bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel handheld ultrasound device equipped with spectral doppler- efficacy of left ventricle diastolic function parameters assessment
Authors: Filipiak D , Kasprzak J D , Lipiec P
Published: January 2025

Background

Echocardiographic assessment of left ventricular (LV) diastolic function is an essential part of the routine evaluation of patients presenting with dyspnea or impaired effort tolerance. Diagnostic algorithm of diastolic dysfunction involves pulsed and continuous wave Doppler measurements, which were not within the range of capabilities of previous generations of handheld ultrasound devices (HUD). However, implementing new modalities into HUD expanded the area in which they may thrive.

Aim

To verify and validate the reliability of diastolic function parameters acquired during the HUD echocardiographic examination

Methods

Study population consisted of the consecutive 100 pts admitted to Cardiology Emergency Room due to the dyspnea and/or impaired effort tolerance. All patients underwent brief bedside echocardiographic screening with HUD which involved the assessment of mitral inflow velocities- early (E) and late (A), septal and lateral mitral annular peak early diastolic velocity (e')- measured with the pulsed wave Doppler modality, E/E’ ratio, E/A ratio, and tricuspid regurgitation velocity (measured with the continuous wave Doppler modality). Within the next 24 hours all patients underwent full echocardiographic examination performed with the use of stationary ultrasonographic station, which results were treated as reference.

Results

Septal E’ did not exceed 7cm/s in 22 patients, lateral E’ was lower than 10cm/s in 24 patients. Correlation between the measurements from HUD and full echocardiography was 0,84 for septal E’ and 0,44 for lateral E’; for both parameters agreement for detection of incorrect, lowered values between methods was high (Kappa coefficient 0,751 i 0,8 respectively). E/E’ was significantly increased in 6 patients, which was detected with high agreement in HUD examination (Kappa coefficient 0,73). Correlation coefficient for E/A parameter was 0,77 and agreement categorized for each group (E/A≤0,8; E/A >0,8 & <2; E/A ≥2 ) was high (kappa coefficient 0,75; 0,74; 1,0 respectively); it is worth noting that all cases with E/A ≥2 were identified in HUD examination. TR velocity exceeded 2,8 m/s in 11pts, in this aspect the agreement between HUD and full examination was 0,65. However the positive predictive value of this parameter was 100%.

Conclusion

HUD equipped with a spectral doppler modality enables for reliable echocardiographic screening of LV diastolic function. Introducing the elements of imaging diagnostics to the initial assessment might markedly hasten the establishing of the final diagnosis.

E/A ratio- HUD & full echocardiography

HUD/fullECHO derived values correlation
Diastolic function in patients with preserved left ventricle ejection fraction: prognostic value and added role of left atrial strain
Authors: Rodriguez-Sanchez I , Onaindia J J , Cacicedo A , Ullate A , Urkullu A , Bravo I , Florido J , Sanz I , Villanueva I , Aguirre U , Salcedo A , Velasco Del Castillo S
Published: January 2025

Background

Few studies have evaluated the prognostic value of diastolic function in patients with preserved left ventricular ejection fraction (LVEF) according to the 2016 ASE/EACVI guidelines, regardless of the specific type of heart disease. Our aim was to evaluate the ability of diastolic function to predict a composite event of heart failure (HF), atrial fibrillation (AF) or ischemic stroke and to determine the added value of left atrial reservoir strain (LARS).

Methods

We performed a retrospective analysis of 364 patients with preserved LVEF and sinus rhythm referred for transthoracic echocardiography and categorized them into four groups based on their diastolic function status according to the 2016 ASE/EACVI guidelines: normal diastolic function (NDF), indeterminate diastolic function and diastolic dysfunction with indeterminate filling pressure (IDT), grade 1 diastolic dysfunction (DD1), and diastolic dysfunction with elevated filling pressure (DD-EFP). The primary endpoint was a composite of AF, HF or ischemic stroke. LARS was measured by 2D speckle tracking. Clinical parameters and specific cardiac diseases were also assessed.

Results

After a mean follow-up of 2.4 years, diastolic function was an independent predictor of events, with patients with DD-EFP having the highest risk (HR 12.73 (95% CI, 1.50-108.17), P=0.02). The addition of LARS improved risk stratification, especially in IDT patients, with a cut-off of ≤24% identifying a high-risk population. Patients at high risk, defined as those with DD-EFP and IDT with LARS ≤24%, had a high event rate of 34% and 46%, respectively.

Conclusions

In patients with preserved LVEF and sinus rhythm, patients classified with DD-EFP have the highest risk for the composite event. LARS improves risk stratification and also identifies IDT patients with LARS≤24% as a high-risk population. High-risk patients (DD-EFP and IDT with LARS ≤24%) had a high event rate (34% and 46%, respectively). Future studies are needed to further confirm these findings.

Survival according to diastolic function

Survival (diastolic f and LARS combined)
Sex-related differences in cardiac damage associated with severe primary mitral regurgitation: impact on surgical outcomes
Authors: O'neill P , Barriales L , Islas F , Parraga R , Gutierrez E , Carnero M , Rivadeneira M , Perez-Camargo D , Mahia P , Montero L , Campelos P , Gil-Abizanda S , De Agustin J A , Olmos C
Published: January 2025

Background and Aim

Previous research has shown that women with primary mitral regurgitation (MPR) have worse surgical outcomes, compared with men.

Our aim was to evaluate whether cardiac damage prior to intervention for severe MPR differs according to gender.

Methods

Retrospective analysis of a prospective cohort of patients with PMR who underwent mitral valve surgery in a tertiary care center from 2014 to 2022.

Echocardiographic parameters measured prior to surgery as well as outcomes at 1-year follow-up (all-cause mortality and heart failure admissions) were analyzed, and potential differences by sex were evaluated.

Results

349 patients were included. The mean age was 69 (12) years and 154 (44%) were female.

Women were older and had a history of atrial fibrillation more frequently than men. Regardind morphological echocardiographic parameters, left ventricular (LV) dimensions were slightly larger in male patients, as expected, and there were no significant differences in left atrial (LA) volume index (Table).

Significant differences were found in functional echocardiographic parameters: women had more impaired LV and LA strain, higher values of LA stiffness, and worse right ventricular-arterial coupling. In addition, concomitant significant tricuspid regurgitation was significantly more frequent in female patients.

At one-year follow-up, the incidence of heart failure hospitalization was significantly higher in women (1% vs 7%; p=0.005) and there was a non-significant trend towards higher all-cause mortality (6.2 vs 11%; p=0.101).

Conclusions

In our cohort of patients with severe PMR who underwent surgery, women had worse biventricular function and more impaired LA function. At one-year follow-up, heart failure hospitalizations rates were significantly higher in female patients.

Earlier indication of surgical timing in women with PMR, taking into account deformation parameters, could improve surgical outcomes in this population.

Clinical and echocardiographic features
Correlation of pulmonary artery systolic pressures derived from echocardiography and hemodynamic catheterization in patients with tricuspid regurgitation: a large single-center study
Authors: Pugliesi G M , Pislaru S , Kane G C , Miranda W R , Frantz R P , Anand V
Published: January 2025

Introduction

Echocardiography is the recommended modality for non-invasive assessment of pulmonary pressures. However, in patients with severe tricuspid regurgitation (TR), the reliability of echocardiographically derived systolic pulmonary artery pressure (sPAP) is questioned. Limited data exists on the correlation between echocardiography and right heart catheterization (RHC) in selected group of patients with severe TR.

Purpose

To evaluate the correlation between echocardiographic and RHC measurements for sPAP in patients with varying TR severity.

Method

Patients who underwent echocardiography and RHC within three days at a large single referral center were retrospectively included. Exclusion criteria included incomplete echocardiographic and RHC data, ≥moderate pulmonary stenosis, low-quality images, and pregnancy. Echocardiographic sPAP was calculated using simplified Bernoulli equation. Echocardiographic right atrial pressure (RAP) was assessed by evaluating inferior vena cava (IVC) dimension and collapsibility. A difference of ≥10 mmHg between the two modalities for sPAP was considered clinically significant.

Results

Of 3696 patients included, mean age was 64±14 years, 1689 (46%) were females, 1659 (45%) had systemic hypertension, and 582 (16%) had atrial fibrillation. TR was <moderate in 2475 (67%) patients, moderate in 499 (14%), moderate-severe in 277 (7%), and severe in 445 (12%). Pulmonary hypertension (PH) was diagnosed in 3079 subjects (83%). A good correlation was found between sPAP derived by echocardiographic and RHC in the whole cohort (correlation coefficient (LCC) 0.79, CI 0.78-0.80), in severe TR subgroup (LCC 0.78, CI 0.75-0.82), and in severe TR with PH subgroup (LCC 0.76, CI 0.71-0.79). The mean echocardiographic misestimation for sPAP in severe TR was 3.97 mmHg (CI -5.24 to -2.71). The correlation between the two modalities for RAP was moderate in the whole cohort (LCC 0.59, CI 0.57-0.61) and fair in severe TR (LCC 0.35, CI 0.27-0.42). A clinically significant difference between the two modalities for sPAP was found in 1504 patients (41%), predominantly due to the right ventricle-right atrium gradient misestimation, rather than RAP misestimation, in patients with no PH (67% vs 33%), patients with mild-moderate PH (mean Pulmonary Artery Pressure (mPAP) 21-34 mmHg) (67% vs 33%) and severe PH (mPAP ≥35 mmHg) (76% vs 24%).

Conclusion

The correlation between echocardiographic and RHC measurements is good for sPAP, even in severe TR patients, while it is only fair to moderate for RAP. A clinically significant difference between echocardiographic and RHC sPAP is more commonly observed in patients with PH, with right ventricle-right atrium gradient misestimation being the most common cause.
Echocardiographic predictors of left ventricular interstitial fibrosis in chronic primary mitral regurgitation with preserved ejection fraction: the underrecognized role of diastolic dysfunction
Authors: Pype L L , Van Laer S L , Paelinck B P , Sturkenboom N , Van Craenenbroeck E M , Van De Heyning C M
Published: January 2025

Background

Myocardial fibrosis is a well-known risk factor for morbidity and mortality in patients with chronic primary mitral regurgitation (MR). Extracellular volume (ECV), a marker of interstitial fibrosis assessed with cardiovascular magnetic resonance imaging (CMR), was correlated with echocardiographic markers of left ventricular (LV) systolic and diastolic dysfunction in a previous study cohort of patients with severe primary MR. In addition, diastolic dysfunction has recently been recognized as a distinct phenotype in patients with primary MR associated with similar prognosis compared to patients with systolic dysfunction.

Purpose

To investigate whether echocardiographic parameters of subclinical LV systolic function, diastolic dysfunction or MR severity are correlated with interstitial fibrosis in chronic primary MR patients with a preserved ejection fraction (EF).

Methods

Prospective inclusion of patients with chronic primary MR and a LVEF>50%. All patients underwent transthoracic echocardiography and CMR scan (1.5T). Echocardiographic assessment of LV systolic and diastolic function was performed, including global longitudinal strain (GLS). MR severity was assessed using a multi-integrative approach. Extracellular volume (ECV) was calculated from the native and post-contrast T1 times.

Results

A total of 50 patients with primary MR were included (58% males, age 56 ± 16 years old). CMR and transthoracic echocardiography were performed within 30 ± 65 days. MR severity was variable with 20% mild, 32% moderate, 12% moderate-severe and 36% severe MR. Mean LVEF and GLS were within normal range (59.1% ± 5.3% and –19.8% ± 2.9% respectively). Mean ECV was 27.8% ± 2.5%. ECV did not show a significant correlation with MR severity grade or markers of LV systolic function like LVEF (Rho=-0.121, p=0.42) or GLS (Rho=0.089, p=0.59). However, we did observe a statistically significant correlation between ECV and markers of LV diastolic dysfunction such as mean E/e’ (Rho=0.291, p=0.050) and deceleration time (Rho=-0.308, p=0.037). Even in patients with non-severe MR (grade 1 to 3), the correlation between ECV and E/e’ remained significant (Rho=0.438, p=0.017). In a multivariate regression analysis E/e’ and MR grade were associated with ECV, even after correction for age and gender (R squared 0.248, p=0.017 and p=0.044 respectively).

Conclusion

In patients with chronic primary MR and a preserved LVEF, the presence of interstitial fibrosis, measured as ECV, was associated with echocardiographic parameters of diastolic rather than systolic dysfunction, independent of MR severity. These findings suggest that diastolic dysfunction can be a subclinical marker of myocardial fibrosis (and subsequently adverse outcomes) in patients with primary MR.

Correlation ECV and E/e'
Left atrial assessment improves prediction of incident atrial fibrillation beyond CHARGE-AF risk score
Authors: Hasegawa R , Fujiwara N , Kato Y , Suzuki S , Oikawa Y , Uejima T
Published: January 2025

Background

Atrial fibrillation (AF) is associated with substantial mortality and morbidity, even when it is asymptomatic and/or remains undetected. Clinical predictive models such as Charge-AF are not robust enough to be used in the clinical practice. We investigated the benefits of adding echocardiographic risk variables to Charge-AF risk model for its potential use in targeted screening for AF.

Methods

This study included 1108 consecutive patients aged 60±14 years old without a previous diagnosis of AF referred for echocardiographic assessment. Left atrial and ventricular functions were measured using strain analysis. Five-year predicted risk for AF was estimated, using Charge-AF risk model. The incidence of AF was ascertained from resting and exercise stress electrocardiograms and Holter recordings. Sequential Cox models were used to identify echocardiographic variables for predicting the incidence of new onset AF.

Results

The overall incident rate of AF was 3.1%, 5.5% and 7.2% at 1 year, 3 year and 5 year, respectively. Left atrial volume index (LAVi) predicted the incidence with a hazard ratio of 1.06 (p<0.001), that was independent of and increment to Charge-AF risk estimates (figure A). The addition of E/e’ (hazard ratio=1.064, p=0.001), left atrial reservoir strain (hazard ratio=0.98, p=0.034), left atrial booster strain (hazard ratio=0.97, p=0.048) to the baseline model including Charge-AF risk estimates also showed a significant, but less incremental benefit for AF prediction, compared with LAVi. When all these echocardiographic variables were added to a stepwise nested Cox model, only LAVi was significantly and independently predictive of AF incidence beyond Charge-AF risk estimates. This finding was confirmed by Kaplan-Meier curves showing that an increase in LAVi was progressively associated with increased risk for AF (figure B). When the cumulative AF incidence was analyzed separately between patients with higher (predicted risk >= 1.5%/year) and lower (predicted risk < 1.5%/year) Charge-AF risk estimates, LAVi was able to sub-stratify only patients with higher Charge-AF risk estimate (figures C and D).

Conclusion

LAVi provided incremental value in predicting incident AF in hospital patients. The inclusion of LAVi to the diagnostic algorithm may help guide screening and further monitoring for AF risk in this population.
Assessment of cardiac reverse remodeling in patients with LV systolic dysfunction receiving vericiguat in addition to optimal GDMT
Authors: Lara Delgado G D , Carrillo Aleman L , Guillamon Sanchez A , Martinez-Perez V , Yepez Naranjo F , Palacio Solis M , Leon Allocca R , Solano Hernandez C , Sanchez Fernandez M J , Cano Alvarez S , Centurion Inda E R
Published: January 2025

Background and Objective

Vericiguat is a soluble guanylate cyclase stimulator which has demonstrated significant clinical and survival benefits in patient with heart failure and reduced ejection fraction (HFrEF) following acute decompensation. We present data on cardiac reverse remodeling assessed by echocardiography in ‘real-world’ patients receiving this therapy in addition to optimal guideline-directed medical therapy (GDM) for at least 6 months prior to initiation.

Material and method

Patients with a clinical indication for Vericiguat therapy were retrospectively analysed from a local registry between December 2022 and September 2023. A comprehensive echocardiography evaluation was performed at baseline (i.e. prior to initiation of this medication), and at 3 months after Vericiguat treatment.

Results

A total of 44 patients were included in this observational study, of which 32 patients were men (77.3%), and 10 patients were women (22.7%). With regards to baseline comorbidities, 17 patients had arterial hypertension, 12 patients had type-2 diabetes mellitus, 21 patients had hypercholesterolaemia, and 6 patients were newly diagnosed with HFrEF. The aetiology of HFrEF was ischaemic in 25 patients, and non-ischaemic in 19 patients. A total of 40 patients were on ARNI therapy prior to initiation of Vericiguat, 40 patients were on beta-blockers, 39 patients were on MRAs, 44 patients were on SGLT2-inhibitors, 18 patients were of loop diuretics, 15 patients had an ICD in situ, and 6 patients had a CRT device implanted. The mean initial LVEF was 31%, with a mean initial end-diastolic volume (EDV) of 178 mL. At 3-month follow-up, the mean LVEF was 39%, which represents an improvement of 9 percentage points; the mean EDV at 3-month follow-up was reduced up to 157 mL.

Conclusions

Vericiguat therapy may exhibit additional anti-remodelling benefits in patients with HFrEF when in combination with optimal GDMT in ‘real-world’ populations. Large randomized and prospective trials are needed to explore this hypothesis.
Echocardiographic estimate of pulmonary capillary wedge pressure improves outcome prediction in chronic heart failure
Authors: Bazan L , Gentile F , Sciarrone P , Buoncristiani F , Panichella G , Gasparini S , Fabiani I , Petersen C , Lio G E , Lancellotti P , Passino C , Emdin M , Chubuchny V , Giannoni A
Published: January 2025

Background

An echocardiographic algorithm to estimate pulmonary capillary wedge pressure (ePCWP) and pulmonary vascular resistance (ePVR) has been recently validated versus right heart catheterization (1).

Purpose

The aim of this study was to assess the prognostic significance of these measures in heart failure (HF) patients.

Methods

Consecutive outpatients with HF and left ventricular ejection fraction (LVEF) <50% undergoing echocardiography were selected and followed-up for the composite endpoint of cardiac death or HF hospitalization.

Results

Out of 2,214 patients (71±12 years, 76% males, LVEF 35±9%), ePCWP (16±6 mmHg) was elevated (>15 mmHg) in 52% of cases and ePVR (1.7±0.7 WU) was elevated (>2 WU) in 25% of cases. Patients with increased ePCWP were older, had a higher NYHA class, more pronounced cardiac remodeling, systo/diastolic dysfunction, and neurohormonal activation, particularly when ePVR was also elevated (p<0.001). Over a median follow-up of 33 (17-48) months, both measures stratified patients for the risk of the primary endpoint (Log-Rank 152 for PCWP, and 44 for ePVR, p<0.001). At adjusted regression analysis, ePCWP (hazard ratio for 1 mmHg increase 1.03 [95%CI 1-01-1-05], p<0.001) but not ePVR (p=0.584) predicted the primary endpoint, even in the subpopulation of patients with atrial fibrillation (p=0.003). ePCWP outperformed current diastolic dysfunction grading (Δ C-statistics 0.068 [95% CI 0.045-0.093], p<0.001), and stratified patients’ risk across each diastolic dysfunction grade at univariate analysis (Grade I: p=0.002; Grade II-III: p<0.001; Indeterminate cases: p=0.010). The addition of ePCWP to a multivariable prognostic model, including patients’ age, NYHA class III-IV, chronic obstructive pulmonary disease, estimated glomerular filtration rate, NT-proBNP, and LVEF, improved the accuracy of risk prediction (Δ C-statistics 0.008 [95% CI 0.002-0.014], p=0.007).

Conclusion

The echocardiographic estimates of PCWP retained clinical and prognostic significance in a large contemporary cohort of patients with chronic HF and LVEF <50%. This algorithm could facilitate early identification of high-risk patients, possibly reducing the need of right heart catheterisation, and allowing a tailored therapeutic approach.

Graphical abstract

KM curves for the primary endpoint - AF
Evolution of cardiovascular imaging surrogate endpoints in heart failure clinical trials: a systematic review
Authors: Vavere A , Lopez Juan V , Millegard M , Gustafsson K , Gunnarsson L , Roso Llorach A , Surkova E
Published: January 2025

Background

Cardiovascular imaging is commonly used for assessment of surrogate endpoints in early phase clinical trials in heart failure (HF). Treatment-induced change in left ventricular (LV) volumes and ejection fraction (EF) were validated against change in outcomes in a meta-analysis from 2011 [1]. However, cardiovascular imaging has evolved significantly since then with new modalities and endpoints introduced in interventional trials.

Purpose

To analyse temporal trends in implementation of cardiovascular imaging modalities and endpoints in HF trials in the last 15 years and identify endpoints with existing data on relationship between short-term change in imaging endpoint and long-term change in hard outcomes.

Methods

Firstly, we performed a systematic review of cardiovascular outcome trials (CVOTs) evaluating treatment effects on outcomes in HF. Secondly, we reviewed remodelling trials (RTs) evaluating effect of drugs identified in CVOTs search on imaging parameters.

Results

The CVOTs search yielded 64 records. Seventeen CVOTs evaluating effect of 10 different interventions on cardiovascular outcomes were considered eligible and included in the final analysis. The RTs search yielded 80 records, 34 publications were considered eligible (Fig.1).

Out of 34 RTs, 29 trials employed transthoracic echocardiography (Echo), 1– low dose Dobutamine stress-Echo, 5– cardiac magnetic resonance (CMR), 1– Dobutamine stress-CMR, 1– Phosphorus CMR spectroscopy, and 1– PET. With exception of one study, Echo was the only imaging modality used in selected RTs until 2020. Four studies utilised >1 imaging modality.

Data on relationship between therapy-induced changes in remodelling parameters and changes in clinical outcomes are mostly available for conventional markers of the LV and left atrium (LA) (LV EF, volumes, mass, E/e’, e’, LA volume), followed by LV global longitudinal strain. Data on how the therapy-induced changes in other novel endpoints (LV global circumferential strain, right ventricular function, or surrogates of myocardial fibrosis), can translate into change in clinical outcomes in HF has been investigated for single interventions only (Fig.2).

Conclusions

While Echo had been dominating the field in interventional HF trials, new imaging modalities and endpoints have been introduced in trials recently. Conventional parameters of LV remodelling and function remain the most validated regarding relationship between change in surrogate endpoint in response to treatment and change in clinical outcomes. More evidence on translatability of changes in imaging markers of LV and LA myocardial deformation, right ventricular function and myocardial tissue characterisation with clinical outcomes need to be generated in future trials.

Fig.1. PRISMA Flow chart diagram

Fig. 2. Imaging endpoints in HF trials
Diagnostic accuracy of echomics in patients with transthyretin-related cardiacamyloidosis
Authors: Mori S , Montobbio N , Sormani M P , Campi C , Vianello P F , Mandoli G E , Zanoletti M , Mazzoni C , Rella V , Crotti L , Cameli M , Cappelli F , Porto I , Badano L P , Canepa M
Published: January 2025

Background/Introduction

The diagnosis of transthyretin-related cardiac amyloidosis (ATTR-CA), while often suggested by red flags observed in echocardiography, still requires a lengthy and multi-step process. Recent evidence indicates the feasibility of using radiomics on echocardiographic images (i.e., echomics) for the early characterization of myocardial texture anomalies in ATTR-CA.

Aims

This study aims to develop a radiomic-based model for the diagnosis of transthyretin-related cardiac amyloidosis (ATTR-CA) by characterizing myocardial tissue through echocardiography (echomics).

Methods

We retrospectively collected echocardiographic images in parasternal long-axis and apical 4-chamber views from ATTR-CA and control patients at four Italian centers. The largest possible region-of-interest (ROI) within the interventricular septum was delineated. Ninety-four radiomic features were extracted, including 9 shape-related features and 85 texture features, 21 of which depend on ROI dimensions and 73 purely texture-based (ROI-independent). Five logistic regression models were used to analyse data from three centres (229 ATTR-CA, 224 controls). The models estimated the diagnostic accuracy and area-under-the-curve (AUC) of different sets of radiomic features. The developed five models were finally tested on a cohort of patients from the fourth centre (32 ATTR-CA and 32 age- and sex-matched control patients) for external validation.

Results

The models that included shape and all texture features, whether separately or in combination, demonstrated very high cross-validated accuracies (93-95%) and AUC values (0.97-0.99). However, when using a fixed-size 0.5x0.5 cm ROI, these values decreased to 85% and 0.91, respectively. This confirms that some measurement depends on ROI size. The chosen model used 73 ROI independent features on the largest ROI and demonstrated significantly better accuracy and AUC (92% and 0.97, respectively, p<0.001). These results were confirmed in the external validation cohort (87% and 0.95, respectively). Removing the least informative features resulted in a slight model improvement 90% accuracy and 0.95 precision when 40 out of 73 features were used.

Conclusions

This study demonstrates the potential of echomics (i.e., radiomics applied to echocardiography data) to distinguish between ATTR-CA and control patients by identifying disease-specific textural features that are independent of ROI dimensions.

Workflow

Results
Valve-sparing aortic root replacement for valves with paracommissural fenestrations: which valve will fail?
Authors: Kari Fabian A , Czerny Martin , Borger Michael , Misfeld Martin , Rylski Bartosz , Zimmer Emmanuel , Siepe Matthias , Hagl Christian , Detter Christian , Petersen Johannes , Richardt Doreen , Ensminger Stephan , Werner Paul , Andreas Martin , Peterss Sven , Pichlmaier Maximilian , Mueller Christoph S
Published: January 2025

OBJECTIVES

To define morphologic risk constellations during valve-sparing aortic root replacement (VSARR) for aortic valves with paracommissural fenestrations.

Patients and Methods

Patients from the multicentre prospective intention-to-treat VSARR- registry German Aortic Root Repair Registry (GEARR) were screened for paracommissural cusp fenestrations. We studied a combined end-point of residual aortic regurgitation (rAR) on post-CPB TEE, mid-term progress of rAR (TTE) and aortic valve replacement for AR.

RESULTS

Of a total of 762 registry patients (operated 2016–2024), 145 were identified with ≥1 paracommissural cusp fenestration. Eighteen patients (12%) were not treated as planned but underwent composite valved graft (CVG) implantation. Mean follow-up time was 3 years. Upon post-CPB TEE rAR grade 1 or 2 were present in 44 (33%) and 3 (2%) patients. 50% of patients with fenestrations in more than one cusp showed early progression of rAR. At three years, freedom from the combined end-point was 78% (99% CI 74–79%) for the complete study cohort. Patients with a maximum free margin length difference of < 5mm, reflecting balanced root anatomy with respect to sinus and cusp sizes, had a significantly better outcome than those with ≥5mm: at three years, freedom from the combined end-point was 86% (99% CI 80–91%) vs 41% (99% CI 38–46%, p = 0.011). Outcome was worst for patients with cusp prolapse and a free margin length difference of > 5mm (30% vs 70%, p = 0.018).

CONCLUSIONS

Fenestrations in more than one cusp, inhomogeneities of cusp free margin lengths, and additional prolapse are associated with inferior outcome after VSARR for valves with paracommissural fenestrations.
Sex-related differences in prosthesis-patient mismatch after surgical aortic valve replacement and long-term outcomes
Authors: Springhetti Paolo , Abdoun Kathia , Dumont Éric , Dagenais François , Kalavrouziotis Dimitri , Mohammadi Siamak , Pibarot Philippe , Clavel Marie-Annick
Published: January 2025

Background and Aims

Prosthesis-patient mismatch (PPM) is associated with dismal prognosis after aortic valve replacement (AVR). Sex differences in PPM outcomes remain poorly explored. Therefore, this study aims to evaluate sex-specific impact in PPM after surgical AVR.

Methods

Between 2000 and 2021, 7319 patients underwent surgical AVR at the Institut Universitaire de Cardiologie et de Pneumologie de Québec. Prosthesis-patient mismatch was defined by using the indexed effective orifice area (EOAi) and by applying the Valve Academic Research Consortium-3 (VARC-3) criteria. The cohort was followed up prospectively from surgical AVR until November 2023. The primary endpoint was defined as long-term mortality and the secondary endpoint as long-term cardiovascular (CV) and perioperative mortality. Mortality was established and CV mortality was adjudicated by Quebec national database.

Results

Any-degree PPM resulted more prevalent in women than in men (31.9% vs. 19.7%, P < .0001) with rare incidence of severe PPM (2.4% vs. 0.6%, P < .0001) according to VARC-3 definition. Over a median follow-up of 12.6 years, there were 3231 (44.1%) all-cause deaths, with 1238 (16.9%) from CV causes. Prosthesis-patient mismatch was associated with all-cause mortality (hazard ratio 1.30, 95% CI 1.20–1.40; P < .0001) and CV mortality (hazard ratio 1.39, 95% CI 1.23–1.57; P < .0001) in the whole cohort without interaction between sexes (P ≥ .74). After comprehensive multivariable adjustment, VARC-3 PPM remained independently associated with outcome only in women (P ≤ .04). Adapting PPM definition according to spline-derived EOAi thresholds disaggregated by sex, PPM was independently associated with outcome in both sexes (P ≤ .04).

Conclusions

Sex-specific EOAi thresholds associated with outcomes emerged in this large regional study. This finding suggests that PPM definition in men may follow higher EOAi thresholds than in women.
The Application of Mechanical Circulatory Support in Special Conditions
Authors: Scandroglio Anna Mara , Baldetti Luca , Oezkur Mehmet , Mahajna Ahmad , Pieri Marina , Kowalewski Mariusz , Pilarczyk Kevin , Lorusso Roberto
Published: January 2025

Special conditions, though not typically associated with cardiovascular distress, may be considered for treatment with temporary mechanical circulatory support (tMCS) devices. Such non-classical examples of cardiovascular compromise include trauma, sepsis, and peripartum cardiomyopathy, among others, and may require urgent treatment with a tMCS device for hemodynamic stabilization and tentatively saving the patient’s life. In this section, examples of the use of tMCS in several special circumstances is presented to garner awareness for such conditions, which have previously been overlooked or even considered contraindications, and highlight the benefit of tMCS devices during treatment of these patients and the need for more research into these circumstances.
Abuse of Relative Dominance by Digital Platforms: A Law and Economics Perspective
Authors: Li Qian , Cauffman Caroline
Published: January 2025

In the age of AI, digital platforms are likely to hold significant market power, giving them a superior bargaining position over their business partners and enabling them to impose unfair trading terms. However, proving that a platform holds a dominant position under Art. 102 of the Treaty on the Functioning of the European Union (TFEU) is challenging. The multi-sided nature of platforms complicates the definition of the relevant market, and their innovative digital business models makes it difficult to assess lasting market power. This could lead to false negatives, resulting in under-enforcement from an economic perspective. To address this market reality, the Digital Markets Act (DMA) has been adopted as an ex ante instrument to, inter alia, complement competition law enforcement. However, since the DMA’s quantitative thresholds remain high, numerous platforms with superior market power vis-à-vis their trading partners may not qualify as ‘gatekeepers’, leaving the risk of under-enforcement unresolved. This article explores the desirability of introducing a prohibition on ‘abuse of relative dominance’, drawing on this long-standing concept in some EU Member States. Such a measure could help tackle the concerns arising from the superior bargaining position of digital platforms.
Human TSC2 mutant cells exhibit aberrations in early neurodevelopment accompanied by changes in the DNA Methylome
Authors: Chalkley Mary-Bronwen L , Guerin Lindsey N , Iyer Tenhir , Mallahan Samantha , Nelson Sydney , Sahin Mustafa , Hodges Emily , Ess Kevin C , Ihrie Rebecca A
Published: January 2025

Tuberous Sclerosis Complex (TSC) is a debilitating developmental disorder characterized by a variety of clinical manifestations. While benign tumors in the heart, lungs, kidney, and brain are all hallmarks of the disease, the most severe symptoms of TSC are often neurological, including seizures, autism, psychiatric disorders, and intellectual disabilities. TSC is caused by loss of function mutations in the TSC1 or TSC2 genes and consequent dysregulation of signaling via mechanistic Target of Rapamycin Complex 1 (mTORC1). While TSC neurological phenotypes are well-documented, it is not yet known how early in neural development TSC1/2-mutant cells diverge from the typical developmental trajectory. Another outstanding question is the contribution of homozygous-mutant cells to disease phenotypes and whether phenotypes are also present in the heterozygous-mutant populations that comprise the vast majority of cells in patients. Using TSC patient-derived isogenic induced pluripotent stem cells (iPSCs) with defined genetic changes, we observed aberrant early neurodevelopment in vitro, including misexpression of key proteins associated with lineage commitment and premature electrical activity. These alterations in differentiation were coincident with hundreds of differentially methylated DNA regions, including loci associated with key genes in neurodevelopment. Collectively, these data suggest that mutation or loss of TSC2 affects gene regulation and expression at earlier timepoints than previously appreciated, with implications for whether and how prenatal treatment should be pursued.
BMP4-GPX4 can improve the ferroptosis phenotype of retinal ganglion cells and enhance their differentiation ability after retinal stem cell transplantation in glaucoma with high intraocular pressure
Authors: Fang Chuankai , He Di , Qian Yafen , Shen Xiaomei
Published: January 2025

Activation of bone morphogenetic protein (BMP) 4 signaling promotes the survival of retinal ganglion cell (RGC) after acute injury. In this study, we investigated the role of the BMP4 signaling pathway in regulating the degeneration of retinal ganglion cells (RGCs) in a mouse glaucoma model and its potential application in retinal stem cell. Our results demonstrate that BMP4-GPX4 not only reduces oxidative stress and iron accumulation but also promotes neuroprotective factors that support the survival of transplanted RSCs into the host retina. These findings suggest a novel therapeutic approach for glaucoma involving the modulation of the BMP4-GPX4 pathway to protect RGCs and improve visual function through enhanced RSC differentiation.
The Impact of Light Availability on the Functional Traits of Quercus Robur L. and Acer Platanoides L. First-Year Seedlings by Direct and Indirect Methods
Authors: Blinkova Olena , Żytkowiak Roma , Jagodziński Andrzej M
Published: January 2025

The resource strategy of seedlings is an important aspect for understanding the adaptation of trees at this ontogenetic phase to abiotic changes. In this study, we sought to determine the patterns of response of functional traits of a shade-tolerant (A. platanoides) and a shade-intolerant (Q. robur) species along natural environmental light gradients. We conducted trait-based analyses at both individual and community levels using direct (leaf area index, LAI; diffuse non-interceptance, DIFN) and indirect (Ellenberg-indicator values, LC) methods in the Arboretum at Kórnik (Poland). Differences between the two species were found for some variables. Analysis of phenotypic plasticity indices of leaf, stem and root traits of seedlings had high values for both species. The values of plasticity indices of A. platanoides root traits were lower compared to the corresponding traits for Q. robur. Relationships between measures obtained from individual-level trait data were stronger than relationships with measures obtained from community-level trait data. The data obtained from the direct method, which included light measurements both at the community level (experimental plots) and at the individual level (seedlings), revealed the closest relationships between functional traits of seedlings and light changes at the individual level trait data for both species. Correlation links between LAI and leaf (leaf mass per area; specific leaf area) and stem (specific stem length; stem mass fraction) traits were less tight for Q. robur compared to A. platanoides. The indirect Ellenberg-indicator analysis revealed relationships between LC and leaf mass per area, and stem-to-root ratio of seedlings based on community-level trait data. Close relationships between LC and leaf mass fraction, and specific leaf area were not established, in contrast to LAI and DIFN. The closest relationships, representing among traits within the same organ system, and links, describing interactions between traits of different organ systems, were established at the community-level trait data.
Bayesian assessment of profitability for products with highly uncertain demand based on multiple samples
Authors: Su Rung-Hung , Yang Hsiu-Han , Hsu Yu-Han
Published: January 2025

Accepted by: M. Zied BABAI

The achievable capacity index (ACI) is well suited to measuring the profitability of a newsboy-type product, wherein profitability is defined as the probability of achieving a target profit under the optimal order quantity. In retail/manufacturing situations where storage and production capacity are limited, profitability evaluation using ACI can be considered to select advantageous products. Although frequentist approaches are useful towards estimating the true ACI, the Bayesian approach may be preferable when prior information about the demand is available. In estimating the ACI, it may be necessary to deal with situations in which the demand is highly uncertain, the sample data consist of distinct subsets drawn from a demand population (i.e., multiple samples), and sampling error must be eliminated to avoid overestimates of profitability. This study seeks to overcome these issues by developing a Bayesian procedure for testing profitability based on multiple samples, focusing on exponentially distributed demand that can exhibit high uncertainty. The lower confidence bound of ACI is derived to express profitability estimates without sampling error. We also provide some tables to facilitate decision-making in evaluating profitability. We find that variations in confidence level and the evaluated criterion significantly influence the direction of decision-making, guiding managers to focus on controlling these factors. The practicality of the proposed method was demonstrated through a case study.
Balanced Metrics and Gauduchon Cone of Locally Conformally Kähler Manifolds
Authors: Ornea Liviu , Verbitsky Misha
Published: January 2025

A complex Hermitian $n$-manifold $(M,I, \omega )$ is called locally conformally Kähler (LCK) if $d\omega =\theta \wedge \omega $, where $\theta $ is a closed 1-form, balanced if $\omega ^{n-1}$ is closed, and SKT if $dId\omega =0$. We conjecture that any compact complex manifold admitting two of these three types of Hermitian forms (balanced, SKT, LCK) also admits a Kähler metric, and prove partial results towards this conjecture. We conjecture that the (1,1)-form $-d(I\theta )$ is Bott–Chern homologous to a positive (1,1)-current. This conjecture implies that $(M,I)$ does not admit a balanced Hermitian metric. We verify this conjecture for all known classes of LCK manifolds.
Surveying genetic markers of antibiotic resistance and genomic background in Chlamydia trachomatis: insights from a multiplex NGS-based approach in clinical strains from Portugal
Authors: Lodhia Zohra , Costa Da Silva Jorge , Correia Cristina , Cordeiro Dora , João Inês , Carreira Teresa , Schäfer Sandra , Aliyeva Elzara , Portugal Clara , Monge Isabel , Gonçalves Elsa , Matos Susana , Dias Ana Paula , Côrte-Real Rita , Carpinteiro Dina , Duarte Sílvia , Vieira Luís , Gomes João Paulo , Borges Vítor , Borrego Maria José
Published: January 2025

Objectives

To survey genetic markers of potential antimicrobial resistance (AMR) to macrolides and fluoroquinolones among Chlamydia trachomatis–positive samples from the collection of the Portuguese National Reference Laboratory for Sexually Transmitted Infections (STIs), and explore a multiplex PCR approach coupled with NGS to provide complementary information regarding a strain’s genomic backbone.

Methods

A total of 502 C. trachomatis–positive samples, mostly anorectal exudates, were subjected to PCR and sequencing of five targets, including loci potentially driving AMR (23S rRNA, gyrA and parC) and loci potentially informative about a strain’s genomic backbone with emphasis on differentiation of lymphogranuloma venereum (LGV)/non-LGV and L2/L2b (a 9 bp insertion in pmpH, a 74 bp insertion upstream from CT105 and the polymorphic CT442).

Results

No samples evidenced 23S rRNA mutations recognizably linked to macrolide resistance. Three samples harboured the Ser83Ile mutation in GyrA putatively driving fluoroquinolone resistance: two recombinant L2-L2b/D-Da (0.4%) and one L2 (0.2%). The screened regions in pmpH, upstream CT105 and CT442 were fully concordant with LGV/non-LGV differentiation. As expected, the pmpH L2b-specific genetic trait locus was detected in all L2b and recombinant L2-L2b/D-Da ompA genotypes, but also in 96.0% of L2 specimens, which also likely possess an L2b genomic backbone. The insertion upstream from CT105 exhibited full LGV specificity, constituting a promising target for the development of rapid LGV diagnostic assays.

Conclusions

This study contributes to enhancing the knowledge of C. trachomatis molecular epidemiology, suggesting that the known genetic determinants of AMR are not disseminated in clinical C. trachomatis strains, and presents an exploratory approach that can be suitable for LGV/non-LGV and L2/L2b genomic background differentiation.
Adrenal Venous Sampling in the Investigation of Hyperaldosteronism: A Retrospective Practice Review from a Large Academic Medical Center
Authors: Ishaq Ariana , Hamidi Oksana , Hashim Ibrahim A
Published: January 2025

Background

Hyperaldosteronism involves complex, multidisciplinary management, including clinical testing, radiological exams, and adrenal venous sampling (AVS). This study assesses AVS outcomes at a large referral center, focusing on cannulation success, lateralization of aldosterone-producing adenomas, and correlation with radiological and surgical findings.

Methods

A retrospective review of 153 patients who underwent AVS from September 2016 to January 2024 was conducted. Data included aldosterone and cortisol levels, procedural details, and outcomes. AVS success was determined by aldosterone-to-cortisol ratios and cortisol levels confirming adequate cannulation.

Results

Of the 153 patients, 49.9% had lateralized adenomas (51.3% left, 48.7% right), while 39.9% had bilateral adrenal hyperplasia. In 10.8% of cases, AVS was inconclusive or unsuccessful. Right adrenal vein cannulation required more attempts due to anatomical challenges. Aldosterone levels were higher in right adrenal adenomas compared to left, though cortisol levels did not predict laterality or hyperplasia. There was strong concordance between AVS, radiological, and surgical findings, except for bilateral hyperplasia cases.

Conclusions

This large series highlights AVS’s central role in diagnosing hyperaldosteronism, with significant insights into cannulation challenges and biochemical correlations. The study underscores the importance of a multidisciplinary approach for accurate diagnosis and effective management.
Network model and application in wellbore wireless communication of extremely low frequency electromagnetic waves
Authors: Wang Zhi , Jia Deli , Sun Fuchao , Hao Zhongxian , Chen Qiang
Published: January 2025

To address the limitations of traditional wellbore communication technologies and address the shortcomings in synchronization and channel analysis of electromagnetic waves wellbore communication models, this paper proposes a novel wellbore wireless communication method using Extremely Low Frequency (ELF) electromagnetic waves. A polygonal multiple-delay complex network model for ELF electromagnetic waves propagation in wellbore and strata was established, which was divided into four subnetworks using network splitting theory: the oil tubing subnetwork, the casing subnetwork, the cement subnetwork, and the strata subnetwork. A controller was designed, successfully validating the stability of the model and achieving fast synchronization. The optimal transmitting frequency range was determined to be between 5 and 20Hz through theoretical derivation of attenuation factors and skin depth, combined with finite element simulations. Simulation results indicate that cement and casing are the primary transmission channels, followed by oil tubing and strata, with electric signals exhibiting significantly higher intensity than magnetic signals. Unlike electric signals, magnetic signals are less affected by shielding effects. Two field experiments confirmed the feasibility of using ELF electromagnetic waves for wellbore wireless communication, which can achieve a wireless communication distance of over 1600 meters without relays. This research provides a critical theoretical foundation and experimental validation for the future development of efficient wellbore wireless communication and intelligent wells.