the operator phantom both with the exoskeleton and a conventional lead apron at the left radial and right femoral positions. Detected radiation doses for the exoskeleton and lead apron for different body parts and positions were compared. RESULTS: At the left radial position, the mean radiation dose (mGy) reduction by the exoskeleton compared with that by the lead apron was >90% for the left eye lens (0.22 ± 0.13 vs 5.18 ± 0.08; P < .0001), right eye lens (0.23 ± 0.13 vs 4.98 ± 0.10; P < .0001), left head (0.11 ± 0.16 vs 3.53 ± 0.07; P < .0001), right head (0.27 ± 0.09 vs 3.12 ± 0.10; P < .0001), and left brain (0.04 ± 0.08 vs 0.46 ± 0.07; P < .0001). At the right femoral position, radiation reduction was >90% for the left eye lens (0.14 ± 0.10 vs 4.16 ± 0.09; P < .0001), right eye lens (0.06 ± 0.08 vs 1.90 ± 0.11; P < .0001), left head (0.10 ± 0.08 vs 4.39 ± 0.08; P < .0001), left brain (0.03 ± 0.07 vs 1.44 ± 0.08; P < .0001), right brain (0.00 ± 0.14 vs 0.11 ± 0.13; P = .06), and thyroid (0.04 ± 0.07 vs 0.27 ± 0.09; P < .0001). Protection of the torso was equivalent to that offered by conventional lead aprons. CONCLUSIONS: The exoskeleton-based system provided superior radiation protection to the physician compared with that provided by conventional lead aprons. The effects are particularly impactful for the brain, eye lens, and head areas.

StemRad MD, An Exoskeleton-Based Radiation Protection System, Reduces Ergonomic Posture Risk Based on a Prospective Observational Study.

OBJECTIVE: Poor ergonomic posture during interventional procedures might lead to increased physical discomfort and work-related musculoskeletal disorders. Adjunctive equipment such as lead aprons (LAs) has been shown to increase ergonomic posture risk (EPR). The objective of this study was to evaluate the effectiveness of StemRad MD (StemRad Ltd., Tel Aviv, Israel), a weightless exoskeleton-based radiation protective ensemble, in reducing EPR on the operator using wearable inertial measurement unit (IMU) sensors. METHODS: A prospective, observational study was conducted at an academic hospital. Inertial measurement unit sensors were affixed to the upper back of 9 interventionalists to assess ergonomic risk posture during endovascular procedures while wearing a traditional LA or the StemRad MD radiation protection system. Total fluoroscopy time, procedure type, and ergonomic risk postures were recorded and analyzed. RESULTS: Twenty-one cases were performed with StemRad MD and 30 with LAs. Mean procedure time for the StemRad MD procedures was 48.4±23.3 minutes (range: 24-106 min), and for LA procedures, it was 34.66±25.83 minutes (range: 6-100 min) (p=.060). The operators assumed low-risk ergonomic positions in 96.1% of StemRad MD cases and in 62.9% of LA cases (p=.001), and high-risk ergonomic positions in 0% and 6.2%, respectively (p=.80). Mean EPR score for StemRad MD was 1.16, and for the LA, it was 1.49 (p=.001). CONCLUSIONS: StemRad MD significantly reduces the EPR to the torso compared with a LA-based radiation protection system. CLINICAL IMPACT: Poor ergonomic posture during interventional procedures might leas to work-related musculoskeletal disorders for healthcare workers. StemRad MD, a weightless, exoskeleton-based radiation protection system was shown to significantly reduce ergonomic posture risk to the torso compared to conventional lead aprons. This might lead to reduced physical discomfort for procedure-based specialists.

Single-Center Experience With Aortic Coarctation Stenting in Adult Patients.

OBJECTIVE: Endovascular repair of aortic coarctation (CoA) has become an important tool in the treatment of an expanding patient population. In this study, we present our 10-year experience with endovascular repair of CoA. METHODS: Between January 2012 and January 2022, a total of 15 patients were treated at our Institution for CoA with catheter-based techniques. Demographics, intraprocedural data, and follow-up data were retrospectively collected from institutional databases and analyzed. The primary endpoint was technical success and secondary endpoints were intraoperative complications and short-, mid-, and long-term follow-up. RESULTS: Mean age was 44.87 ± 15.52 years (range, 15-64) and 12 patients (80%) were male. Fourteen patients (93.3%) were hypertensive, and 4 patients (26.7%) had a bicuspid aortic valve. Three patients (20%) had undergone open repair in the pediatric age. Fourteen patients (93.3%) received stenting of CoA and 1 patient (6.7%) received thoracic endovascular aortic repair and left subclavian artery stenting for proximal pseudoaneurysmatic dilation and symptomatic restenosis. Mean pretreatment trans-stenotic gradient was 23.25 ± 11.16 mm Hg and posttreatment trans-stenotic gradient was 1.3 ± 1.33 mm Hg. Primary technical success was achieved in 15 cases (100%). One right inguinal hematoma (6.7%) was observed. One patient (6.7%) had an aortic rupture at the left subclavian artery origin after poststent dilation. Mean follow-up time was 34.75 ± 34.38 months. A total of 2 patients had an increased trans-stenotic gradient at long-term follow-up, and 1 reintervention (6.7%) for somatic growth was performed. CONCLUSIONS: Endovascular repair of CoA is effective and safe, with excellent mid-term and long-term success rates.

"Octafen": A Noninvestigational Alternative Endograft Configuration for the Treatment of Thoracoabdominal Aortic Aneurysms.

PURPOSE: To demonstrate the feasibility of Octafen technique, a novel endovascular configuration for the treatment of thoracoabdominal aortic aneurysms (TAAA). TECHNIQUE: Two patients with complex TAAA and high surgical risk were treated with Octafen endograft configuration in a hybrid operating room with computed tomography (CT)-fluoroscopy image fusion guidance, using 3D-3D fusion techniques to facilitate procedural success. The procedure is a modification of the previously-described Octopus technique for endovascular repair of TAAA. The main advantage of this technique is the ability to use devices to repair a TAAA with the combination of off-the-shelf and noninvestigational custom-made devices. The devices used are readily available to most practicing vascular surgeons, which provides an alternative treatment in case of limited access to investigational devices, in time-sensitive cases, and in patients with limited functional capacity who cannot undergo open repair. In the modification described herein, we use a combination of standard bifurcated endovascular aneurysm repair (EVAR) devices (Excluder; W.L. Gore & Associates, Flagstaff, Arizona) in combination with a 2-vessel renal fenestrated device (Z-Fen; Cook Medical, Bloomington, Indiana). The article describes a step-by-step approach to this technique to elucidate pitfalls, benefits, and advantages. CONCLUSION: The Octafen technique might offer an alternative option for thoracoabdominal aneurysm treatment circumventing the need for access to custom-made, investigational devices. CLINICAL IMPACT: In this manuscript, we describe a technique for endovascular repair of thoraco-abdominal aortic aneurysms that involves the combination of off-the-shelf and non-investigational, custom-made devices. The 'Octafen' technique provides a treatment alternative in case of limited access to investigational devices and can be adjusted according to patient anatomy.

Multimodality Image-Guided Embolization of Bronchial Artery Pseudoaneurysm in a Patient With Aortopathy.

A 59-year-old man received an incidental diagnosis of a 5-cm right para-aortic mass that was initially thought to be of venous origin. Multimodality imaging revealed a right bronchial artery pseudoaneurysm that was treated with endovascular embolization. Bronchial artery pseudoaneurysms are extremely rare and can be fatal if ruptured. (Level of Difficulty: Advanced.).

Elective Multistaged Endovascular Repair of Thoraco-abdominal Aneurysms with Fenestrated and Branched Endografts to Mitigate Spinal Cord Ischaemia.

OBJECTIVE: To evaluate the safety and effectiveness of a multistaged approach for elective thoraco-abdominal aneurysm (TAAAs) repair by means of endovascular fenestrated and/or branched (F/B-EVAR) grafts. METHODS: Between 2013 and 2018, 80 high risk surgical patients received elective F/B-EVAR for TAAAs with a protocolled multistaged approach (thoracic, visceral, and limb steps) and were enrolled in an ambispective single centre study called STEAR (STaged Endovascular Aortic Repair - NCT03342755). Data regarding all study participants, single step mortality and morbidity (systemic complications) rates were recorded and the overall results were considered for statistical analysis. RESULTS: Previous aortic interventions (61/80 cases, 76.3%) combined with the TAAA extents resulted in different staging strategies: 58 patients (73%) had a thoracic step and 33 (41%) a limb step. The median TAAA treatment time was 77 days (50-107). The overall mortality was six cases (8%) and 30 day clinical success rate 64 cases (80%). The overall rate of grade 2 or 3 (including death) systemic complications was 19 cases (24%) and 20 patients (25%) experienced grade 1 complications. Three patients with type II or III TAAAs (4%) had permanent and fatal spinal cord (SC) impairment. On multivariable analysis, SC ischaemia was associated with an aortic coverage ≥350 mm (OR: 9.15, p = .03, 95% CI: 1.3-66.4) and bovine arch (OR: 10.6, p = .01, 95% CI: 1.6-68.6). The overall short term (six month) clinical success was 72 cases (90%) and none experienced SC ischaemia after late endoleak resolution or treatment. At mid term (mean follow up: 13.3 ± 15.4 months), the overall freedom from conversions, re-interventions, late rupture, or type I and III endoleaks was 57 of 72 survivors (79%). CONCLUSION: A multistaged approach with a third limb step in case of TAAAs is safe and technically feasible, with an acceptable rate of permanent spinal cord ischaemia. Different staging methods and protocols have been proposed and standardisation is required, especially for type I-II-III aneurysms.

Surgical transaxillary placement of the Impella 5.0 ventricular assist device.

OBJECTIVE: The aim of this study is to evaluate the open transaxillary placement of the Impella 5.0 with a modified surgical technique. METHODS: From January to July 2018, nine patients (eight males; mean age 60 years) underwent surgical transaxillary Impella 5.0 (Abiomed Inc., Danvers, MA) implantation. Patient and periprocedural data were recorded in a prospectively maintained institutional database. The primary endpoint was technical success. The secondary endpoints were: neurological complications (peripheral or central), bleeding, and wound infection, duration of Impella support, and device failure requiring device replacement. RESULTS: Assisted technical success was 100%. The right axillary artery was used in 8/9 cases. Three patients (all on extracorporeal membrane oxygenation) suffered from access site bleeding which required surgical reintervention. One patient suffered from peripheral neurological dysfunction which recovered in 1 month and one patient had a local hematoma which was managed conservatively. The median length of treatment was 16 days (range 8-35). Five patients had myocardial recovery and the Impella could be explanted; the remaining were transitioned to a durable left ventricular assist device with an uneventful postoperative course. Hospital mortality was 33%. CONCLUSIONS: Open Impella 5.0 device implantation through the axillary artery is safe and effective; technical success was 100% and low rates of major complications are reported.

Thermodynamic destabilization and aggregation propensity as the mechanism behind the association of apoE3 mutants and lipoprotein glomerulopathy.

Lipoprotein glomerulopathy (LPG) is a rare renal disease, characterized by lipoprotein thrombi in glomerular capillaries. A series of apoE mutations have been associated with LPG development. We previously showed that three mutants based on apoE3 sequence, in which an arginine was substituted by proline, are thermodynamically destabilized and aggregation-prone. To examine whether other LPG-associated apoE3 mutations induce similar effects, we characterized three nonproline LPG-associated apoE3 mutations, namely, R25C (apoEKyoto), R114C (apoETsukuba), and A152D (apoELasVegas). All three apoE3 variants are found to have significantly reduced helical content and to be thermodynamically destabilized, both in lipid-free and lipoprotein-associated form, and to expose a larger portion of hydrophobic surface to the solvent compared with WT apoE3. Furthermore, all three apoE3 variants are aggregation-prone, as shown by dynamic light-scattering measurements and by their enhanced capacity to bind the amyloid probe thioflavin T. Overall, our data suggest that the LPG-associated apoE3 mutations R25C, R114C, and A152D induce protein misfolding, which may contribute to protein aggregation in glomerular capillaries. The similar effects of both LPG-associated proline and nonproline mutations on apoE3 structure suggest that the thermodynamic destabilization and enhanced aggregation of apoE3 may constitute a common underlying mechanism behind the pathogenesis of LPG.

Mitochondrial delivery of doxorubicin by triphenylphosphonium-functionalized hyperbranched nanocarriers results in rapid and severe cytotoxicity.

PURPOSE: To develop a novel hyperbranched polymer-based nanocarrier for efficient drug delivery to cell mitochondria. Also to study for the first time the cytotoxic effect of doxorubicin via mitochondria-specific delivery system. METHODS: We introduced alkyltriphenylphosphonium groups (TPP) to a poly(ethylene imine) hyperbranched polymer (PEI). We harnessed the hydrophobic assembly of these alkylTPP functionalized PEI molecules into ~100 nm diameter nanoparticles (PEI-TPP) and further encapsulated the chemotherapy agent doxorubicin (DOX), to produce the mitotropic nanoparticles PEI-TPP-DOX. RESULTS: By administering PEI-TPP-DOX to human prostate carcinoma cells DU145, we found that: (i) PEI-TPP-DOX specifically localized at cell mitochondria as revealed by the inherent DOX fluorescence; (ii) in contrast to the slow apoptotic cell death incurred by DOX over the period of days at micromolar concentrations, PEI-TPP-DOX triggered rapid and severe cytotoxicity within few hours of incubation and at submicromolar incubation concentrations. This cytotoxicity was mainly found to be of a necrotic nature, not precluding autophagy related death pathways to a smaller extent. CONCLUSIONS: We have elaborated a versatile mitotropic nanocarrier; furthermore, using this platform, we have developed a mitochondrial-doxorubicin formulation with exceptional cytocidal properties, even in nanomolar concentrations.

Discovery of potent vascular endothelial growth factor receptor-2 inhibitors.

Substantial evidence over the last decades has implicated uncontrolled angiogenesis with various pathological states, including cancer. Vascular endothelial growth factor (VEGF) plays a critical role in its regulation. Because the tyrosine kinase VEGF receptor-2 (VEGFR-2) is the major mediator of the mitogenic, angiogenic, and permeability-enhancing effects of VEGF, it has become one of the most profound anti-angiogenesis targets. Inspired by the anthranilamide class of VEGFR-2 inhibitors, we performed a computational analysis of some potent representative members, using docking and molecular dynamics calculations. Based on the observations drawn from introducing the effect of the receptor's flexibility in implicit aqueous environment, we designed, synthesized, and characterized several new analogues of related scaffolds with modifications in their steric and electronic characteristics. In vitro evaluation of these compounds revealed several novel VEGFR-2 inhibitors that are less cytotoxic and more potent than the parent compounds.

Synthesis and characterization of novel natural product-Gd(III) MRI contrast agent conjugates.

Several novel gadolinium chelates conjugated with paclitaxel, colchicine and thyroxine have been prepared as MRI contrast agents targeted to tubulin and thyroxine-binding globulin, respectively.

Copper(II) complexes with sparfloxacin and nitrogen-donor heterocyclic ligands: Structure-activity relationship.

Three novel neutral mononuclear copper(II) complexes of the third-generation quinolone antibacterial drug sparfloxacin in the presence of a nitrogen donor heterocyclic ligand 2,2'-bipyridine, 1,10-phenanthroline or 2,2'-dipyridylamine have been prepared and characterized physicochemically and spectroscopically. The resultant complexes are of the type Cu(sparfloxacinato)(N-donor)Cl. Copper(II) is pentacoordinate having a distorted square pyramidal geometry. Molecular modeling calculations have been performed in order to propose the lowest energy model structure of the complexes. The interaction of the complexes with calf-thymus DNA has been investigated with diverse spectroscopic techniques and has shown that the complexes can bind to calf-thymus DNA by the intercalative mode. The antimicrobial activity of the complexes has been tested on three different microorganisms. The Cu(sparfloxacinato)(N-donor)Cl complexes are among the most active ones against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus, when compared to the other corresponding copper-quinolone complexes studied by our group and their antimicrobial activity is increased in the order bipyam