Functional Mitral Valve Regurgitation: Mitral Valve Repair or Replacement? Our "Road Map" for the Appropriate Strategy.

Objectives: The optimal surgical approach for the treatment of functional mitral regurgitation (FMR) remains controversial. Current guidelines suggest that the surgical approach has to be tailored to the individual patient. The aim of the present study was to clarify further aspects of this tailored treatment. Methods: From 01/2006 to 12/2015, 390 patients underwent mitral valve (MV) surgery for FMR (ischemic n = 241, non-ischemic n = 149) at our institution. A regression analysis was used to determine the effect of MV repair or replacement on survival. The patients were analyzed according to the etiology of the MR (ischemic or non-ischemic), different age groups (<65 years, 65-75 years, and >75 years), LV function, and LV dimensions, as well as the underlying heart rhythm. Results: The overall survival rates for the repair group at 1, 5, and 8 years were 86.1 ± 1.9%, 70.6 ± 2.6%, and 55.1 ± 3.1%, respectively. For the same intervals, the survival rates in patients who underwent MV replacement were 75.9 ± 4.5%, 58.6 ± 5.4%, and 40.9 ± 6.4%, respectively (p = 0.003). Patients younger than 65 years, with an ischemic etiology of FMR, poor ejection fraction (<30%), severe dilatation of left ventricle (LVEDD > 60mm), and presence of atrial fibrillation had significantly higher mortality rates after MV replacement (HR, 3.0; CI, 1.3-6.9; p = 0.007). Patients between 65 and 75 years of age had a higher risk of death when undergoing mitral valve replacement (HR, 1.7; CI, 1.0-2.8; p = 0.04). In patients older than 75 years, the surgical approach (MV repair or replacement) had no effect on postoperative survival (HR, 0.8; CI, 0.4-1.3; p = 0.003). Conclusions: Our data demonstrate that, in patients younger than 65 years, the treatment of choice for FMR should be MV repair. This advantage was even more evident in patients with an ischemic origin of MR, a poor ejection fraction, a severe LV dilatation, and atrial fibrillation.

Mind-body practices, interoception and pain: a scoping review of behavioral and neural correlates.

OBJECTIVE: Chronic pain is a significant source of suffering in the United States, and many individuals increasingly turn towards yoga for pain relief. However, little is known regarding how yoga improves pain. Herein we seek to examine the scope of the literature linking mind-body practices, pain and interoception; an emerging mechanism by which yoga may improve chronic pain. METHODS: This scoping review followed the five-stage methodological framework proposed by Arksey and O'Malley to examine behavioral and neural correlates of interoception in mind-body practices and pain. A broad search of the Pubmed, CINAHL, SportDiscus, Scopus, PsychInfo, and SocIndex databases was conducted, utilizing three clusters of search terms: (1) interoceptive terms, (2) mind-body terms, and (3) pain terms. RESULTS: A combined total of 690 articles were screened, and 24 findings included for analysis. Sixteen studies examined interoceptive outcomes in response to mind-body practices for chronic pain, and 8 studies examined interoceptive outcomes in response to evoked-pain tasks in experienced mind-body practitioners. Only three studies linked yoga, interoception and pain. CONCLUSION: This review relied on the broader mind-body literature to inform our analyses as the literature examining yoga, pain and interoception remains limited. Interoceptive techniques including attending to and acceptance of bodily sensations, appear to be key therapeutic mechanisms in mind-body practices for chronic pain. Future yoga-based interventions would benefit examining interoceptive outcomes and integrating interoceptive strategies to facilitate the pain-modulating benefits of yoga.

Incidence and Predictors of Ventricular Arrhythmias in Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: Wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is characterized by heart failure, conduction abnormalities and arrhythmias. The incidence of ventricular arrhythmias, particularly ventricular tachycardias (VTs), in wtATTR-CM is unclear. With the development of targeted therapies and improved overall prognosis, there is an unmet need to identify patients at high risk for VTs who might benefit from ICD therapy. METHODS: Between 2017 and 2022, 72 patients diagnosed with wtATTR-CM were prospectively evaluated for the presence of ventricular arrhythmias using a Holter ECG. VTs were defined as >3 consecutive beats with a heart rate > 100 beats per minute originating from a ventricle. RESULTS: The incidence of VTs was 44% (n = 32/72) in unselected wtATTR-CM patients. Patients with VT showed significantly more severe left ventricular (LV) hypertrophy (septum diameter 21 ± 2.6 vs. 19 ± 3.0 mm, p = 0.006), reduced LV ejection fraction (47 ± 8 vs. 52 ± 8%, p = 0.014) and larger left atria (32 ± 7 vs. 28 ± 6 mm2, p = 0.020), but no differences in cardiac markers such as NTproBNP and troponin. In a multivariable model, LV hypertrophy (LV mass indexed, OR = 1.02 [1.00-1.03], p = 0.031), LV end-diastolic diameter (OR = 0.85 [0.74-0.98], p = 0.021) and LV end-systolic diameter (OR = 1.19 [1.03-1.349], p = 0.092) were predictive for VT occurrence with an area under the receiver operating characteristic of 0.76 [0.65-0.87]. CONCLUSIONS: The incidence of ventricular arrhythmia in wtATTR-CM is high and is associated with an advanced stage of left ventricular disease. Further studies are needed evaluating the role of VTs in predicting sudden cardiac death and the benefit of ICD therapy in wtATTR-CM.

Yoga, aerobic and stretching exercise effects on neurocognition: Randomized controlled trial protocol.

As the global population ages, the prevalence of cognitive decline and dementia is expected to rise, creating a significant health and economic burden. The purpose of this trial is to rigorously test, for the first time, the efficacy of yoga training as a physical activity intervention to mitigate age-related cognitive decline and impairment. We are conducting a 6-month randomized controlled trial (RCT) of exercise among 168 middle aged and older adults to compare the efficacy of yoga vs. aerobic exercise on cognitive function, brain structure and function, cardiorespiratory fitness, and circulating inflammatory and molecular markers. Using a single-blind, three arm RCT, 168 older adults ages 55-79 will be assigned to either: a Hatha yoga group, an aerobic exercise group or a stretching-toning active control group. Participants will engage in hour long group exercise 3x/week for 6-months. A comprehensive neurocognitive test battery, brain imaging, cardiovascular fitness test, and a blood draw will take place at baseline; end of the 6-month intervention, and at 12-month follow-up. Our primary outcomes of interest are brain regions, such as hippocampal volume and prefrontal cortex, and cognitive functions, such as episodic memory, working memory and executive functions, that are typically affected by aging and Alzheimer's disease. Not only will this RCT test whether yoga is a means to mitigate age-related cognitive decline, but it may also offer an alternative to aerobic exercise, which could be particularly appealing to older adults with compromised physical functioning. ClinicalTrials.gov Identifier: NCT04323163.

Development of a Remote Version of the Graded Redefined Assessment of Strength, Sensation, and Prehension (GRASSP): Validity and Reliability.

BACKGROUND: The Graded Redefined Assessment of Strength, Sensation, and Prehension (GRASSP V1.0) was developed in 2010 as a 3-domain assessment for upper extremity function after tetraplegia (domains: Strength, Sensibility, and Prehension). A remote version (rGRASSP) was created in response to the growing needs of the field of Telemedicine. OBJECTIVE: The purpose of this study was to assess the psychometric properties of rGRASSP, establishing concurrent validity and inter-rater reliability. METHODS: Individuals with tetraplegia (n = 61) completed 2 visits: 1 in-person and 1 remote. The first visit was completed in-person to administer the GRASSP, and the second visit was conducted remotely to administer the rGRASSP. The rGRASSP was scored both by the administrator of the rGRASSP (Examiner 1), and a second assessor (Examiner 2) to establish inter-rater reliability. Agreement between the in-person and remote GRASSP evaluations was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman agreement plots. RESULTS: The remote GRASSP demonstrated excellent concurrent validity with the GRASSP (left hand intraclass correlation coefficient (ICC) = .96, right ICC = .96). Concurrent validity for the domains was excellent for strength (left ICC = .96, right ICC = .95), prehension ability (left ICC = .94, right ICC = .95), and prehension performance (left ICC = .92, right ICC = .93), and moderate for sensibility (left ICC = .59, right ICC = .68). Inter-rater reliability for rGRASSP total score was high (ICC = .99), and remained high for all 4 domains. Bland-Altman plots and limits of agreements support these findings. CONCLUSIONS: The rGRASSP shows strong concurrent validity and inter-rater reliability, providing a psychometrically sound remote assessment for the upper extremity in individuals with tetraplegia.

Yoga Impacts Cognitive Health: Neurophysiological Changes and Stress Regulation Mechanisms.

Yoga, a physical and contemplative practice, offers the practitioner a unique mind-body exercise experience demonstrating preliminary efficacy in improving cognitive health. We examine the evidence for underlying mechanisms that explain the yoga-cognition relationship in healthy older adults. The cognitive benefits of yoga may be the result of improved stress regulation and neurocognitive resource efficiency that facilitate bidirectional brain-body communication.

Surgical treatment of isolated tricuspid valve endocarditis: Midterm data.

BACKGROUND: Isolated tricuspid valve endocarditis (TVE) is a rare disease which is managed medically in most patients. Only in specific cases, surgical intervention becomes necessary. Hence, data about surgical outcomes are sparse. This study reports on the operative experience in patients with isolated TVE over a period of 20 years. METHODS: We retrospectively analyzed 32 patients with isolated TVE who underwent surgery from February 2001 to June 2021 at the German Heart Centre Munich. RESULTS: Thirty-day mortality was 3.1%. Overall survival was 89.9± 5.5% at 1 year and 76.9 ± 8.5% at 5 years. Cumulative incidence for reoperation was 11.1 ± 6.0% at 5 years. Four patients (12.5%) were treated for recurrent endocarditis. Tricuspid valve repair (TVr) was achieved in 16 patients (50%). If the subvalvular apparatus (n = 10) was involved, tricuspid valve replacement was performed more frequently. CONCLUSIONS: Mortality in patients with isolated TVE undergoing cardiac surgery is high. In half of the cases, TVr was achieved but was less likely in patients with affected subvalvular apparatus.

Stroke after transcatheter aortic valve replacement: A severe complication with low predictability.

OBJECTIVES: We aimed to describe stroke and transient ischemic attacks (TIAs) after transcatheter aortic valve replacement (TAVR) and to identify associated risk factors. BACKGROUND: Stroke/TIA after TAVR is a major complication. METHODS: A total of 1919 concomitant patients underwent TAVR in a single center from 2007 to 2017. Pre-, intra-, and postprocedural data were collected prospectively in a database and analyzed retrospectively. Stroke and TIA were documented according to the Valve Academic Research Consortium-II criteria. Logistic regression was used to determine risk factors for stroke after TAVR. RESULTS: Mean age was 79.5 ± 6.8 years, mean logistic EuroScore was 17.6% ± 12.8%, and 51.8% (n = 994) of the patients were female. Stroke/TIA occurred in 76 patients (3.9%), 1.9% were disabling, and 1.6% nondisabling. The predominant type of stroke were territorial ischemic lesions (82.4%), with primary bleeding in 4.4% and border zone infarctions in 4.4%. Left-sided lesions were more common (45.6% left sided vs. 25% right sided) and 13.2% of the lesions were bilateral (4.4% no finding and 11.8% missing data). In multivariate logistic regression, prior stroke (odds ratio [OR] = 1.83, p = 0.046) and initial experience (first 300 TAVR implanted at our center) were identified as independent risk factors for stroke/TIA during the first 30 days (OR = 1.95, p = 0.045). Overall, the occurrence of stroke had a highly significant impact on a 30-day mortality (13.2% vs. 4.9% in patients without stroke (p = 0.005). CONCLUSION: Stroke within the first 30 days after TAVR severely impairs 30-day survival. We identified prior stroke and initial experience as significant independent risk factors for the occurrence of stroke after TAVR.

Results after Repair of Functional Tricuspid Regurgitation with a Three-Dimensional Annuloplasty Ring.

BACKGROUND: Tricuspid valve (TV) repair is the recommended treatment for severe functional tricuspid regurgitation (fTR) in patients undergoing left-sided surgery. For this purpose, a wide range of annuloplasty devices differing in form and flexibility are available. This study reports the results using a three-dimensional annuloplasty ring (Medtronic, Contour 3D Ring) for TV repair and analysis of risk factors. METHODS: A cohort of 468 patients who underwent TV repair (TVr) with a concomitant cardiac procedure from December 2010 to January 2017 was retrospectively analyzed. RESULTS: At follow-up, 96.1% of patients had no/trivial or mild TR. The 30-day mortality was 4.7%; it significantly differed between electively performed operations (2.7%) and urgent/emergent operations (11.7%). Risk factors for recurrent moderate and severe TR were LVEF < 50%, TAPSE < 16 mm, and moderate mitral valve (MV) regurgitation at follow-up. Preoperatively reduced renal function lead to a higher 30-day and overall mortality. Reoperation of the TV was required in six patients (1.6%). Risk factors for TV related reoperations were preoperative TV annulus over 50 mm and an implanted permanent pacemaker. CONCLUSIONS: TVr with the Contour 3D annuloplasty ring shows low TR recurrence and reoperation rates. Risk-factor analysis for the recurrence of TR revealed the importance of left- and right-ventricular function.

Anatomical reasons for failure of dual-filter cerebral embolic protection application in TAVR: A CT-based analysis.

BACKGROUND: The dual-filter Sentinel™ Cerebral Protection System (Sentinel-CPS) is increasingly used during transcatheter aortic valve replacement (TAVR). However, complex vascular anatomy may challenge Sentinel-CPS deployment. AIM OF THE STUDY: We sought to investigate the impact of anatomic features of the aortic arch and the supra-aortic arteries on technical device failure of Sentinel-CPS application. METHODS: Analysis of the multislice computed tomography pre-TAVR aortograms of all patients undergoing TAVR with Sentinel-CPS between 2016 and 2020 (n = 92) was performed. We investigated the impact of aortic arch anatomy, configuration, and the angles of the supra-aortic arteries, including the determination of vascular tortuosity index on device failure of Sentinel-CPS application. RESULTS: The Sentinel-CPS was applied successfully in 83 patients (90.2%). Device failure in nine patients (9.8%) was due to the infeasibility to perform correct deployment of both filters (n = 7) and to obtain peripheral radial access (n = 2). Patients with a failure of Sentinel-CPS application had a higher right subclavian tortuosity index (217 [92-324] vs. 150 [42-252], p = .046), a higher brachiocephalic tortuosity index (27 [5-51] vs. 10 [0-102], p = 0.033) and a larger angulation of the brachiocephalic artery (59° [22-80] vs. 39° [7-104], p = .014) compared with patients with successful application. A brachiocephalic angle more than 59° was predictive for device failure. No differences in aortic arch anatomy or common carotid artery tortuosity were detected between the groups. CONCLUSIONS: Brachiocephalic tortuosity was found to be associated with failure of Sentinel-CPS application. Filter-based usage should be avoided in TAVR patients with a brachiocephalic angle more than 59°.

Normative database of postural sway measures using inertial sensors in typically developing children and young adults.

OBJECTIVE: Reference values utilizing the APDM MobilityLab® inertial sensor system have not been established in children and young adults ages 5-30. These values are necessary for clinicians and researchers to compare to children with balance impairments. METHODS: A group of 144 typically developing children and young adults from age 5-30 years completed the instrumented SWAY test during 6 test conditions: normal stance, firm surface, eyes open (EO) and closed (EC); normal stance, foam surface, EO and EC; and tandem stance, firm surface, EO and EC. Selected variables for normative outcomes included total sway area, and the mean, sagittal and coronal values for RMS sway, jerk, sway velocity and path length. Sex differences were examined within age groups via t tests. The effect of age on postural sway variables was analyzed using a one-way ANOVA for the mean values of total sway area, RMS sway, velocity and jerk, followed by post-hoc pairwise comparisons. RESULTS: All sway parameters decreased significantly with age (p < 0.0001). Adult-like total sway area and jerk were achieved by ages 9-10 except for jerk during EC on foam. RMS sway and sway velocity reached adult levels by ages 11-13 during all EO and tandem stance conditions, and 14-21 with EC during normal stance on firm and foam surfaces for RMS sway and EC on firm surfaces for velocity. Females ages 5-6 performed more poorly during EO firm and EC foam for certain variables, but better during EO tandem and females ages 7-13 outperformed males when sex differences were found. SIGNIFICANCE: These reference values can now be used by clinicians and researchers to evaluate abnormal postural sway and response to interventions in children and young adults.

Mitral valve repair with the edge-to-edge technique: A 20 years single-center experience.

OBJECTIVES: For tailored treatment of primary mitral regurgitation (MR), surgeons developed different repair techniques. One of them, the edge-to-edge repair has recently seen a revival, especially for Barlow's disease. METHODS: This study was designed to assess the outcomes of the edge-to-edge technique in mitral valve (MV) repair. Preoperative, periprocedural, and postoperative data were prospectively collected in a dedicated database and analyzed retrospectively. RESULTS: Between March 1999 and July 2019, a total of 152 patients (mean age: 60 ± 13) received an edge-to-edge repair combined with annuloplasty for degenerative MR at our institution. MR resulted from posterior leaflet prolapse in 23 patients (15.1%), anterior leaflet prolapse in 19 (12.5%), and bileaflet prolapse in 110 (72.4%). Of those who had a bileaflet prolapse, 91 (82.7%) had Barlow's disease. Follow-up was complete in 97.4% (6.4 ± 5.7 years). Echocardiographic assessment was achieved in 85.5% (5.1 ± 5.6 years). Overall survival after 10 years was 73.7 ± 5.0%. Twelve patients required valve-related reoperations due to ring dehiscence (n = 2), leaflet suture dehiscence (n = 2), progression of native valve disease (n = 6), or due to device failure (ring fracture) (n = 2). The cumulative incidence of valve-related reoperation at 10 years was 8.4 ± 3.0% (5.2 ± 4.1% in patients with Barlow's disease). At latest follow-up, echocardiography revealed excellent valve function with no or mild MR in 93 patients (88.6%). The mean gradient was 2.9 ± 1.3 mmHg at discharge and decreased to 2.4 ± 1.3 mmHg. Three patients (2.8%) had more than moderate MR. CONCLUSION: Edge-to-edge MV repair is a simple method with excellent results in terms of valvular function and durability especially in patients with Barlow's disease.

Effects of a dual-filter-based cerebral embolic protection device in transcatheter aortic valve replacement on cerebral oxygen saturation: A prospective pilot study.

PURPOSE: The Sentinel Cerebral Protection System (Sentinel-CPS) is increasingly used in transcatheter aortic valve replacement (TAVR). However, the impact of inserting the Sentinel-CPS inside the brain-supplying arteries on cerebral perfusion and oxygenation is unknown. METHODS: Twenty patients undergoing transfemoral TAVR with (n = 10) and without (n = 10) cerebral embolic protection using the Sentinel-CPS were prospectively observed. All patients received conscious sedation and cerebral oxygen saturation (rSO2 ) was continuously measured with near-infrared spectroscopy (NIRS). The cumulative perioperative cerebral desaturation was calculated for each patient by multiplying rSO2 below an individualized desaturation threshold by time. In addition, rSO2 values at the time of Sentinel-CPS insertion, filter positioning, and device retraction were analyzed. RESULTS: There was no significant difference in cumulative cerebral desaturation in patients with Sentinel-CPS (median [IQR]) (0 [0/81] s%) and without (median [IQR]) (0 [0/23] s%), p = .762. A total of 6 patients (33.3%) experienced a perioperative decrease in rSO2 below the individualized desaturation threshold (n = 3 with Sentinel-CPS, n = 3 without Sentinel-CPS; p = 1.000). Cerebral desaturation was detected during valve deployment (n = 5) and after postdilatation (n = 1). No desaturation events occurred during Sentinel-CPS insertion, filter positioning, or retraction. CONCLUSION: Our pilot study revealed no difference in cumulative perioperative cerebral desaturation between TAVR with and without Sentinel-CPS. Catheter- and filter-based manipulations in the brain-supplying arteries for Sentinel-CPS application were not associated with a decrease of cerebral perfusion and oxygenation.

RAB33B recruits the ATG16L1 complex to the phagophore via a noncanonical RAB binding protein.

Autophagosome formation is a fundamental process in macroautophagy/autophagy, a conserved self-eating mechanism in all eukaryotes, which requires the conjugating ATG (autophagy related) protein complex, ATG12-ATG5-ATG16L1 and lipidated MAP1LC3/LC3 (microtubule associated protein 1 light chain 3). How the ATG12-ATG5-ATG16L1 complex is recruited to membranes is not fully understood. Here, we demonstrated that RAB33B plays a key role in recruiting the ATG16L1 complex to phagophores during starvation-induced autophagy. Crystal structures of RAB33B bound to the coiled-coil domain (CCD) of ATG16L1 revealed the recognition mechanism between RAB33B and ATG16L1. ATG16L1 is a novel RAB-binding protein (RBP) that can induce RAB proteins to adopt active conformation without nucleotide exchange. RAB33B and ATG16L1 mutually determined the localization of each other on phagophores. RAB33B-ATG16L1 interaction was required for LC3 lipidation and autophagosome formation. Upon starvation, a fraction of RAB33B translocated from the Golgi to phagophores and recruited the ATG16L1 complex. In this work, we reported a new mechanism for the recruitment of the ATG12-ATG5-ATG16L1 complex to phagophores by RAB33B, which is required for autophagosome formation.Abbreviations: ATG: autophagy-related; Cα: alpha carbon; CCD: coiled-coil domain; CLEM: correlative light and electron microscopy; DTE: dithioerythritol; EBSS: Earle's balanced salt solution; EDTA: ethylenediaminetetraacetic acid; EGFP: enhanced green fluorescent protein; FBS: fetal bovine serum; FLIM: fluorescence lifetime imaging microscopy; FRET: Förster resonance energy transfer; GDP: guanosine diphosphate; GOLGA2/GM130: golgin A2; GppNHp: guanosine 5'-[ß,γ-imido]triphosphate; GST: glutathione S-transferase; GTP: guanosine triphosphate; GTPγS: guanosine 5'-O-[gamma-thio]triphosphate; HA (tag): hemagglutinin (tag); HEK: human embryonic kidney; HeLa: Henrietta Lacks; HEPES: (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid); IgG: immunoglobulin G; Kd: dissociation constant; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCF7: Michigan cancer foundation-7; MEF: mouse embryonic fibroblast; MEM: minimum essential medium Eagle; MST: microscale thermophoresis; NEAA: non-essential amino acids; PBS: phosphate-buffered saline; PE: phosphatidylethanolamine; PtdIns3P: phosphatidylinositol-3-phosphate; RAB: RAS-associated binding; RB1CC1/FIP200: RB1 inducible coiled-coil protein 1; RBP: RAB-binding protein; SD: standard deviation; SDS: sodium dodecyl sulfate; SQSTM1/p62: sequestosome 1; TBS-T: tris-buffered saline-tween 20; WD (repeat): tryptophan-aspartic acid (repeat); WIPI2B: WD repeat domain phosphoinositide interacting 2B; WT: wild type.

Different Rates of Bioprosthetic Aortic Valve Failure With Perimount™ and Trifecta™ Bioprostheses.

OBJECTIVES: The use of bioprostheses in surgical aortic valve replacement (SAVR) has increased in younger patients. Comparative analysis of different types of bioprostheses is lacking. We aimed to compare two proprietary bioprostheses with different designs, i.e., internally and externally mounted leaflets, focusing on the long-term durability and survival. METHODS: We conducted a large single-center retrospective analysis of all consecutive patients who underwent SAVR with either Perimount™ or Trifecta™ bioprostheses between 2001 and 2019. The patient groups were further subdivided by age <65 and >65. Endpoints of the study were all-cause mortality and reoperation due to bioprosthetic valve failure (BVF). RESULTS: Selection criteria resulted in a total sample of 5,053 patients; 2,630 received a Perimount prosthesis (internally mounted leaflets) and 2,423 received a Trifecta prosthesis (externally mounted leaflets). The mean age at surgery was similar (69 ± 11 y, PM, and 68 ± 10 y, TF, p = 0.9), as was estimated survival at 8 years (76.1 ± 1.3%, PM, and 63.7 ± 1.9% TF; p=0.133). Patients in the Trifecta group had a significantly higher cumulative reoperation rate at 8 years compared to those in the Perimount group (16.9 ± 1.9% vs. 3.8 ± 0.4%; p < 0.01). This difference persisted across age groups (<65 y, 13.3% TF vs. 8.6% PM; >65 y, 12% TF vs. 7% PM). CONCLUSION: Bioprostheses for SAVR with externally mounted leaflets (Trifecta) showed significantly higher long-term reoperation rates compared to those with internally mounted leaflets (Perimount), regardless of the patient's age at SAVR. Survival was similar with both bioprostheses.

Normative database of spatiotemporal gait parameters using inertial sensors in typically developing children and young adults.

BACKGROUND: Inertial sensors are increasingly useful to clinicians and researchers to detect gait deficits. Reference values are necessary for comparison to children with gait abnormalities. OBJECTIVE: To present a normative database of spatiotemporal gait and turning parameters in 164 typically developing children and young adults ages 5-30 utilizing the APDM Mobility Lab® system. METHODS: Participants completed the i-WALK test at both self-selected (SS) and fast as possible (FAP) walking speeds. Spatiotemporal gait and turning parameters included stride length, stride length variability, gait speed, cadence, stance, swing, and double support times, and foot strike, toe-off, and toe-out angles, turn duration, peak turn velocity and number of steps to turn. RESULTS: Absolute stride length and gait speed increased with age. Normalized gait speed, absolute and normalized cadence, and stride length variability decreased with age. Normalized stride length and all parameters of gait cycle phase and foot position remained unaffected by age except for greater FSA in children 7-8. Foot position parameters in children 5-6 were excluded due to aberrant values and high standard deviations. Turns were faster in children ages 5-13 and 7-13 in the SS and FAP conditions, respectively. There were no differences in number of steps to turn. Similar trends were observed in the FAP condition except: normalized gait speed did not demonstrate a relationship with age and children ages 5-8 demonstrated increased stance and double support times and decreased swing time compared to children 11-13 and young adults (ages 5-6 only). Females ages 5-6 demonstrated increased stride length variability in the SS condition; males ages 7-8 and 14-30 ha d increased absolute stride length in the FAP condition. Similarities and differences were found between our values and previous literature. SIGNIFICANCE: This normative database can be used by clinicians and researchers to compare abnormal gait patterns and responses to interventions.

Patient eligibility for application of a two-filter cerebral embolic protection device during transcatheter aortic valve implantation: does one size fit all?

OBJECTIVES: This study sought to determine the percentage of patients potentially eligible for implantation of the Sentinel™ Cerebral Protection System (Sentinel-CPS) during transcatheter aortic valve implantation (TAVI) and to identify the reasons for treatment exclusion. METHODS: We retrospectively performed an analysis of pre-TAVI multislice computed tomography (MSCT) aortograms and data review of all patients undergoing a TAVI procedure in 2017 (n = 317). MSCT evaluation included the assessment of aortic arch anatomy and the vascular dimensions of the brachiocephalic and left common carotid artery. Data analysis focused on comorbid conditions, precluding 6-Fr sheath radial access and filter deployment due to history of previous artery interventions. RESULTS: MSCT and data analysis showed Sentinel-CPS compatibility in 61.5% of patients (n = 195). Sentinel-CPS would have been contraindicated in 38.5% (n = 122) due to one or more of the following: (i) measured diameters of the filter-landing zones <9 or >15 mm in the brachiocephalic artery and <6.5 or >10 mm in the left common carotid artery (n = 116; 88 with carotid dimensions too small); (ii) significant subclavian artery stenosis (n = 4) or an aberrant subclavian artery (n = 3) precluding Sentinel-CPS implantation and (iii) clinical characteristics including hypersensitivity to nickel-titanium (n = 1), radial artery occlusion (n = 1) or previous left common carotid artery interventions (n = 5). CONCLUSIONS: MSCT and clinical data supported Sentinel-CPS compatibility in 61.5% of patients. The most common reason for treatment exclusion was inappropriate diameter within the target landing zone of the left carotid artery. Future device development should address this limitation.

Impact of a Two-Filter Cerebral Embolic Protection Device on the Complexity and Risk of Transcatheter Aortic Valve Replacement.

BACKGROUND: There is a growing use of cerebral protection devices in patients undergoing transcatheter aortic valve replacement (TAVR). We aimed to analyze if the use of these devices itself has an impact on the complexity and the risk of TAVR. METHODS: Between February 2016 and July 2017, 391 patients underwent transfemoral TAVR with Medtronic CoreValve Evolut R (n = 196) or Edwards Sapien 3 (n = 195). In 39 patients, the Claret Sentinel™ embolic protection device (CS-EPD) was used. Prospectively collected data were retrospectively analyzed, comparing fluoroscopy/operation time, amount of contrast used, vascular events, and postprocedural renal function in TAVR patients with (n = 39) and without (n = 352) CS-EPD. RESULTS: The CS-EPD was placed through the right radial (n = 35) or brachial (n = 4) artery. Procedural success rate defined as correct deployment and retraction of both filters was 94.9%. No device-related vascular complications occurred. TAVR patients with CS-EPD showed a significantly higher total operation time, total fluoroscopy time, and amount of used contrast (85.4 ± 39.3 vs. 64 ± 29.8 minutes, p = 0.002; 20.7 ± 9.3 vs. 13.7 ± 7 minutes, p ≤ 0.001; 133.7 ± 42.6 vs. 109.7 ± 44.5 mL, p = 0.001). Comparing the initial third of patients receiving a CS-EPD with the last third of CS-EPD cases, procedural time had decreased significantly (102.5 ± 34.9 vs. 67 ± 11.9; p = 0.002). There were no differences in postprocedural renal failure (p = 0.80). CONCLUSION: Our data add evidence that the application of the CS-EPD is not associated with an additional risk for the patient. Although procedural time and amount of contrast are still higher when using the CS-EPD, there were no device-related complications or increased incidence of renal failure.

Electroporated recombinant proteins as tools for in vivo functional complementation, imaging and chemical biology.

Delivery of native or chemically modified recombinant proteins into mammalian cells shows promise for functional investigations and various technological applications, but concerns that sub-cellular localization and functional integrity of delivered proteins may be affected remain high. Here, we surveyed batch electroporation as a delivery tool for single polypeptides and multi-subunit protein assemblies of the kinetochore, a spatially confined and well-studied subcellular structure. After electroporation into human cells, recombinant fluorescent Ndc80 and Mis12 multi-subunit complexes exhibited native localization, physically interacted with endogenous binding partners, and functionally complemented depleted endogenous counterparts to promote mitotic checkpoint signaling and chromosome segregation. Farnesylation is required for kinetochore localization of the Dynein adaptor Spindly. In cells with chronically inhibited farnesyl transferase activity, in vitro farnesylation and electroporation of recombinant Spindly faithfully resulted in robust kinetochore localization. Our data show that electroporation is well-suited to deliver synthetic and chemically modified versions of functional proteins, and, therefore, constitutes a promising tool for applications in chemical and synthetic biology.

Spatial Cycling of Rab GTPase, Driven by the GTPase Cycle, Controls Rab's Subcellular Distribution.

Rab GTPases (>60 members in humans) function as master regulators of intracellular membrane trafficking. Correct and specific localization of Rab proteins is required for their function. How the distinct spatial distribution of Rab GTPases in the cell is regulated remains elusive. To globally assess the subcellular localization of Rab1, we determined kinetic parameters of two pathways that control the spatial cycles of Rab1, i.e., vesicular transport and GDP dissociation inhibitor (GDI)-mediated recycling. We demonstrate that the switching between GTP and GDP binding states, which is governed by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs), GDI, and GDI displacement factor (GDF), is a major determinant of Rab1's ability to effectively cycle between cellular compartments and eventually its subcellular distribution. In silico perturbations of vesicular transport, GEFs, GAPs, GDI, and GDF using a mathematical model with simplified cellular geometries showed that these regulators play an important role in the subcellular distribution and activity of Rab1.