Transcarotid transcatheter aortic valve replacement utilizing monitored anesthesia care: a case report.

Transcatheter aortic valve replacement (TAVR) has become the standard of care for high surgical risk patients with aortic stenosis. The most common approach to TAVR is transfemoral utilizing monitored anesthesia care or general anesthesia. On occasion, transfemoral access is not possible and alternative access to TAVR is required. Herein, we describe the case of a patient undergoing a transcarotid approach to TAVR with regional anesthesia and monitored anesthesia care utilizing a multidisciplinary heart team.

Transcatheter aortic valve replacement (TAVR) involves replacement of one of the valves of the heart through a minimally invasive procedure and has become the standard of care for high surgical risk patients with a narrowed aortic heart valve. The most common approach to TAVR is through one of the femoral arteries utilizing sedation monitored anesthesia care or general anesthesia. On occasion, transfemoral access is not possible and alternative access to TAVR is required. Herein, we describe the case of a patient undergoing a TAVR using the carotid artery with regional anesthesia and monitored anesthesia care utilizing a multidisciplinary heart team.

Safety of Retrograde Tibial-Pedal Access and Intervention in Patients with Single Remaining Non-Occluded Infra-Popliteal Runoff Artery.

BACKGROUND: The adaptation of retrograde tibial-pedal access for peripheral angiogram and intervention is limited by the lack of operator experience and concern for small distal vessel injury. This study evaluates the safety of the retrograde tibial-pedal access for peripheral angiogram and intervention in patients with two vessel infra-popliteal artery chronic total occlusions, where the access point is the sole remaining non-occluded infra-popliteal artery. METHODS: A retrospective analysis of 5687 consecutive patients who underwent peripheral angiograms by retrograde tibial-pedal access via the single remaining non-occluded infra-popliteal artery was performed. Patients who had retrograde tibial-pedal access at the sole remaining infra-popliteal artery confirmed by angiography were included. Clinical and ultrasound data of the accessed infra-popliteal vessel up to 6 months were collected. RESULTS: The cohort consisted of 314 patients (152 males; mean age 77.9 years). At 6 months, access vessel complications occurred in 15 patients (4.8%). Access vessel occlusion occurred in 9 out of 314 patients (2.9%), arteriovenous fistula in 4 (1.3%), with spontaneous resolution in 2, pseudoaneurysm requiring thrombin injection in 2 (0.6%) and non-cardiovascular death in 1 (0.3%). No uncontrolled bleeding, procedure-related hospitalizations or limb amputations occurred. CONCLUSIONS: Routine primary retrograde tibial-pedal access for lower extremity peripheral artery diagnostic angiography and intervention in patients with single infra-popliteal artery runoff can be safety performed in an outpatient setting with infrequent and manageable complications.

Structural Pharmacology of Cation-Chloride Cotransporters.

Loop and thiazide diuretics have been cornerstones of clinical management of hypertension and fluid overload conditions for more than five decades. The hunt for their molecular targets led to the discovery of cation-chloride cotransporters (CCCs) that catalyze electroneutral movement of Cl- together with Na+ and/or K+. CCCs consist of two 1 Na+-1 K+-2 Cl- (NKCC1-2), one 1 Na+-1 Cl- (NCC), and four 1 K+-1 Cl- (KCC1-4) transporters in human. CCCs are fundamental in trans-epithelia ion secretion and absorption, homeostasis of intracellular Cl- concentration and cell volume, and regulation of neuronal excitability. Malfunction of NKCC2 and NCC leads to abnormal salt and water retention in the kidney and, consequently, imbalance in electrolytes and blood pressure. Mutations in KCC2 and KCC3 are associated with brain disorders due to impairments in regulation of excitability and possibly cell volume of neurons. A recent surge of structures of CCCs have defined their dimeric architecture, their ion binding sites, their conformational changes associated with ion translocation, and the mechanisms of action of loop diuretics and small molecule inhibitors. These breakthroughs now set the stage to expand CCC pharmacology beyond loop and thiazide diuretics, developing the next generation of diuretics with improved potency and specificity. Beyond drugging renal-specific CCCs, brain-penetrable therapeutics are sorely needed to target CCCs in the nervous system for the treatment of neurological disorders and psychiatric conditions.

On the feasibility of simple brain-computer interface systems for enabling children with severe physical disabilities to explore independent movement.

Introduction: Children with severe physical disabilities are denied their fundamental right to move, restricting their development, independence, and participation in life. Brain-computer interfaces (BCIs) could enable children with complex physical needs to access power mobility (PM) devices, which could help them move safely and independently. BCIs have been studied for PM control for adults but remain unexamined in children. In this study, we explored the feasibility of BCI-enabled PM control for children with severe physical disabilities, assessing BCI performance, standard PM skills and tolerability of BCI. Materials and methods: Patient-oriented pilot trial. Eight children with quadriplegic cerebral palsy attended two sessions where they used a simple, commercial-grade BCI system to activate a PM trainer device. Performance was assessed through controlled activation trials (holding the PM device still or activating it upon verbal and visual cueing), and basic PM skills (driving time, number of activations, stopping) were assessed through distance trials. Setup and calibration times, headset tolerability, workload, and patient/caregiver experience were also evaluated. Results: All participants completed the study with favorable tolerability and no serious adverse events or technological challenges. Average control accuracy was 78.3 ± 12.1%, participants were more reliably able to activate (95.7 ± 11.3%) the device than hold still (62.1 ± 23.7%). Positive trends were observed between performance and prior BCI experience and age. Participants were able to drive the PM device continuously an average of 1.5 meters for 3.0 s. They were able to stop at a target 53.1 ± 23.3% of the time, with significant variability. Participants tolerated the headset well, experienced mild-to-moderate workload and setup/calibration times were found to be practical. Participants were proud of their performance and both participants and families were eager to participate in future power mobility sessions. Discussion: BCI-enabled PM access appears feasible in disabled children based on evaluations of performance, tolerability, workload, and setup/calibration. Performance was comparable to existing pediatric BCI literature and surpasses established cut-off thresholds (70%) of "effective" BCI use. Participants exhibited PM skills that would categorize them as "emerging operational learners." Continued exploration of BCI-enabled PM for children with severe physical disabilities is justified.

Reconstrucción endovascular ilíaca usando accesos alternativos / Endovascular reconstruction of the iliac arteries using alternate accesses

Paciente de 65 años de edad que acude a consulta por claudicación corta limitante de la extremidad inferior izquierda, refractaria a tratamiento médico. El angio TAC realizado reveló una oclusión total crónica de la arteria ilíaca externa izquierda y ateroesclerosis extensa de las arterias ilíacas común e interna. Se intervino de manera percutánea la vía radial y la arteria femoral superficial con la técnica through and through y se realizó una reconstrucción de la bifurcación ilíaca. Ambas arterias ilíacas quedaron permeables. El paciente fue dado de alta un día después de la intervención, con una mejoría significativa de los síntomas durante el seguimiento (de un año).Presentamos este caso para exponer la técnica de revascularización de ambas ilíacas (interna y externa) en un caso complejo de enfermedad de bifurcación ilíaca (TASC C-D).(AU)

A 65-year-old male patient presented for evaluation of severe lifestyle-limiting left-sided claudication refractory to maximal medical therapy. CT revealed a chronic total occlusion of the left external iliac artery and severe disease of common and internal iliac arteries, which was treated successfully by percutaneous intervention via radial and superficial femoral artery approach and with the assistance of the through-and-through technique, doing a partial covered endovascular reconstruction of the iliac bifurcation, thus maintaining both arteries (internal and external) patent. The patient was discharged one day after the procedure and reported significant symptom improvement at follow-up (1 year).We present this case to show the technique of revascularization of both iliac arteries (internal and external) in a complex case of iliac bifurcation disease (TASC C-D).(AU)

Exploring the path less traveled: Distal radial access for diagnostic and interventional neuroradiology procedures.

BACKGROUND: Recently there is a trend for radial first which advocates radial artery access as the first choice to perform diagnostic and interventional neurovascular procedures. Although safer than the conventional common femoral artery access, it is associated with a high rate of radial artery occlusion. Distal radial artery access is recently proposed to avoid this complication. This study aims to assess the feasibility and safety of distal radial artery access across a wide range of interventional neurovascular procedures. MATERIALS AND METHODS: All Interventional neurovascular cases attempted via distal radial artery access from September 2019 till March 2021 were included in the study. Data regarding patient demographics, distal radial artery diameter, access site cannulation, size of the sheath, procedural details including success rate and complications were collected. RESULTS: During the study period, 102 patients underwent 114 procedures via the distal radial artery approach. The mean age of patients was 41.9 ± 15.2 years. Overall procedure success rate via DRA was 94.7% (108/114). 72 diagnostic cerebral angiograms and 36 interventional procedures were successfully completed while six procedures required switching to alternate access. CONCLUSION: Distal radial artery access is a safe and feasible option for diagnostic cerebral angiography and a wide range of neurovascular procedures.

Transpedal approach for femoral-popliteal chronic total occlusions using the outback® elite re-entry device.

BACKGROUND: Transpedal access is increasingly utilized for the treatment of peripheral artery disease (PAD). Femoral-popliteal artery chronic total occlusions (CTOs) are some of the most difficult lesion subsets that sometimes require the use of re-entry support devices during percutaneous intervention. Limited data is available on the use of re-entry devices when treating femoral-popliteal CTOs via transpedal access. The aim of this study was to demonstrate the feasibility of using the Outback® Elite re-entry device for the treatment of femoral-popliteal CTOs via the transpedal approach in an outpatient based lab setting. METHODS: Seventeen patients presented with femoral-popliteal CTOs in which treatment required the use of the Outback® Elite re-entry device. All procedures were performed in a single outpatient based lab. Patients were followed at 1 week and 1 month post-procedure, with lower extremity arterial duplex ultrasound assessment during the 1 month follow-up. RESULTS: The average patient age was 78 years-old, with 71% being males. Most patients presented with Rutherford class IV symptoms. Procedural success was achieved in all patients with no requirement to convert to femoral artery access in any of the cases. No immediate post-procedural complications nor at any time during follow-up were observed. Ultrasonography at 1 month follow-up showed patent intervention sites and access site vessels in all patients. CONCLUSION: The use of the Outback® Elite re-entry device for the treatment of femoral-popliteal CTOs via transpedal access is a feasible option and may have potential benefits by avoiding risks associated with traditional femoral artery access.

Utility of Suprasternal Transinnominate Artery for Alternate Access in Transcatheter Aortic Valve Replacement.

OBJECTIVE: Despite advancements in transcatheter aortic valve replacement (TAVR) technology, alternate access strategies are still required when transfemoral access is unsuitable. In these often anatomically complex group of patients, we sought to evaluate the safety and feasibility of suprasternal transinnominate (TI) artery access for TAVR. METHODS: At our institution, 652 patients underwent TAVR from November 2011 through February 2020. Of these, 23 patients underwent TI TAVR via a 5-cm suprasternal incision without special instrumentation. Outcomes of interest were technical considerations, postoperative complications, and perioperative recovery in relation to established access strategies. RESULTS: The mean Society of Thoracic Surgeons risk score was 8.6 ± 4.2 and the average age was 75 ± 8. All patients underwent TI TAVR using a self-expanding (12), or balloon-expandable (11) transcatheter heart valve. Average postoperative stay was 2 ± 0.7 days (range 2 to 4) with most 20/23 (87%) being discharged to home. There was no 30-day mortality or readmission. There was 1 access-site complication and 1 cerebrovascular accident within 30 days, both intraoperative, with excellent recovery. All patients had either trivial (19) or mild (4) aortic regurgitation on 30-day echocardiography. CONCLUSIONS: TAVR via suprasternal TI access is feasible, safe, provides satisfactory perioperative recovery and adds to the options when patients require alternate access. Further data would be optimal to validate this single-center experience.

Carotid access for transcatheter aortic valve replacement: A meta-analysis.

OBJECTIVE: We sought to evaluate the feasibility and safety of carotid access transcatheter aortic valve replacement (TAVR) by performing a meta-analysis of published cases. BACKGROUND: Several case series and regional data have provided initial basis for carotid access TAVR in patients with prohibitive femoral approach. We performed this meta-analysis to provide further evidence of feasibility and safety of carotid TAVR. METHODS: We searched PubMed, EMBASE, CINAHL, and Cochrane CENTRAL for any study on carotid access TAVR involving ⩾5 patients since inception till March 1, 2020. Random-effects model was used to compute overall effects. The outcomes analyzed were all-cause mortality, Transient ischemic attack (TIA)/stroke, need for permanent pacemaker (PPM) implantation, pericardial tamponade, access site complications, major bleeding, and length of stay. RESULTS: There was a total of 17 retrospective studies (n = 2082) with a median follow-up of 1 month. Mean age of the patient was 80 years. Mean Euroscore and STS scores were 15 ± 6.2 and 7.9 ± 3.3, respectively. The procedural success rate was 99%. The rate of all-cause mortality was 6.7% (range 4.6-9.7%, p < .001, I2 = 67%). Incidence of TIA/stroke was 3.9% (range 3.1-4.8%, p < .001, I2 = 0%) and PPM implantation was 16.7% (range 12.5-21.9%, p < .001, I2 = 56%). Rate of pericardial tamponade, vascular complication, and major bleeding were 1.7, 2.5, and 7%, respectively. Average length of hospital stay was 7.7 days. CONCLUSION: Our results show that transcarotid approach is a feasible option in patients with prohibitive femoral access for TAVR.

Dual alternate access sites for the treatment of an ostial left common iliac artery chronic total occlusion.

Growing endovascular strategies with TASC D lesions in aortoiliac disease reflect increasing technical success with evidenced safety and efficacy. In cases of failed transfemoral access, revascularization of iliac chronic total occlusions has prompted the utilization of other alternate access sites (e.g. transradial and transbrachial approaches) as important options in aortoiliac TASC D lesions. We describe a case of successful revascularization of an occluded ostial left common iliac artery in an 81-year-old man using a dual ulnar and tibioperoneal approach (absent radial artery). A Controlled Antegrade and Retrograde Tracking technique was performed where a balloon was advanced from the peroneal artery into the distal cap of the chronic total occlusion in the proximal common femoral artery. Balloon inflation was performed and a glidewire from transulnar access was advanced and re-entered into the true lumen in the common femoral artery. The wire was then snared and externalized out the transpedal access site creating a continuous true lumen from the ulnar artery to the peroneal artery. To reconstruct the aortic bifurcation, kissing balloon inflations were performed from the peroneal as well as the ulnar artery approaches. A 10 mm × 59 mm balloon expandable stent was placed in the ostial left common iliac artery and a 8 mm × 60 mm self-expanding stent was placed in the left external iliac artery successfully.

3D Model Guiding Transcatheter Aortic Valve Replacement in a Patient With Aortic Coarctation.

We demonstrate the utility of a printed 3-dimensional model to assist in the vascular access planning for a transcatheter aortic valve replacement in an elderly woman with complicated vascular anatomy including aortic coarctation, severe iliofemoral disease, and a small and tortuous left subclavian artery. (Level of Difficulty: Intermediate.).

Cryo-EM structures and functional characterization of murine Slc26a9 reveal mechanism of uncoupled chloride transport.

The epithelial anion transporter SLC26A9 contributes to airway surface hydration and gastric acid production. Colocalizing with CFTR, SLC26A9 has been proposed as a target for the treatment of cystic fibrosis. To provide molecular details of its transport mechanism, we present cryo-EM structures and a functional characterization of murine Slc26a9. These structures define the general architecture of eukaryotic SLC26 family members and reveal an unusual mode of oligomerization which relies predominantly on the cytosolic STAS domain. Our data illustrates conformational transitions of Slc26a9, supporting a rapid alternate-access mechanism which mediates uncoupled chloride transport with negligible bicarbonate or sulfate permeability. The characterization of structure-guided mutants illuminates the properties of the ion transport path, including a selective anion binding site located in the center of a mobile module within the transmembrane domain. This study thus provides a structural foundation for the understanding of the entire SLC26 family and potentially facilitates their therapeutic exploitation.

Treatment of an external iliac artery chronic total occlusion using alternate access sites.

BACKGROUND: With the advent of endovascular techniques, alternate sites such as the pedal and radial arteries can now be accessed when treating peripheral arterial disease to reduce procedural complications, shorten recovery time, and improve patient comfort. However, a paucity of literature exists on the availability of support devices that can be utilized during challenging cases. CASE PRESENTATION: A 70 year-old female patient presented for evaluation of severe lifestyle-limiting left-sided claudication refractory to maximal medical therapy. Angiography revealed a chronic total occlusion of the left external iliac artery, which was treated successfully by percutaneous intervention via a primary transpedal approach and with the assistance of the Outback® Elite re-entry device. The patient was discharged 2 h after the procedure and reported significant symptom improvement at follow-up. CONCLUSION: This case highlights a newly adopted endovascular approach through an alternate access site and illustrates how the Outback® Elite device can be used as an adjunctive tool in the treatment of complex lower-extremity vascular lesions.

Probing Conformational States of a Target Protein in Escherichia coli Cells by in vivo Cysteine Cross-linking Coupled with Proteolytic Gel Analysis.

Transporters are dynamic membrane proteins that are essential to the physiology of cells. To function, transporters must cycle between various conformational states, so to understand their mechanistic details, it is critical to characterize how their structure changes during the transport cycle. One approach to studying the dynamics of transporters takes advantage of the chemistry of cysteine by using sulfhydryl-reactive, bi-functional cross-linkers to probe changes in the distance between two specific residues that have been substituted to cysteine. This approach is mostly used to study transporters in vitro, not in their natural cellular environment. Here we describe a protocol based on structure-guided cysteine cross-linking and proteolysis-coupled gel analysis to probe conformational changes of a target transporter in live Escherichia coli cells. Although cross-linking approaches have been used to probe the proximity between transmembrane segments in membrane proteins in vivo, to our knowledge this protocol is the first to be used to interrogate transporter dynamics in cells. The use of this protocol is optimal for proteins with known or modeled structures to guide the replacement of specific residues with cysteines and the selection of cross-linking agents with various spacer arm lengths. This protocol allows for discriminating easily cross-linked and uncross-linked species and does not require the often difficult or unavailable reconstitution of transport activity in an in vitro system. In addition, this protocol could be used to probe the conformation of transporters in cells treated with transport inhibitors in order to better understand their mechanism of action, and potentially dynamic interactions between domains in proteins that are not transporters.

Predicted magnitude of alternate access in the contemporary transcatheter aortic valve replacement era.

OBJECTIVES: We aimed to evaluate the true extent of alternate access in a contemporary cohort of transcatheter aortic valve replacement (TAVR) patients. BACKGROUND: Appropriate access selection for TAVR impacts clinical outcomes. Despite device miniaturization, some patients remain ineligible for transfemoral arterial access. METHODS: Five hundred seventy-five consecutive TAVR patients were classified according to iliofemoral artery diameters measured by computed tomography (<5.0 mm, 5.0-5.4 mm, 5.5-5.9 mm, or ≥6 mm) and need for alternate access rate was estimated according to commercially available transcatheter heart valve Instructions For Use (IFU). RESULTS: Based on iliofemoral artery diameters alone, 11.5% of patients were predicted to require alternate access. After patient-level adjustment for the size of the planned THV and severe tortuosity or severe calcification, 14.9% and 20.8% of patients, respectively were predicted to require alternate access. Overall, 87.8% of patients underwent transfemoral TAVR and 12.3% underwent alternate access. There was no difference in the rate of major vascular complications and life threatening or major bleeding between groups, but transfusion rate was higher in smaller vessel groups. CONCLUSIONS: Despite device miniaturization, a substantial minority of contemporary TAVR patients still require alternate access. Most are eligible for newer extrathoracic approaches including transcaval, subclavian, and transcarotid that avoid the morbidity of transthoracic access.

Formation of a Chloride-conducting State in the Maltose ATP-binding Cassette (ABC) Transporter.

ATP-binding cassette transporters use an alternating access mechanism to move substrates across cellular membranes. This mode of transport ensures the selective passage of molecules while preserving membrane impermeability. The crystal structures of MalFGK2, inward- and outward-facing, show that the transporter is sealed against ions and small molecules. It has yet to be determined whether membrane impermeability is maintained when MalFGK2 cycles between these two conformations. Through the use of a mutant that resides in intermediate conformations close to the transition state, we demonstrate that not only is chloride conductance occurring, but also to a degree large enough to compromise cell viability. Introduction of mutations in the periplasmic gate lead to the formation of a channel that is quasi-permanently open. MalFGK2 must therefore stay away from these ion-conducting conformations to preserve the membrane barrier; otherwise, a few mutations that increase access to the ion-conducting states are enough to convert an ATP-binding cassette transporter into a channel.

Sequential Action of MalE and Maltose Allows Coupling ATP Hydrolysis to Translocation in the MalFGK2 Transporter.

ATP-binding cassette (ABC) transporters have evolved an ATP-dependent alternating-access mechanism to transport substrates across membranes. Despite important progress, especially in their structural analysis, it is still unknown how the substrate stimulates ATP hydrolysis, the hallmark of ABC transporters. In this study, we measure the ATP turnover cycle of MalFGK2 in steady and pre-steady state conditions. We show that (i) the basal ATPase activity of MalFGK2 is very low because the cleavage of ATP is rate-limiting, (ii) the binding of open-state MalE to the transporter induces ATP cleavage but leaves release of Pi limiting, and (iii) the additional presence of maltose stimulates release of Pi, and therefore increases the overall ATP turnover cycle. We conclude that open-state MalE stabilizes MalFGK2 in the outward-facing conformation until maltose triggers return to the inward-facing state for substrate and Pi release. This concerted action explains why ATPase activity of MalFGK2 depends on maltose, and why MalE is essential for transport.

The SLC24 family of K⁺-dependent Na⁺-Ca²âº exchangers: structure-function relationships.

The human SLC24 gene family contains five members encoding the NCKX1-5 proteins that function as K(+)-dependent Na⁺-Ca²âº exchangers. NCKX proteins have been shown to play critical roles in retinal rod and cone photoreceptors, olfactory neurons, epidermal melanocytes, and the retinal pigment epithelium. NCKX transcripts are also found in many other tissues, in particular throughout the brain, but their specific physiological roles yet need to be elucidated in most cases. Here, we focus on our current knowledge of NCKX transport function as has been described in detail only for in situ NCKX1 in the outer segments of retinal rod photoreceptors and on structure-function relationships elucidated for the NCKX2 isoform after expression of its (mutated) cDNA in cell lines.

Conformational changes of the bacterial type I ATP-binding cassette importer HisQMP2 at distinct steps of the catalytic cycle.

Prokaryotic solute binding protein-dependent ATP-binding cassette import systems are divided into type I and type II and mechanistic differences in the transport process going along with this classification are under intensive investigation. Little is known about the conformational dynamics during the catalytic cycle especially concerning the transmembrane domains. The type I transporter for positively charged amino acids from Salmonella enterica serovar Typhimurium (LAO-HisQMP2) was studied by limited proteolysis in detergent solution in the absence and presence of co-factors including ATP, ADP, LAO/arginine, and Mg(2+) ions. Stable peptide fragments could be obtained and differentially susceptible cleavage sites were determined by mass spectrometry as Lys-258 in the nucleotide-binding subunit, HisP, and Arg-217/Arg-218 in the transmembrane subunit, HisQ. In contrast, transmembrane subunit HisM was gradually degraded but no stable fragment could be detected. HisP and HisQ were equally resistant under pre- and post-hydrolysis conditions in the presence of arginine-loaded solute-binding protein LAO and ATP/ADP. Some protection was also observed with LAO/arginine alone, thus reflecting binding to the transporter in the apo-state and transmembrane signaling. Comparable digestion patterns were obtained with the transporter reconstituted into proteoliposomes and nanodiscs. Fluorescence lifetime spectroscopy confirmed the change of HisQ(R218) to a more apolar microenvironment upon ATP binding and hydrolysis. Limited proteolysis was subsequently used as a tool to study the consequences of mutations on the transport cycle. Together, our data suggest similar conformational changes during the transport cycle as described for the maltose ABC transporter of Escherichia coli, despite distinct structural differences between both systems.