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OBJECTIVES/HYPOTHESIS Evaluate technical success, tolerability, and safety of lidocaine iontophoresis and tympanostomy tube placement for children in an office setting. STUDY DESIGN Prospective individual cohort study. METHODS This prospective multicenter study evaluated in-office tube placement in children ages 6 months through 12 years of age. Anesthesia was achieved via lidocaine/epinephrine iontophoresis. Tube placement was conducted using an integrated and automated myringotomy and tube delivery system. Anxiolytics, sedation, and papoose board were not used. Technical success and safety were evaluated. Patients 5 to 12 years old self-reported tube placement pain using the Faces Pain Scale-Revised (FPS-R) instrument, which ranges from 0 (no pain) to 10 (very much pain). RESULTS Children were enrolled into three cohorts with 68, 47, and 222 children in the Operating Room (OR) Lead-In, Office Lead-In, and Pivotal cohorts, respectively. In the Pivotal cohort, there were 120 and 102 children in the

Whether due to illness, weather, safety, or other concerns, it is very difficult for biology students to gather meaningful and timely data without access to campus. This has been especially evident during the COVID-19 pandemic, in which most laboratory exercises have been conducted as a simulation. Simulated experiments provide a stopgap for certain courses, but for upper-level and research courses, they are often insufficient. Many new microscopy tools now on the market can be adapted to allow students to generate and analyze novel data with little aid from instructors. Remote brightfield-based systems like the CytoSMART Lux2 can be used to gather real-time insight into the progression of cell growth, cell migration, and cell viability over time. The data from these systems can be viewed via the Internet or downloaded for later analysis. Confocal microscopy also offers unique remote-learning opportunities. Because these fluorescence-based microscopes are controlled almost exclusively by a computer, free “remote desktop” software can allow students to learn how to use this cutting-edge technology and can also allow for the generation and analysis of novel data. While these systems can be expensive, they offer a variety of benefits for undergraduate students and researchers, whether they are in the laboratory or working remotely.

We previously showed that coincident exposure to heat shock (HS; 42°C for 2 h) and TNF-α synergistically induces apoptosis in mouse lung epithelium. We extended this work by analyzing HS effects on human lung epithelial responses to clinically relevant injury. Cotreatment with TNF-α and HS induced little caspase-3 and poly(ADP-ribose) polymerase cleavage in human small airway epithelial cells, A549 cells, and BEAS2B cells. Scratch wound closure rates almost doubled when A549 and BEAS2B cells and air-liquid interface cultures of human bronchial epithelial cells were heat shocked immediately after wounding. Microarray, qRT-PCR, and immunoblotting showed fibroblast growth factor 1 (FGF1) to be synergistically induced by HS and wounding. Enhanced FGF1 expression in HS/wounded A549 was blocked by inhibitors of p38 MAPK (SB203580) or HS factor (HSF)-1 (KNK-437) and in HSF1 knockout BEAS2B cells. PCR demonstrated FGF1 to be expressed from the two most distal promoters in wounded/HS cells. Wound closure in HS A549 and BEAS2B cells was reduced by FGF receptor-1/3 inhibition (SU-5402) or FGF1 depletion. Exogenous FGF1 accelerated A549 wound closure in the absence but not presence of HS. In the presence of exogenous FGF1, HS slowed wound closure, suggesting that it increases FGF1 expression but impairs FGF1-stimulated wound closure. Frozen sections from normal and idiopathic pulmonary fibrosis (IPF) lung were analyzed for FGF1 and HSP70 by immunofluorescence confocal microscopy and qRT-PCR. FGF1 and HSP70 mRNA levels were 7.5- and 5.9-fold higher in IPF than normal lung, and the proteins colocalized to fibroblastic foci in IPF lung. We conclude that HS signaling may have an important impact on gene expression contributing to lung injury, healing, and fibrosis.

Objectives: To demonstrate safety, feasibility and short-term clinical outcomes after transcatheter aortic valve-in-valve (ViV) implantation under local anesthesia without contrast aortography or echocardiographic guidance. Background: Transcatheter ViV implantation is an emerging treatment modality for patients with degenerative surgical bioprostheses. Given the radiopaque properties of the surgical aortic valve (SAV) frame, ViV procedures can often be performed with fluoroscopic guidance alone. Methods: ViV implantation was performed in 37 patients with SAV failure under local anesthesia without contrast aortography. Clinical and echocardiographic data were obtained at baseline, discharge, and 30 days. Results: Mean age was 74 ± 10 years and STS predicted risk of mortality was 5.6 ± 2.4%. Mean transaortic gradient decreased from 39.4 ± 15.5 mmHg to 13 ± 6.3 mmHg at discharge (p

Resumen Introduccion y objetivos La valvula autoexpandible Portico es una nueva valvula de implante transcateter que ha mostrado resultados prometedores en estudios preliminares; sin embargo, no existen estudios que comparen este dispositivo con sistemas previos de valvula aortica transcateter. El objetivo de este estudio es comparar los resultados hemodinamicos de la valvula autoexpandible Portico con los de la valvula expandible mediante balon SAPIEN XT en un estudio de casos apareados con analisis en un laboratorio central de ecocardiografia Metodos Se emparejo a 22 pacientes tratados mediante implante transcateter de la valvula Portico de 23 mm con 40 pacientes tratados con la valvula SAPIEN XT de 23 mm, segun los siguientes parametros: area y diametro medio del anillo aortico por tomografia computarizada multidetector, fraccion de eyeccion del ventriculo izquierdo, area de superficie corporal e indice de masa corporal. El diametro medio del anillo aortico fue de 19,6 ± 1,3 mm por ecocardiografia transtoracica y de 21,4 ± 1,2 mm por tomografia computarizada, sin diferencias significativas entre los grupos. Se obtuvieron imagenes de ecocardiografia Doppler antes de la intervencion y en el seguimiento realizado al cabo de 1 mes y se analizaron en un laboratorio central de ecocardiografia. Resultados No se objetivaron diferencias significativas entre los grupos en el gradiente transaortico medio residual (SAPIEN XT, 10,4 ± 3,7 mmHg; Portico, 9,8 ± 1,1 mmHg; p = 0,49) ni en el area efectiva del orificio valvular (SAPIEN XT, 1,36 ± 0,27 cm2; Portico, 1,37 ± 0,29 cm2; p = 0,54). La incidencia del desajuste protesico (area efectiva del orificio valvular Conclusiones El implante transcateter de la valvula autoexpandible Portico produjo resultados hemodinamicos a corto plazo similares a los de la valvula expandible por balon SAPIEN XT en el tratamiento de pacientes con estenosis aortica grave y anillo aortico pequeno. Son necesarios estudios prospectivos con seguimiento a mas largo plazo y en pacientes con anillo aortico mayor.

Objectives This study evaluated the results of transcatheter aortic valve replacement (TAVR) in bicuspid aortic stenosis (AS) using a new-generation TAVR device. Background A bicuspid AS is often considered a relative contraindication to TAVR. Although initial reports have demonstrated feasibility using early-generation devices, outcomes have not matched those seen with tricuspid AS. Paravalvular aortic regurgitation (AR) has been particularly problematic. Methods We collected baseline characteristics, procedural data, and 30-day clinical follow-up findings from 8 centers in Europe and Canada that had performed TAVR in bicuspid AS using the SAPIEN 3 valve. Results 51 patients underwent TAVR using the SAPIEN 3 valve. Patient mean age was 76.2 ± 9.3 years and the Society of Thoracic Surgeons predicted risk of mortality scores were 5.2 ± 3.7%. Bicuspid valve types were: type 0, 11.8%; type 1, 82.3%; and type 2, 1.9%. There were no cases of valve embolization or need for a second valve. Post-dilation was performed in 7.8%. The mean aortic gradient decreased from 49.4 ± 16.0 mm Hg to 11.2 ± 4.7 mm Hg. Post-implantation AR was none/trivial in 63% and mild in 37%. There were no cases of moderate or severe AR. At 30-day follow-up, there were 2 deaths (3.9%), 2 major vascular complications, and 12 patients (23.5%) required pacemaker implantation. Conclusions TAVR in bicuspid AS using a new-generation device was feasible and effective with favorable valve performance and no cases of moderate or severe AR.

Background Stent thrombosis (ST) is rare, but is associated with significant morbidity and mortality. Methods We analyzed data from the British Columbia (BC) Registry from April 2011–January 2012. Results 101 ST cases were reported and verified. Based on timing, ST was considered early (≤30days) in 35.6%, late (>30days–1year) in 17.8% and very late (>1year) in 46.5%. The majority (68.5%) presented with STEMI, and the remaining with non-STEMI (31.5%). Most vessels were functionally occluded (TIM1 flow grade ≤1 in 67.1%). Thrombus burden was high (TIMI thrombus grade ≥4 in 77.2%). Aspiration thrombectomy was performed in 41% of cases. New stents were implanted in 62.4% cases. Intra-coronary imaging was low (11%). At the original stent implantation, STEMI was the clinical presentation in 39.6%, the lesion was complex in 62.1%, and thrombus was visualized in 23.0%. Prognosis after ST was unfavorable with high mortality (11.9% at 30days and 16.8% at one year), and further revascularization (5.0% repeat PCI and 6.9% coronary artery bypass graft surgery). Early ST was associated with worse clinical outcome compared to late/very late ST: 30-day mortality at 22.2% versus 6.2% (p=0.02), and 1-year mortality at 27.8% versus 10.8% (p=0.05). Conclusions In this prospective registry from BC, all ST presented with myocardial infarction, and the majority was treated with emergency PCI. Additional stents were commonly implanted with infrequent use of intracoronary imaging. Mortality rate was higher for early ST in comparison with late/very late ST. A comprehensive approach should be developed to treat this difficult complication.

Background Isolated tricuspid valve surgery is associated with high morbidity and mortality, especially in patients with prior cardiac surgery. The transcatheter Forma Repair System (Edwards Lifesciences, Irvine, California) is designed to provide a surface for native leaflet coaptation to reduce tricuspid regurgitation (TR) by occupying the regurgitant orifice area. Objectives This study sought to evaluate the feasibility and exploratory efficacy with this transcatheter repair system for the treatment of severe TR. Methods Seven high-risk patients with severe TR and clinical signs of heart failure were declined for surgery and offered transcatheter treatment with this device. All procedures were performed within a cardiac catheterization laboratory or hybrid operating room under general anesthesia with transesophageal echocardiographic guidance. Vascular access was via the left axillary vein. Baseline characteristics, procedural and in-hospital outcomes, as well as 30-day follow-up were prospectively collected. Results All patients had severe TR and New York Heart Association (NYHA) functional class II to IV (mean age 76 ± 13 years; mean logistic EuroSCORE 25.7 ± 17.4%), and underwent device implantation to improve tricuspid leaflet coaptation, thereby reducing TR. Device implantation was successful without procedural complications in all patients, with significant reductions in TR severity (moderate in 3 patients and mild in 4 patients). Median hospital length of stay was 4 days. At 30-day follow-up, all patients but 1 demonstrated improvements in NYHA functional status (to class II) with pronounced reductions in the presence and severity of peripheral edema. TR severity was assessed as being moderate at 30-day transthoracic echocardiography follow-up in all patients. No complications related to the device or vascular access were observed during follow-up. Conclusions A transcatheter-based treatment option for severe TR appears safe and feasible with this repair system. Improvements in TR severity were documented in all patients, which were accompanied by improvements in peripheral edema and functional status.

Objectives This study sought to describe the development of a multicenter, transcatheter aortic valve replacement program and regional systems of care intended to optimize coordinated, efficient, and appropriate delivery of this new therapy. Background Transcatheter aortic valve replacement (TAVR) has become an accepted treatment option for patients with severe aortic stenosis who are at high surgical risk. Regional systems of care have led to improvements in outcomes for patients undergoing intervention for myocardial infarction, cardiac arrest, and stroke. We implemented a regional system of care for patients undergoing TAVR in British Columbia, Canada. Methods We describe a prospective observational cohort of 583 patients who underwent TAVR in British Columbia between 2012 and 2014. Regionalization of TAVR care in British Columbia refers to a centrally coordinated, funded, and evaluated program led by a medical director and a multidisciplinary advisory group that oversees planning, access to care, and quality of outcomes at the 4 provincial sites. Risk-stratified case selection for transfemoral TAVR is performed by heart teams at each site on the basis of consensus provincial indications. Referrals for lower volume and more complicated TAVR, including nontransfemoral access and valve-in-valve procedures, are concentrated at a single site. In-hospital and 30-day outcomes are reported. Results The median age was 83 years (interquartile range [IQR]: 78 to 87 years) and median STS score was 6% (IQR: 4% to 8%). Transfemoral access was performed in 499 (85.6%) cases and nontransfemoral in 84 (14.4%). Transcatheter valve-in-valve procedures in for failed bioprosthetic valves were performed in 43 patients (7.4%). A balloon-expandable valve was inserted in 386 (66.2%) and a self-expanding valve in 189 (32.4%). All-cause 30-day mortality was 3.5%. All-cause in-hospital mortality and disabling stroke occurred in 3.1% and 1.9%, respectively. Median length of stay was 3 days (IQR: 3 to 6 days), with 92.8% of patients discharged directly home. Conclusions This experience demonstrates the potential benefits of a regional system of care for TAVR. Excellent outcomes were demonstrated: most patients had short in-hospital stays and were discharged directly home.

Objectives We report our 8-year experience in transcatheter aortic and mitral valve-in-valve (VinV) implantation. Background Feasibility and good early outcomes associated with transcatheter aortic and mitral VinV implantation into failed surgical bioprostheses have been confirmed, but the mid-term and long-term outcomes of transcatheter aortic and mitral VinV is unknown. Methods A total of 73 patients with aortic (n = 42) and mitral (n = 31) bioprosthetic valve dysfunction underwent transcatheter VinV implantation between April 2007 and December 2013. Edwards balloon-expandable transcatheter valves (Edwards Lifesciences Inc., Irvine, California) were used. Median follow-up was 2.52 years with a maximum of 8 years. Results Seventy-two patients (mean age 79.7 ± 9.4 years, 32 women) underwent successful VinV implantation (success rate 98.6%). At 30 days, all-cause mortality was 1.4%, disabling stroke 1.4%, life-threatening bleeding 4.1%, acute kidney injury requiring hemodialysis 2.7%, and coronary artery obstruction requiring intervention 1.4%. No patient had greater than mild paravalvular leak. Estimated survival rates were 88.9%, 79.5%, 69.8%, 61.9%, and 40.5% at 1, 2, 3, 4, and 5 years, respectively. The small surgical valve size (19 and 21 mm) was an independent risk factor for reduced survival in aortic VinV patients. At 2-year follow-up, 82.8% of aortic and 100% of mitral VinV patients were in New York Heart Association functional class I or II. Conclusions Transcatheter VinV for failed surgical bioprostheses can be performed safely with a high success rate and minimal early mortality and morbidity. Transcatheter VinV provides encouraging mid-term clinical outcomes in this high-risk elderly cohort of patients. Transcatheter VinV is an acceptable alternative therapy for failed aortic or mitral bioprostheses in selected high-risk patients.

Objectives The aim of this study was to evaluate a strategy of intentional underexpansion of excessively oversized balloon-expandable transcatheter heart valves (THVs) in terms of clinical outcomes, valve function, and frame durability at 1 year. Background Transcatheter aortic valve replacement requires the selection of an optimally sized THV to ensure paravalvular sealing and fixation without risking annular injury. However, some patients have “borderline” annular dimensions that require choosing between a THV that may be too small or another that may be too large. Methods We evaluated 47 patients at risk of annular injury who underwent transcatheter aortic valve replacement (TAVR) with an oversized, but deliberately underexpanded, THV followed by post-dilation if required. Clinical evaluation, echocardiography, and cardiac computed tomography were performed pre-TAVR, post-TAVR, and at 1 year. Results Deployment of oversized THVs with modest underfilling of the deployment balloon ( Conclusions In carefully selected patients with borderline annulus dimensions and in whom excessive oversizing of a balloon-expandable SAPIEN XT valve (Edwards Lifesciences, Inc., Irvine, California) is a concern, a strategy of deliberate underexpansion, with ad hoc post-dilation, if necessary, may reduce the risk of annular injury without compromising valve performance.

There is little data on right ventricular (RV) remodeling patterns in complex congenital heart disease (CHD) patients with right ventricle to pulmonary artery (PA) conduits, and novel RV imaging modalities have not been explored in this population. Knowledge of the RV remodeling process is an important first step to future understanding and tracking of the RV response to pressure and volume overload in this diverse population. Three-dimensional knowledge-based reconstruction (3DKBR) derived from two-dimensional transthoracic echocardiography (TTE-3DKBR) is a novel approach to RV assessment. The aims of this study were twofold: (1) to assess the feasibility and accuracy of 3DKBR in patients with CHD with RV to PA conduits and (2) to characterize the three-dimensional shape of the RV across the spectrum of CHD with RV to PA conduits.Seventeen patients with tetralogy of Fallot, pulmonary atresia with ventricular septal defect, or truncus arteriosus (mean age, 29 ± 8 years; 24% women) and a conduit referred for cardiac magnetic resonance imaging (CMR) were prospectively recruited and underwent TTE-3DKBR. TTE-3DKBR echocardiographic image acquisition was performed using a standard ultrasound scanner linked to a Ventripoint Medical Systems unit. The surface RV volumetric reconstruction was performed by transmitting two-dimensional data points to an online database and comparing these with a lesion-specific catalog to derive the RV reconstruction. Parameters analyzed were end-diastolic volume (EDV), end-systolic volume, and ejection fraction. Intertechnique agreement was assessed using Pearson's correlation analysis, coefficients of variation, and Bland-Altman analysis. Three-dimensional shape comparisons of RV surface reconstructions were performed via automated validation testing of CMRs from 43 patients (mean age, 30 ± 8 years; 32% women) with RV to PA conduits (tetralogy of Fallot, n = 15; pulmonary atresia, n = 19; and truncus arteriosus, n = 9) distinct from patients in the 3DKBR comparison.There was good correlation and agreement between the two modalities: EDV, R = 0.77, P = .0004; end-systolic volume, R = 0.93, P .0001; ejection fraction, R = 0.75, P .0005. On Bland-Altman analyses, CMR EDV was slightly larger TTE-3DKBR, while EF was slightly higher by 3DKBR. Qualitative and quantitative assessment both demonstrated RV shape diversity based on surface reconstructions.This study demonstrates that TTE-3DKBR is an alternative technology that can be used to assess the RV in patients with complex CHD with a conduit. A novel method was used to compare RV shapes in this important population, and our results draw specific attention to the fact that the RV both within and outside diagnostic groups has very different unpredictable shapes and should not be treated equally. Our findings should set into motion future work focused on indices of RV shape and their impact on overall RV function and clinical outcomes, hence defining optimal timing of conduit revision, which at the current time is very unclear.

With the advent of transcatheter mitral valve replacement (TMVR) [(1)][1], the assessment of mitral annular dimensions by computed tomography (CT) is of increasing relevance. The nonplanar, saddle-shaped, 3-dimensional structure of the mitral annulus has been well established [(2)][2] with the

Purpose Lymphatic impairment is known to reduce quality of life in some of the most crippling diseases of the 21st century, including obesity, lymphedema, and cancer. However, the lymphatics are not nearly as well-understood as other bodily systems, largely owing to a lack of sensitive imaging technologies that can be applied using standard clinical equipment. Here, proton exchange-weighted MRI is translated to the lymphatics in patients with breast cancer treatment-related lymphedema (BCRL). Methods Healthy volunteers (N = 8) and BCRL patients (N = 7) were scanned at 3 Tesla using customized structural MRI and amide proton transfer (APT) chemical exchange saturation transfer (CEST) MRI in sequence with the hypothesis that APT effects would be elevated in lymphedematous tissue. APT contrast, lymphedema stage, symptomatology, and histology information were evaluated. Results No significant difference between proton-weighted APT contrast in the right and left arms of healthy controls was observed. An increase in APT contrast in the affected arms of patients was found (P = 0.025; Cohen's d = 2.4), and variability among patients was consistent with documented damage to lymphatics as quantified by lymphedema stage. Conclusion APT CEST MRI may have relevance for evaluating lymphatic impairment in patients with BCRL, and may extend to other pathologies where lymphatic compromise is evident. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

Objectives This study sought to compare the influence of the extent of multidetector computed tomography (MDCT) area oversizing on the incidence of paravalvular aortic regurgitation (PAR) between the Sapien 3 and the Sapien XT transcatheter heart valve (THV) to define a new MDCT sizing guideline suitable for the Sapien 3 platform. Background The inverse relationship of PAR occurrence and oversizing has been demonstrated for the Sapien XT but the incidence of PAR with comparable oversizing with the Sapien 3 is not known. Methods Sixty-one prospectively enrolled patients who underwent transcatheter aortic valve replacement with the Sapien 3 THV were compared with 92 patients who underwent transcatheter aortic valve replacement with the Sapien XT THV. Patients were categorized depending on the degree of MDCT area oversizing percentage: undersizing (below 0%), 0% to 5%, 5% to 10%, and above 10%. The primary endpoint was mild or greater PAR on transthoracic echocardiography. Results Mild or greater PAR was present in 19.7% of patients (12 of 61) in the Sapien 3 group and in 54.3% of patients (50 of 92) in the Sapien XT group (p 10% (p for interaction = 0.54). Moderate or severe PAR rates were also lower in the Sapien 3 group than in the Sapien XT group (3.3% vs. 13.0%, p = 0.04). In the Sapien 3 group, a MDCT area oversizing percentage value of ≤4.17% was identified as the optimal cutoff value to discriminate patients with or without mild or greater PAR. Conclusions Our retrospective analysis suggests that the Sapien 3 THV displays significantly lower rates of PAR than does the Sapien XT THV. A lesser degree of MDCT area oversizing may be employed for this new balloon-expandable THV.

The nonplanar, saddle-shaped structure of the mitral annulus has been well established through decades of anatomic and echocardiographic study. Its relevance for mitral annular assessment for transcatheter mitral valve implantation is uncertain.Our objectives are to define the methodology for CT-based simplified "D-shaped" mitral annular assessment for transcatheter mitral valve implantation and compare these measurements to traditional "saddle-shaped" mitral annular assessment.The annular contour was manually segmented, and fibrous trigones were identified using electrocardiogram-gated diastolic CT data sets of 28 patients with severe functional mitral regurgitation, yielding annular perimeter, projected area, trigone-to-trigone (TT) distance, and septal-lateral distance. In contrast to the traditional saddle-shaped annulus, the D-shaped annulus was defined as being limited anteriorly by the TT distance, excluding the aortomitral continuity. Hypothetical left ventricular outflow tract (LVOT) clearance was assessed.Projected area, perimeter, and septal-lateral distance were found to be significantly smaller for the D-shaped annulus (11.2 ± 2.7 vs 13.0 ± 3.0 cm(2); 124.1 ± 15.1 vs 136.0 ± 15.5 mm; and 32.1 ± 4.0 vs 40.1 ± 4.9 mm, respectively; P.001). TT distances were identical (32.7 ± 4.1 mm). Hypothetical LVOT clearance was significantly lower for the saddle-shaped annulus than for the D-shaped annulus (10.7 ± 2.2 vs 17.5 ± 3.0 mm; P.001).By truncating the anterior horn of the saddle-shaped annular contour at the TT distance, the resulting more planar and smaller D-shaped annulus projects less onto the LVOT, yielding a significantly larger hypothetical LVOT clearance than the saddle-shaped approach. CT-based mitral annular assessment may aid preprocedural sizing, ensuring appropriate patient and device selection.

Aims The aim of this study was to examine the short- and medium-term outcomes of transcatheter aortic valve replacement (TAVR) with the self-expanding and repositionable Portico valve (St. Jude Medical, St. Paul, MN, USA). Methods and results A total of 57 patients underwent TAVR with the Portico valve between March 2012 and August 2014, representing the first-in-human experience and the entire early experience in Canada. Patients were followed up at 30 days and one year with repeat echocardiography and clinical review. Patients were 80.8±7.3 years of age, and the Society of Thoracic Surgeons predicted risk of mortality was 7.7±5.7%. All patients had a valve implanted and four patients (7%) required a second valve. At 30 days, there were two deaths (3.5%), three disabling strokes (5.3%), and new pacemakers in five (8.8%) patients. Echocardiography revealed moderate/severe aortic regurgitation in two patients (3.6%). At one year, survival was 84.2% and echocardiographic findings were unchanged. Conclusions Transcatheter aortic valve replacement with the repositionable Portico valve provides satisfactory short- and medium-term haemodynamic and clinical results.

Objectives Significant tricuspid regurgitation (TR) is a marker for late-stage myocardial and valvular heart disease. Whether preoperative TR affects clinical outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) has never been investigated. This study sought to identify the impact of moderate and severe TR on outcomes after TAVR. Methods All patients undergoing TAVR from January 2007 to August 2012 at St. Paul's Hospital, Vancouver, Canada, (n = 518) were dichotomized according to the severity of preoperative TR (moderate/severe vs. none/mild). All clinical outcomes were defined according to the valve academic research consortium-2 definitions. Results At baseline, moderate or severe TR was reported in 79 patients (15.2%). At 30 days, moderate/severe TR had improved in 12 patients (15.2%), was unchanged in 46 patients (58.3%), and worsened in 7 patients (8.9%). Of those with none/mild TR at baseline, 35 (7.9%) patients had moderate TR at 30-day follow-up. Two-year all-cause (38.4% vs. 20.0%, Log-rank test, P = 0.001) and cardiac mortality (12.9% vs. 4.6%, Log-rank test, P = 0.004) as estimated by Kaplan-Meier analysis were considerably higher in patients with significant TR. However, significant TR did not emerge as independent risk factor for 2-year all-cause mortality (adjusted OR: 1.55, 95% confidence interval (CI): 0.91–2.64, P = 0.105). Pre-specified subgroups showed an interaction between TR and left ventricular systolic function (Pinteraction = 0.047). Indeed, moderate/severe TR was significantly related to mortality only in patients with left ventricular ejection fraction (LVEF) > 40% (adjusted OR: 2.01, CI: 1.05–3.84, P = 0.036). In patients with LVEF ≤ 40%, TR had no significant impact on all-cause mortality (adjusted OR: 1.04, CI: 0.34–3.16, P = 0.946). No significant interactions were identified regarding patients with perioperative moderate/severe mitral regurgitation (Pinteraction = 0.829) and patients with baseline systolic pulmonary artery pressure ≥ 60 mm Hg (Pinteraction = 0.669). Conclusions In patients undergoing TAVR, significant preoperative TR was present in 15% of patients and associated with more comorbidities. Despite being associated with a doubling of mortality rate, after a robust adjustment, significant TR was not an independent predictor of 2-year mortality. However, a significant interaction between TR and left ventricular systolic function was found. The response of TR to TAVR was extremely variable. © 2014 Wiley Periodicals, Inc.

Recent research has identified younger women as an "at-risk" population with rising prevalence of cardiac risk factors and excess mortality risk following acute myocardial infarction (AMI). However, population-based data on trends in AMI hospitalization and early mortality post AMI among younger adults is scarce. We, therefore, aimed to provide a 10-year, descriptive analysis of these trends in a Canadian setting.We assessed trends and sex differences in AMI hospitalization and 30-day mortality rates using negative binomial and logistic regression, respectively. From 2000 to 2009, there were 70,628 AMI hospitalizations in adults aged ≥20 years, in British Columbia, Canada, with 17.1% of cohort being younger adults ≤55 years. Overall, age-standardized AMI rates (per 100,000 population) declined similarly in men (295.8 to 247.7) and women (152.1 to 128.8) [sex-year interaction p=0.81]. However, these trends differed according to age (age-sex-year interaction p=0.02) with increased rates observed only in younger women (+1.7% per year; p=0.04). The 30-day mortality rates declined similarly for women (19.4% to 13.9%) and men (13.0% to 9.3%) (sex-year interaction p=0.33). Yet, younger women continued to have excess mortality risk, compared with younger men, even in the most recent period [odds ratio: (2008-09)=1.61 (95% onfidence interval: 1.25, 2.08)].While the overall AMI hospitalization and 30-day mortality rates significantly declined in women and men, hospitalization rates in women ≤55 years increased and their excess risk of 30-day mortality persisted. These findings highlight the need to intensify strategies to reduce the incidence of AMI and improve outcomes after AMI in younger women.

Background— The effect of preoperative mitral regurgitation (MR) on clinical outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) is controversial. This study sought to examine the impact of moderate and severe MR on outcomes after TAVR and surgical aortic valve replacement (SAVR). Methods and Results— Data were drawn from the randomized Placement of Aortic Transcatheter Valve (PARTNER) Trial cohort A patients with severe, symptomatic aortic stenosis undergoing either TAVR (n=331) or SAVR (n=299). Both TAVR and SAVR patients were dichotomized according to the degree of preoperative MR (moderate/severe versus none/mild). At baseline, moderate or severe MR was reported in 65 TAVR patients (19.6%) and 63 SAVR patients (21.2%). At 30 days, among survivors who had isolated SAVR/TAVR, moderate/severe MR had improved in 25 SAVR patients (69.4%) and 30 TAVR patients (57.7%), was unchanged in 10 SAVR patients (27.8%) and 19 TAVR patients (36.5%), and worsened in 1 SAVR patient (2.8%) and 4 TAVR patients (5.8%; all P =NS). Mortality at 2 years was higher in SAVR patients with moderate or severe MR than in those with mild or less MR (49.8% versus 28.1%; adjusted hazard ratio, 1.73; 95% confidence interval, 1.01–2.96; P =0.04). In contrast, MR severity at baseline did not affect mortality in TAVR patients (37.0% versus 32.7%, moderate/severe versus none/mild; hazard ratio, 1.14; 95% confidence interval, 0.72–1.78; P =0.58; P for interaction=0.05). Conclusions— Both TAVR and SAVR were associated with a significant early improvement in MR in survivors. However, moderate or severe MR at baseline was associated with increased 2-year mortality after SAVR but not after TAVR. TAVR may be a reasonable option in selected patients with combined aortic and mitral valve disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00530894.

Animal remains represent ephemeral resources that provide nutrients to a wide range of organisms. On death, vertebrate carrion is immediately colonized with a variety of microorganisms (typically obligate or facultatively anaerobic bacteria from the air, from insects, or from the corpse itself), which produce odors through the breakdown of tissues, the alteration of volatile chemicals present in the environment, or both. Within minutes, certain necrophagous flies are attracted by these chemical signals, resulting in waves of oviposition and larviposition activity. Although there are certainly detrimental (pathogenic) bacteria in the milieu, there is significant evidence suggesting that the presence of bacteria in or on the corpse seems to aid in larval development and pupariation. This may be because of a change in larval nutrition, with the bacteria either being used as a food source themselves or making nutrients more available to larvae. Maggots also produce and secrete or excrete antimicrobial molecules that are effective in killing certain bacteria. It is unclear whether this is a defensive mechanism, a selective measure to enhance the survival of bacteria beneficial to the larva, or a combination of both. Significant research is still needed to fully appreciate the potential role that these bacteria—insect interactions have in conferring a competitive advantage for surviving in a carrion community.

Objectives This study prospectively investigated the impact of integration of a multidetector computed tomography (MDCT) annular area sizing algorithm on transcatheter aortic valve replacement (TAVR) outcomes. Background Appreciation of the 3-dimensional, noncircular geometry of the aortic annulus is important for transcatheter heart valve (THV) sizing. Methods Patients being evaluated for TAVR in 4 centers underwent pre-procedural MDCT. Recommendations for balloon-expandable THV size selection were based on an MDCT sizing algorithm with an optimal goal of modest annulus area oversizing (5% to 10%). Consecutive patients who underwent TAVR with the algorithm (MDCT group) were compared with consecutive patients without the algorithm (control group). The primary endpoint was the incidence of more than mild paravalvular regurgitation (PAR), and the secondary endpoint was the composite of in-hospital death, aortic annulus rupture, and severe PAR. Results Of 266 patients, 133 consecutive patients underwent TAVR (SAPIEN XT THV) in the MDCT group and 133 consecutive patients were in the control group. More than mild PAR was present in 5.3% (7 of 133) of the MDCT group and in 12.8% (17 of 133) in the control group (p = 0.032). The combined secondary endpoint occurred in 3.8% (5 of 133) of the MDCT group and in 11.3% (15 of 133) of the control group (p = 0.02), driven by the difference of severe PAR. Conclusions The implementation of an MDCT annulus area sizing algorithm for TAVR reduces PAR. Three-dimensional aortic annular assessment and annular area sizing should be considered for TAVR.

ObjectivesThe study sought to describe the authors' experience with mitral transapical transcatheter valve-in-valve implantation (TVIV).BackgroundIncreasing numbers of mitral biological prostheses are being implanted in clinical practice. Transcatheter valve-in-valve implantation may be a lower risk alternative treatment for high-risk patients with mitral valve degeneration.MethodsTwenty-three consecutive patients with severe mitral bioprosthetic valve dysfunction underwent transapical mitral TVIV between July 2007 and September 2012. Bioprosthetic failure was secondary to stenosis in 6 (26.1%), regurgitation in 9 (39.1%), and combined in 8 (34.8%) patients.ResultsAll patients were elderly (mean age 81 ± 6 years) and at high-risk for conventional redo surgery (Society of Thoracic Surgeons score 12.1 ± 6.8%). Successful transapical mitral TVIV was accomplished in all patients using balloon expandable valves (Edwards Lifesciences, Irvine, California) with no intraoperative major complications. One (4.4%) major stroke and 6 (26.1%) major bleeds were reported during hospitalization. Mitral transvalvular gradient significantly decreased from 11.1 ± 4.6 mm Hg to 6.9 ± 2.2 mm Hg following the procedure (p < 0.01). Intervalvular mitral regurgitation was absent (47.8%) or mild (52.2%) in all cases after mitral TVIV. No cases of transvalvular regurgitation were seen. All patients were alive on 30-day follow-up. At a median follow-up of 753 days (interquartile range: 376 to 1,119 days) survival was 90.4%. One patient underwent successful mitral TVIV reintervention at 2 months due to atrial migration of the transcatheter valve. All patients alive were in New York Heart Association functional class I/II with good prosthetic valve performance.ConclusionsTranscatheter transapical mitral valve-in-valve implantation for dysfunctional biological mitral prosthesis can be performed with minimal operative morbidity and mortality and favorable midterm clinical and hemodynamic outcomes.

This article describes school's obligations related to bullying behavior, the assessment of bullying students and their victims, the evaluation of claimed damages due to bullying, and potential interventions for both individuals and school systems to reduce the frequency of bullying behavior. This article assists evaluators when assessing youth who are involved in bullying behavior, either as victims or perpetrators. Key areas highlighted include an overview of bullying behaviors, legal issues related to a school's responsibility in preventing or curtailing bullying behaviors, important components of a bullying assessment, and proposed interventions to minimize bullying.

Objectives This study sought to evaluate the long-term outcomes after transcatheter aortic valve implantation (TAVI) in the Multicenter Canadian Experience study, with special focus on the causes and predictors of late mortality and valve durability. Background Very few data exist on the long-term outcomes associated with TAVI. Methods This was a multicenter study including 339 patients considered to be nonoperable or at very high surgical risk (mean age: 81 ± 8 years; Society of Thoracic Surgeons score: 9.8 ± 6.4%) who underwent TAVI with a balloon-expandable Edwards valve (transfemoral: 48%, transapical: 52%). Follow-up was available in 99% of the patients, and serial echocardiographic exams were evaluated in a central echocardiography core laboratory. Results At a mean follow-up of 42 ± 15 months 188 patients (55.5%) had died. The causes of late death (152 patients) were noncardiac (59.2%), cardiac (23.0%), and unknown (17.8%). The predictors of late mortality were chronic obstructive pulmonary disease (hazard ratio [HR]: 2.18, 95% confidence interval [CI]: 1.53 to 3.11), chronic kidney disease (HR: 1.08 for each decrease of 10 ml/min in estimated glomerular filtration rate, 95% CI: 1.01 to 1.19), chronic atrial fibrillation (HR: 1.44, 95% CI: 1.02 to 2.03), and frailty (HR: 1.52, 95% CI: 1.07 to 2.17). A mild nonclinically significant decrease in valve area occurred at 2-year follow-up (p Conclusions Approximately one-half of the patients who underwent TAVI because of a high or prohibitive surgical risk profile had died at a mean follow-up of 3.5 years. Late mortality was due to noncardiac comorbidities in more than one-half of patients. No clinically significant deterioration in valve function was observed throughout the follow-up period.

Background— Previously, through the use of computed tomography (CT), it has been proposed that D-shaped versus saddle-shaped mitral annulus (MA) segmentation is more biomechanically appropriate to determine transcatheter mitral valve implantation size and eligibility. Methods and Results— Forty-one patients with severe mitral regurgitation being considered for transcatheter mitral valve implantation who had undergone cardiac CT and 3-dimensional transesophageal echocardiography (3D-TEE) were retrospectively evaluated. A standardized segmentation protocol for the D-shaped MA was developed using Philips Q-Laboratory mitral valve quantification software. MA dimensions were compared using Spearman’s rank correlation and Bland–Altman analysis. Inter- and intraobserver agreement was quantified by intraclass correlation coefficient and Bland–Altman analysis. Mean age was 77±14 years; 71% male (n=29); mitral regurgitation pathogenesis was functional in 54% (n=22) and myxomatous in 46% (n=19). Mean MA area and circumference by 3D-TEE and CT were 11.3±2.7 versus 11.4±3.0 ( P =0.67) and 124.1±15.6 versus 123.9±15.5 ( P =0.79), respectively, with excellent correlation between modalities ( r =0.84 and r =0.86; P 2 [−3.7 cm 2 ; 3.3 cm 2 ], 0.37±9 mm [−18.0 mm; 17.27 mm]). Mean septal-to-lateral and inter-trigone distances by 3D-TEE and CT were 33.2±4.7 versus 32.5±4.4 ( P =0.24) and 31.7±3.5 versus 32.6±3.6 ( P =0.06), respectively, with good correlation ( r =0.69 and r =0.71; P 0.90 for all parameters. Conclusions— Similar to cardiac CT, 3D-TEE allows for D-shaped MA segmentation with no systematic difference in MA dimensions between modalities. This study supports the utilization of 3D-TEE as a complementary tool to CT assessment of the D-shaped MA to determine transcatheter mitral valve implantation size.

This paper is an experience report that deals with engagement and sustainability in a data structures course in C for non-specialists. The course is offered annually to about 200 engineering students who are not in the computer engineering option. We describe and justify a variety of engaging and sustainable practices, and provide benefits and caveats from the lessons we learned. These may be useful to instructors who are interested in either creating such a course or using some of its practices, while trying to achieve both high engagement and high sustainability when teaching non-specialists.

How similar are the brains of listeners who hear the same content expressed in different languages? We directly compared the functional magnetic resonance (fMRI) brain responses of English speakers and Russian speakers who listened to a real-life Russian narrative and its English translation. During the translation we tried to preserve the content of the narrative while reducing the structural similarities across languages. The story evoked similar brain responses across languages, which were invariant to the structural changes, beginning just outside early auditory areas and extending through temporal, parietal and frontal cerebral cortices. Surprisingly, the inter-language similarity in these areas is nearly as strong as the similarity of the brain responses within each language group. The present results demonstrate that the human brain processes real-life information in a manner that is largely insensitive to the language in which that information is conveyed. The methods introduced here can potentially be used to quantify the transmission of meaning across cultural and linguistic boundaries.

Objectives The aim of this study was to evaluate the impact of mitral regurgitation (MR) on outcomes after transcatheter aortic valve replacement (TAVR) and the impact of TAVR on MR. Background Little is known of the influence of MR on outcomes after TAVR. Methods The outcomes of patients with mild or less (n = 319), moderate (n = 89), and severe (n = 43) MR were evaluated after TAVR at 2 Canadian centers. Results Patients with moderate or severe MR had a higher mortality rate than those with mild or less MR during the 30 days after TAVR (adjusted hazard ratio: 2.10; 95% confidence interval: 1.12 to 3.94; p = 0.02). However, the mortality rates after 30 days were similar (adjusted hazard ratio: 0.82; 95% confidence interval: 0.50 to 1.34; p = 0.42). One year after TAVR, moderate MR had improved in 58%, remained moderate in 17%, and worsened to severe in 1%, and 24% of patients had died. Severe MR had improved in 49% and remained severe in 16%, and 35% of patients had died. Multivariate predictors of improved MR at 1 year (vs. unchanged MR, worse MR, or death) were a mean transaortic gradient ≥40 mm Hg, functional (as opposed to structural) MR, the absence of pulmonary hypertension, and the absence of atrial fibrillation. Conclusions Moderate or severe MR in patients undergoing TAVR is associated with a higher early, but not late, mortality rate. At 1-year follow-up, MR was improved in 55% of patients with moderate or severe MR at baseline. Improvement was more likely in patients with high transaortic gradients, with functional MR, without pulmonary hypertension and without atrial fibrillation.

OBJECTIVES This study sought to evaluate outcomes after implantation of a second transcatheter heart valve (THV in THV) for acute THV failure. BACKGROUND Aortic regurgitation after transcatheter aortic valve replacement (TAVR) may be valvular due to prosthetic leaflet dysfunction or paravalvular due to poor annular sealing. METHODS Patients undergoing aortic balloon expandable TAVR at 3 centers were prospectively evaluated at baseline intraprocedurally at hospital discharge and annually. RESULTS Of 760 patients undergoing TAVR 21 (2.8) received a THV in THV implant due to acute severe regurgitation. Aortic regurgitation was paravalvular in 18 patients and transvalvular in the remaining 3 patients. THV in THV implantation was technically successful in 19 patients (90) and unsuccessful in 2 patients (10) who subsequently underwent open heart surgery. Mortality at 30 days and 1 year was 14.3 and 24 respectively. After successful THV in THV mean aortic valve gradient fell from 37 ± 12 mm Hg to 13 ± 5 mm Hg (p < 0.01); aortic valve area increased from 0.64 ± 0.14 cm(2) to 1.55 ± 0.27 cm(2) (p < 0.01); and paravalvular aortic regurgitation was none in 4 patients mild in 13 patients and moderate in 2 patients. At 1 year follow up 1 patient had moderate and the others had mild or no paravalvular leaks. The mean transvalvular gradient was 15 ± 4 mm Hg which was higher than in patients undergoing conventional TAVR (11 ± 4 mm Hg p = 0.02). CONCLUSIONS THV in THV implantation is feasible and results in satisfactory short and mid term outcomes.

Objectives This study sought to analyze multidetector computed tomography (MDCT) 3-dimensional aortic annular dimensions for the prediction of paravalvular aortic regurgitation (PAR) following transcatheter aortic valve replacement (TAVR). Background Moderate or severe PAR after TAVR is associated with increased morbidity and mortality. Methods A total of 109 consecutive patients underwent MDCT pre-TAVR with a balloon expandable aortic valve. Differences between transcatheter heart valve (THV) size and MDCT measures of annular size (mean diameter, area, and circumference) were analyzed concerning prediction of PAR. Patients with THV malposition (n = 7) were excluded. In 50 patients, MDCT was repeated after TAVR to assess THV eccentricity (1 – short diameter/long diameter) and expansion (MDCT measured THV area/nominal THV area). Results Moderate or severe PAR (13 of 102) was associated with THV undersizing (THV diameter – mean diameter = –0.7 ± 1.4 mm vs. 0.9 ± 1.8 mm for trivial to mild PAR, p Conclusions MDCT-derived 3-dimensional aortic annular measurements are predictive of moderate or severe PAR following TAVR. Oversizing of THVs may reduce the risk of moderate or severe PAR.

Objectives This study sought to determine the most reproducible multidetector computed tomography (MDCT) measurements of the aortic annulus and to determine methods to improve the applicability of these measurements for transcatheter aortic valve implantation. Background The reproducibility and applicability of MDCT annular measurements to guide transcatheter aortic valve implantation remain unclear. Methods Annular measurements were performed in 50 patients planed for transcatheter aortic valve implantation in multiple planes: basal ring (short- and long-axis, mean diameter, area-derived diameter), coronal, sagittal, and 3-chamber projections. A theoretical model was developed taking into account the differences between the most reproducible MDCT measurements and transesophageal echocardiography to guide valve size choice. Results The most reproducible measurements were the area-derived diameter and basal ring average diameter (inter-reader intraclass correlation coefficient: 0.87 [95% confidence interval: 0.81 to 0.92] and 0.80 [95% confidence interval: 0.70 to 0.87]; respectively; intrareader >0.90 for all readers). These were generally larger than transesophageal echocardiography diameters (mean difference of 1.5 ± 1.6 mm and 1.1 ± 1.7 mm, respectively). When a strategy of valve-sizing is undertaken using these CT measurements using an echocardiographic sizing scale, a different THV size would be selected in 44% and 40% of cases, respectively. When adjusting the sizing cutoffs to account for the differences in observed diameters, this was reduced to 10% to 12% (p Conclusions The most reproducible MDCT measurements of the annulus are the area-derived diameter and basal ring average diameter, with derived values generally larger than those obtained with echocardiography. If MDCT is used for valve sizing, a strategy incorporating these differences may be important. MDCT using these easily derived measurements may be ideally suited to sizing transcatheter aortic valves as they account for the eccentricity of the aortic annulus, are reproducible, and are noninvasive.

Necrophagous flies that colonize human and animal corpses are extremely efficient at locating and utilizing carrion. Adult flies deposit eggs or larvae on the ephemeral food resource, which signals the beginning of intense inter- and intra-species competition. Within a short period of time after egg hatch, large larval aggregations or maggot masses form. A period of intense larval feeding ensues that will culminate with consumption/decomposition of all soft tissues associated with the corpse. Perhaps the most distinctive feature of these feeding aggregations is heat production; that is, the capacity to generate internal heat that can exceed ambient temperatures by 30°C or more. While observations of maggot mass formation and heat generation have been described in the research literature for more than 50 years, our understanding of maggot masses, particularly the physiological ecology of the aggregations as a whole, is rudimentary. In this review, an examination of what is known about the formation of maggot masses is presented, as well as arguments for the physiological benefits and limitations of developing in feeding aggregations that, at times, can represent regions of intense competition, overcrowded conditions, or a microclimate with elevated temperatures approaching or exceeding proteotoxic stress levels.

The BioHealth Capital Region (Maryland, Virginia, and Washington, DC; BHCR) is flush with colleges and universities training students in science, technology, engineering, and mathematics disciplines and has one of the most highly educated workforces in the United States. However, current educational approaches and business recruitment tactics are not drawing sufficient talent to sustain the bioscience workforce pipeline. Surveys conducted by the Mid-Atlantic Biology Research and Career Network identified a disconnect between stakeholders who are key to educating, training, and hiring college and university graduates, resulting in several impediments to workforce development in the BHCR: 1) students are underinformed or unaware of bioscience opportunities before entering college and remain so at graduation; 2) students are not job ready at the time of graduation; 3) students are mentored to pursue education beyond what is needed and are therefore overqualified (by degree) for most of the available jobs in the region; 4) undergraduate programs generally lack any focus on workforce development; and 5) few industry–academic partnerships with undergraduate institutions exist in the region. The reality is that these issues are neither surprising nor restricted to the BHCR. Recommendations are presented to facilitate improvement in the preparation of graduates for today’s bioscience industries throughout the United States.

ObjectivesThis study was undertaken to compare the hemodynamic performance of a percutaneous bioprosthesis to that of surgically implanted (stented and stentless) bioprostheses for the treatment of severe aortic stenosis.MethodsFifty patients who underwent percutaneous aortic valve implantation (PAVI) with the Cribier-Edwards or Edwards SAPIEN bioprosthetic valve (Edwards Lifesciences, Inc., Irvine, California) were matched 1:1 for sex, aortic annulus diameter, left ventricular ejection fraction, body surface area, and body mass index, with 2 groups of 50 patients who underwent surgical aortic valve replacement (SAVR) with a stented valve (Edwards Perimount Magna [SAVR-ST group]), or a stentless valve (Medtronic Freestyle, Medtronic, Minneapolis, Minnesota [SAVR-SL group]). Doppler echocardiographic data were prospectively obtained before the intervention, at discharge, and at 6- to 12-month follow-up.ResultsMean transprosthetic gradient at discharge was lower (p < 0.001) in the PAVI group (10 ± 4 mm Hg) compared with the SAVR-ST (13 ± 5 mm Hg) and SAVR-SL (14 ± 6 mm Hg) groups. Aortic regurgitation (AR) occurred more frequently in the PAVI group (mild: 42%, moderate: 8%) compared with the SAVR-ST (mild: 10%, moderate: 0%) and SAVR-SL (mild: 12%, moderate: 0%) groups (p < 0.0001). At follow-up, the mean gradient in the PAVI group remained lower (p < 0.001) than that of the SAVR-ST group, but was similar to that of the SAVR-SL group. The incidence of severe prosthesis-patient mismatch was significantly lower (p = 0.007) in the PAVI group (6%) compared with the SAVR-ST (28%) and SAVR-SL (20%) groups. However, the incidence of AR remained higher (p < 0.0001) in the PAVI group compared with the 2 other groups.ConclusionsPAVI provided superior hemodynamic performance compared with the surgical bioprostheses in terms of transprosthetic gradient and prevention of severe prosthesis-patient mismatch, but was associated with a higher incidence of AR.

Transcatheter aortic valve replacement (TAVR) required precise knowledge of the anatomic dimensions and physical characteristics of the aortic valve, annulus, and aortic root. Most groups currently use angiography, transthoracic echocardiography (TTE), or transesophageal echocardiography (TEE) to assess aortic annulus dimensions and anatomy. However, multislice computed tomography (MSCT) may allow more detailed 3-dimensional assessment of the aortic root. Twenty-six patients referred for TAVR underwent MSCT. Scans were also obtained for 18 patients after TAVR. All patients underwent pre- and postprocedural aortic root angiography, TTE, and TEE. Mean differences in measured aortic annular diameters were 1.1 mm (95% confidence interval 0.5, 1.8) for calibrated angiography and TTE, -0.9 mm (95% confidence interval -1.7, -0.1 mm) for TTE and TEE, -0.3 mm (95% confidence interval -1.1, 0.6 mm) for MSCT (sagittal) and TTE, and -1.2 mm (95% confidence interval -2.2, -0.2 mm) for MSCT (sagittal) and TEE. Coronal systolic measurements using MSCT, which corresponded to angiographic orientation, were 3.2 mm (1st and 3rd quartiles 2.6, 3.9) larger than sagittal systolic measurements, which were in the same anatomic plane as standard TTE and TEE views. There was no significant association between either shape of the aortic annulus or amount of aortic valve calcium and development of perivalvular aortic regurgitation. After TAVR, the prosthesis extended to or beyond the inferior border of the left main ostium in 9 of 18 patients (50%), and in 11 patients (61%), valvular calcium was

Background We reported the first case of successful transapical transcatheter aortic valve implantation in a human subject in 2005 and have now completed a 12-month follow-up on our first 26 patients. This is, to date, the longest follow-up of patients undergoing transapical aortic valve implantation. Methods Between October 2005 and January 2007, 26 patients (13 female) underwent transcatheter transapical aortic valve implantation with either 23- or 26-mm Edwards Lifesciences transcatheter bioprostheses. All patients with symptomatic aortic stenosis were declined for conventional aortic valve replacement because of unacceptable operative risks and were not candidates for transfemoral aortic valve implantation because of poor arterial access. Clinical and echocardiographic follow-up was performed before discharge and at 1, 6, and 12 months. Data from the 17 patients who survived over 12 months were used for comparisons of the baseline and follow-up results. Results The mean age was 80 ± 9 years, and the predicted operative mortality was 37% ± 20% by using logistic EuroSCORE and 11% ± 6% by using the Society of Thoracic Surgeons Risk Calculator. Valves were successfully implanted in all patients. Six patients died within 30 days (30-day mortality, 23%), and 3 patients died from noncardiovascular causes after 30 days (late mortality, 12%). Among patients who survived at least 30 days, 12-month survival was 85%. There were no late valve-related complications. New York Heart Association functional class improved significantly. The aortic valve area and mean gradient remained stable at 12 months (1.6 ± 0.3 cm 2 and 9.6 ± 4.8 mm Hg, respectively). Conclusion Our 1-year clinical and echocardiographic outcomes suggest that transapical transcatheter aortic valve implantation is a viable alternative to conventional aortic valve replacement in selected high-risk patients.

Objectives: Early clinical outcomes in selected high-risk patients undergoing catheter-based aortic valve replacement (AVR) compare favorably with conventional surgical AVR. Improved understanding of the mechanisms of success and failure of transcatheter AVR will likely improve outcomes further. To this end, we examined our experience during the developmental phases of transcatheter AVR and describe the causes and management of prosthetic valve malposition. Methods: Transcatheter balloon-expandable AVR was performed in 170 patients at two centers. Malposition was defined as prosthetic valve implantation in a location other than within the native valve. Patients were prospectively identified and followed as part of an ongoing database. Results: Valve malposition occurred in 9 of 170 patients (5.3%). Final position was supravalvular in eight of nine cases. In all cases, embolization to the ascending aorta occurred within a few cardiac cycles following deployment. Importantly, late embolization was not observed. In most cases, the prosthesis was uneventfully repositioned in the more distal aorta. Positioning was subvalvular in one patient (0.6%), resulting in a severe regurgitation with residual native valve stenosis. Implantation of a second transcatheter valve was attempted in six patients and was successful in all. Conventional AVR was performed in two patients, with early mortality in one. At late follow-up (mean 412 days), seven of nine patients remain alive (78%) with a functioning prosthesis and relief of aortic stenosis. Conclusions: Malposition of current balloon-expandable aortic valves is a largely preventable complication. An improved understanding of the procedure will likely minimize this possibility and mitigate the consequences should malposition occur. © 2008 Wiley-Liss, Inc.

Background— Percutaneous aortic valve replacement represents an endovascular alternative to conventional open heart surgery without the need for sternotomy, aortotomy, or cardiopulmonary bypass. Methods and Results— Transcatheter implantation of a balloon-expandable stent valve using a femoral arterial approach was attempted in 50 symptomatic patients with severe aortic stenosis in whom there was a consensus that the risks of conventional open heart surgery were very high. Valve implantation was successful in 86% of patients. Intraprocedural mortality was 2%. Discharge home occurred at a median of 5 days (interquartile range, 4 to 13). Mortality at 30 days was 12% in patients in whom the logistic European System for Cardiac Operative Risk Evaluation risk score was 28%. With experience, procedural success increased from 76% in the first 25 patients to 96% in the second 25 ( P =0.10), and 30-day mortality fell from 16% to 8% ( P =0.67). Successful valve replacement was associated with an increase in echocardiographic valve area from 0.6±0.2 to 1.7±0.4 cm 2 . Mild paravalvular regurgitation was common but was well tolerated. After valve insertion, there was a significant improvement in left ventricular ejection fraction ( P P =0.01), and functional class ( P Conclusion— Percutaneous valve replacement may be an alternative to conventional open heart surgery in selected high-risk patients with severe symptomatic aortic stenosis.

The physiologic and pathologic functions of sphingosine kinase (SK) require translocation to specific membrane compartments. We tested the hypothesis that interactions with actin filaments regulate the localization of SK1 to membrane surfaces, including the plasma membrane and phagosome. Macrophage activation is accompanied by a marked increase in association of SK1 with actin filaments. Catalytically-inactive (CI)- and phosphorylation-defective (PD)-SK1 mutants exhibited reductions in plasma membrane translocation, colocalization with cortical actin filaments, membrane ruffling, and lamellipodia formation, compared with wild-type (WT)-SK1. However, translocation of CI- and PD-SK1 to phagosomes were equivalent to WT-SK1. SK1 exhibited constitutive- and stimulus-enhanced association with actin filaments and F-actin-enriched membrane fractions in both intact macrophages and a novel in vitro assay. In contrast, SK1 bound G-actin only under stimulated conditions. Actin inhibitors disrupted SK1 localization and modulated its activity. Conversely, reduction of SK1 levels or activity via RNA interference or specific chemical inhibition resulted in dysregulation of actin filaments. Thus, the localization and activity of SK1 are coordinately regulated with actin dynamics during macrophage activation.

Background: The current treatment of choice for symptomatic aortic stenosis is aortic valve replacement (AVR) with cardiopulmonary bypass (CPB),butAVRisassociatedwithsignificantoperativemorbidityandmortalityinelderlypatientswithmultipleco-morbidconditions.Werecently reported the first successful aortic valve implantation procedure (AVI) via a mini-thoracotomy and left ventricular apical puncture without cardiopulmonary bypass. We now report 6-month follow-up in our initial seven patients. Methods: Seven patients (77 10 years old) with symptomatic aortic stenosis were deemed to be non-surgical candidates for AVR and not suitable for a transfemoral percutaneous heart valve implantation due to aorto-iliac disease. The predicted 30-day operative mortality was 31 23% according to logistic Euroscore. Patients underwent minimally invasive transapical AVI. With the guidance of fluoroscopy and transesophageal echocardiography, balloon predilation was followed by deployment of a 26 mm Cribier—Edwards TM valve (Edwards Lifesciences Inc., Irvine, CA) during rapid ventricular pacing to reduce forward flow and cardiac motion. Results: Valve implantation was successful in all seven patients. There were no intra-procedural mortalities or complications. Thirty-day operative mortality was 14%. One patient died at day 12 due to pneumonia. Two patients died from non-cardiac diseases at day 51 and 85. The remaining four patients completed 6-month follow-up. The aortic valve area increased from 0.7 0.3 to 1.8 0.7 and 1.5 0.5 cm 2 at 1 and 6 months, respectively. The mean transaortic gradient was reduced from 32 8t o 10 5 and 11 8 mmHg at 1 and 6 months, respectively. Following AVI, none or trivial, mild, and moderate aortic regurgitation was observed in 4, 2, and 1 patients, respectively. There were no valve-related complications during the follow-up. Conclusion: Aortic valve implantation can successfully be performed via a minimally invasive apical approach without the need for cardiopulmonary bypass. The early results in this initial series are encouraging. This initial experience suggests that the minimally invasive transapical approach is a viable alternative for patients in whom open-heart surgery is not feasible or poses unacceptable risks. # 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Introduction and objectives The self-expanding Portico valve is a new transcatheter aortic valve system yielding promising preliminary results, yet there are no comparative data against earlier generation transcatheter aortic valve systems. The aim of this study was to compare the hemodynamic performance of the Portico and balloon-expandable SAPIEN XT valves in a case-matched study with echocardiographic core laboratory analysis. Methods Twenty-two patients underwent transcatheter aortic valve implantation with the Portico 23-mm valve and were matched for aortic annulus area and mean diameter measured by multidetector computed tomography, left ventricular ejection fraction, body surface area, and body mass index with 40 patients treated with the 23-mm SAPIEN XT. Mean aortic annulus diameters were 19.6 ± 1.3 mm by transthoracic echocardiography and 21.4 ± 1.2 mm by computed tomography, with no significant between-group differences. Doppler echocardiographic images were collected at baseline and at 1-month of follow-up and were analyzed in a central echocardiography core laboratory. Results There were no significant between-group differences in residual mean transaortic gradients (SAPIEN XT: 10.4 ± 3.7 mmHg; Portico: 9.8 ± 1.1 mmHg; P = .49) and effective orifice areas (SAPIEN XT: 1.36 ± 0.27 cm 2 ; Portico, 1.37 ± .29 cm 2 ; P = .54). Rates of severe prosthesis-patient mismatch (effective orifice area 2 /m 2 ) were similar (SAPIEN XT: 13.5%; Portico: 10.0%; P = .56). No between-group differences were found in the occurrence of moderate-severe paravalvular leaks (5.0% vs 4.8% of SAPIEN XT and Portico respectively; P = .90). Conclusions Transcatheter aortic valve implantation with the self-expanding Portico system yielded similar short-term hemodynamic performance compared with the balloon-expandable SAPIEN XT system for treating patients with severe aortic stenosis and small annuli. Further prospective studies with longer-term follow-up and in patients with larger aortic annuli are required.