bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ablation of right ventricular endocavitary arrhythmias
Authors: Haq I , Ezzedine F , Sugrue A , Asirvatham S J , Killu A M 
Published: October 2024

Abstract

Background
The right ventricular moderator band-papillary muscle (RV MB-PM) complex has a rich subendocardial network of purkinje fibers which can lead to ventricular arrhythmias (VA)1. Catheter ablation of such arrhythmias is procedurally challenging and there remains limited studies on long-term procedural success.

Purpose
We aimed to systematically study RV MB-PM complex VA.

Methods
A single center retrospective study from January 2013 to December 2023 identified 3249 patients who underwent VA ablation. The RV MB-PM complex was targeted in 47 patients. Acute success was defined as suppression of the targeted VA &gt;=30 minutes post ablation. Long-term success was defined as the absence of symptoms, total PVC burden &lt;5% or improvement in EF in patients presenting with isolated PVCs and as freedom from appropriate ICD therapy in patients presenting with malignant PVCs inducing VF, sustained VT or VT storm.

Results
Mean age was 51.9 ± 16.7 years and 64% were male. 40 (85%) patients had VA targeted from the MB and 7 (15%) from the PM complex (2 anterior, 2 inferior and 3 septal PM). 34 (72%) had no underlying structural heart disease, 3 (6%) ischemic cardiomyopathy and 10 (21%) non-ischemic cardiomyopathy. No patient had delayed gadolinium enhancement in the RV MB-PM complex. VA were inducible in 42 (89%) of patients and activation mapping was used in 9 (19%), pace mapping in 5 (11%) and a combination of activation and pace mapping used in 33 (70%) patients. Intracardiac echocardiography was used in all cases. Pre-QRS duration was 34.0 ± 10.4 ms. Radiofrequency ablation was used in 37 (78.7%) cases, cryotherapy in 4 (8.51%) cases and a combination of the 2 energy sources in 6 (12.8%) cases. In all cases, acute peri-procedural success was achieved. 24 (51.1%) patients presented with isolated PVCs and were followed up for 4.72 ± 3.55 years after their index procedure. 3 patients underwent repeat catheter ablation targeting the same PVC focus but all patients had long term success with a PVC burden of 16.1 ± 12.5% prior to ablation and 2.40 ± 2.44% at last follow-up. 16 patients underwent ablation for recurrent ICD shocks after initially presenting with PVC induced VF. Patients were followed up for 3.22 ± 2.09 years and 14 (88%) patients remained free from ICD therapy. 7 patients had MB ablation for sustained VT and were followed up for 4.06 ± 3.77 years. 5 (71%) patients remained free from ICD therapy. A purkinje potential was seen in 8% (2/24) cases of isolated PVCs and in 39% (9/23) cases of PVC induced VF or VT (p=0.13).

Conclusions
RV MB-PM VA commonly present with malignant VF and a purkinje potential is more likely to be seen in these cases suggesting different VA mechanisms to isolated PVCs and catheter ablation is an effective long-term strategy.
Long noncoding RNA Sngh20 promotes vascular smooth muscle cell senescence and abdominal aortic aneurysm growth by interacting with dead-box helicase 5
Authors: Li J , Yang D F , Zhou Y Z , Deng Z Y , Liu F , Yang C Z 
Published: October 2024

Abstract

Background
Development of non-surgical treatment of human abdominal aortic aneurysm (AAA) has clinical significance. Long noncoding RNAs (lncRNAs) are emerging as powerful mediators participated in cellular senescence process that a critical pathological alteration prompting AAA development.

Purpose
To investigate the role and underlying mechanism of lncRNA Small nucleolar RNA host gene-20 (Snhg20) in AAA formation.

Methods
Experimental AAA mice models were produced by peri-aortic CaPO4 injury in C57bl/6J mice or Subcutaneousangiotensin-II (Ang-II) infusion in Apoe–/– mice and gapmeR was used to knockdown Snhg20 expression. Adeno-associated virus and anti-IL-6 monoclonal antibody was used to knockdown dead-box helicase 5 (DDX5) and neutralize IL-6, respectively.Immunohistochemical and immunofluorescent staining, ELISA and real-time PCR were performed to determine the vascular structure and inflammation, cellular senescence and senescence-associated secretory phenotype (SASP) content in human and mouse AAA lesions. Human aortic SMC cell line was used to investigate the effect of Snhg20 knockdown on senescence and SASP in vitro. LncRNA pulldown and mass spectrometry were used to identify potential targets that interact with Snhg20. p53 DNA binding affinity was examined by EMSA.

Results
The expression of Snhg20 was downregulated in both human and mice AAA lesion. Snhg20 knockdown promoted SMC senescence and loss, vascular inflammation and AAA growth in both experimental AAA mice models. Mechanistically, Snhg20 interacted with DDX5, an important transcriptional coactivator of p53. The absence of snhg20 increased DDX5 and p53 interaction and thereby promoted p53 DNA binding affinity to transcriptionally initiate p21expression, resulting in increased cellular senescence and senescence-associated secretory phenotype (SASP) secretion, including IL-6. Moreover, DDX5 silencing or anti-IL-6 therapy rescued the SMC senescence and loss, vascular inflammation and AAA growth mediated by Snhg20 knockdown. Furthermore, human AAA lesions showed increased DDX5 co-localization with p53 and abundant senescent vascular SMC.

Conclusion
These findings identify an important role of Snhg20 in controlling vascular SMC senescence and SPAP expression and suggest that Snhg20 is a potential target for AAA treatment aimed at reducing VSMCs senescence.Schematic summary
Deletion of the asialyloglycoprotein receptor-1 (ASGR1) causes atheroprotective effects in vitro and in vivo
Authors: Bursill C , Pullen B J , Debebe D , Sandeman L , Wattchow N E , Vidanapathirana A , Stretton L , Nicholls S J , Chen Y C , Peter K , Nankivell V A , Blake S , Tan J T M , Psaltis P J , Packer N H 
Published: October 2024

Abstract

Introduction
The asialoglycoprotein receptor 1 (ASGR1) is a hepatic receptor that clears desialylated glycoproteins from the circulation. A loss-of-function mutation in ASGR1 was reported to associate with a 34% reduction in coronary artery disease (CAD) risk, suggesting a role for ASGR1 in CAD.

Aim
To determine the role of ASGR1 in atherosclerosis and whether deletion of ASGR1 elicits atheroprotective effects.

Methods
Western blotting, mass spectrometry and flow cytometry assessed ASGR1 expression in cultured macrophages or immune cells collected from the blood and aortas of wildtype mice. Bone marrow-derived macrophages (BMDMs) from wildtype and Asgr1-/- mice were subjected to cholesterol efflux and oxidised low-density lipoprotein (oxLDL) uptake in vitro functionalassays. ELISA and qPCR measured changes in lipid regulators in BMDMs. Asgr1-/- mice were crossed with atherosclerosis-prone apolipoprotein (Apo)e-/- mice (Apoe-/-Asgr1-/-). Stable plaque area was assessed histologically in the aortic sinuses of mice fed a high-cholesterol diet for 8 weeks (n=16/group). Using the tandem stenosis surgical model, unstable plaque was assessed in carotid arteries (n=10/group). Human ASGR1 was measured by ELISA in peripheral blood mononuclear cells (PBMCs) isolated from patient samples (n=18).

Results
Western blotting and mass spectrometry discovered ASGR1 is expressed in macrophages. Immunofluorescence identified the presence of ASGR1 in aortic sinus plaque. Flow cytometry revealed ASGR1 is expressed in both inflammatory and patrolling monocytes, neutrophils, macrophages and dendritic cells of blood and aortas. Asgr1-/- BMDMs elicited greater cholesterol efflux (+39%, P&lt;0.05) and decreased oxLDL uptake (-15%, P&lt;0.05), compared to wildtype BMDMs. Moreover, Asgr1-/- BMDMs had significantly higher LDL receptor protein levels (+2-fold), and Lxra (+2-fold) and Pparg (+1.5-fold) mRNA levels than wildtype BMDMs, P&lt;0.001. Plasma from Asgr1-/- mice had lower total (-25%, P&lt;0.05) and LDL (-36%, P&lt;0.05) cholesterol concentrations than wildtype mice. Apoe-/-Asgr1-/- mice developed less stable plaque in aortic sinuses (-37%, P&lt;0.001) than Apoe-/- controls, as well as smaller unstable plaques in carotid arteries (-49%, P&lt;0.05). Finally, in a human population, ASGR1 protein levels were higher in PBMCs from patients with coronary plaque (+61%, P&lt;0.05), than those without plaque, determined from coronary angiograms.

Conclusion
ASGR1 is expressed on monocytes, macrophages and in plaques, and human PBMC ASGR1 associates with coronary plaque. Deletion of ASGR1 causes atheroprotective functions in macrophages in vitro and reduced plaque burden in vivo. Our findings demonstrate ASGR1 is important in atherosclerosis with implications for ASGR1 as a therapeutic target.
Direct IL-6 inhibition prevents arterial thrombosis by reducing collagen-mediated platelets activation
Authors: Ministrini S , Puspitasari Y M , Han J , Kirmes K , Niederberger R , Bengs S , Montecucco F , Libby P , Luescher T F , Bongiovanni D , Liberale L , Camici G G 
Published: October 2024

Abstract

Introduction
Interleukin 6 (IL-6) has a pivotal role in atherothrombosis. Yet, targeting IL-6 to prevent atherothrombotic events still requires validation of efficacy and safety. The recent phase 2 RESCUE trial reported that direct inhibition of IL-6 ligand by the monoclonal antibody (mAb) Ziltivekimab is safe in patients with elevated cardiovascular risk.

Purpose
This project investigated the effects of direct IL-6 inhibition on arterial thrombosis, and assessed the underlying cellular mechanisms.

Methods
Three month old C56Bl/6 male mice received very-low dose LPS i.p. for 4 weeks. During the last week they were randomized to receive in addition either anti-mouse IL-6 mAb 200 μg i.p. every other day or IgG1 isotype control. Then thrombosis of left common carotid artery (LCCA) was induced by laser injury under anesthesia. Platelets of treated mice were isolated and stimulated with either adenosine di-phosphate (ADP), collagen-related peptide (CRP) or thrombin receptor activating peptide (TRAP). Platelets activation was measured by flow-cytometry, as expression of P-selectin and JON/A.The effect of direct IL-6 inhibition was confirmed in patients with stable coronary artery disease (sCAD) by ex-vivo incubation of isolated platelets with either anti-human IL-6 mAb 1.5 μg/mL or IgG1 isotype control. Platelet activation was measured by flow-cytometry, as expression of P-selectin.

Results
Mice treated with anti-IL6 antibody displayed a significantly longer time-to-occlusion after the LCCA (Figure 1), without any significant difference in coagulation parameters. After stimulation with CRP, platelets were significantly activated in control mice, but not in mice treated with anti-IL6 mAb. Similarly, activation of isolated platelets from patients with sCAD was significantly reduced (Figure 2) by the ex-vivo treatment with anti-IL6 mAb.

Conclusion
The direct inhibition of IL-6 reduces platelets reactivity to collagen, thereby blunting arterial thrombosis upon endothelial damage. These results provide a potential mechanism to explain the reduction of cardiovascular risk associated to direct IL-6 inhibition.

Conclusion
The direct inhibition of IL-6 reduces platelets reactivity to collagen, thereby blunting arterial thrombosis upon endothelial damage. These results provide a potential mechanism to explain the reduction of cardiovascular risk associated to direct IL-6 inhibition.Figure 1Figure 2
Deficiency of transcription factor E4BP4 suppresses neointimal formation after vascular injury
Authors: Niida T , Ohtomo F , Isoda K , Minamino T 
Published: October 2024

Abstract

Aim
In addition to traditional risk factors such as hypertension, diabetes, and dyslipidemia, chronic inflammation is deeply involved in the onset and pathogenesis of atherosclerotic diseases. Furthermore, diurnal fluctuations are observed in the rupture of atherosclerotic plaques and the onset of myocardial infarction. There are still many patients for whom medical treatments such as statins and antihypertensive drugs do not respond adequately, and new treatment methods are expected. E4BP4 (also known as NFIL3) is a basic leucine zipper (bZIP)-type transcription factor associated with circadian rhythms and cell viability, and it has been reported that E4BP4 regulates inflammation. Therefore, to investigate how the circadian transcription factor E4BP4 which is involved in inflammation, we decided to examine the role of E4BP4 in neointimal formation after vascular injury.

Methods and Results
Using E4BP4-deficient (E4BP4−/−) and wild-type (WT) mice, we investigated neointimal formation 2 weeks after femoral artery injury induced by an external vascular cuff model. Intimal and medial area were measured, and the intima/media ratio was calculated. Systolic blood pressure was similar between groups (WT mice: 92 ± 5 mmHg [n = 5] vs. E4BP4−/− mice: 90 ± 4 mmHg [n = 5]). And there was no significant difference in baseline body weight between groups (WT mice: 22.4 ± 0.8 g [n = 5] vs. E4BP4−/− mice: 22.0 ± 1.1 g [n = 5]). The mean intimal area and the intima/media ratio of E4BP4−/− mice decreased by 86 % (WT mice: 3,683 ± 512 μm2 [n = 10] vs. E4BP4−/− mice: 521 ± 363 μm2 [n = 10]; P &lt; 0.0001) and 97% (WT mice: 0.33 ± 0.05 vs. E4BP4−/− mice: 0.01 ± 0.03; P &lt; 0.0001), compared with WT mice. However, we observed no significant difference in the medial area (WT mice: 11,019 ± 358 μm2 vs. E4BP4−/− mice: 11,281 ± 401 μm2; P = NS) between groups (Figure). Immunohistochemistry for NK cell (NKp46) revealed the percentage of NKp46 positive area in the adventitia of E4BP4−/− mice was significantly lower compared with WT mice at 14 days post-injury (P &lt;0.05). Furthermore, the positive area of IL-6 (P&lt;0.05), TNF-α (P&lt;0.05) and IFN-γ (P&lt;0.05) in the intima of E4BP4−/− mice tended to be much smaller than those of WT mice. Our findings indicate that E4BP4 might induce vascular inflammation following vascular injury.

Conclusions
Deficiency of E4BP4 reduced the inflammatory cytokines and suppressed neointimal formation after injury. We also observed a decrease in NKp46, suggesting that NK cell development is impaired by E4BP4 deficiency. The present study is the first to demonstrate that E4BP4 plays an important role in the increase of neointimal formation after injury in vivo, thus suggesting that E4BP4 inhibition may represent a useful strategy to inhibit vascular inflammation.Neointimal formation after cuff injury
Long-term follow-up after catheter ablation of atrial fibrillation and atrial tachycardia in patients with pulmonary hypertension
Authors: Dusik M , Fingrova Z , Wichterle D , Jansa P , Ambroz D , Dytrych V , Linhart A , Havranek S 
Published: October 2024

Abstract

Introduction
Catheter ablation of atrial fibrillation and atrial tachycardia (AF / AT) is established treatment in selected population. Only limited data, including long-term results, exist in patients with pulmonary hypertension (PH). Recently published prospective multicentric trial showed that more extensive radiofrequency catheter ablation of the bi-atrial arrhythmogenic substrate instead of clinical arrhythmia ablation alone is not beneficial in terms of arrhythmia recurrence in patients with AF / AT and PH. Now, we present the results of an extended, long-term follow-up from one of the study centres.

Methods
Patients with combined post- and pre-capillary or isolated pre-capillary PH and AF / AT indicated to catheter ablation were enrolled and randomised 1:1 into two parallel treatment arms. Patients underwent either clinical arrhythmia ablation only (Limited ablation group) or clinical arrhythmia plus substrate-based ablation (Extended ablation group). The primary endpoint was arrhythmia recurrence &gt;30 s without antiarrhythmic drugs after the 3-month blanking period.

Results
A total of 52 patients (median age 71 years (IQR 62-75); 27 males) were enrolled. The presumable clinical arrhythmia was AF in 20 and AT in 32 patients, including typical AFL in 22 patients. Limited and extended ablation group included 28 and 24 patients, respectively. During the extended follow-up period of median 31 (IQR: 18; 46) months, the primary endpoint occurred in 17 patients (71 %) vs. 13 patients (46 %) in the Extended vs. Limited ablation group (p = 0.096). In parallel, overall mortality was comparable between groups (9 [38 %] vs. 11 [39 %]). Only 2 patients had recurrence of AFL during the extended follow-up. However, new different arrhythmia was documented in another 7 patients after the AFL ablation.

Conclusion
In PH patients, recurrence of AF / AT after a catheter ablation is frequent and the recurrence rate increases with the duration of follow-up. Ablation strategy seems to have no impact on arrhythmia free survival. Patients with typical atrial flutter have significantly higher chance to maintain sinus rhythm after a catheter ablation compared to AF or other AT.
Discordance between left atrial volume and scar burden in patients with atrial fibrillation and its impact on atrial fibrillation recurrence after catheter ablation
Authors: Lee K , Lee S R , Choi J M , Ahn H J , Kwon S I , Choi E K , Oh S I 
Published: October 2024

Abstract

Background
Large left atrial (LA) volume and a high burden of LA low voltage zone (LVZ) are associated with atrial fibrillation (AF) recurrence after AF catheter ablation. There is a scarcity of information on the association between LA volume and LVZ and its impact on the risk of AF recurrence.

Purpose
To investigate the relationship between the LA volume and LVZ, as well as how these factors contribute to the recurrence of atrial fibrillation (AF).

Methods
From Nov 2021 to Oct 2023, drug-refractory AF patients who underwent AF catheter ablation were included. LA volume was assessed using the LA volume index (LAVI) using echocardiography. The LVZ was evaluated by conducting high-density electroanatomical mapping using a multipolar catheter. The cut-off value associated with AF recurrence was 48ml/m2 in LAVI and 4.5% in scar burden. Patients were categorised into four groups according to the LAVI and scar burden: Group 1 (Low LVZ and small LA), group 2 (Low LVZ and large LA), group 3 (High LVZ and small LA), and group 4 (High LVZ and large LA).

Results
A total of 170 patients were included (mean age 62± 9 years, 82% of men, 68.2% of non-paroxysmal AF and 81 [48%] in group 1; 32 [19%] in group 2, 27 [16%] in group 3, 30 [17%] in group 4, respectively). Among total, mean follow-up duration was 266.5 ± 174.4 days, and 8.8% of patients received additional LA ablation beyond pulmonary vein isolation. Among the four groups, group 2 and 4 were significantly associated with higher risks of AF recurrence compared to group 1 (HR 2.36 [1.04-5.34], p=0.039; 3.56 [1.59-7.95], p=0.002, respectively). The risk of AF recurrence was highest in group 4, followed by group 2 (log-rank P=0.002). Comparing group 2 and 3, AF recurrence occurred predominantly within 6-month after catheter ablation in group 2, while after 1-year in group 3 (log-rank P=0.83).

Conclusion
About one-third of patients showed discordance between the LAVI and LVZ, which are both independent predictors for AF recurrence. A substantial LA volume seems to contribute to early AF recurrence, whereas a high scar burden appears to affect late AF recurrence.
Catheter ablation vs medical management for atrial fibrillation in patients with heart failure: a systematic review and metanalysis
Authors: Mathew Kalathil R , Machanahalli Balakrishna A , Ahmed H , Patel R , Aboeata A 
Published: October 2024

Abstract

Background
Current guidelines recommend a class IIa recommendation for catheter ablation in Atrial Fibrillation [AFIB]. Traditionally, catheter ablation has been known to be more effective in maintaining sinus rhythm than pharmacological management. However, there is sparse evidence to suggest that this translates to improved clinical outcomes in patients with heart failure. We did a systematic review and meta-analysis of randomized trials to compare the efficacy of ablation vs medical management for AFIB in heart failure.

Methods
A systematic search was conducted for randomized trials from inception to Jan 2024 for studies comparing the outcomes of catheter ablation vs medical management for AFIB in heart failure. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular (CV) mortality, heart failure hospitalizations, change in LV ejection fraction (LVEF), AF recurrence rate, 6-minute walk test (6MWT), change in MLHFQ scores and cerebrovascular events. Random-effects models were used to calculate the pooled incidence, mean difference (MD), and risk ratios (RRs) with 95% confidence intervals (CIs).

Results
A total of 10 RCTs with 2,348 patients were included in this study. Pulmonary vein isolation was the mainstay ablation strategy used. Compared with medical management, Ablation was associated with a significant reduction in all-cause mortality (RR- 0.61; 95% CI, 0.48-0.78; P&lt;0.0001). Ablation was also associated with lower cardiovascular (CV) mortality (RR- 0.52; 95% CI, 0.36-0.75; P&lt;0.0004), heart failure hospitalizations (RR- 0.67; 95% CI, 0.54-0.82; P&lt;0.0001) and AF recurrence rate (RR- 0.43; 95% CI, 0.25-0.75; P&lt;0.003). The study showed an improvement in LVEF (RR - 6.05; 95% CI, 3.35-8.75; P&lt;0.0001), 6MWT (RR- 13.99; 95% CI, 4.18-23.81; P&lt;0.005) and in MLHFQ score (RR -6.98; 95% CI, -12.03 to -1.93; P&lt;0.007. There was a statistically significant difference between the 2 cohorts in the rates of cerebrovascular events (RR- 0.68; 95% CI, 0.35-1.30; P&lt;0.24).

Conclusion
Randomized trials have shown clear benefits with catheter ablation compared to medical management for AFIB in heart failure. Ablation has demonstrated significantly lower all-cause mortality, reduced CV mortality, HF hospitalizations, AFIB recurrence rate, and improvement in LVEF. Patients who underwent catheter ablation showed improvement in functional outcomes like 6MWT and MLHFQ scores. There was no difference in the incidence of cerebrovascular events compared to medical management. This study adds to the growing evidence in the literature for ablation therapy; however, more trials are needed to identify patients for optimal benefits across the spectrum of heart failure patients.Forest PlotsForest Plots