bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of Soluble ST2 biomarker to predict recurrence after electrical cardioversion in patients with atrial fibrillation
Authors: Gonzalez-Melchor L , Garcia-Seara J , Martinez-Sande J L , Rodriguez-Manero M , Fernandez-Lopez X A , Alvarez Villamarin C , Gonzalez-Juanatey J R , Minguito-Carazo C , Gonzalez T 
Published: October 2022

Abstract

Background
Atrial fibrillation (AF) is the more frequent arrhythmia in clinical practice. The ST2S is a biomarker that has demonstrated to be predictor of cardiovascular outcomes in patients with heart failure but there is scarce information of his utility in patients with AF.

Purpose
Considering the characteristics of the ST2S we hypothesize this biomarker could correlate to recurrence in patients with AF and electrical cardioversion (ECV).

Methods
This was an observational and prospective clinical trial. We compared all patients with AF referred for ECV with a control group without AF, from September 1th 2016 to September 30 2019. Clinical, ECG, echocardiographic and ST2S levels were analyzed in both groups at basal, at 3 and 6 months of follow-up in such cases with AF. Patients with inflammatory or allergic diseases, moderate/severe ventricular dysfunction, structural cardiomyopathy, moderate/severe hepatic, renal or respiratory disease were excluded.

Results
We included a total of 94 patients with AF and 40 paired controls. Clinical variables are presented in Table 1. Fifty-eight (61.7%) patients with AF had recurrence at follow-up. There was a significant difference between the ST2S levels at baseline between AF patients (17163.8 pg/mL) and controls (11016.2 pg/mL) (p=0.001). ST2S biomarker levels at 3 and 6 months of follow-up decreased in those patients without AF recurrence as shown in Figure 1. Covariable models were performed and ST2S biomarker levels at 3 months were significant to predict recurrence at 6 months follow-up (Table 2). The calculated cut-point of the biomarker was of 15511.51 pg/ml with a c-value: 0.669.

Conclusions
In our experience ST2S was a useful biomarker to predict recurrence of AF after ECV. Considering the size of the study more studies should be performed to confirm this results.

Funding Acknowledgement
Type of funding sources: None.
Cardiac troponin T degradation in end-stage renal disease patients appears to occur in vivo
Authors: Denessen E , Vroemen W H M , Litjens E J R , Henskens Y M C , Van Der Sande F M , Kooman J P , Bekers O , De Boer D , Mingels A M A 
Published: October 2022

Abstract

Background
Cardiac troponin T (cTnT) is a cornerstone biomarker for diagnosing myocardial infarction (MI). However, since the introduction of the high-sensitivity assays, cardiac troponins are also measured in pathologies with cardiac risk factors, such as end-stage renal disease (ESRD), making it more difficult for clinicians to diagnose MI. Previous studies of our group identified specific larger cTnT proteoforms for the acute phase of MI, while a study in serum of ESRD patients showed solely small cTnT fragments. However, others allocated the small cTnT fragments in serum of ESRD patients to a pre-analytic effect due to abundant thrombin generation in serum, as thrombin is known to cause fragmentation of cTnT.

Purpose
This study investigated the effect of multiple anticoagulation methods on cTnT proteoforms in vitro and in the blood of ESRD patients.

Methods
First, cTnT negative serum and lithium-heparinized (LH), ethylenediaminetetraacetic-acid (EDTA), and hirudin plasma tubes were spiked with human cTnT standard, incubated at 37°C till 48 hours, and analysed with Western Blotting using anti-cTnT Roche antibodies. Second, similar blood tubes were collected from ESRD patients (n=10) conform the Declaration of Helsinki, patient samples and spiked cTnT standards were separated using gel filtration chromatography (GFC) and cTnT was subsequently analysed using the Cobas 6000 analyser.

Results
After 48 hours of in vitro incubation of cTnT in hirudin plasma, no cTnT degradation was observed, while LH only showed minor degradation of 10% from intact 40 kDa cTnT to 29 kDa fragments (figure 1). Also, for both EDTA and serum, a time-dependent degradation from 40 kDa cTnT to 29 kDa fragments to 15–18 kDa fragments was observed. Moreover, in ESRD patients, GFC elution profiles of all blood tubes revealed that 85–98% of cTnT corresponded to small 15–18 kDa fragments (41–42 mL), while 2–15% were 29/40 kDa cTnT forms (27–28 mL). For comparison, standards of ternary T-I-C complex and intact cTnT eluted at 21 mL and 28 mL, respectively.

Conclusions
The extent of cTnT degradation in vitro is dependent on the anticoagulation method of the blood tubes, with absence of degradation exclusively in hirudin plasma. Since in ESRD patients for all blood tubes mainly small 15–18 kDa cTnT fragments were found, including hirudin plasma, cTnT degradation appears to occur in vivo. This observation supports the hypothesis that larger cTnT proteoforms might indeed be specific for the acute phase of MI, thereby supporting the opportunity for developing a more specific cTnT method.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ZonMw Veni grant
Expression changes of circulating ACE2 regulating-microRNA profiles in patients with COVID-19 during hospitalisation
Authors: Jarosz-Popek J , Eyileten C , Wicik Z , Nowak A , Wolska M , Shahzadi A , Jakubik D , Simoes S N , Martins D C , Siller-Matula J , Postula M 
Published: October 2022

Abstract

Background
Various miRNAs, as well as their target genes are involved in the complex pathophysiology of inflammation, immune response, coagulation and CVDs. Thus, they may be useful for diagnosis, prognosis and as a potential therapeutic strategy in multiple pathologies.

Aim
According to our previously published bioinformatics analysis, we aimed to analyze the diagnostic and predictive utility of miRNAs regulating ACE2 network (miR-26b-5p, miR-10b-5p, miR-302c-5p, hsa-miR-200b-3p, hsa-miR-124-3p) in patients with COVID-19.

Results
The expression levels of miR-26b-5p in COVID-19 patients were found lower at the baseline, 7 and 21-days after admission. compared to the healthy controls (p&lt;0.0001 for all time points). Similarly, miR-10b-5p expression levels were lower at the baseline and 21-days post admission in COVID-19 patients when compared to the healthy individuals (p=0.001 in both time points). Moreover, expression levels of this miRNA were higher 7-days post-admission when compared to the baseline (p=0.003). According to the ROC curve analysis, low miR-200b-3p expression presents predictive utility in assessment of the hospital length of stay and/or death (AUC: 0.730, p=0.002). According to the multivariable logistic regression model, low delta miR-200p expression, together with diabetes mellitus (DM), are independent predictors of increased hospital length of stay and/or death (OR: 5.775; 95% CI, 1.572–21.214; p=0.008 and OR: 4.888; 95% CI, 1.001–23.858; p=0.050, respectively).

Conclusions
This study enabled us to better characterize changes in gene expression and signaling pathways related to COVID-19 thrombosis. In this study we identified, characterized and validated miRNAs which could serve as novel, thrombosis-related biomarkers of the COVID-19, can be used for early stratification of patients and prediction of severity of infection development in an individual.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): Medical University of Warsaw
Proteomic analysis of exercise-induced hypertrophy reveals sex-related mitochondrial differences mediated by AMPK
Authors: Olah A , Barta B A , Ruppert M , Sayour A A , Bottlik O , Merkely B , Schilling O , Radovits T 
Published: October 2022

Abstract

Background
Regular physical activity results in characteristic structural and functional changes in the heart, which are collectively referred to as the athlete's heart. However, the extent of exercise-induced left ventricular (LV) hypertrophy and functional changes show significant differences between men and women, the molecular background of which is not fully elucidated.

Objective
The aim of this study was to provide a proteomic characterization of long-term, intense exercise-induced LV myocardial hypertrophy in a rat model, with a focus on sex-related differences.

Methods
Our rats were divided into trained (FEx) and control female (FCo) as well as trained (MEx) and control male (MCo) groups. In the trained groups, athlete's heart was induced by a 12-week swimming protocol. Myocardial hypertrophy was confirmed by echocardiography and functional adaptation by pressure-volume analysis. Proteomic measurements based on liquid chromatograph-coupled mass spectrometry were performed on proteins isolated from our LV myocardial samples.

Results
Echocardiography and post-mortem myocardial mass showed significant LV hypertrophy in both sexes, which was more pronounced in female animals (tibial length normalized LV muscle mass: + 17.4% MEx vs. MCo, + 31.0% FEx vs. FCo). LV contractility increased to the same extent in both sexes. Relative expression of 3074 proteins were determined by proteomics. There was a significant change in expression of 229 proteins in males and 599 in females compared to the level of same-sex controls. Based on our gene ontological analysis, physiological LV remodeling in females is characterized by increased expression of proteins in mitochondrial function (cellular respiration and fatty acid oxidation) and biogenesis, whereas in males, proteins that bind to the actin cytoskeleton is primarily increased. Further investigation revealed that the quantity of AMP-activated protein kinase (AMPK) and sirtuin 3 (SIRT3) was increased only in female animals.

Conclusions
Our data suggests that physiological LV hypertrophy resulting from regular, balanced exercise is associated with sex-specific changes in the myocardial proteome. The main differences might be associated with different regulation of mitochondrial function and biogenesis, related to AMPK pathway. Our results contribute to the understanding of the development of physiological myocardial hypertrophy.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Bolyai János Research Scholarship (BO/00837/21) to OANational Research, Development and Innovation Office (NKFIH) K135076 to B.M.
A promising rat model of heart failure with preserved ejection fraction associated to multiple comorbidities
Authors: Dubroca C , Costard C , Maupoint J , Waget A , Brousseau E , Briand F , Sulpice T 
Published: October 2022

Abstract

Background and aims
Heart failure with preserved ejection fraction (HFpEF) is a complex clinical phenotype often associated to the presence of multiple non-cardiac interrelated comorbidities including diabetes, obesity, hypertension. A major challenge in the development of new therapies for HFpEF is the lack of animal models that truly recapitulate the complexities of the disease. One promising candidate is the Lund MetS rat, a congenic BBDR.cg-lepr.cp model generated by introgression of the Koletsky leptin receptor mutation into the BioBreeding Diabetes Resistant (BBDR) rat.

Methods
14-week-old Lund MetS obese T2D rats were exposed to salt enriched diet (0.8% NaCl in diet) for 6 weeks. Age-matched lean rats (ctrl) were fed a normal chow diet. Cardiovascular phenotyping was assessed by echocardiography and blood pressure measurement. Vascular function of isolated thoracic aortas, as well as kidney and cardiac parameters were also evaluated at the end of the 6-week diet period.

Results
After 6-week enriched salt diet period, mean arterial pressure increased from 120mmHg to 160mmHg (vs 100mmHg in chow-fed lean rat). The hypertensive state also led to renal hypertrophy with up to a 2-fold higher kidney weights. Echocardiography showed a preserved systolic function with quite similar ejection fraction and fractional shortening in Lund MetS and lean rats. In contrast, high salt-fed Lund MetS rats developed cardiac hypertrophy confirmed by a large increase in heart, left ventricle, and left atria weights as compared to lean rats. Diastolic dysfunction was also highlighted with inverted E/A and E'/A' ratios along with a prolongation of the isovolumic relaxation time (IVRT). This was accompanied by an increase in circulating levels of soluble ST2 and NT- proBNP. Finally, aortic rings assays showed that both endothelium dependent and independent vasodilating properties were impaired in the high salt-fed Lund MetS rats.

Conclusions
The present data demonstrate that the Lund MetS rat fed a high salt diet developed a marked hypertension, pathological cardiac remodeling and diastolic dysfunction without modification of ejection fraction, along with obesity and type 2 diabetes. Thus, this could be a relevant model to bring forward effective new treatments for HFpEF patients.

Funding Acknowledgement
Type of funding sources: None.
Alterations in the gut microbiota composition in the obesity phenotype of heart failure with preserved ejection fraction
Authors: Rokach Y , Abedat S , Nachman D , Dana S , Qadan A , Beeri R , Amir O , Asleh R 
Published: October 2022

Abstract

Introduction
Obesity is one of the most common phenotypes of heart failure with preserved ejection fraction (HFpEF). A growing body of evidence indicates that obesity is characterized by compositional alterations in the intestinal microbiota and its metabolites, collectively referred as dysbiosis.

Purpose
We sought to investigate whether the obese phenotype of HFpEF is mediated by further alterations in the microbiota and whether gut dysbiosis fuels metabolic inflammation leading to progression of HFpEF.

Methods
HFpEF was induced in C57/black mice by high-fat diet and inhibition of NO synthesis (a “2-hit-model”) (Figure 1A). High-frequency echocardiography was performed to assess diastolic function. Blood pressure (BP) was measured using CODA non-invasive tail-cuff system. For human studies, patients with obese HFpEF as well as obese and non-obese healthy individuals were prospectively recruited. Gut microbial DNA was subjected to 16S ribosomal RNA gene sequencing, and the differences in abundance and composition of bacteria were defined both in humans and mice.

Results
In mice, the 2-hit model demonstrated significantly increased BP and impaired diastolic function in the obese HFpEF group (Figure 1B). Microbiome analysis showed significant differences in the gut microbial diversity and composition in the obese HFpEF compared to the non-HFpEF obese and chow-fed mice (Figure 1C). Similarly, human microbiome sequencing showed significant gut bacterial alterations in the diversity and composition of bacteria with more profound dysbiosis observed in the obese HFpEF patients compared to the obese and lean healthy individuals (Figure 1D).

Conclusions
We provide evidence in humans as well as in a murine animal model that the obese HFpEF phenotype is associated with more pronounced gut dysbiosis compared to the non-HFpEF obesity state. Further research will elucidate the causative link between gut dysbiosis and HFpEF manifestation and the mechanistic insights into the implication of gut microbiota in HFpEF progression.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Israel science foundation
Acute afterload leads to increased electrophysiological heterogeneity after myocardial infarction
Authors: Ingelaere S , Vermoortele D , Holemans P , Claus P , Willems R 
Published: October 2022

Abstract

Background
Myocardial infarction (MI) results in altered mechanical loading and changes in the cardiac electrical properties. The infarct border zone is pro-arrhythmic but the exact role of mechano-electrical coupling remains unclear.

Objective
We studied spatial electrical heterogeneity in MI animals during acute afterload increase using a novel E-field methodology for high resolution mapping of local activation-repolarization intervals (ARI) in vivo.

Methods
Anterior-septal MI was induced in five domestic pigs by 120-minute occlusion of the left anterior descending artery followed by reperfusion. This led to an infarct size of 17.7±2.1% of the left ventricle. After 1 month, electro-anatomical mapping was performed before and during an acute afterload challenge induced by partially inflating a balloon in the descending aorta. A non-contact recording of a 64-electrode array was translated to 2048 non-contact electrograms distributed over the left ventricle. The non-contact electrograms were processed to determine the ARIs using a custom-made algorithm, previously validated against monophasic action potential recordings. Based on the contact map we defined border zone (BZ, voltage 0.5 to 1.5 mV) and remote (&gt;1.5mV) regions. Heterogeneity was defined as the interquartile range (IQR) of ARIs in fixed neighborhoods of 1cm radius (figure 1A) and analyzed in 10 segments (5 BZ and 5 remote) of a modified version of the AHA model (49 segments by dividing the 16 non-apical segments). Other segments were discarded due to artefacts mainly caused by the array touching the septal and apical wall.

Results
Acute afterload challenge resulted in an increase of the systolic left ventricular pressure of 41.7±5.4% and increased left ventricular repolarization heterogeneity (IQR 4.03±1.23ms baseline to 4.85±1.38ms during inflation, p=0.004). There was a significant increase in heterogeneity in both BZ (4.78±1.60ms to 5.64±1.66ms, p=0.020) and remote (2.24±0.17ms to 3.00±0.86ms, p=0.034) regions (figure 1B). The IQR in the infarct BZ was higher compared to the remote zone at rest (4.78±1.60ms vs 2.24±0.17ms, p=0.010) as well as during inflation (5.64±1.66ms vs 3.00±0.86ms, p=0.008) (figure 1B). Both BZ and remote regions responded equally to acute afterload (p for interaction = 0.803).

Conclusion
Increased afterload leads to increased repolarization heterogeneity. This heterogeneity is higher in the infarct BZ. These alterations could provide a functional substrate for reentry.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): KU Leuven - C1 funding
Real-time electrophysiological characterization of acute and chronic radiofrequency ablation lesions
Authors: Amoros-Figueras G , Casabella-Ramon S , Moreno-Weidmann Z , Company-Ramon G , Jorge E , Rosell-Ferrer J , Cinca J , Guerra J M 
Published: October 2022

Abstract

Background
Assessment of lesion formation remains one of the most important goals to guide radiofrequency (RF) procedures in the cardiac electrophysiology laboratory. Cardiac navigation systems use specific algorithms to predict the effective lesion size, but these metrics are based only on ablation parameters and ignore local electric tissue characteristics. [1] Recent studies show that local multiparametric impedance is influenced by the intrinsic structural characteristics of the tissue. [2]

Purpose
This study aimed to assess the ability of local multiparametric impedance to characterize acute and chronic RF ablation lesions in the right atrium of pigs.

Methods
Four anesthetized closed-chest pigs were submitted to two interventions. The first intervention aimed at creating RF ablation lesions (30W, 60s, 55°) in the right atrium using an electrocatheter connected to a conventional cardiac navigation system, while mapping the local multiparametric impedance (LMI), the generator impedance (GI) and the bipolar voltage (BiV). All RF ablation lesions were performed with a stable contact force. Four weeks later, the second intervention aimed at mapping again the previous ablation sites. After the second intervention animals were euthanized and the hearts were removed and processed to identify the presence of fibrosis in the previously ablated lesions (Figure).

Results
We performed 19 ablations (5±2 per animal) with an average contact force of 14.2±4.6g. Four weeks later, 14/19 (74%) ablation lesions were identified as fibrotic points in the explanted heart (Figure 1). These showed decreased acute LMI and BiV values that persisted low after 4 weeks (Table 1). The remaining 5/19 ablations that did not present fibrosis had lower baseline LMI and bipolar values that resulted in lower LMI and BiV drops (Table 1). The absolute drop in LMI between effective and non-effective lesions was around 50%, while GI drop was only 21% (LMI drop @51KHz: From −3.0±1.4° to −1.5±0.3°, T-TEST p&lt;0.05; GI drop: From 12.7±27.6Ω to 10.5±21.3Ω, T-TEST p=0.89).

Conclusion
The local baseline electrical properties of atrial myocardium are directly related to the effectiveness of RF ablation lesions. RF ablation sites that resulted into persistent fibrosis points had larger LMI and BiV values, with higher absolute drops than non-effective lesions. The use of LMI in clinical practice could improve the outcome of the procedures of arrhythmia ablation in the electrophysiology lab.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Supported by grants from ISCI-MINECO (FIS PI21/00392), FEDER, CIBERCV (CB16/11/00276)
Empagliflozin attenuates arrhythmogenesis via inhibition of O-GlcNAcylation in diastolic phase of diabetic cardiomyopathy
Authors: Kadosaka T , Watanabe M , Natsui H , Koizumi T , Koya T , Nakao M , Hagiwara H , Kamada R , Temma T , Anzai T 
Published: October 2022

Abstract

Background
Diabetic cardiomyopathy is an important complication of diabetes mellitus (DM) and reported to increase the risk of fatal ventricular arrhythmias. Recent clinical trials showed that empagliflozin (EMPA), a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, improved cardiovascular outcomes regardless of the presence of diabetes and the traditional cardiovascular risk factors. Despite the promising benefit of EMPA on heart failure treatment, its beneficial effect in the context of anti-arrhythmic therapy has not been fully examined. We therefore aimed to examine anti-arrhythmic effect of acute EMPA treatment especially onto calcium (Ca2+) handling in diabetic cardiomyocytes.

Methods
We assessed echocardiography, hemodynamic study, electrophysiology, Ca2+ handling and protein expression in C57BLKS/J-leprdb/db mice (db/db mice), a leptin receptor-deficient model of obesity and Type 2 diabetes, and their non-diabetic lean heterozygous Leprdb/+ littermates (db/+ mice).

Results
The 16-week-old db/db mice had preserved systolic function but exhibited diastolic dysfunction. In arrhythmia induction using ex-vivo Langendorff-perfused hearts, db/db mice showed a significantly increased premature ventricular complex (PVC) by 2x Ca2+ and 1μM isoproterenol load than control, which was attenuated by EMPA perfusion (1 μM). Diabetic cardiomyocytes showed an increased frequency of spontaneous Ca2+ sparks and waves, and decreased Ca2+ transient amplitude and sarcoplasmic reticulum (SR) Ca2+ content. Ca2+ transient decay tau and time to 50% decay were significantly prolonged in diabetic cardiomyocytes. These data indicating the impaired Ca2+ handling in diabetic cardiomyocytes were normalized by acute administration of EMPA (1 μM), while the administration of NHE inhibitor (Cariporide 10 μM) did not show significant differences. In the protein expression analysis, CaMKII Thr287 autophosphorylation and CaMKII-dependent RyR2 S2814 phosphorylation were significantly increased in diabetic hearts, which were inhibited by short-term (30 min) perfusion of EMPA (1 μM). The expressions of SERCA2a and phospholamban were not significantly different among three groups. Lastly, whole hearts O-GlcNAcylation, one of the important post translational modifications, was significantly reduced by EMPA treatment.

Conclusion
EMPA improved intracellular Ca2+ handling and attenuated arrhythmogenesis in mice with diabetic cardiomyopathy at the diastolic dysfunction phase, suggesting that EMPA may exhibit this anti-arrhythmic effect by normalization of intracellular calcium handling via inhibiting O-GlcNAcylation.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Boehringer Ingelheim