ATP-binding cassette protein ABCA7 deficiency impairs sphingomyelin synthesis, cognitive discrimination, and synaptic plasticity in the entorhinal cortex.

Sphingomyelin (SM) is an abundant plasma membrane and plasma lipoprotein sphingolipid. We previously reported that ATP-binding cassette family A protein 1 (ABCA1) deficiency in humans and mice decreases plasma SM levels. However, overexpression, induction, downregulation, inhibition, and knockdown of ABCA1 in human hepatoma Huh7 cells did not decrease SM efflux. Using unbiased siRNA screening, here, we identified that ABCA7 plays a role in the biosynthesis and efflux of SM without affecting cellular uptake and metabolism. Since loss of function mutations in the ABCA7 gene exhibit strong associations with late-onset Alzheimer's disease across racial groups, we also studied the effects of ABCA7 deficiency in the mouse brain. Brains of ABCA7-deficient (KO) mice, compared with WT, had significantly lower levels of several SM species with long chain fatty acids. In addition, we observed that older KO mice exhibited behavioral deficits in cognitive discrimination in the active place avoidance task. Next, we performed synaptic transmission studies in brain slices obtained from older mice. We found anomalies in synaptic plasticity at the intracortical synapse in layer II/III of the lateral entorhinal cortex but not in the hippocampal CA3-CA1 synapses in KO mice. These synaptic abnormalities in KO brain slices were rescued with extracellular SM supplementation but not by supplementation with phosphatidylcholine. Taken together, these studies identify a role of ABCA7 in brain SM metabolism and the importance of SM in synaptic plasticity and cognition, as well as provide a possible explanation for the association between ABCA7 and late-onset Alzheimer's disease.

Association of ACEI/ARB and statin prescribing patterns with mortality after Transcatheter Aortic Valve Replacement (TAVR): Findings from real-world claims data.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has become the standard of care for most patients with severe aortic stenosis (AS), but the impact of medical therapy prescribing patterns on post-TAVR patients has not been thoroughly investigated. METHODS: We analyzed Optum claims data from 9,012 adults who received TAVR for AS (January 2014-December 2018). Pharmacy claims data were used to identify patients who filled ACEI/ARB and/or statin prescriptions during the study's 90-day landmark period post-TAVR. Kaplan-Meier and adjusted Cox Proportional Hazards models were used to evaluate the association of prescribing patterns with mortality during the 3-year follow-up period. Subgroup analyses were performed to examine the impact of 11 potential confounders on the observed associations. RESULTS: A significantly lower adjusted 3-year mortality was observed for patients with post-TAVR prescription for ACEI/ARBs (hazard ratio [HR] = 0.82, 95% confidence interval [CI] 0.74-0.91, P = .0003) and statins (HR = 0.85, 95% CI 0.77-0.94, P = .0018) compared to patients who did not fill prescriptions for these medications post-TAVR. Subgroup analyses revealed that the survival benefit associated with ACEI/ARB prescription was not affected by any of the potential confounding variables, except preoperative ACEI/ARB prescription was associated with significantly lower risk of mortality vs postoperative prescription only. No other subgroup variables had significant interactions associated with survival benefits, including preoperative use of statins. CONCLUSIONS: In this large-scale, real-world analysis of patients undergoing TAVR, the prescription of ACEI/ARB and statins was associated with a significantly lower risk of mortality at 3-years, especially in those where the medications were initiated preoperatively.

Treatment of Bicuspid Aortic Valve Stenosis with TAVR: Filling Knowledge Gaps Towards Reducing Complications.

PURPOSE OF REVIEW: Bicuspid aortic valve (BAV) disease is the most common congenital heart defect worldwide. When severe, symptomatic aortic stenosis ensues, the treatment has increasingly become transcatheter aortic valve replacement (TAVR). The purpose of this review is to identify BAV classification and imaging methods, outline TAVR outcomes in BAV anatomy, and discuss how computational modeling can enhance TAVR treatment in BAV patients. RECENT FINDINGS: TAVR use in BAV patients, when compared to use in tricuspid aortic valves, showed lower device success rate, and there remains no long-term randomized trial data. It has been reported that BAV patients with severe calcification increase the rate of complications. Additionally, the asymmetrical morphology of BAVs often results in asymmetric stent geometries which have implications for increased thrombosis risk and decreased durability. These adverse outcomes are currently very difficult to predict from routine pre-procedural imaging alone. Recently developed patient specific experimental and computational techniques have the potential to assist in filling knowledge gaps in the mechanisms of these complications and provide more information during preclinical planning for better TAVR selection in low surgical risk BAV patients. Efficacy of TAVR for irregular BAV anatomies remains concerning due to the lack of a long-term randomized trial data, their increased rate of short-term complications, and signs that long-term durability could be an issue. More knowledge on identifying which BAV anatomies are at greater risk for these adverse outcomes can potentially improve patient selection for TAVR versus SAVR in low surgical risk BAV patients.

SCAI publications committee manual of standard operating procedures.

Evidence-based recommendations for clinical practice are intended to help health care providers and patients make decisions, minimize inappropriate practice variation, promote effective resource use, improve clinical outcomes, and direct future research. The Society for Cardiovascular Angiography and Interventions (SCAI) has been engaged in the creation and dissemination of clinical guidance documents since the 1990s. These documents are a cornerstone of the society's education, advocacy, and quality improvement initiatives. The publications committee is charged with oversight of SCAI's clinical documents program and has created this manual of standard operating procedures to ensure consistency, methodological rigor, and transparency in the development and endorsement of the society's documents. The manual is intended for use by the publications committee, document writing groups, external collaborators, SCAI representatives, peer reviewers, and anyone seeking information about the SCAI documents program.

Causes and hemodynamic findings in chronic severe pulmonary regurgitation.

Severe pulmonary regurgitation (PR) most commonly occurs as a sequelae of treatment of pulmonic stenosis or Tetralogy of Fallot with fewer cases of primary pulmonic valvular regurgitation. The amount of PR is influenced by valvular integrity, right ventricular (RV) size, and RV diastolic pressures. In chronic severe PR, the RV remodels to accommodate the regurgitant flow and RV stroke volume increases to maintain effective forward blood flow. Hemodynamic changes include a widened pulmonary artery (PA) pulse pressure and low PA diastolic pressures. As the amount of regurgitation increases, RV end diastolic pressure becomes elevated and systemic cardiac output is reduced, especially with exercise. "Ventricularization" of the PA pressure tracing, in which the contour of the PA pressure is similar to the contour of the RV pressure, is a specific but not sensitive finding in severe PR. © 2015 Wiley Periodicals, Inc.

Watchman in ascending aorta for systemic protection (WAASP): Novel use of Watchman in ascending aorta for embolic protection-first in man.

We report two cases where left atrial appendage closure (LAA) with Watchman was successfully performed despite presence of definite LAA thrombus. Because there was the risk of thrombus dislodgement, we transiently placed an additional Watchman device in the ascending aorta for embolic protection. © 2017 Wiley Periodicals, Inc.

Post-TAVR aortogram: Transform it into a modern tool for prognosis and efficiency.

Video densitometry after aortography can provide objective assessment of aortic regurgitation post-transcatheter aortic valve replacement (TAVR) Contrast density ratio between the left ventricular outflow track and proximal aorta (LVOT-AR) of >0.17 suggests greater than mild aortic insufficiency and correlates with echo findings LVOT-AR of >0.17 is associated with higher 30-day and 1-year mortality.

Size does matter but is there an obesity paradox in TAVR?

Patients with low body mass index (<20 kg/m(2) ) undergoing transcatheter aortic valve replacement have higher short- and long-term mortality Low BMI is an important tool to consider in patient screening and prognostication Prospective study is needed to accurately assess the effects of BMI in TAVR patients, to prove or refute the obesity paradox.

Early Intervention in Asymptomatic Aortic Stenosis: What Are We Waiting For?

Aortic stenosis (AS) contributes to significant cardiovascular morbidity and mortality worldwide, and the natural history from symptoms to ventricular decompensation, heart failure, and death has been well documented. For more than 2 decades, technologies including imaging and biomarkers have shown a promising ability to detect myocardial damage associated with AS before symptoms arise. Current treatment guidelines rely heavily on symptoms or ventricular decompensation as triggers for aortic valve intervention. There is increasing appreciation of the relationship between myocardial damage due to AS before the emergence of symptoms, and a number of published randomised trials suggest a benefit to early intervention in asymptomatic AS, with additional trials actively enrolling. Future treatment paradigms may incorporate early detection of ventricular damage by noninvasive new technologies as triggers for asymptomatic intervention. Enthusiasm for early aortic valve replacement should be tempered by consideration of the competing risks of early valve intervention, but an increasing preponderance of evidence continues to suggest that earlier intervention in AS is warranted.

3D Characterization of the Aortic Valve and Aortic Arch in Bicuspid Aortic Valve Patients.

Patients with bicuspid aortic valve (BAV) commonly have associated aortic stenosis and aortopathy. The geometry of the aortic arch and BAV is not well defined quantitatively, which makes clinical classifications subjective or reliant on limited 2D measurements. The goal of this study was to characterize the 3D geometry of the aortic arch and BAV using objective and quantitative techniques. Pre-TAVR computed tomography angiogram (CTA) in patients with BAV and aortic stenosis (AS) were analyzed (n = 59) by assessing valve commissural angle, presence of a fused region, percent of fusion, and calcium volume. The ascending aorta and aortic arch were reconstructed from patient-specific imaging segmentation to generate a centerline and calculate maximum curvature and maximum area change for the ascending aorta and the descending aorta. Aortic valve commissural angle signified a bimodal distribution suggesting tricuspid-like (≤ 150°, 52.5% of patients) and bicuspid-like (> 150°, 47.5%) morphologies. Tricuspid like was further classified by partial (10.2%) or full (42.4%) fusion, and bicuspid like was further classified into valves with fused region (27.1%) or no fused region (20.3%). Qualitatively, the aortic arch was found to have complex patient-specific variations in its 3D shape with some showing extreme diameter changes and kinks. Quantitatively, subgroups were established using maximum curvature threshold of 0.04 and maximum area change of 30% independently for the ascending and descending aorta. These findings provide insight into the geometric structure of the aortic valve and aortic arch in patients presenting with BAV and AS where 3D characterization allows for quantitative classification of these complex anatomic structures.

Mortality Associated With Proportionality of Secondary Mitral Regurgitation After Transcatheter Mitral Valve Repair: North American Mitraclip for Functional Mitral Regurgitation Registry.

The association, if any, between the effective regurgitant orifice area (EROA) to left ventricular end-diastolic volume (LVEDV) ratio and 1-year mortality is controversial in patients who undergo mitral transcatheter edge-to-edge repair (m-TEER) with the MitraClip system (Abbott Vascular, Santa Clara, CA). This study's objective was to determine the association between EROA/LVEDV and 1-year mortality in patients who undergo m-TEER with MitraClip. In patients with severe secondary (functional) mitral regurgitation (MR), we analyzed registry data from 11 centers using generalized linear models with the generalized estimating equations approach. We studied 525 patients with secondary MR who underwent m-TEER. Most patients were male (63%) and were New York Heart Association class III (61%) or IV (21%). Mitral regurgitation was caused by ischemic cardiomyopathy in 51% of patients. EROA/LVEDV values varied widely, with median = 0.19 mm2/ml, interquartile range [0.12,0.28] mm2/ml, and 187 patients (36%) had values <0.15 mm2/ml. Postprocedural mitral regurgitation severity was substantially alleviated, being 1+ or less in 74%, 2+ in 20%, 3+ in 4%, and 4+ in 2%; 1-year mortality was 22%. After adjustment for confounders, the logarithmic transformation (Ln) of EROA/LVEDV was associated with 1-year mortality (odds ratio 0.600, 95% confidence interval 0.386 to 0.933, p = 0.023). A higher Society of Thoracic Surgeons risk score was also associated with increased mortality. In conclusion, lower values of Ln(EROA/LVEDV) were associated with increased 1-year mortality in this multicenter registry. The slope of the association is steep at low values but gradually flattens as Ln(EROA/LVEDV) increases.

Structural Heart Imaging Using 3-Dimensional Intracardiac Echocardiography: JACC Cardiovascular Imaging Position Statement.

3-dimensional (3D) intracardiac echocardiography (ICE) is emerging as a promising complement and potential alternative to transesophageal echocardiography for imaging guidance in structural heart interventions. To establish standardized practices, our multidisciplinary expert position statement serves as a comprehensive guide for the appropriate indications and utilization of 3D-ICE in various structural heart procedures. The paper covers essential aspects such as the fundamentals of 3D-ICE imaging, basic views, and workflow recommendations specifically tailored for ICE-guided structural heart procedures, such as transeptal puncture, device closure of intracardiac structures, and transcatheter mitral and tricuspid valve interventions. Current challenges, future directions, and training requirements to ensure operator proficiency are also discussed, thereby promoting the safety and efficacy of this innovative imaging modality to support expanding its future clinical applications.

A descriptive study to assess knowledge related to hypertension and its impact upon exercises and sleep pattern among adults from communities of Uttarakhand.

INTRODUCTION: Hypertension nowadays is a major community health problem. It is high prevalence, which becomes an important area of research which is also a major possibility for circulatory diseases and other complications. It is a silent killer, which does not show any warning sign until a severe medicinal crisis occurs. The study aims to assess the knowledge regarding hypertension and its effect on the amount of exercise and sleep among adults at risk of hypertension from both rural and urban communities of Uttarakhand. METHODS AND MATERIALS: A descriptive cross-sectional research design with the total sample size was calculated as 542 adults at risk of hypertension. A purposive sampling method was used for sample selection in this study. A semi-structured questionnaire regarding knowledge related to hypertension and amount of exercise and sleep patterns was administered as tools for data collection. Analysis was done by using SPSS 23.0 version software, descriptive statistics with the use of frequency %, inferential statistics with Chi-square test, and P value ≤ 0.05 considered as significant. RESULTS: Majority (58%) of them were male, living with a nuclear family with very poor educational status. It showed that whenever they have free time, only then they were performing simple work without having any experience with regular exercise and yoga. Less than half of them (45%) were having good knowledge about increased blood pressure is a disease, medical management, and how to prevent it. Knowledge regarding hypertension showed significant association with less amount of exercise (use of a motored vehicle to going to job/work) (p value = 0.0001*) and satisfactory pattern of sleep among adults at risk of hypertension (p value = 0.001*). CONCLUSION: In this study, a lack of education and very poor knowledge regarding the management of hypertension found to be associated with less amount of exercise but satisfactory sleep among adults at risk of hypertension.

Calcium Fracture and Device Over Expansion in Transcatheter Aortic Valve Replacement for Bicuspid Aortic Valves.

Transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve disease (BAV) has potential risks of under expansion and non-circularity which may compromise long-term durability. This study aims to investigate calcium fracture and balloon over expansion in balloon-expandable TAVs on the stent deformation with the aid of simulation. BAV patients treated with the SAPIEN 3 Ultra with pre- and post-TAVR CTs were analyzed (n = 8). Simulations of the stent deployment were performed (1) with baseline simulation allowing calcium fracture, (2) without allowable calcium fracture and (3) with balloon over expansion (1 mm larger diameter). When compared to post CT, baseline simulations had minimal error in expansion (2.5% waist difference) and circularity (3.0% waist aspect ratio difference). When compared to baseline, calcium fracture had insignificant impact on the expansion (- 0.5% average waist difference) and circularity (- 1.6% average waist aspect ratio difference). Over expansion had significantly larger expansion compared to baseline (15.4% average waist difference) but had insignificant impact on the circularity (- 0.5% waist aspect ratio difference). We conclude that stent deformation can be predicted with minimal error, calcium fracture has small differences on the final stent deformation except in extreme calcified cases, and balloon over expansion expands the waist closer to nominal values.

Cardiac Computed Tomography Angiography Anatomical Characterization of Patients Screened for a Dedicated Transfemoral Transcatheter Valve System for Primary Aortic Regurgitation.

Background: Cardiac computed tomography angiography was used to identify anatomical characteristics of the aortic root in patients with severe aortic regurgitation (AR) as compared to those with aortic stenosis (AS) to judge feasibility of transcatheter aortic valve replacement (TAVR) with the JenaValve Trilogy system. Methods: Cardiac computed tomography angiography was performed prior to planned TAVR for 107 patients with severe AR and 92 patients with severe AS. Measurements related to aortic root and coronary artery anatomy were obtained and compared between groups. Perimeter >90 mm and aortic annulus angle â€‹>70 degrees were defined as the theoretical exclusion criteria for TAVR. A combination of sinus of Valsalva diameter <30 mm and coronary height <12 mm was defined as high risk for coronary occlusion. Results: The mean age of patients in the AR group was 74.9 ± 11.2 years, 46% were women, and the mean Society of Thoracic Surgeons risk score for mortality was 3.6 ± 2.1. Comparatively, the mean age of patients in the AS group was 82.3 ± 5.53 years, 65% were women, and the mean Society of Thoracic Surgeonsrisk score was 5.5 ± 3.3. Annulus area, perimeter, diameter, and angle were larger in patients with severe AR. Sinus of Valsalva diameters and heights were larger in patients with severe AR. More AR patients were excluded based on perimeter (14 vs. 2%) and annulus angle (6 vs. 1%). More AS patients exhibited high-risk anatomy for left main coronary occlusion (21 vs. 7%) and right coronary occlusion (14 vs. 3%). The maximum dimension of the ascending aorta was larger in patients with severe AR (39 vs. 35 mm). The percentage of referred AR patients with significant aortopathy requiring surgical intervention was very low (only 1 AR patient with ascending aorta diameter >5.5 cm). Conclusions: A significantly larger proportion of patients with severe AR are excluded from TAVR as compared to AS due to large aortic annulus size and steep annulus angulation. By far the most prevalent excluding factor is aortic annulus size, with fewer patients excluded due to angulation. AR patients have lower-risk anatomy for coronary occlusion. Larger transcatheter valve sizes and further delivery system modifications are required to treat a larger proportion of AR patients.

Comparative sessile drop and dip pen nanolithography investigation for various hydrophilic ink/surface systems.

We present a dip pen nanolithography study of various hydrophilic ink/surface systems with application in the field of biosensors and novel nano-materials. The inking process was investigated by studying a number of inks, such as Deoxyribonucleic acid (DNA), Bovine serum albumin (BSA), Streptavidin, 16-mercaptohexadecanoic acid (MHA) and a 20 nm nanosphere (NS) polystyrene solution onto a range of substrates, namely glass, silicon, gold and tetrahedral amorphous carbon (taC). In the majority of cases, this resulted in patterns with sub-100 nm line widths and dot diameters. Importantly, contact angle measurements in the microl range showed a decrease of contact angle with drop volume, interpreted as a line tension effect. The significance of this to the nanoscale wetting behaviour is discussed. The effect of dwell time and writing speed indicates that the inking process is not solely defined by surface diffusion but also influenced by the ink dissolution rate from the tip.

Transcatheter aortic valve replacement for bicuspid aortic valve disease: does conventional surgery have a future?

Bicuspid aortic valve (BAV) disease is the most common form of congenital heart valve defect. It is associated with aortic stenosis (AS), aortic insufficiency, and aortopathy. Treatment of severe AS requires valve replacement which historically has been performed with surgical aortic valve replacement (SAVR). Recently, transcatheter aortic valve replacement (TAVR) has emerged as a promising alternative. However, increased rates of adverse outcomes following TAVR have been shown in BAV patients with high amounts of calcification. Comparison between TAVR and SAVR in low surgical risk BAV patients in a randomized trial has not been performed and TAVR for BAV long-term performance is unknown due to lack of clinical data. Due to the complexity of BAV anatomies and the significant knowledge gap from the lack of clinical data, SAVR still has many benefits over TAVR in low surgical risk BAV patients. It also remains common for BAV patients to have an aortopathy, which currently can be treated with surgical techniques. This review aims to outline BAV associated diseases and their treatment strategies, the main TAVR adverse outcomes associated with anatomically complex BAV patients, TAVR strategies for mitigating these risks and the current state of cutting-edge 3D printing and computer modeling screening methods that can provide otherwise unobtainable preoperative information during the BAV patient selection process for TAVR.

A systematic review on the outcome of distraction osteogenesis in TMJ ankylosis.

INTRODUCTION: TMJ ankylosis (TMJa) management by arthroplasty alone fails to address the deformity and the compromised airway. Distraction osteogenesis (DO) can offer a pragmatic solution to TMJa. The aim of the study was to generate evidence towards the role of DO in TMJa, evaluate its efficiency and develop an algorithm for use of DO in TMJa. MATERIAL AND METHODS: The research question was formulated using the PICOS statement for reporting guidelines in systematic reviews, where the efficiency of DO was evaluated in terms of mouth opening, correction of facial deformity and asymmetry, airway correction, and its long term effects. RESULTS: 1130 articles reported DO as a treatment modality for TMJ ankylosis, of which 32 prospective studies, 16 retrospective and 2 RCTs were included in the study. DO was used for mandibular distraction in 45 studies and for simultaneous maxillamandibular distraction in only five studies. An algorithm for use of DO in TMJa was developed. CONCLUSION: Although DO has proven its application in TMJ ankylosis cases, its best use is for correction of obstructive sleep apnoea. Relapse causing loss of posterior ramal height is a concern after transport DO. Prearthroplastic DO appears to best correct mandibular deformity. A maxillomandibular deformity requires simultaneous maxillomandibular distraction. However, a metanalysis is still awaited for effectiveness of DO in TMJ ankylosis.