bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subendocardial ischemic-like state in patients with severe aortic stenosis: insights from myocardial histopathology and ultrastructure
Authors: Reis Santos R , Abecasis J , Maltes S , Lopes P , Manso R T , Gil V , Cardim N , Ramos S , Felix A 
Published: October 2024

Abstract

Background
myocardial adaptation to severe aortic stenosis (AS) is a complex process that involves myocardial fibrosis (MF) beyond cardiomyocyte hypertrophy. Perfusion impairment is believed to be involved in myocardial remodeling in chronic pressure overload.

Aim
to describe morphological and ultrastructural myocardial changes at EMB, possibly reflecting subendocardial ischemia, in a group of patients with severe AS referred to surgical aortic valve replacement (AVR), with no previous history of ischemic cardiomyopathy.

Methods
one-hundred-fifty-eight patients (73 [68-77] years, 50% women) referred for surgical AVR because of severe symptomatic AS with pre-operative clinical and imaging study and no previous history of ischemic cardiomyopathy. Intra-operative septal EMB was obtained in 129 patients. Tissue sections were stained with Masson ́s Trichrome for MF quantification and periodic acid-Schiff (PAS) staining was performed to assess the presence of intracellular glycogen. Ultrastructure was analyzed through Transmission electron microscopy (TEM).

Results
MF totalized a median fraction of 11.90% [6.54-19.97%] of EMB, with highly prevalent perivascular involvement (95.3%). None of the samples had histological evidence of myocardial infarction. In 58 patients (45%) we found subendocardial groups of cardiomyocytes with cytoplasmatic enlargement, vacuolization and myofiber derangement, surrounded by extensive interstitial fibrosis. These cardiomyocytes were PAS positive, PAS-diastase resistant and Alcian Blue/PAS indicative of the presence of neutral intracellular glyco-saccharides. At TEM there were signs of cardiomyocyte degeneration with sarcomere disorganization and reduction, organelle rarefaction but no signs of intracellular specific accumulation.

Conclusion
almost half of the patients with severe AS referred for surgical AVR have histological and ultrastructural signs of subendocardial cardiomyocyte ischemic insult. It might be inferred that local perfusion imbalance contributes to myocardial remodeling and fibrosis in chronic pressure overload.
LncRNA MEG3 promotes aortic valve calcification by inducing osteoblast differentiation via Wnt catenin signaling pathway
Authors: Tang L , Yang Y , Wang Z J , He Y , Zhou S H 
Published: October 2024

Abstract

Background
Calcific aortic valve stenosis (CAVS) is the most common valvular heart disease in elderly population. This study aimed to investigate the role of long non-coding RNAs (lncRNAs) in the development of CAVS.

Methods
ldlr-/-mice were feeding with western diet for 6 months to induce CAVS. RNA-seq analysis was performed to identify differentially expressed molecular signaling between aortic valves of CAVS mice and control mice. The degree of aortic stenosis was detected by ultrasound. Calcium salt deposits were detected by Haematoxylin and eosin (H&E) staining, Von Kossa staining and alizarin red S staining. PCR and western blotting were employed to detect osteogenic differentiation markers after various interventions.

Results
A mouse CAVS model was successfully established, as evidenced by increased thickness and calcium deposition in the aortic valve leaflets and increased transvalvular peak jet velocity. RNA-seq analysis showed that lncRNA MEG3 was significantly enriched in aortic valves of CAVS mice as compared to that of control mice. MEG3 expression in aortic valve, assessed by RNA in situ hybridization and PCR, was also significantly upregulated during the osteoblast differentiation of AVICs in vitro. Gain- and loss-of-function experiments indicate that MEG3 could indeed promote osteoblast differentiation of primary AVICs as evidenced by increased calcified nodule formation and expressions of osteoblast differentiation markers (Runx2 and osterix). Consistent with these in vitro data, MEG3 knockdown in vivo through tail injection of antisense oligonucleotide chain MEG3 (ASO-MEG3) at 6 weeks interval for 12 weeks significantly attenuated aortic valve calcification in CAVS mice. Subsequent KEGG analysis demonstrated that the Wnt/β-catenin signaling pathway was significantly enriched during the CAVS progression. Overexpression of MEG3 activated the Wnt/β-catenin signaling pathway and upregulated osteogenic protein expressions, while this upregulation could be significantly ameliorated by Dickkopf 1, a Wnt/β-catenin pathway inhibitor.

Conclusion
Present study demonstrates that LncRNA MEG3 could promote aortic valve calcification by inducing osteoblast differentiation via activating Wnt/β-catenin signaling pathway. Our results provide experimental evidence of targeting MEG3 and Wnt/β-catenin signaling pathway as potential promising therapeutic option for prevention and treatment of aortic valve calcification.
Increased risk of infective endocarditis following transurethral resection of the prostate (TUR-P)
Authors: Stahl A , Loldrup Fosboel E , Roeder A , Bagi Nordsten C , Oestergaard L , Sehested T S G , Dahl A , Ihlemann N , Bundgaard H , Iversen K , Valeur N , Gislason G , Torp-Pedersen C , Bagi P , Koeber L 
Published: October 2024

Abstract

Background
Transient bacteremia is a well-known complication of transurethral resection of the prostate (TUR-P). Still, the associated risk of bacteremia and subsequent infective endocarditis (endocarditis) after TUR-P has been sparsely examined.

Purpose
To examine the risk of bacteremia and infective endocarditis following TUR-P.

Methods
We identified all patients who underwent TUR-P between 2010-2020 with ICD-10 codes from Danish nationwide registries. Patients were compared to an age-matched cohort of males from the general population (1:1 match-ratio). We defined a 6-month exposure window following TUR-P and examined the risk of bacteremia and endocarditis within the first 6 months and compared with the following 6-12 months after TUR-P. Microbiology findings were based on complete data on blood culture results. Incidences of bacteremia and endocarditis were calculated, and groups were compared with cumulative incidences. To account for predisposing endocarditis risk factors, multivariable time-dependent Cox regression analyses were performed on the associated risk of bacteremia and endocarditis.

Results
In total, 25.781 patients underwent TUR-P. Median age was 70.7 years (IQR: 64.9-76.3). Incidence of bacteremia was higher in the TUR-P group than the control group (727.47 [681.49-776.56] per 10,000 person years vs 84.75 [95% CI: 70.19-102.35)] per 10,000 person years). Incidence of endocarditis was also higher in the TUR-P group than the control group (34.64 [95% CI: 25.78-46.55] per 10,000 person years vs 3.14 [95% CI: 1.18-8.35] per 10,000 person years). In 72.7% of endocarditis-cases, Enterococcus Faecalis was the disease-causing pathogen in the TUR-P group. As compared with an age-matched control group, we found an increased associated risk of bacteremia in patients undergoing TUR-P within the first 6 months from the procedure (adj. HR: 7.72 [95% CI: 6.25-9.53]) and the increased risk persisted within the following 6-12 months (adj. HR 2.31 [95% CI: 1.83-2.91]). TUR-P was also associated with endocarditis within 6 months from the procedure (8.16 [95% CI 3.06-21.79]), but not significantly the following 6-12 months after (2.15 [95% CI: 0.91-5.07]) as compared with the age-matched control group.

Conclusion
Transurethral resection of the prostate (TUR-P) is associated with an almost 8 times increased risk of bacteremia and an 8 times increased risk of infective endocarditis. Our findings emphasize the necessity for development of better preventive strategies against infective endocarditis after TUR-P.Risk of endocarditis post-TUR-P
Aortic valve tissue quantification in bicuspid aortic valve stenosis
Authors: Ye Z , Foley T , Sarano M , Michelena H 
Published: October 2024

Abstract

Background
The relative contribution of calcific versus noncalcific aortic valve tissue volume to aortic stenosis (AS) in bicuspid aortic valve (BAV) is unclear.

Purpose
We aimed to assess the association of aortic valve tissue volume quantified by contrast-enhanced CT with echocardiographic AS severity, and diagnostic implication of noncalcific tissue volume for severe AS.

Methods
We retrospectively identified 234 patients with BAV who had echocardiographic AS severity and contrast-enhanced CT evaluation within six months and left ventricular ejection ≥50%, including 150 severe AS (aortic valve area≤1 cm2 or indexed valve area≤0.6cm2/m2 plus mean grdient≥40mmHg or peak velocity≥4 m/s), 84 nonsevere AS (61 with at least mild AS: peak veloicty≥2.0 m/s plus mean gradient ≥10mmHg, and 23 with normal aortic valve function). Contrast-enhanced CT aortic valve calcific volume and noncalcific (fibrosis) volume were quantified using patient-specific Hounsfield unit thresholds (Figure). Noncontrast CT aortic valve calcium score (AVCscore) was quantified by the Agaston method. CT measurements were indexed to echocardiographic aortic valve annulus area and square-root transformed for the analysis.

Results
Of 234 patients, the mean age was 64±11 years, and 64% were men. There were positive correlations of indexed calcific volume, noncalcific volume, and inverse correlations of percentages of noncalcific volume (noncalcific volume divided by the sum of calcific and noncalcific volume) with peak velocity and mean gradient (|r|=0.30 to 0.68). Among 150 patients with severe AS, 28 had an AVCscore below the severe AVC threshold (1200 AU in women and 2000 AU in men) while exhibited a higher percentage of noncalcific volume compared to 122 patients with severe AVCscore (67±15% vs. 39±15%, p&lt;0.001). After excluding 122 patients with severe AS and severe AVCscore, the indexed noncalcific volume was associated with severe AS (β±S.E: 0.18±0.07, p=0.005) with an area under the curve of 0.71; in contrast, AVCscore was not (p=0.55).

Conclusion
Both calcific and noncalcific aortic valve tissue volume contribute to AS severity in patients with BAV. Notably, noncalcific tissue volume is a key factor in determining severe AS in patients without severe AVCscore, suggesting its potential diagnostic value.Figure
Prognostic role of exercise stress echocardiography in asymptomatic severe aortic stenosis
Authors: Agostini R , Mori F , D'alfonso M G , Ciampi Q , Saad A K , Zagatina A , Colonna P , Merli E , Van De Heyning C M , Russo M , Padang R , Pellikka P A , Picano E 
Published: October 2024

Abstract

Background
Guidelines recognize the role of exercise stress testing in evaluating functional capacity in patients with asymptomatic severe aortic stenosis (AS). The study aimed to identify the prognostic role of exercise stress echocardiography (ESE) in asymptomatic severe AS.

Methods
We enrolled 153 asymptomatic patients (70±13 years; 88 male, 57%) with severe AS, aortic valve area (AVA) &lt;1.0 cm2, mean aortic gradient ≥ 40 mmHg, ejection fraction (EF) ≥55%. All were referred for ESE in 7 quality-controlled centers from 5 countries. Rest and ESE assessment also included global longitudinal strain (GLS) and left atrial volume index (LAVI). B-lines were assessed by LUS with the 4-site simplified scan of the third intercostal space. A 4-point ESE score was based on 4 parameters (0 for normal, 1 for abnormal), with the following pre-determined cutoffs of abnormality: ∆-maximal aortic gradient (MAG) ≥20 mmHg; GLS at peak ≤ 19%, according to receiver operating characteristics curve analysis, stress B-lines ≥2; stress LAVI ≥ 34 mL/m2. Follow-up was completed in 142/153 patients (92%).

Results
At rest, AVA was 0.85±0.14 cm2, maximal aortic gradient: 79±14 mmHg, and peak aortic velocity: 4.42 ± 0.41 m/s. Mean EF at rest: 63.4±5.3% During a median follow-up of 1802 days (IQ range 651-2302), 41 events occurred in 39 patients: 15 all-cause deaths, 17 acute HF, 1 stroke, 1 myocardial infarction, and 7 coronary revascularization. Patients experiencing events displayed a greater increase in MAG during peak ESE, more B-lines with exercise, greater degree of LAVI dilation with exercise and slightly lower GLS compared to those without events (Table). Increase in ESE score was associated with a significant rise (p=0.001) in event incidence from score 0 (n=0/13, 0%) to score 1 (n=2/21, 9.5%), score 2 (n=10/42, 23.8%), and ≥3 (n=27/66, 40.9%), see figure.

Conclusions
In asymptomatic severe AS cases with preserved LV EF, comprehensive ESE provides early marker of potential cardiac decompensation at follow-up. The composite ESE index, including MAG, GLS, LAVI, and B-lines, holds promise as a prognostic predictor.TableFigure
Good agreement between cardiac magnetic imaging protocols using free-breathing and breath-holding techniques for flow quantification in valvular heart disease
Authors: Gao S , Bech-Hanssen O , Lagerstrand K M , Polte C , Polte C L 
Published: October 2024

Abstract

Background
Cardiac magnetic resonance (CMR) evaluation of valvular heart disease is an important diagnostic tool when echocardiography is inconclusive. Flow quantification is usually performed during breath hold, which can be challenging in valvular heart disease patients often suffering from dyspnea and heart failure.

Purpose
The purpose of the present study is to evaluate a free-breathing protocol of flow measurement in the aortic, pulmonary and tricuspid valves in healthy subjects (HS) and patients with tricuspid regurgitation (TR).

Methods
Phase contrast flow volume measurements were performed in 20 HS and 25 patients with TR using standard breath-holding (BH) and a free-breathing (FB) technique. Two venc-adjusted volume acquisition were acquired in the aortic, pulmonary and tricuspid valve during BH and one during FB. Mean, standard deviation (SD) and limits of agreement (LoA) for aortic forward flow volume (AoFF), pulmonary forward flow volume (PuFF) and tricuspid inflow volume (TrIF) were evaluated.

Results
Figure 1 presents flow volume (ml) of AoFF, PuFF and TrIF during BH (mean of 2 measurements) and FB.

Conclusions
The present study demonstrated good agreements between phase contrast flow measurements using FB and BH techniques. These parameters are used in the evaluation of aortic, mitral, pulmonary and tricuspid regurgitations using CMR imaging. Thus, free-breathing CMR acquisition can be an important complement in the assessment of valvular heart disease and may be applied in patients with difficulty to hold their breath.
Permanent pacemaker implantation is associated with an increased risk of heart failure hospitalization in transcatheter aortic valve implantation patients with reduced systolic function
Authors: Nass J , Liu D , Hu K , Dormann A , Buravezky L , Sokalski V , Lau K , Morbach C , Lengenfelder B , Ertl G , Frantz S , Nordbeck P 
Published: October 2024

Abstract

Background
The impact of permanent pacemaker implantation (PPI) on outcome of patients following transcatheter aortic valve implantation (TAVI) is not fully understood.

Purpose
This study aimed to assess the impact of PPI on risk of two-year mortality and hospitalization due to heart failure (HF) in TAVI patients.

Methods
A total of 1275 consecutive patients who underwent TAVI at our hospital between 2009 and 2021 were enrolled in this study (mean age 81.4±5.6 years, 51.8% male). The primary endpoint was defined as two-year all-cause death after TAVI. The second endpoints included cardiovascular (CV) death and HF related hospitalization after TAVI.

Results
Among the 1275 patients following TAVI, 297 (23.3%) patients received PPI, with 134 receiving PPI before TAVI and 163 receiving PPI after TAVI. The patients were categorized into two groups: no PPI group (n=978) and PPI group (n=297). Compared to patients without PPI, patients who received PPI were more likely to be male (60.9% vs. 49.1%, P&lt;0.001), higher prevalence of atrial fibrillation (51.2% vs. 43.3%, P=0.016), coronary artery disease (61.6% vs. 53.8%, P=0.017), use aldosterone receptor antagonists (MRAs, 25.3% vs. 15.2%, P&lt;0.001), and lower left ventricular ejection fraction (LVEF, 54.9±13.1% vs. 57.5±11.4%, P&lt;0.001). There were no significant differences in all-cause mortality (16.6% vs. 18.5%), CV mortality (11.3% vs. 13.5%), as well as HF hospitalization rate (18.5% vs, 21.2%) between the two groups (P&gt;0.05).
In this cohort, 1012 (79.4%) TAVI patients had a preserved LVEF (≥50%), 122 (9.6%) had a mildly reduced LVEF (41-49%), and 141 (11.1%) had reduced LVEF (≤40%). Their primary and secondary outcomes were similar among LVEF subgroups (all P&gt;0.05). In the subgroup of reduced LVEF, the HF related hospitalization rate after TAVI was significantly higher in TAVI patients with PPI compared to those without PPI (30.6% vs. 13.0%, P=0.003). Multivariable Cox regression models demonstrated a 3-fold increased risk of HF related hospitalization in TAVI patients with PPI in comparison to those without PPI in the subgroup of LVEF≤40% (HR 3.057, 95% CI 1.311-7.130, P=0.010) after adjusting for age, sex, TAVI approach, atrial fibrillation, coronary artery disease, and the use of MRAs.

Conclusion
All-cause mortality and CV mortality are similar between TAVI patients with and without PPI. However, in the subset of TAVI patients with reduced LVEF (≤40%), PPI is associated with an increased risk of HF hospitalization. Efforts are thus needed to reduce the risk of HF hospitalization in these patients.
Right chambers deformation after tricuspid edge-to-edge percutaneous repair
Authors: Bassa R , Bourdin J P , Anguita Gamez M , Mahia P , Gomez De Diego J J , Marcos-Alberca P , Olmos C , Paredes Vazquez J , Vilacosta I , Fernandez-Ortiz A , Jimenez Quevedo P , Nombela-Franco L , Perez-Villacastin J , De Agustin A , Pozo Osinalde E 
Published: October 2024

Abstract

Background
The development of new analysis software has allowed to broaden myocardial deformation study to right chambers. There are already reference values for right ventricle (RV) and more recently for right atrium (RA). Tricuspid edge-to-edge repair (TEER) potentially causes changes in right chambers mechanics.

Purpose
Our aim is to evaluate the impact of TEER in the myocardial deformation of RV and RA.

Methods
Observational retrospective study including all the consecutive patients undergoing TEER in our tertiary centre. Additionally, a control group of healthy volunteers was included. Baseline and 3 months postprocedural echocardiograms were analyzed with a dedicated software to obtain RV, free wall (FW-) and 4 chambers (4C-) global longitudinal strain (GLS), and RA, reservoir (SrRA), conduit (ScdRA) and centrality (SctRA) strains , deformation values. Interobserver variability was evaluated in the control group with the intraclass correlation coefficient (ICC). Differences in baseline values between cases and control group were evaluated with Mann-Whitney U test. Evolutive changes in deformation parameters were studied using paired Wilcoxon W test.

Results
15 healthy controls and 29 patients undergoing TEER (79.3% female, 79 [75-82] years-old) were included. Baseline tricuspid regurgitation (TR) was severe in 21 (72.4%), whereas the others were massive or torrential, and the most frequent mechanism was functional (22, 75,9%). Interobserver agreement in the control group was excellent for FW-GLS (0.88; p &lt;0.001), SrRA (0.99; p &lt;0.001) y ScdRA (0.93; p &lt;0.001), good for SctRA (0.68; p= 0.019) and insufficient for 4C-SGL (0.36; p= 0.20). RV deformation values were significantly worse in patients than in controls (Table). However, solely FW-GLS showed improvement 3 months after the procedure (-15.7 vs -20.5 %; p= 0.022).

Conclusions
Right chamber deformation analysis is feasible and significantly reduced in patients undergoing TEER. Nevertheless, percutaneous treatment of TR has scarce effect in mechanics at early phases. Longer follow up may be required to evaluate the impact in right strain parameters.
Table. Right chambers myocardial deformation values in healthy controls and patients undergoing TEER.Figure
Calculation of intraprocedural hemodynamics with computational functional dynamic in mitral valve edge-to-edge repair
Authors: Kirchner J , Gercek M , Rudolph F , Omran H , Kassar M , Friedrichs K , Rudolph V , Graeni C , Praz F , Rudolph T K 
Published: October 2024

Abstract

Background
Hemodynamic outcomes in patients undergoing transcatheter edge-to-edge-repair of the mitral valve (M-TEER) are difficult to predict. Computational functional dynamic (CFD) is frequently used in biomedical engineering to simulate blood flow patterns under various conditions. The authors developed a standardized workflow for individualized analyses and investigated the hemodynamic of mitral regurgitation volumes and gradients by using CFD.

Methods
20 patients from two high volume centers who suffered from severe mitral regurgitation (MR) and underwent full cycle cardiac computed tomography (CT) prior procedure were enrolled. Baseline computed tomography and intraprocedural data were analyzed. Based on the specific valve morphology, individualized CFD-simulations were performed to calculate MR volumes prior to intervention and estimate hemodynamics after M-TEER.

Results
CFD-analyses of 20 patients (mean age 80±4 years, 60% male) showed excellent correlation between baseline PISA method-based MR volumes (45±23ml) measured in transesophageal echocardiography (TEE) and CFD-based calculation (45±26ml; R=0.917; P&lt;0.001) as well as between TEE-measured mean baseline effective regurgitant orifice area (EROA; 27±16mm²) and CFD-measured EROA (24±18mm²; R=0.869; P&lt;0.001)). After device implantation, correlation between intraprocedural TEE-measured and CFD-estimated correlation for residual MR volumes (R=0.949; P&lt;0.001) and EROA (R=0.841; P&lt;0.001) remained robust. Post-interventional mean diastolic pressure gradient (TEE) was 3.6±2.8mmHg which was in close correlation with the CFD estimated gradient (3.0±1.8mmHg, R=0.905; P&lt;0.001).

Conclusions
This is the first study to use a CFD-standardized workflow for predicting hemodynamic changes in patients undergoing M-TEER using data from two different centers. In the future, CFD-based analyses might serve as a key-diagnostic tool for predicting residual MR volumes and gradients for M-TEER-procedures.Comparison of TEE and CFD flow patternBland-Altman-Blots