bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher order visual areas enhance stimulus responsiveness in mouse primary visual cortex
Authors: Oude Lohuis Matthijs N , Canton Alexis Cervan , Pennartz Cyriel M A , Olcese Umberto 
Published: October 2021

Abstract
Over the past few years, the various areas that surround the primary visual cortex (V1) in the mouse have been associated with many functions, ranging from higher order visual processing to decision-making. Recently, some studies have shown that higher order visual areas influence the activity of the primary visual cortex, refining its processing capabilities. Here, we studied how in vivo optogenetic inactivation of two higher order visual areas with different functional properties affects responses evoked by moving bars in the primary visual cortex. In contrast with the prevailing view, our results demonstrate that distinct higher order visual areas similarly modulate early visual processing. In particular, these areas enhance stimulus responsiveness in the primary visual cortex, by more strongly amplifying weaker compared with stronger sensory-evoked responses (for instance specifically amplifying responses to stimuli not moving along the direction preferred by individual neurons) and by facilitating responses to stimuli entering the receptive field of single neurons. Such enhancement, however, comes at the expense of orientation and direction selectivity, which increased when the selected higher order visual areas were inactivated. Thus, feedback from higher order visual areas selectively amplifies weak sensory-evoked V1 responses, which may enable more robust processing of visual stimuli.
Real Effects of Financial Distress: The Role of Heterogeneity
Authors: Buera Francisco , Karmakar Sudipto 
Published: October 2021

Abstract
Which firms are more sensitive to an aggregate financial shock? What can be learnt from these heterogeneous responses? We evaluate and answer these questions from both empirical and theoretical perspectives. Using microdata from Portugal during the sovereign debt crisis we find that highly leveraged firms and firms with a larger share of short-term debt on their balance sheets contracted more in the aftermath of the financial shock. We analyse the conditions under which leverage and debt maturity determine the sensitivity of firms’ investment decisions to financial shocks in standard models of investment under financial frictions. In doing so, we extend these models to feature a maturity choice. We show that simple versions of these models are not consistent with the observed heterogeneous responses. The model needs the presence of frictions when issuing long-term debt to rationalise the empirical findings.
Predictive model for in-hospital mortality following cardiogenic shock
Authors: Garcia-Rodeja Arias F , Perez Dominguez M , Martinon Martinez J , Garcia Acuna J M , Abou Joch Casas C , Rigueiro Veloso P , Agra Bermejo R M , Iglesias Alvarez D , Alvarez Alvarez B , Gonzalez Ferrero T , Cacho Antonio C , Antunez Muinos P J , Gonzalez Juanatey J R 
Published: October 2021

Abstract

Introduction and objectives
Cardiogenic shock is a condition caused by reduced cardiac output and hypotension, resulting in end-organ damage and multiorgan failure. Although prognosis has been improved in recent years, this state is still associated with high morbidity and mortality. The aim of our study was to perform a predictive model for in-hospital mortality that allows stratifying the risk of death in patients with cardiogenic shock.

Methods
This is a retrospective analysis from a prospective registry, that included 135 patients from one Spanish Universitary Hospital between 2011 and 2020. Multivariate analysis was performed among those variables with significant association with short-term outcome of univariate analysis with a p-value &lt;0.2. Those variables which had a p-value &gt;0.1 in the multivariable analysis were excluded of the final model. Our method was assessed using the area under the ROC-curve (AUC). Goodness of fit was tested using Hosmer-Lemeshow statistic test. Finally, we performed a risk score using the pondered weight of the coefficients of a simplified model created after categorizing the continuous quantitative variables included in the final model, giving a maximum of 16 points and creating three categories of risk.

Results
The in-hospital mortality rate was 41.5%, the average of age was 74.2 years, 35.6% were females and acute coronary syndrome (ACS) was the main cause of shock (60.7%). Mitral regurgitation (moderate-severe), age, ACS etiology, NT-proBNP, blood hemoglobin and lactate at admission were included in the final model. Risk-adjustment model had good accuracy in predicting in-hospital mortality (AUC 0.85; 95% CI 0,78–0,90) and the goodness of fit test was p-value&gt;0.10. According to the risk score made with the simplified model, these patients were stratified into three categories: low (scores 0–6), intermediate (scores 7–10), and high (scores 11–16) risk with observed mortality of 12.9%, 49.1% and 87.5% respectively (p&lt;0,001).

Conclusions
Our predictive model using six variables, shows good discernment for in-hospital mortality and the risk score has identified three groups with significant differences in prognosis. This model could help in guiding treatments and clinical decision-making, so it needs external validation and to be compared with other models already published.

Funding Acknowledgement
Type of funding sources: None. ROC curveRisk Score
Atherosclerosis associated pathways are upregulated in stenotic aortic valves from patients with severe concomitant coronary artery disease
Authors: Plunde O , Sarajlic P , Franco-Cereceda A , Back M 
Published: October 2021

Abstract

Aortic valve stenosis (AVS) share pathobiology and risk factors with atherosclerosis. However, medical treatment effective against atherosclerosis lack ability to halt the progression of AVS. The aims of this study were to (i) determine the prevalence of coronary artery disease (CAD) in surgical AVS patients and (ii) to establish predictors of CAD in AVS patients and (iii) to identify differential aortic valve transcriptomic profiles depending on concomitant CAD.
The study cohort consisted of 256 consecutive AVS patients with surgically verified tricuspid aortic valves, of which 74 aortic valves were collected. CAD defined as coronary artery stenosis requiring concomitant bypass surgery or previous acute coronary syndrome or percutaneous coronary intervention Transcriptomic data were obtained from microarray analysis of tissues from three different stages of AVS process (healthy, intermediate, and calcified tissue). All comparisons were sex and tissue adjusted. Non-coding probes were removed and a variance filter was applied prior to analysis which yielded 5121 genes.
The prevalence of CAD in AVS was 49%. A logistic regression model revealed male sex, claudication, diabetes and current smoking as significant predictors of CAD when age, sex, peak transaortic velocity, hsCRP, eGFR and BMI were held constant.
28 genes were significantly (q&lt;0.05) differentially expressed when aortic valves from patients with (n=43) and without (n=31) CAD were compared. A comparison of patients with concomitant multi vessel disease (2–3 affected vessel territories, n=20) and patients without CAD or single vessel disease (n=54) revealed 189 significantly expressed genes and an optimal visual separation on heatmap (Figure 2). Active-subnetwork-oriented-enrichment analysis identified upregulated aortic valve atherosclerosis associated pathways in multi vessel disease patients related to reactive oxygen species and cytokine signaling.
This study provides a novel observation of differential aortic valve gene expression profile depending on concomitant severe CAD. The results revealed that patients with concomitant severe CAD exhibited underlying atherosclerosis-related mechanisms to their aortic valve disease. Therefore, future precision medicine against AVS may be facilitated by assessing concomitant CAD.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Karolinska Institute - Clinical Science Training ProgrammeSwedish Heart Lung Foundation Predictors of concomitant CADDEGs in AVs stratified on severe CAD
Routine advanced echocardiography in the evaluation of cardiovascular sequelae of COVID19 survivors with elevated cardiovascular biomarkers
Authors: Rodenas Alesina E , Rodriguez-Palomares J , Oller-Bach M , Jordan P , Badia C , Herrador L , Garcia-De-Acilu M , Clau-Terre F , Gonzalez-Del-Hoyo M , Fernandez-Galera R , Servato L , Casas G , Baneras J , Ferreira-Gonzalez I 
Published: October 2021

Abstract

Background
COVID19 has been related to elevated CVB and biventricular dysfunction during hospitalization. However, it is unknown whether patients with biomarker elevation exhibit long-lasting abnormalities in cardiac function.

Purpose
To determine, using advanced echocardiography, the prevalence and type of cardiovascular sequelae after COVID19 infection with marked elevation of cardiovascular biomarkers (CVB), and their prognostic implications.

Methods
All patients admitted from March 1st to May 25th, 2020 to a tertiary referral hospital were included. Patients with cardiovascular disease antecedent, death during admission, or the first 30 days after discharge were excluded. Patients with hs-TnI &gt;45 ng/L, NT-proBNP &gt;300 pg/ml, and D-dimer &gt;8000 ng/ml were separated based on each CVB elevation and matched with COVID controls (three biomarkers within the normal range) based on intensive care requirements and age.

Results
From a total of 2025 hospitalized COVID19 patients, 80 patients with significantly elevated CVB and 29 controls were finally included. No differences in baseline characteristics were observed among groups, but elevated CVB patients were sicker. Follow-up echocardiograms showed no differences among groups regarding LVEF or RV diameters, but TAPSE was lower if hs-TnI or D-dimer were elevated. Hs-TnI patients also had lower global myocardial work and global longitudinal strain. The presence of an abnormal echocardiogram was more frequent in the elevated CVB group compared to controls (23.8 vs 10.3%, P=0.123) but mainly associated with mild abnormalities in deformation parameters. Management did not change in any case and no major cardiovascular events except deep vein thrombosis occurred after a median follow-up of 7 months (Figure 1).

Conclusions
Minimal abnormalities in cardiac structure and function are observed in COVID19 survivors without previous cardiovascular diseases who presented a significant CVB rise at admission, with no impact on patient management or short-term prognosis. These results do not support a routine screening program after discharge in this population.

Funding Acknowledgement
Type of funding sources: None. Figure 1
Prognostic value of three dimensional-vena contracta area in patients with secondary mitral regurgitation
Authors: Yedidya I , Mantegazza V , Namazi F , Lustosa R , Butcher S C , Milhorini Pio S , Vo N M , Tamborini G , Garlasche A , Pepi M , Bax J J , Ajmone Marsan N , Delgado V 
Published: October 2021

Abstract

Background
Effective regurgitant orifice area (EROA) is an important quantitative measurement for mitral regurgitation (MR) grading. Yet, the accuracy of this method is limited in patients with secondary mitral regurgitation (SMR). Three-dimensional (3D) color Doppler echocardiography allows for the direct assessment of the vena contracta area (VCA). The prognostic value of 3D-VCA in patients with secondary MR has not been investigated.

Purpose
The aim of the present study was to assess the association between 3D-VCA and prognosis of patients with SMR.

Methods
A total of 218 patients (69% men, median age 74 years) with significant SMR were retrospectively analyzed. 3D-VCA was measured offline with dedicated software, from restored 3D color Doppler full volume datasets of the mitral valve (Figure 1). The population was divided according to the American College of Cardiology expert recommendation for the grading of severe MR (VCA ≥50 mm2 and VCA &lt;50 mm2). Patients were followed up for the combined end point of all-cause mortality or heart failure hospitalization.

Results
Of the total population, 63% had an ischemic etiology, 60% had atrial fibrillation and 25% cardiac resynchronization therapy. Patients with 3D-VCA ≥50 mm2 needed more diuretic therapy, had a larger left ventricle and atrium, and had more post-procedural residual MR. A total of 82% of patients underwent MitraClip device implantation, 17% had mitral valve repair and 1% had mitral valve replacement. During a median follow-up of 28 months, 130 (60%) met the combined end point (101 (46%) patients died and 81 (37%) were hospitalized due to heart failure). When dividing the population according to the cut-off of 3D-VCA, patients with a 3D-VCA≥50 mm2 had a worse prognosis compared with their counterparts (Figure 2). In a multivariable Cox regression analysis, 3D-VCA≥50 mm2 remained independently associated with the composite endpoint of all-cause mortality or heart failure hospitalization (HR=1.454, 95% CI 1.020–2.072, p=0.038).

Conclusion
In patients with SMR, a 3D-VCA ≥50 mm2 was independently associated with a combined endpoint of death or heart failure hospitalization.

Funding Acknowledgement
Type of funding sources: None. Figure 1. Method of 3D-VCA measurementFigure 2. Kaplan-Meier survival curve
Use of left ventricular support devices during transcatheter aortic valve replacement and balloon aortic valvuloplasty: a single center experience
Authors: Mahmood S , Gelovani D , Nona P , Lemor A , Basir M , Frisoli T , Lee J , Wang D , O'Neill B , Eng M , O'Neill W , Villablanca P 
Published: October 2021

Abstract

Background
Transcatheter aortic valve replacement (TAVR) and balloon aortic valvuloplasty (BAV) are definitive and bridging therapies in patients with aortic stenosis. Data on utilization of mechanical circulatory support (MCS) in this population is scarce. This study sought to evaluate the clinical outcomes of the use of Impella (Abiomed, Danvers, MA) in patients undergoing TAVR or BAV at a tertiary-care center.

Methods
We reviewed all TAVRs and BAVs that required Impella from 2012 and 2020. Patient demographics, procedural outcomes, complications, and 30-day mortality were analyzed.

Results
A total of 1,965 TAVR and 715 BAV cases were performed in the study period. 30 TAVR and 94 BAV cases required an Impella. 65% of these cases were due to cardiogenic shock (CS) (100% of TAVR and 55% of BAV). 31% were performed in female patients. Transfemoral access was utilized in 98% of cases. Impella CP was used in 98% of cases, other types of MCS were used in 8.7% of cases. 32.2% of cases required MCS for more than 24 hours. In the TAVR population the indication for MCS was 46.6% profound hypotension post valve deployment requiring vasopressors, 16.6% cardiac arrest, 10% sustained ventricular arrhythmia, 10% cardiac tamponade [Office1] and 10% coronary occlusion. In the BAV group the indication was 44% high-risk PCI and 56% CS. The 30-day mortality in TAVR was 40% and 28% in BAV; from the BAV group in CS the mortality was 45%. VARC-2 vascular complications and bleeding complications were observed in 4.8% and 1.5%, respectively. 0.7% of the total cohort required conversion to open-heart surgery.

Conclusions
Impella support is required in a minority of TAVR or BAV cases. In those who require MCS with Impella for either BAV or TAVR, the total mortality remains high especially in those experiencing CS.

Funding Acknowledgement
Type of funding sources: None.
Primary hemostatic disorders drive early and late major bleedings of patients with atrial fibrillation after transcatheter aortic valve replacement
Authors: Matsushita K , Marchandot B , Hess S , Kibler M , Sato C , Heger J , Truong D P , Trimaille A , Sattler L , Grunebaum L , Reydel A , Jesel L , Ohlmann P , Morel O 
Published: October 2021

Abstract

Introduction
Patients with atrial fibrillation (AF) are likely to have multiple co-morbidities and receive anticoagulants after TAVR, which lead to a poor prognosis including bleeding events. Closure time adenosine diphosphate (CT-ADP) is a primary hemostasis point-of-care test used as a surrogate marker of high molecular weight (HMW) multimers defect of Von Willebrand factor (VWF). Our prior studies suggest that prolongation of CT-ADP (&gt;180 seconds) after TAVR is a major determinant of early and late major/life-threatening bleeding complications (MLBCs).

Purpose
To evaluate the impact of post-procedural CT-ADP &gt;180sec on bleeding events in AF patients.

Methods
We included 878 patients from our prospective TAVR registry between 2010 and 2019. Bleeding complications were assessed according to the VARC-2 (Valve Academic Research Consortium-2) criteria. Major adverse cardiac and cerebrovascular events (MACCE) was defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization within 1-year after TAVR. Ongoing primary haemostasis disorder was defined by post-procedure CT-ADP &gt;180sec. Primary endpoint was the occurrence of MLBCs during the first year and the second endpoint was 1-year MACCE.

Results
Patients with AF had a higher incidence of all-cause mortality (15% vs. 8%, p=0.002), MACCE (29% vs. 20%, p=0.002), and MLBCs (20% vs. 12%, p=0.001) within 1-year compared to non-AF patients. When the cohort was split into 4 subgroups according to AF and CT-ADP &gt;180sec, patients with AF and CT-ADP &gt;180sec had the highest risk of MLBCs (log-rank test; p&lt;0.001) (Figure). Multivariate Cox regression analysis confirmed that the patients with AF and CT-ADP &gt;180sec had 4.6-fold higher risk of MLBCs within 1 year compared to non-AF patients with CT-ADP ≤180sec (hazard ratio: 4.60; 95% confidence interval: 2.18 - 9.68; p&lt;0.001).

Conclusion
Among TAVR patients, AF with post-procedural CT-ADP &gt;180 sec was identified as a strong independent predictor of MLBCs at 1-year follow-up. Our study suggest that persistent primary haemostasis disorders contribute to a higher risk of bleeding events particularly in AF patients and may be considered for a tailored and risk-adjusted antithrombotic therapy after TAVR.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Dr Matsushita received a grant from Edwards Lifesciences.
How to distinguish between hypertrophic cardiomyopathy and left ventricular hypertrophy secondary to Fabry disease?
Authors: Menezes Fernandes R , Azevedo O , Cordeiro F , Lourenco M R , Lourenco A 
Published: October 2021

Abstract

Introduction
Fabry disease (FD) commonly leads to left ventricular hypertrophy (LVH) that could mimic sarcomeric hypertrophic cardiomyopathy (HCM).

Purpose
To determine the differences in echocardiographic parameters between FD patients with LVH and HCM patients.

Methods
We conducted a prospective study encompassing FD patients followed in a Reference Center of Lysosomal Storage Disorders. All patients performed a complete echocardiographic evaluation, including left ventricular strain analysis by two-dimensional speckle tracking imaging. Demographic, clinical characteristics and echocardiographic parameters were analysed. FD patients with LVH were compared with HCM patients, using Chi-square test for categorical variables and Student's T-test for continuous variables. The significance level was 0,05.

Results
A total of 91 FD patients were included, with a median age of 51 years-old and 62,6% of female predominance. 16,5% of patients were under enzymatic replacement therapy with agalsidase alpha and 7,7% were treated with chaperone therapy (migalastat). 33 FD patients (36%) had LVH and were older than HCM patients (63,6 vs 59,3 years-old; p=0,106). FD patients with LVH had lower interventricular septum (IVS) thickness (16,4 vs 19,6 mm, p&lt;0,001), IVS/posterior wall ratio (1,3 vs 1,8, p&lt;0,001), and left atrial volume index (34,45 vs 42,2 ml/m2; p=0,014). Left ventricle mass index was similar between the two groups (157,7 vs 155,5 g/m2; p=0,819), with lower left ventricular ejection fraction in FD patients (64,5% vs 70,5%; p&lt;0,001). There were no significant differences in global longitudinal strain (−15,6% vs 15,9%; p=0,687), global circumferential strain (−19,9% vs −21,1%; p=0,218) and global radial strain (35,3% vs 33,7%; p=0,623). Interestingly, FD patients had lower base-to-apex circumferential strain gradient (5,7% vs 9,1%; p=0,002) and lower twist (17,5° vs 26,1°; p=0,001) than HCM patients. No significant differences were reported regarding mechanical dispersion (72,4 vs 71,2 ms; p=0,841).

Conclusion
The pattern of LVH is different between FD and HCM patients. In our study, we revealed that base-to-apex circumferential strain gradient and twist are echocardiographic parameters that could help distinguish both entities.

Funding Acknowledgement
Type of funding sources: None.
Development of a risk-score for pericarditis recurrence in patients with a first episode of acute pericarditis
Authors: Lazarou E , Lazaros G , Antonopoulos A S , Imazio M , Vasileiou P , Karavidas A , Toutouzas K , Vassilopoulos D , Tsioufis C , Tousoulis D , Vlachopoulos C 
Published: October 2021

Abstract

Background/Introduction
Currently we remain uncertain about which patients are at increased risk for recurrent pericarditis.

Purpose
We developed a risk score for pericarditis recurrence in patients with acute pericarditis.

Methods
We prospectively recruited 262 patients with acute pericarditis. Patients' demographics, clinical, imaging and laboratory data at presentation, were collected. Patients were followed-up for a median of 51 months (interquartile range 21–71) for recurrence. Variables with &lt;10% missingness were entered into multivariable logistic regression models with stepwise elimination to explore independent predictors of recurrence. The performance of the final model was assessed by the c-index and model's calibration and the optimism corrected c-index were evaluated after 10-fold cross-validation.

Results
We identified six independent predictors for pericarditis recurrence i.e., age, effusion size, platelet count (negative predictors) and reduced inferior vena cava collapse, in-hospital use of corticosteroids, and heart rate (positive predictors). The final model had good performance for recurrence, c-index 0.783 (95% CI 0.725–0.842), while the optimism corrected c-index after cross-validation was 0.752. Based on these variables we developed a risk score point system for recurrence (0–22 points) with equally good performance (c-index 0.740, 95% CI 0.677–0.803). Patients with a low score (0–7 points) had 21.3% risk for recurrence, while those with high score (≥12 points) had a 69.8% risk for recurrence (Figure 1). The score was predictive of recurrence among most patient subgroups.

Conclusions
A simple risk score point system based on 6 variables can be used to predict the individualized risk for pericarditis recurrence among patients with a first episode of acute pericarditis.

Funding Acknowledgement
Type of funding sources: None. Figure 1