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IMPORTANCE: In older patients with atrial fibrillation who take anticoagulants for stroke prevention, bleeding is increased compared with younger patients, thus, clinicians frequently prescribe lower than recommended doses in older patients despite limited randomized data. OBJECTIVE: To evaluate ischemic and bleeding outcomes in patients 80 years and older with atrial fibrillation receiving edoxaban, 60 mg vs 30 mg, and edoxaban, 30 mg vs warfarin. DESIGN, SETTING, AND PARTICIPANTS: The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) was a parallel-design, double-blind, global clinical trial that randomized patients with atrial fibrillation to either one of 2 edoxaban dosing regimens or warfarin. This secondary analysis focused on patients 80 years or older without dose-reduction criteria receiving edoxaban, 60 mg vs 30 mg, as well as patients with or without dose-reduction criteria receiving edoxaban, 30 mg, vs warfarin. Study data were analyzed between October 2022 and December 2023. INTERVENTIONS: Oral edoxaban, 30 mg once daily; edoxaban, 60 mg once daily; or warfarin. MAIN OUTCOMES AND MEASURES: Primary net clinical outcome of death, stroke or systemic embolism, and major bleeding and each individual component. RESULTS: The current analysis included 2966 patients 80 years and older (mean [SD] age, 83 [2.7] years; 1671 male [56%]). Among 1138 patients 80 years and older without dose-reduction criteria, those receiving edoxaban, 60 mg vs 30 mg, had more major bleeding events (hazard ratio [HR], 1.57; 95% CI, 1.04-2.38; P = .03), particularly gastrointestinal hemorrhage (HR, 2.24; 95% CI, 1.29-3.90; P = .004), with no significant difference in efficacy end points. Findings were supported by analyses of endogenous factor Xa inhibition, a marker of anticoagulant effect, which was comparable between younger patients receiving edoxaban, 60 mg, and older patients receiving edoxaban, 30 mg. In 2406 patients 80 years and older with or without dose-reduction criteria, patients receiving edoxaban, 30 mg, vs warfarin had lower rates of the primary net clinical outcome (HR, 0.78; 95% CI, 0.68-0.91; P = .001), major bleeding (HR, 0.59; 95% CI, 0.45-0.77; P < .001), and death (HR, 0.83; 95% CI, 0.70-1.00; P = .046), whereas rates of stroke or systemic embolism were comparable. CONCLUSIONS AND RELEVANCE: In this post hoc analysis of the ENGAGE AF-TIMI 48 randomized clinical trial, in patients 80 years and older with atrial fibrillation, major bleeding events were lower in patients randomized to receive edoxaban, 30 mg per day, compared with either edoxaban, 60 mg per day (in patients without dose-reduction criteria), or warfarin (irrespective of dose-reduction status), without an offsetting increase in ischemic events. These data support the concept that lower-dose anticoagulants, such as edoxaban, 30 mg, may be considered in older patients with atrial fibrillation even in the absence of dose-reduction criteria. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00781391

To investigate short‐term neonatal developmental outcomes in fetuses with an isolated wide or narrow cavum septi pellucidi (CSP) using new reference ranges. A cross‐sectional study on fetuses at 16 + 0 to 36 + 6 weeks of gestation between December 2020 and January 2022. CSP width reference ranges were constructed from low‐risk pregnancies. Wide and narrow CSPs were defined as measurements above the 95th percentile and below the 5th percentile, respectively. For the primary outcome fetuses with normal neurosonograms were included. Neonatal developmental outcomes were assessed using the Survey of Well‐being of Young Children (SWYC). A total of 352 fetuses were included in this study, of whom 138 were healthy and had uncomplicated neonatal outcomes. These fetuses constituted the control group and were used to construct the CSP width reference ranges. Of 185 fetuses in the neurosonography group, 9.7% had wide and 7.6% had narrow CSPs, of whom 33.3% and 22.2%, respectively, scored below the SWYC threshold for expected developmental milestones, a rate similar to that reported in the general population. The presence of a prenatally isolated wide or narrow CSP does not appear to increase the risk of neonatal neurodevelopmental delay.

The risks of prefrail and frail women undergoing transcatheter aortic valve replacement (TAVR) have not been fully examined. The aim of the analysis was to assess the prognostic impact of prefrailty and frailty in women undergoing TAVR.

Unwitnessed out-of-hospital cardiac arrest is associated with low survival chances because of the delayed activation of the emergency medical system in most cases. Automated cardiac arrest detection and alarming using biosensor technology would offer a potential solution to provide early help. We developed and validated an algorithm for automated circulatory arrest detection using wrist-derived photoplethysmography from patients with induced circulatory arrests.

AbstractIn contrast to other fermented beverages, beer quality generally diminishes over time. This diminishing quality hinges heavily on the oxidative degradation of beer compounds by reactive oxygen species (ROS), whose formation is in part catalyzed by Fe(II) ions via the Fenton and Haber-Weiss reactions. Consequently, ROS accumulation throughout the brewing process results in oxidative instability and accelerates numerous beer staling reactions, like those frequently associated with the onset of unwanted flavors, aromas, and an unaesthetic appearance. However, despite its critical importance to beer stability, the oxidative state of iron in wort and finished beer continues to be poorly characterized. In this investigation, the influence of kilned specialty malt utilization on total free iron and iron ion speciation in wort was determined by EBC Method 9.13.1. Further, the reducing power of each wort was determined via 2,2-diphenyl-1-picrylhydrazyl (DPPH). Here, we demonstrate that kilned specialty malt utilization influences total iron concentration, the balance between Fe(II) and Fe(III) ion species, and the reducing power of wort. Furthermore, our results reveal a negative correlation between mash pH and total iron concentration in finished wort. These results indicate that beer’s oxidative flavor stability may be improved by using lower kilned malts and adjusting mash pH.

Over the past 50 years, the number and invasiveness of percutaneous cardiovascular procedures globally have increased substantially. However, cardiovascular interventions are inherently associated with a risk of acute brain injury, both periprocedurally and postprocedurally, which impairs medical outcomes and increases health-care costs. Current international clinical guidelines generally do not cover the area of acute brain injury related to cardiovascular invasive procedures. In this international Consensus Statement, we compile the available knowledge (including data on prevalence, pathophysiology, risk factors, clinical presentation and management) to formulate consensus recommendations on the prevention, diagnosis and treatment of acute brain injury caused by cardiovascular interventions. We also identify knowledge gaps and possible future directions in clinical research into acute brain injury related to cardiovascular interventions.

ObjectivesThe burden of HIV and other sexually transmitted infections (STIs) remains high in sex workers globally, calling for strengthening targeted prevention strategies, including HIV pre-exposure prophylaxis (PrEP). The study’s objective was to assess HIV and STI burden among female, male and transgender sex workers in Flanders, Belgium, to guide targeting of PrEP strategies for sex workers.MethodsWe conducted a retrospective analysis of routine data collected between January 2016 and December 2019 by community-based organisations providing sexual healthcare services for sex workers in Flanders. HIV prevalence stratified by gender was assessed and associations with sociodemographic characteristics were explored using bivariable and multivariable logistic regression. Positivity rates of chlamydia, gonorrhoea and syphilis tests were used as proxy indicators for STI burden.ResultsThe study included a total of 6028 sex workers, comprising 5617 (93.2%) female, 218 (3.6%) male and 193 (3.2%) transgender sex workers. The HIV prevalence was 0.3% among female, 8.9% among male and 12.3% among transgender sex workers. Engaging in escort sex work and originating from South America or Sub-Saharan Africa were associated with a higher likelihood of having acquired HIV. The positivity rate for gonorrhoea was higher among male sex workers (5.2% vs 2.2%) and syphilis was more frequently detected among male and transgender sex workers (3.0% and 6.1% vs 0.5%), all compared with female sex workers.ConclusionsHIV combination prevention, including improved access to PrEP, should be strengthened among sex workers in Flanders, with particular attention to male and transgender sex workers.

In patients with acute coronary syndrome and multivessel coronary disease, complete revascularisation by percutaneous coronary intervention (PCI) is associated with improved clinical outcomes. We aimed to investigate whether PCI for non-culprit lesions should be attempted during the index procedure or staged.

Short-term percutaneous mechanical circulatory support by a micro-axial flow pump is increasingly used to support the left ventricle in cardiogenic shock. After a correct indication and placement, appropriate device management in the cardiac intensive care unit is vital to ensure optimal pump function and adequate haemodynamic support. A key element hereby is a correct percutaneous ventricular assist device (pVAD) position. This review explains how an optimal left-sided pVAD position can be achieved and maintained, focusing on the correct insertion depth and rotational angle. Useful imaging techniques, placement and replacement manoeuvres, and monitoring options through the console are discussed. The frequently encountered problem of mal-rotation towards the mitral valve, which may cause suction alarms, haemolysis, aortic regurgitation, and inadequate haemodynamic support, is explained. Finally, a practical bedside approach to assess pVAD position and discern suction alarms due to mal-positioning from haemodynamic problems is proposed.Graphical AbstractIntegrative approach to percutaneous ventricular assist device (pVAD) position monitoring in the cardiac intensive care unit. First, one must evaluate whether the motor current (green waveform) is pulsatile. Very poor native heart contractility may cause a non-pulsatile motor current. Otherwise, a lack of pulsatility indicates that the inlet and outlet of the micro-axial flow pump are within the same heart chamber. In case of an overly deep insertion, both the placement signal (red waveform) and the left ventricular pressure waveform (white waveform) show a ventricular signal. When the pVAD is dislocated towards the ascending aorta, both the placement signal and the left ventricular pressure waveform demonstrate an arterial waveform. If the motor current is pulsatile, the shape of the left ventricular pressure waveform and its relationship with the aortic waveform on the placement signal are evaluated. When the systolic part of the ventricular waveform is at or above the level of the placement signal, but a decrease in the left ventricular diastolic pressure is observed, the problem is ventricular preload. When preload decreases further, this may lead to diastolic suction alarms when the pressure drops below −40 mmHg. If, on the other hand, the ventricular systolic pressure is incongruent and beneath the level of the placement signal, it indicates a problematic positioning. Echocardiography is needed to evaluate the exact type of abnormality. When motor speed is increased in such cases, a continuous suction alarm is created. LV, left ventricle; pVAD, percutaneous ventricular assist device.

AbstractBeer inherently contains a diverse combination of metal ions, a part of which is iron. Brewers strive to keep iron levels as low as possible in wort and beer due to its negative influence on beer stability. Iron occupies a prominent role within the Fenton reaction, where Fe(II) ions are oxidized to Fe(III) by hydrogen peroxide, forming a hydroxyl radical and a hydroxyl ion. The accumulation of reactive oxygen species in wort and beer is detrimental to its oxidative stability, as their presence will accelerate many of the oxidation reactions commonly associated with the onset of unwanted flavor, aroma, and appearance. Aside from iron’s adverse influence on oxidative stability, iron concentrations as low as 0.05 mg/L can also impart an unpleasant metallic off-flavor. This review discusses the points of entry for iron across the brewing process, the role of iron in the oxidative deterioration of beer, and how iron contributes to metallic off-flavors.

IMPORTANCE: The frequency and clinical importance of structural valve deterioration (SVD) in patients undergoing self-expanding transcatheter aortic valve implantation (TAVI) or surgery is poorly understood. OBJECTIVE: To evaluate the 5-year incidence, clinical outcomes, and predictors of hemodynamic SVD in patients undergoing self-expanding TAVI or surgery. DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis pooled data from the CoreValve US High Risk Pivotal (n = 615) and SURTAVI (n = 1484) randomized clinical trials (RCTs); it was supplemented by the CoreValve Extreme Risk Pivotal trial (n = 485) and CoreValve Continued Access Study (n = 2178). Patients with severe aortic valve stenosis deemed to be at intermediate or increased risk of 30-day surgical mortality were included. Data were collected from December 2010 to June 2016, and data were analyzed from December 2021 to October 2022. INTERVENTIONS: Patients were randomized to self-expanding TAVI or surgery in the RCTs or underwent self-expanding TAVI for clinical indications in the nonrandomized studies. MAIN OUTCOMES AND MEASURES: The primary end point was the incidence of SVD through 5 years (from the RCTs). Factors associated with SVD and its association with clinical outcomes were evaluated for the pooled RCT and non-RCT population. SVD was defined as (1) an increase in mean gradient of 10 mm Hg or greater from discharge or at 30 days to last echocardiography with a final mean gradient of 20 mm Hg or greater or (2) new-onset moderate or severe intraprosthetic aortic regurgitation or an increase of 1 grade or more. RESULTS: Of 4762 included patients, 2605 (54.7%) were male, and the mean (SD) age was 82.1 (7.4) years. A total of 2099 RCT patients, including 1128 who received TAVI and 971 who received surgery, and 2663 non-RCT patients who received TAVI were included. The cumulative incidence of SVD treating death as a competing risk was lower in patients undergoing TAVI than surgery (TAVI, 2.20%; surgery, 4.38%; hazard ratio [HR], 0.46; 95% CI, 0.27-0.78; P = .004). This lower risk was most pronounced in patients with smaller annuli (23 mm diameter or smaller; TAVI, 1.32%; surgery, 5.84%; HR, 0.21; 95% CI, 0.06-0.73; P = .02). SVD was associated with increased 5-year all-cause mortality (HR, 2.03; 95% CI, 1.46-2.82; P < .001), cardiovascular mortality (HR, 1.86; 95% CI, 1.20-2.90; P = .006), and valve disease or worsening heart failure hospitalizations (HR, 2.17; 95% CI, 1.23-3.84; P = .008). Predictors of SVD were developed from multivariate analysis. CONCLUSIONS AND RELEVANCE: This study found a lower rate of SVD in patients undergoing self-expanding TAVI vs surgery at 5 years. Doppler echocardiography was a valuable tool to detect SVD, which was associated with worse clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT01240902, NCT01586910, and NCT01531374

In addition to appropriate patient screening, pre-procedural preparation is essential to optimize both technical success and patient outcome for protected percutaneous coronary intervention (PCI). A critical component of optimization is the identification and preparation of a suitable femoral access site. Here, we describe several options for both imaging and image-guided access to optimize the approach.

IMPORTANCE: In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. OBJECTIVE: To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. DESIGN, SETTING, AND PARTICIPANTS: SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. INTERVENTION: Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. MAIN OUTCOMES AND MEASURES: The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. RESULTS: A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm2 vs 1.8 [0.6] cm2; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. CONCLUSIONS AND RELEVANCE: Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

By digitizing operations, companies may replace manual work with increased automation, but they may also augment human work through smarter execution. Robert Boute and Jan Van Mieghem present a conceptual framework that distinguishes the different levels of digitization, automation, and intelligence. This framework can serve as an audit, helping companies to assess where they are now and where they could be in the future.

IMPORTANCE: Transcatheter aortic valve replacement (TAVR) failure is often managed by an urgent implantation of a supplementary valve during the procedure (2-valve TAVR [2V-TAVR]). Little is known about the factors associated with or sequelae of 2V-TAVR. OBJECTIVE: To examine the incidence, causes, and outcomes of 2V-TAVR. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was performed using data from an international registry of 21 298 TAVR procedures performed from January 1, 2014, through February 28, 2019. Among the 21 298 patients undergoing TAVR, 223 patients (1.0%) undergoing 2V-TAVR were identified. Patient-level data were available for all the patients undergoing 2V-TAVR and for 12 052 patients (56.6%) undergoing 1V-TAVR. After excluding patients with missing 30-day follow-up or data inconsistencies, 213 2V-TAVR and 10 010 1V-TAVR patients were studied. The 2V-TAVR patients were compared against control TAVR patients undergoing a 1-valve TAVR (1V-TAVR) using 1:4 17 propensity score matching. Final analysis included 1065 (213:852) patients. EXPOSURES: Urgent implantation of a supplementary valve during TAVR. MAIN OUTCOMES AND MEASURES: Mortality at 30 days and 1 year. RESULTS: The 213 patients undergoing 2V-TAVR had similar age (mean [SD], 81.3 [0.5] years) and sex (110 [51.6%] female) as the 10 010 patients undergoing 1V-TAVR (mean [SD] age, 81.2 [0.5] years; 110 [51.6%] female). The 2V-TAVR incidence decreased from 2.9% in 2014 to 1.0% in 2018 and was similar between repositionable and nonrepositionable valves. Bicuspid aortic valve (odds ratio [OR], 2.20; 95% CI, 1.17-4.15; P = .02), aortic regurgitation of moderate or greater severity (OR, 2.02; 95% CI, 1.49-2.73; P < .001), atrial fibrillation (OR, 1.43; 95% CI, 1.07-1.93; P = .02), alternative access (OR, 2.59; 95% CI, 1.72-3.89; P < .001), early-generation valve (OR, 2.32; 95% CI, 1.69-3.19; P < .001), and self-expandable valve (OR, 1.69; 95% CI, 1.17-2.43; P = .004) were associated with higher 2V-TAVR risk. In 165 patients (80%), the supplementary valve was implanted because of residual aortic regurgitation after primary valve malposition (94 [46.4%] too high and 71 [34.2%] too low). In the matched 2V-TAVR vs 1V-TAVR cohorts, the rate of device success was 147 (70.4%) vs 783 (92.2%) (P < .001), the rate of coronary obstruction was 5 (2.3%) vs 3 (0.4%) (P = .10), stroke rate was 9 (4.6%) vs 13 (1.6%) (P = .09), major bleeding rates were 25 (11.8%) vs 46 (5.5%) (P = .03) and annular rupture rate was 7 (3.3%) vs 3 (0.4%) (P = .03). The hazard ratios for mortality were 2.58 (95% CI, 1.04-6.45; P = .04) at 30 days, 1.45 (95% CI, 0.84-2.51; P = .18) at 1 year, and 1.20 (95% CI, 0.77-1.88; P = .42) at 2 years. Nontransfemoral access and certain periprocedural complications were independently associated with higher risk of death 1 year after 2V-TAVR. CONCLUSIONS AND RELEVANCE: In this cohort study, valve malposition was the most common indication for 2V-TAVR. Incidence decreased over time and was low overall, although patients with a bicuspid or regurgitant aortic valve, nontransfemoral access, and early-generation or self-expandable valve were at higher risk. These findings suggest that compared with 1V-TAVR, 2V-TAVR is associated with high burden of complications and mortality at 30 days but not at 1 year.

By a thorough performance comparison, we compare the recently proposed, operator-basedlinear clustering process on a network with classical, existing clustering algorithms. The linear clustering process produces clusters or partitions based on the eigenstructure of a linear operator on a graph that replaces nodes to ‘more natural’ positions by attractive and repulsive forces. Synthetic benchmarks, along with real-world networks possessing or lacking a known community structure, are considered. Our comparative analysis demonstrates that our linear clustering process generates superior partitions compared to the algorithms assessed in most instances, while of comparable computational complexity with the simplest existing clustering algorithms.

Introduction Although fetal brain injury due to COL4A1gene mutation is well documented, fetal central nervous system (CNS) and placental histopathology lack description. We report CNS and placental pathology in fetal cases with symptomatic COL4A1mutation.Methods We retrieved four autopsy cases of COL4A1 related disease, confirmed by genetic sequencing after fetal brain injury was detected.Results One case was a midgestation fetus with residua of ventricular zone hemorrhage and normal placental villi. Three cases were 30-32 week gestation fetuses: two demonstrated CNS small vessel thrombosis, with CNS injury. Both demonstrated high grade placental fetal vascular malperfusion (FVM). One additionally showed villous dysmorphism, the other demonstrated mild villous immaturity. The fetus whose placenta demonstrated high grade FVM was growth restricted. A fourth fetus demonstrated schizencephaly with a CNS arteriopathy with smooth muscle cell degeneration and cerebral infarcts; the placenta demonstrated severe villous dysmorphism and low grade FVM.Discussion These cases confirm that small vessel disease is important in producing intracranial pathology in COL4A1mutation. We report an arteriopathy distinct from microvascular thrombosis and demonstrate that placental pathology is common in fetal COL4A1 related disease. This tentatively suggests that placental pathology may contribute to CNS abnormalities by affecting circulatory sufficiency.

There has been a significant increase in the use of short-term percutaneous ventricular assist devices (pVADs) as acute circulatory support in cardiogenic shock and to provide haemodynamic support during interventional procedures, including high-risk percutaneous coronary interventions. Although frequently considered together, pVADs differ in their haemodynamic effects, management, indications, insertion techniques, and monitoring requirements. This consensus document summarizes the views of an expert panel by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and the Association for Acute Cardiovascular Care (ACVC) and appraises the value of short-term pVAD. It reviews the pathophysiological context and possible indications for pVAD in different clinical settings and provides guidance regarding the management of pVAD based on existing evidence and best current practice.

AbstractBackgroundElevated pulmonary artery pressure (PAP) in patients with severe aortic stenosis (AS) is a strong predictor of adverse prognosis. This study sought to assess the relation between PAP and clinical and echocardiographic parameters in elderly patients with severe AS, as well as to identify the determinants of the change in PAP after transcatheter aortic valve implantation (TAVI).MethodsThe study included 170 subjects (age 81 ± 7 years, 45% men) with symptomatic severe AS who were treated by TAVI. They underwent a clinical evaluation and a transthoracic echocardiography before the TAVI procedure and 6 months after.ResultsIn a multivariable analysis, the independent predictors for baseline PAP were the body mass index (BMI) (β = 0.21, p = .006), COPD GOLD class (β = 0.20; p = .009), the E/e′ ratio (β = 0.20; p = .02) and the degree of aortic regurgitation (β = 0.20; p = .01). After TAVI, there was significantly less (51% vs. 29%, p<.0001) pulmonary hypertension, defined as a tricuspid regurgitation velocity ≥2.8 m/s. The baseline variables related to an improvement in PAP were the tricuspid regurgitation velocity (p = .0001) and the E/e′ (p = .005). From the parameters potentially modified with TAVI, the only independent predictor of PAP variation was the change in the E/e′ ratio (β = 0.23; p = .01).ConclusionsIndependent predictors for baseline PAP in elderly patients with symptomatic AS were the BMI, GOLD class, the aortic regurgitation and the E/e′ ratio. The baseline predictors for a change in PAP 6 months after TAVI were the baseline PAP and E/e′, with only the change in the E/e′ ratio being correlated to the change in PAP.

In fetal congenital complete heart block, the slow fetal heart rate prolongs the diastolic phase of the cardiac cycle, which may affect Doppler measurements that are typically used to quantify placental function. We here describe the umbilical artery (UA) and middle cerebral artery (MCA) Dopplers in a cohort of fetuses with heart block, hypothesizing that values will be increased but nevertheless remain associated with placental function and fetal outcome.

Background: Human biomonitoring (HBM) has been repeatedly recommended for and applied to post-incident chemical exposure assessment. The applicability of HBM and the validity of its results, however, closely depend on the existence and quality of preparatory measures such as information and instruction materials, sampling procedures, transport and storage facilities, and on the selection of appropriate biomarkers, sampling time, transport and storage conditions. Objective: To establish a standardized HBM program for emergency responders of a large chemical production site, considering the aforementioned aspects. Methods: An HBM program based on a comprehensive questionnaire, information and training of emergency responders, and availability of sampling material was established. The quantitative determination of metabolites of hazardous substances was carried out based on quality-controlled analytical methods. Results: The use of HBM after emergency operations was significantly increased immediately after the implementation of the program. Only in single cases, however, established HBM assessment values were exceeded. After one major incident, an increased exposure to benzene exceeding the internal action value was observed after firefighting and safeguarding. Significance: The experience with several minor and one major incident at a chemical production site suggests that the implementation of easily accessible and applicable routines is one paramount prerequisite for the success of HBM programs after chemical incidents.

Supplemental Digital Content is available in the text.

IMPORTANCE: Whether intervention should be performed in patients with asymptomatic severe aortic stenosis (AS) remains debated. OBJECTIVE: To meta-analyze the natural history of asymptomatic severe AS and examine the association of early intervention with survival. DATA SOURCES: PubMed, Embase, and Cochrane databases were searched from inception to February 1, 2020. STUDY SELECTION: Observational studies of adult patients with asymptomatic severe AS. DATA EXTRACTION AND SYNTHESIS: Two investigators independently extracted study and patient characteristics, follow-up time, events, and prognostic indicators of events. Random-effects models were used to derive pooled estimates. MAIN OUTCOMES AND MEASURES: The meta-analysis on natural history was performed on the primary end point of all-cause death occurring during a conservative treatment period, with secondary end points consisting of cardiac death, death due to heart failure, sudden death, development of symptoms, development of an indication for aortic valve intervention, and aortic valve intervention. The primary end point for the meta-analysis of early intervention vs a conservative strategy was all-cause death during long-term follow-up. Finally, meta-analysis was performed on the association of prognostic indicators with the composite of death or aortic valve intervention found in multivariable models. RESULTS: A total of 29 studies with 4075 patients with 11 901 years of follow-up were included. Pooled rates per 100 patients per year were 4.8 (95% CI, 3.6-6.4) for all-cause death, 3.0 (95% CI, 2.2-4.1) for cardiac death, 2.0 (95% CI, 1.3-3.1) for death due to heart failure, 1.1 (95% CI, 0.6-2.1) for sudden death, 18.1 (95% CI, 12.8-25.4) for an indication for aortic valve intervention, 18.5 (95% CI, 13.4-25.5) for development of symptoms, and 19.2 (95% CI, 15.5-23.8) for aortic valve intervention. Early intervention was associated with a significant reduction in long-term mortality (hazard ratio, 0.38; 95% CI, 0.25-0.58). Factors associated with worse prognosis were severity of AS, low-flow AS, left ventricular damage, and atherosclerotic risk factors. CONCLUSIONS AND RELEVANCE: Data from observational studies and a recent randomized clinical trial suggest that many patients with asymptomatic severe AS develop an indication for aortic valve intervention, and their deaths are mostly cardiac but not only sudden. Other end points besides sudden death should be considered during the decision to perform early intervention that are associated with improved survival.

Process improvement begins with the process view: understanding patient care from the patient’s point of view. Organizations must also clearly articulate for themselves how they define operational excellence so that the tradeoffs taken in process improvement can be clearly made. Constructing a process map allows application of powerful analytical tools, such as Little’s law, which in turn uncovers targets for process improvement from the patient’s point of view. Often tradeoffs among process performance metrics, such as quality, cost, time, personalization, and innovation, must be made when deciding upon improvements to be made in certain processes.

It remains unclear how often coronary revascularization is necessary after aortic valve interventions, either by surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement. However, these data are relevant for treatment and prosthesis choice. The authors sought to analyze the incidence and characteristics of coronary revascularization after SAVR during follow-up.

ABSTRACTObjectives:A retrospective observational cohort study to report on contemporary indications of balloon aortic valvuloplasty (BAV).Background:As indications for transcatheter aortic valve replacement (TAVR) are increasing, BAV is reinforced as a bridging therapy.Methods:A total of 47 consecutive patients who underwent BAV in parallel to an existing TAVR program was retrospectively assessed for BAV indications and clinical events during 1 year of follow-up.Results:The following indications were distinguished: bridge to destination aortic valve replacement therapy (BTD), bridge to urgent non-cardiac therapy (BTN) or palliation. BAV was performed in 20 (43%) patients as BTD, in 18 (38%) as BTN and in 9 (19%) as palliative treatment. Patients in the BTN cohort were younger (age 74.1 ± 8.3% vs. 80.7 ± 8.3% years in BTD, p= 0.02) with lower STS-scores (2.2% [IQR 1.3–4.6] vs. 13.0% [IQR 7.6–22.2] p< 0.001). Overall baseline mean transaortic gradient was 43.2 mmHg and reduced by a mean of 16.0 ± 10.1 mmHg after BAV (p< 0.001). Procedural mortality was 8.5% (n = 4). All-cause mortality at 30 days and 1 year was 20% and 45% in BTD, 6% and 39% in BTN and 44% and 67% in the palliative group. Aortic valve replacement (AVR) was performed in 55% of the BTD and 50% of the BTN group at 1 year. Reasons for not undergoing definite AVR were clinical deterioration in BTD and terminal comorbidity in BTN. Compared to a contemporary TAVR cohort, procedural and 1 year mortality was significantly increased in the BAV cohort.Conclusion:BAV remains a valuable option in well-defined patient phenotypes to determine AVR feasibility, bridge to urgent non-cardiac therapy, and at times, palliation. These phenotypes represent vulnerable patients with overall poor clinical outcome.

To assess the natural evolution of the size of the fetal lateral ventricles throughout pregnancy in fetuses with callosal anomalies. Cases of fetal callosal anomalies were retrospectively classified as isolated or complex based on the presence of other structural or genetic anomalies. Longitudinal ultrasound studies were reviewed, and postnatal outcomes were retrieved for isolated cases. In 135 fetuses, those who first presented after 24 weeks’ gestation were more likely to have ventriculomegaly (n = 58 of 68 [85%]) than those who presented before 24 weeks (n = 39 of 67 [58%]; P< .001). In 79 cases that had longitudinal follow‐up, the mean increase in ventricular width was 0.6 mm/wk, without a significant difference between isolated and complex cases (mean ± SD, 0.6 ± 1.5 versus 0.6 ± 1.1 mm; P= .45). Callosal anomalies are associated with progressive ventriculomegaly on prenatal ultrasound imaging, without a difference between isolated and complex anomalies. This feature should be considered part of the disease spectrum. The consequence of progressive ventriculomegaly on the long‐term neurodevelopmental outcome is still unknown, and further studies should be aimed at obtaining long‐term follow‐up of these cases.

Transcatheter aortic valve implantation (TAVI) has revolutionized the treatment of symptomatic severe aortic valve stenosis. Current guidelines recommend TAVI in patients at increased operative risk of death. Advanced imaging planning, new transcatheter valve platforms, procedure streamlining and growing operator experience have improved procedural safety and bioprosthetic valve performance. As a result, TAVI has been explored for other indications. Two randomized trials published in 2019 to assess TAVI in patients with symptomatic severe aortic stenosis at low operative risk have set the stage for a new wave of indications. In younger and low-risk patients, TAVI had an early safety benefit over surgical aortic valve replacement and was associated with faster discharge from hospital and recovery and fewer rehospitalizations. In patients with symptomatic severe aortic stenosis, TAVI has now been explored across the entire spectrum of operative risk, from inoperable to low-risk populations, in properly designed, randomized clinical trials, although data on the long-term durability of these valves are lacking. The use of TAVI in severe bicuspid aortic valve stenosis, asymptomatic severe aortic stenosis, moderate aortic stenosis in combination with heart failure with reduced ejection fraction, and isolated pure aortic regurgitation is now under investigation in clinical trials. In this Review, we provide our perspective on these evolving indications for TAVI, discuss relevant available data from clinical trials, and highlight procedural implications and caveats of new and future indications.

ABSTRACTBackground:Vascular complications (VCs) after transcatheter aortic valve implantation (TAVI) are associated with impaired outcome. We performed a meta-analysis to determine in-hospital/30-day major VCs rate after transfemoral-TAVI adjudicated by an independent clinical-event-committee, and to compare the major VCs rate with regard to consecutive generations of balloon-expandable and self-expanding platforms, device profile, experience and patient risk-profile.Methods:A systematic, computerized search with predefined criteria was performed in PubMed, Embase and Cochrane on March 27, 2018. The overall pooled proportion of VC was calculated using a random-effects model. Subgroups were examined based on sheath size, STS-score and start-date of inclusion (early (< January 2012); late-phase (≥ January 2012) studies).Results:A total of 24 studies with 14308 patients were included. The pooled major VCs rate was 7.71% and was lower in low-profile vs. high-profile device studies (5.51% vs. 8.46%, p= 0.0015). Major VCs rate decreased significantly with transition to newer generation balloon-expandable valves ((Sapien vs. Sapien XT (15.18% vs. 8.48%, p< 0.00001); Sapien XT vs. Sapien 3 (8.48% vs. 4.48%, p= 0.005)) and there was a tendency towards fewer major VCs in EvolutR vs. CoreValve (5.98% vs. 7.97%, p= 0.094). Major VC rate was lower in late-phase vs. early-phase studies (5.82% vs. 7.84%, p= 0.048) and a tendency towards a lower rate was seen in intermediate vs. high-risk studies (7.09% vs. 9.62%, p= 0.059).Conclusion:The pooled rate of independently adjudicated major VCs after transfemoral-TAVI was 7.71%. Experience and device profile are associated with fewer major VCs.

ABSTRACTBackground:The Lotus aortic valve system is a transcatheter heart valve (THV) designed with a seal to minimize paravalvular leak (PVL). We evaluated hemodynamic performance, PVL and ventricular function up to 1-year after transcatheter aortic valve replacement (TAVR) using the Lotus THV in patients with severe aortic stenosis.Methods:RESPOND was a prospective, single-arm, multicenter registry evaluating outcomes after Lotus TAVR in routine clinical practice. Core Laboratory adjudicated echocardiograms at baseline, discharge and 1-year were analyzed in a subgroup (N = 550) of patients with paired transthoracic echocardiography (TTE) at the 3 time points.Results:Mean effective aortic valve orifice area (EOA) in cm2increased from 0.74 ± 0.25 at baseline to 1.83 ± 0.46 at discharge and to 1.78 ± 0.45 at 1-year. Mean transvalvular gradient in mmHg was reduced from 38.7 ± 15.2 at baseline to 10.9 ± 4.2 at discharge and to 10.8 ± 5.1 at 1-year. VARC-2 hemodynamic success was achieved in 92% and 95% of patients at discharge and 1-year, respectively. Mild or more PVL was seen in 7.3% and 5.5% and moderate or more PVL was seen in 0.6% and 0.4% of the patients at discharge and 1-year, respectively. Stroke volume index (mL/m2) increased from 35 ± 10 at baseline to 40 ± 11 at discharge and to 41 ± 11 at 1-year (p< 0.001).Conclusions:This RESPOND sub-study demonstrates persistently favorable hemodynamic performance and a low rate of PVL in unselected patients through 1-year in the largest Lotus-treated population to date.(Repositionable Lotus Valve System–Post Market Evaluationof Real WorldClinical Outcomes [RESPOND]; NCT02031302).

•An activated clotting time <250 ​seconds after an initial unfractionated heparin dose often coincided with sufficient antifactor Xa activity >0.50 U/mL, which may result in additional unfractionated heparin administration, with an increased bleeding risk.•The point-of-care-activated partial thromboplastin time may be a safer and more reliable anticoagulation monitoring tool during transcatheter aortic valve replacement procedures.

Several clinical and procedural factors determine outcomes after transcatheter aortic valve replacement (TAVR), but data are scarce on the impact of post-TAVR discharge disposition on long-term outcomes. We sought to analyse whether discharge location after TAVR is associated with 1-year outcomes in women undergoing contemporary TAVR.

Moderate aortic stenosis is increasingly recognized as a disease entity with reduced prognosis. Diagnosis of moderate aortic stenosis may be complemented by laboratory tests and advanced imaging techniques focused at detecting signs of cardiac damage such as increase of cardiac enzymes (N-terminal pro B-type Natriuretic Peptide, troponin), left ventricular remodeling (hypertrophy, reduced left ventricular ejection fraction), or myocardial fibrosis. Therapy should include guideline-directed optimal medical therapy for heart failure. Patients with signs of cardiac damage may benefit from early intervention and therefore is the focus of several randomized controlled trials. As of yet, no evidence-based therapy exists to halt the progression of aortic valve calcification.

Induced spreading aims to maximize the infection probabilities of some target nodes by adjusting the nodal infection rates, which can be applied in biochemical and information spreading. We assume that the adjustment of the nodal infection rates has an associated cost and formulate the induced spreading for susceptible-infected-susceptible (SIS) epidemics in networks as an optimization problem under a constraint on total cost. We address and solve both a static model and a dynamic model for the optimization of the induced SIS spreading. By numerical results in some artificial and real networks, we investigate the effect of the network topology on the optimal induced strategy with a quadratic cost function. In the static method, the infection rate increment on each node is coupled to both the degree and the average hops to the targets. In the dynamic method, we show that the effective resistance could be a good metric to indicate the minimum total cost for targeting a single node. We also illustrate that the minimum total cost increases much more slowly with the increasing fraction of targets in the SIS model than in linear control systems.

Supplemental Digital Content is available in the text.

Multiple transcatheter heart valve iterations have created an interesting range of options with which to perform transcatheter aortic valve replacement. The Lotus valve has several attractive features. The ability to eradicate even mild paravalvular leak mirrors the outcomes of surgical aortic valve replacement. New design iterations of the Lotus valve and refined sizing algorithms may help mitigate the need for permanent pacemaker implantation and consolidate its best-in-class results in terms of paravalvular leak. Ongoing trials should help define the safety and efficacy of the Lotus transcatheter heart valve in contemporary practice.

ABSTRACTBackground:Myocardial injury (MI) is common with transcatheter aortic valve implantation (TAVI) and may predict poor outcome. We aim: 1) to evaluate the difference in change of high-sensitivity-Troponin-T (hsTnT) within 24h after transfemoral-TAVI between mechanically-expanded (MEV), self-expanding (SEV) and balloon-expandable-valves (BEV); 2) to determine predictors for MI post-TAVI; and 3) to assess whether MI is associated with 30-day mortality.Methods:This multicenter retrospective observational study included 1208 consecutively treated transfemoral-TAVI patients from three European centers. All patients treated with a MEV, SEV or BEV with available hsTnT measurements at baseline and within 24 h post-TAVI were included. Significant MI was defined as an elevation of hsTnT ≥ 15x the upper-reference-limit.Results:Overall, the median hsTnT rise was 741 ng/L and was lower with MEV (MEV 335 vs. SEV 901 vs. BEV 649 ng/L, p< 0.001). MI occurred in 925 patients (77%) and was less frequent with MEV (MEV 67%, SEV 79% and BEV 76%, p= 0.007). Occurrence of MI was similar after implantation of first vs. second- generation SEV (79 vs. 80%, p= 0.72) and BEV (77 vs. 76%, p= 0.90). There was no association between frequency of annulus manipulation and MI. On multivariable analysis (OR (95% CI) non-MEV (1.63 (1.06–2.49)), mean aortic gradient (1.02 (1.01–1.03)), left ventricular ejection fraction (1.03 (1.01–1.04)), and previous myocardial infarction (1.62 (1.04–2.56)) were positively associated with MI. There was no association between MI and 30-day mortality.Conclusion:Transcatheter valve design determines peri-procedural MI and is less frequent with MEV. MI is not associated with 30-day mortality.

Chronic kidney disease (CKD) has a negative impact on outcomes after transcatheter aortic valve replacement (TAVR). Data on outcomes in renal transplant recipients (RTRs) undergoing TAVR are scarce. We compared the outcomes in RTRs undergoing TAVR with matched patients who have native kidneys and similar kidney function.

IMPORTANCE: Surgical aortic valve replacement (SAVR) has increased risk for patients with aortic stenosis (AS) and a history of coronary artery bypass graft (CABG) surgery. Transcatheter aortic valve replacement (TAVR) may be an alternative. OBJECTIVE: To compare TAVR with SAVR outcomes in patients at intermediate operative risk with prior CABG surgery. DESIGN, SETTING, AND PARTICIPANTS: In this post hoc analysis of the Surgical Replacement and Transcatheter Aortic Valve Implantation (SURTAVI) noninferiority randomized clinical trial, patients with severe, symptomatic AS at intermediate operative risk were enrolled from 87 centers across the United States, Europe, and Canada from June 2012 to June 2016 and followed-up with up to July 2017. Those with a history of CABG surgery were considered for analysis. Data were analyzed from September to December 2017. INTERVENTIONS: A total of 1746 patients were enrolled and randomized 1:1 to self-expanding TAVR or SAVR. An implant was attempted in 1660 patients, of whom 273 had prior CABG surgery, including 136 who underwent attempted TAVR and 137 who underwent attempted SAVR. MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality or disabling stroke at 1-year follow-up. Efficacy outcomes included quality of life, measured using the Kansas City Cardiomyopathy Questionnaire at 30 days, 6 months, and 1 year, and distance walked in 6 minutes, measured using the 6-minute walk test at 30 days and 1 year. RESULTS: Of the 136 patients in the TAVR cohort, 111 (81.6%) were male, and the mean (SD) age was 76.9 (6.5) years; of the 137 in the SAVR cohort, 117 (85.4%) were male, and the mean (SD) age was 76.6 (6.5) years. The mean (SD) Society of Thoracic Surgeons Predicted Risk of Mortality score was 5.0% (1.6%) in the TAVR cohort and 5.2% (1.7%) in the SAVR cohort. All-cause mortality or disabling stroke at 1-year follow-up was 8.9% (95% CI, 5.2-15.2) in the TAVR cohort and 6.7% (95% CI, 3.5-12.8) in the SAVR cohort (log-rank P = .53). Compared with patients receiving SAVR, the mean (SD) Kansas City Cardiomyopathy Questionnaire summary score was significantly better among patients receiving TAVR at 30 days (81.4 [19.2] vs 69.7 [22.6]; P &lt; .001); treatments were similar at 1 year (85.7 [14.6] vs 82.8 [18.4]; P = .19). Compared with patients in the SAVR cohort, those in the TAVR cohort showed greater mean (SD) improvement in distance walked at 1 year (48.3 [120.6] m vs 16.8 [88.7] m; P = .04). CONCLUSIONS AND RELEVANCE: Both TAVR and SAVR were safe for intermediate-risk patients with AS and prior CABG surgery. The transcatheter approach facilitated faster improvement in quality of life and better exercise capacity at 1-year follow-up. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01586910