bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidentally induced atrial fibrillation during programmed electrical stimulation in patients with depressed left ventricular systolic function after an acute myocardial infarction: a CARISMA substudy
Authors: Sakthivel T , Thomsen A F , Jacobsen P K , Koeber L , Joergensen R M , Jacobsen U G , Huikuri H V , Bloch Thomsen P E , Joens C 
Published: November 2023

Abstract

Background
The aim of this study was to investigate the clinically significant value of incidentally induced atrial fibrillation (AF) during programmed electrical stimulation (PES) in patients with left ventricular systolic dysfunction (≤40%) after an acute myocardial infarction (MI).

Methods
In this study we included 231 patients from the Cardiac Arrhythmias and RIsk Stratification after Myocardial InfArction (CARISMA) study. These patients were identified 3-21 days after being diagnosed with an MI, had left ventricular ejection fraction ≤40% and had no prior history of AF. They all received an implantable cardiac monitor (ICM) and were continuously monitored for cardiac arrhythmias for 2 years. A PES was performed 6 weeks post-MI with pacing from the right atrium and coronary sinus for induction of SVT and from the ventricular apex and outflow tract with up to three extra stimuli for induction of VT. Induction of AF was unwanted but reported if this incidentally occurred.

Results
AF was induced in 34 patients (15%) during the PES of which 10 (29%) later developed AF. A total of 61 patients (26%) developed AF within 2-years follow-up and the overall risk of AF was not significantly increased in patients with PES induced AF compared to patients without inducible AF (HR 1.6, P=0.14), however, the risk of AF ≤188 days post-MI was slightly increased (HR 3.0, P=0.01). The risk of bradyarrhythmia (HR=0.2, P=0.07), ventricular arrhythmias (HR=0.7, P=0.77) and MACE (HR 0.5, P=0.28) was reduced in patients with inducible AF compared to patients without inducible AF.

Conclusions
Incidentally induced AF during an electrophysiological study in post-MI patients was relatively frequent (15%) but was not associated with a higher risk of atrial fibrillation, other cardiac brady- or tachy-arrhythmias or major cardiac events. Even though the short-term risk for AF slightly increased, this does not seem to justify anticoagulation treatment or intensified follow-up in these patients.
Histone Mono-methylation by SETD7 Orchestrates Angiogenic Response in Diabetic Limb Ischemia
Authors: Mohammed S A , Gorica E , Karsay G , Albiero M , Ambrosini S , Fadini G P , Ruschitzka F , Costantino S , Paneni F 
Published: November 2023

Abstract

Background
Peripheral artery disease (PAD) is highly prevalent in patients with diabetes (DM) and associates with a high rate of limb amputation and poor prognosis. Surgical and catheter-based revascularization have failed to improve outcome in DM patients with PAD. Hence, a need exists to develop new treatment strategies able to promote blood vessel growth in this setting. Mono-methylation of histone 3 at lysine 4 (H3K4me1) - a specific epigenetic signature induced by the histone methyltransferase SETD7 - favours an open chromatin thus enabling gene transcription. Purpose: To investigate whether SETD7-dependent epigenetic changes modulate angiogenic response in diabetes. Methodology: Primary human aortic endothelial cells (HAECs) were exposed to normal glucose (NG, 5 mM) or high glucose (HG, 25 mM) concentrations for 48 hours. Unbiased gene expression profiling was performed by RNA sequencing (RNA-seq) followed by Ingenuity Pathway Analysis (IPA). In vitro assays, namely cell migration and tube formation were employed to study angiogenic properties in HAECs. SETD7 and H3K4me1 levels were investigated by Western blot and Chromatin immunoprecipitation (ChIP). Pharmacological blockade of SETD7 was achieved by using the highly selective inhibitor (R)-PFI-2. Mice with streptozotocin-induced diabetes were orally treated with (R)-PFI-2 or vehicle and underwent hindlimb ischemia by femoral artery ligation for 14 days. Blood flow recovery was analysed at 30 minutes, 7 and 14 days by laser Doppler imaging. Our experimental findings were also translated in gastrocnemius muscle samples from patients with and without diabetes.

Results
RNA-seq in HG-treated HAECs revealed a profound upregulation of the methyltransferase SETD7, an enzyme involved in mono-methylation of lysine 4 at histone 3 (H3K4me1). SETD7 upregulation in HG-treated HAECs was associated with increased H3K4me1 levels as well as with impaired endothelial cell migration and tube formation. Both SETD7 gene silencing and pharmacological inhibition by (R)PFI-2 rescued hyperglycemia-induced impairment of HAECs migration and tube formation, while SETD7 overexpression blunted the angiogenic response. RNA-seq and ChIP assays showed that SETD7-dependent H3K4me1 regulates the transcription of the angiogenesis inhibitor semaphorin-3G (SEMA-3G, (Figure 1). Moreover, SEMA-3G overexpression blunted migration and tube formation in SETD7-depleted HAECs. In diabetic mice with hindlimb ischemia, treatment with (R)-PFI-2 improved limb vascularization and perfusion as compared to vehicle (Figure 2). Finally, SETD7/SEMA3G axis was upregulated in muscle specimens from T2D patients as compared to controls (Figure 2) Conclusion: Targeting SETD7 represents a novel epigenetic-based therapy to boost neovascularization in diabetic patients with PAD.
Increased levels of platelet function-related miR-16-5p predicts increased severity of ischemic stroke: in silico validation analysis
Authors: Eyileten C , Nowak A , Wicik Z , Keshwani D , Marszalek M , Domitrz I , Wierzchowska-Ciok A , Mirowska-Guzel D , Czlonkowska A , Postula M 
Published: November 2023

Abstract

Background
Ischemic stroke (IS) is one of the most frequent causes of death. Since miRNAs have been illustrated to play an important role in various processes through regulation of multiple genes, and platelet function, their utility as novel biomarkers should be determined. We aimed to identify and validate circulating miRNAs, modulated in acute ischemic stroke (IS) patients in order to distinguish the most specific as biomarkers to facilitate diagnosis and prognosis.

Method
Sixty patients with acute IS (24-h and 7-days after IS) and 30 age- and gender-matched individuals free of stroke with multiple risk factors for cardiovascular disease. Studied miRNAs were selected based on bioinformatic analysis that was previously published by our team (1-2-3). PlasmaRNA was extracted; quality RNA was assessed: fluorometric assay; RT-PCR for miRNAs expression measurement p&lt;0.05.

Results
Let-7e expression 7-day of IS was significantly lower than both controls and first day of IS (p=0.007, p=0.001, res). miR-125a-3p was lower both at day-1 and day-7 of IS compared to controls (p=0.008, p=0.020, res). miR-125a-5p on the other hand, had significantly higher expression at day-1 compared to controls (p=0.002). Both miR-125a-3p and -5p showed diagnostic value in ROC curve analysis (AUC= 0.705, AUC= 0.709, res). Patients with moderate stroke (based on NIHSS) had significantly higher miR-16-5p expression levels compared to patients with minor stroke at the first day of IS (AUC: 0.718, (95% CI, 0.59-0.85) p = 0.004). High baseline expression of miR-16-5p and diabetes mellitus are independent predictors of increased severity of stroke to a multivariate analysis (OR: 4.341; 95% CI, 1.15–16.42; p = 0.031 and OR: 4.653; 95% CI, 1.07–20.19; p = 0.040, res).

Conclusion
In this study we validated miRNAs based on our previous bioinformatic analysis which could serve as novel, platelet-related predictive biomarkers of the IS severity, and can be used for early stratification of patients and prediction of severity of disease development in an individual.
A selective mineralocorticoid receptor blocker, esaxerenone, attenuates vascular dysfunction and inhibits atherogenesis in apolipoprotein e-deficient mice
Authors: Munkhjargal U , Daiju F , Masataka S 
Published: November 2023

Abstract

Introduction
Pharmacological blockade of mineralocorticoid receptors (MR) is a potential therapeutic approach to reduce cardiovascular complications because MR play a crucial role in cardiovascular regulation. Recent studies suggest that MR antagonists affect several extrarenal tissues, including vascular function. We investigated the effects of a novel non-steroidal selective MR blocker, esaxerenone (ESAX), recently approved for hypertension treatment in Japan, on vascular function and the development of atherosclerosis.

Methods and results
ESAX (3mg/kg/day) or vehicle was orally administered to western type diet-fed apolipoprotein E-deficient mice for 20 weeks or for 8 weeks to investigate the effects on atherogenesis or vascular dysfunction. Administration of ESAX for 20 weeks suppressed the development of atherosclerotic plaques in the aortic arch compared with the vehicle group (p&lt;0.001) without alteration of blood pressure. In addition, ESAX reduced the expression of intercellular cell adhesion molecule-1 (p&lt;0.05), macrophage infiltration (p&lt;0.01), lipid deposition (p&lt;0.05) and tended to decrease the expression of vascular cell adhesion molecule-1 as determined by immunohistochemical analysis. Moreover, phosphorylation of eNOSSer1177 (p&lt;0.05) and Akt (p&lt;0.05) were increased in the aorta of ESAX-treated mice. Administration of ESAX for 8 weeks attenuated western type diet-induced endothelial dysfunction (p&lt;0.05) accompanied with the decrease in expression of ICAM1 (p&lt;0.05) and phosphorylation of JNK (p&lt;0.05) in the descending aorta. In in vitro experiment, aldosterone decreased the phosphorylation of eNOSSer1177 and increased the phosphorylation of eNOSThr495 in a dose dependent manner, which were attenuated by ESAX in HUVECs. In ex vivo vascular reactivity assay, ESAX diminished the aldosterone-induced endothelial dysfunction.

Conclusion
ESAX ameliorated hyperlipidemia-induced atherosclerosis and vascular dysfunction in mice, suggesting that ESAX is a promising therapeutic approach for cardiovascular complications.
Ischemic stroke is associated with reduced sclerostin expression in human atherosclerotic plaques
Authors: Miteva K , Burger F , Roth A , Thouverey C , Ferrari S L , Mach F 
Published: November 2023

Abstract

Objectives
Vascular calcification (VC) is a hallmark of atherosclerosis and commonly found in aging population, increasing the risk of myocardial infarction (MI), stroke and mortality. Our data shows that Wnt/β-catenin signaling pathway and its main inhibitor, sclerostin (Scl, Sost) could be central to this process. However, Scl inhibition with romosozumab has been associated with a higher incidence of major adverse cardiovascular events (MACE). This increases in MACE call into question the safety of romosozumab use, particularly in patients with cerebrovascular and cardiovascular history. However, whether Scl expression levels in atherosclerotic plaques are associated with clinical ischemic events remains unknown. Here we explored the association between Scl expression in human atherosclerosis plaques and the extend of VC, VSMCs phenotypic switch to osteoblast-like cells (OBL), and its correlation to clinical cerebrovascular events.

Methods
Carotid plaque specimens of symptomatic (ischemic stroke) and asymptomatic patients undergoing endarterectomy for severe carotid stenosis were co-stained with VSMCs specific marker (Myh11), OBL marker (RUNX2), microcalcification sensitive fluorescent imaging probes (OsteoSense) and Scl and used for quantification analyses.

Results
scRNA seq data showed that Sost is upregulated by VSMCs in the aortic region protected against VC, suggesting an inhibitory role of Sost on VSMCs differentiation into OBL. Carotid plaque specimens from asymptomatic patients exhibited a significantly higher percentage of VSMCs expressing Scl (Myh11+Scl+) in parallel with a greater Scl+ area versus symptomatic patients. A negative correlation was observed between the percentage of Myh11+Scl+ cells and the extent of microcalcification (OsteoSense) as well as between the percentage of total Scl+ cells and induction of VSMCs phenotype switch to osteoblast-like cells (quantified as RUNX positive area).

Conclusion
In atherosclerotic plaques of patients with ischemic stroke, total and VSMCs -specific Scl expression levels were reduced as compared to asymptomatic patients. Furthermore, reduction in Scl levels was positively associated with the extent of microcalcification, and VMSCs phenotypic switch to OBL. The presented findings suggest that sclerostin expression in human atherosclerotic plaques could contribute to plaque stabilization and be protective against ischemic stroke, explaining why Scl inhibition with romosozumab resulted in a higher incidence of MACE.Figure 1Figure 2
Increased 12/15-lipoxygenase by disturbed flow promotes endothelial dysfunction and the development of atherosclerosis
Authors: Wang X Q , Chen J W , Lu L , Yang C D 
Published: November 2023

Abstract

Introduction
Atherosclerosis is predisposed at bifurcations, branch points and arterial curvatures where the blood flow is disturbed. Deposition and oxidative modification of low-density lipoprotein (LDL) in the subendothelial intima is an early event in the pathogenesis of atherosclerosis. However, the effect of disturbed flow (d-flow) on LDL oxidation and the underlying mechanisms remain unclear.

Purpose
In this study, we investigated the role of 12/15-lipoxygenase (LOX) in LDL oxidation in endothelial cells (EC) and the development of atherosclerosis at d-flow sites.

Methods
En face immunofluorescence was performed to analyze the expression of 12/15-LOX in EC under exposure to different flow patterns. Protein expression and LDL oxidation was studied in vitro by using 2 different flow apparatuses. Animal model of d-flow was established by partial ligation of the carotid artery.

Results
En face staining exhibited a significant increase in 12/15-LOX protein expression in EC in areas exposed to d-flow than those exposed to steady flow (s-flow). Carotid partial ligation in ApoE knockout mice led to substantially increased deposition of oxidized LDL in the subendothelial intima and formation of atherosclerotic plaques in the carotid artery, whereas these detrimental effects by d-flow were markedly attenuated in ApoE/12/15-LOX double knockout mice. In cultured EC, d-flow generated by a reversal flow pump markedly promoted the expression of 12/15-LOX and translocation of the protein onto the cell membrane. Inhibition of 12/15-LOX in EC, either by knockdown with its specific siRNA or a pharmacological inhibitor, suppressed production of 15s-HETE and LDL oxidation in response to d-flow. Mechanically, we found d-flow induced the expression of 12/15-LOX by activating a specific responsive element in the 12/15-LOX promoter through recruiting a shear stress-sensitive transcriptional factor SREBP2. Chromatin immunoprecipitation further confirmed the interaction of SREBP2 with the promoter of 12/15-LOX upon d-flow exposure.

Conclusions
These data define an essential role of 12/15-LOX in promoting the pathogenesis of atherosclerosis under d-flow by increasing LDL oxidation in EC through SREBP2 signaling.
Quantification of local heterogeneity from activation maps of omnipolar multielectrode recordings
Authors: Ruiperez-Campillo S , Pancorbo L , Castells F , Crespo M , Chorro F J , Merino J L , Casado-Arroyo R , Millet J 
Published: November 2023

Abstract

Background and Purpose
The study of cardiac arrhythmias requires understanding the heart's electrical conduction patterns. Using multielectrode catheters and other mapping systems have allowed a futher understanding of the wavefront. In particular, novel high-density (HD) grid catheters, enable the recording of omnipolar electrograms, which are purportedly not influenced by catheter orientation, allowing real-time determination of signal propagation direction. We propose a novel heterogeneity metric to quantify the degree of disorganisation in the vector maps from reconstructed omnipolar electrograms, which could potentially be utilised to detect and assess the degree of fibrosis in cardiac tissue.

Methods
We utilised basal and stimulated recordings from 5 Langendorff-perfused rabbit hearts, where signals were obtained using a multielectrode mapping catheter with 128 electrodes spaced at 1mm. Three recordings were taken for each series, basal at 37°C, plus stimulation performed using a bipolar electrode at 4 Hz and 6 Hz . An angle propagation matrix is computed for the local area of recording, by means of the orthogonal bipolar loops of each clique. A local heterogeneity metric is derived from the summation of angular variations of neighbouring elements. An illustration of the heterogeneity map, and heterogeneity metric for the recording area (H) is illustrated in figure 1. A statistical analysis is performed then to assess the distribution of heterogeneity values.

Results
Heterogeneity values for each experimental heart, and the distributions of H values obtained according to the stimulation type are shown in figure 2A. The ROC curve obtained from the values of H has an AUC of 0.996, with an optimal threshold value of 0.113, resulting in a confusion matrix presented in 12 TP, 30 TN, 3 FP and 0 FN. The study shows that the proposed heterogeneity metric can quantify the degree of disorganization in the vector maps and can be used to differentiate between basal and stimulated groups with p&lt;0.001.

Conclusion
This study proposes a novel heterogeneity metric to quantify the degree of disorganization in the vector maps from reconstructed omnipolar electrograms. The methodology was assessed on basal and stimulated epicardial rabbit recordings and found to be effective in differentiating between the two groups with high accuracy. Future studies should focus on the efficiency of assessing fibrotic tissue using the proposed metric.Figure 1Figure 2
Direct oral anticoagulants versus vitamin K antagonists for left ventricular thrombus: a systematic review and meta-analysis
Authors: Pasqualotto E , Gewehr D M , Ferreira R , Silva C H A , Choque J W L , Cruz S A , Park A , Kubrusly L F 
Published: November 2023

Abstract

Introduction
Left ventricular thrombi (LVTs) increase the risk of stroke and systemic embolism and are commonly seen after acute myocardial infarction. While vitamin K antagonists (VKAs) are the recommended first-line treatment for LVT, direct oral anticoagulants (DOACs) are being used as an alternative. However, the comparative efficacy and safety of DOACs and VKAs in LVT treatment are unclear.

Purpose
We conducted a systematic review with meta-analysis to evaluate the impact of DOACs compared with VKAs therapy in patients with LVT.

Methods
PubMed, Embase, and Cochrane were systematically searched for studies that compared DOACs versus VKAs and reported efficacy and safety endpoints. We performed meta-analyses with fixed or random effect models based on the level of heterogeneity determined by the Cochrane Q-test and I2 statistics.

Results
Three randomised controlled trials (RCTs) and 29 cohort studies were included, with 4,400 patients assigned to either DOACs (1,307 patients) or VKAs (3,093 patients). Our findings indicate that DOACs therapy did not significantly reduce stroke/systemic embolic events (OR 0.90; 95% CI 0.65-1.26; p=0.54; I2=33%), stroke (OR 0.90; 95% CI 0.59-1.36; p=0.60; I2=7%), systemic embolic events (OR 0.65; 95% CI 0.39-1.06; p=0.08; I2=0%), thrombus resolution (OR 1.11; 95% CI 0.92-1.33; p=0.27; I2=0%), minor bleeding (OR 0.68; 95% CI 0.39-1.18; p=0.17; I2=0%), major bleeding (OR 0.84; 95% CI 0.47-1.49; p=0.54; I2=16%), or all-cause mortality (OR 1.01; 95% CI 0.75-1.36; p=0.97; I2=0%) compared to VKAs. However, DOACs therapy was associated with a statistically significant reduction in any bleeding (OR 0.72; 95% CI 0.55-0.96; p=0.02; I2=0%) and clinically relevant bleeding (OR 0.62; 95% CI 0.41-0.92; p=0.02; I2=0%) compared to VKAs therapy. Our subgroup analysis of patients treated with apixaban revealed no significant differences between DOACs and VKAs therapies for stroke, clinically relevant bleeding, and all-cause mortality. Conversely, rivaroxaban therapy was associated with a statistically significant reduction in systemic embolic events and clinically relevant bleeding compared to VKAs therapy.

Conclusion
DOACs therapy was not associated with reduced efficacy and safety endpoints compared to VKAs therapy, except for fewer haemorrhagic events. Rivaroxaban therapy had a significant reduction in systemic embolic and hemorrhagic events. These findings support the superiority of DOACs over VKAs therapy for LVT.PRISMA Flow-ChartForest plot of odds ratios (OR)
Efficacy and safety of antiarrhythmic drugs for pharmacological cardioversion of atrial fibrillation depending on gender: a subanalysis of CANT II Study
Authors: Wybraniec M , Maciag A , Miskowiec D , Balsam P , Wojcik M , Wrobel W , Farkowski M , Cwiek-Rebowska E , Szolkiewicz M , Bula K , Krzowski B , Kozinski M , Kasprzak J , Szwed H , Mizia-Stec K 
Published: November 2023

Abstract

Background/introduction
The data on gender differences concerning antiarrhythmic drugs (AAD) applied in atrial fibrillation (AF) patients is scarce.

Purpose
The aim of the study was to evaluate gender differences in terms of clinical profile of AF patients, and efficacy and safety of AAD used for pharmacological cardioversion (PCV) of AF.

Methods
This research was a sub-analysis of retrospective multicenter Cardioversion with ANTazoline II (CANT) registry, which comprised 1365 patients with short-duration AF referred for urgent PCV with the use of AAD. Patients were categorized in terms of gender and compared in terms of clinical parameters and outcome of PCV. The primary endpoint was return of sinus rhythm within 12 hours after drug infusion and the composite safety endpoint involved bradycardia &lt;45 bpm, hypotension, syncope or death.

Results
The majority of patients qualified for PCV were men (n=725, 53.1%). Females were older and more symptomatic, had higher CHA2DS2-VASc score, greater prevalence of tachyarrhythmia and higher utilization of chronic anticoagulation. The overall efficacy (71.4% vs. 70.1%,P=0.588) and safety (5.2% vs. 4.6%,P=0.603) of PCV was comparable in men and women. Amiodarone (68.3% vs. 65.9%, P=0.664) and antazoline (77.1% vs. 80.0%, P=0.19) had similar efficacy in men and women, but propafenone had lower rate of rhythm conversion in men (64.7% vs. 79.3%, P=0.046; Figure). None of the assessed AAD differed in terms of safety profile in both genders. Logistic regression showed that, among other predictors, in women the use of amiodarone vs. other AAD (odds ratio [OR] 0.569, P=0.033), while in men administration of a amiodarone (OR 0.379, P=0.001) or propafenone (OR 0.331, P=0.002) vs. other AAD were associated with lower chance of successful rhythm conversion.

Conclusions
Female patients with AF share different clinical profile and similar efficacy and safety of AAD used for PCV as compared to male participants. Propafenone has significantly lower efficacy in men, which requires further prospective investigation.