bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of proNGF/NGF-NGFR-axis on the regulation of arterial remodelling
Authors: Takashima S , Usui S , Goten C , Inoue O , Takeda Y , Yamaguchi K , Hashimuko D , Sugita M , Sakai Y , Sakata K , Takamura M 
Published: October 2024

Abstract

Background
Peripheral blood mononuclear cells (MNCs) contribute to the pathogenesis of arteriosclerosis. Nerve growth factor receptor (NGFR) is present in peripheral blood and the ischemic coronary artery. NGFR transduces neurotrophin signals towards cell survival or apoptosis in different cell types dependent on coupling co-receptors. However, the role of NGFR-positive (NGFR+) MNCs in arterial remodelling is unknown.

Purpose
To investigate the functional mechanisms under which NGFR+ MNCs are involved in arterial remodelling.

Methods
Adult C57BL/6J male NGFR-wild-type (WT) or -bone marrow (BM)-specific (KO) mice were subjected to unilateral carotid artery ligation. The ligated and the opposite-sided, sham-operated arteries were assessed by immunohistology and gene expression analysis using a PCR on day 28. Also, human NGFR+ MNCs from a healthy volunteer were sorted using fluorescence-activated cell sorting and characterised using RNA sequencing. The cell apoptosis (AnnexinV+7AAD-) and chemotaxis in response to the ligands, NGF and its precursor proNGF, were assessed using flow cytometry and a Transwell migration.

Results
In WT mice, BM-derived NGFR+ cells accumulated in the neointima after ligation. The neointimal area was significantly greater in the BM-specific depletion of NGFR than in WT mice. NGFR+ cells in the neointima exhibited apoptosis (TUNEL+ and cleaved caspase-3+) accompanied by promoted F4/80+ macrophage and anti-inflammatory IL-10. By contrast, in the BM-specific NGFR-KO model, non-BM-derived SMCs increased in the neointima with augmented proliferation, and the accumulation of BM-derived cells and the expression of IL-10 were decreased. The expressions of proNGF/NGF and inflammatory cytokines, including IL-6, were not changed in a ligated artery, irrespective of NGFR+ depletion. Human NGFR+ MNCs expressed TrkB, TrkC, and sortilin co-receptors but not macrophage markers. Human NGFR+ MNCs, but not NGFR- MNCs, co-cultured with artery SMCs were susceptible to apoptosis in response to proNGF. Additionally, PDGF stimulated proNGF/NGF expression in SMCs, and proNGF/NGF did not affect the proliferation of SMCs in vitro. Furthermore, NGFR+ MNCs, but not NGFR- MNCs, increased migration toward NGF and did not show chemotaxis toward proNGF.

Conclusions
These data imply that local NGF might draw NGFR+ MNCs to the injured artery, in which proNGF induces NGFR+ MNCs apoptosis. Apoptotic NGFR+ cells promoted macrophage chemotaxis to resolve inflammation and decrease neointimal formation. Thus, we propose the proNGF/NGF-NGFR axis as potentially contributing to the suppression of arterial remodelling.
Clinical characteristic and zero-fluoroscopy ablation outcomes of tachyarrhythmias in pregnant: a single center study
Authors: Smagulova A , Ainabekova B , Albaev R , Abdrakhmanova Z H , Suleymen Z H , Abdrakhmanov A 
Published: October 2024

Abstract

Background
Although recommended avoid any intervention during gestation in cases of drug refractory of arrhythmias catheter ablation may be necessary in pregnant women.

Purpose
To present clinical characteristics and outcomes of zero-fluoroscopy catheter ablation during gestation.

Methods
This prospective, single center study included 84 cases of tachyarrhythmias during gestation. In 44 cases of drug refractory was performed catheter ablation without fluoroscopy (main group). We evaluated the further course of gestation and obstetric outcomes after ablation in comparison with pregnant with antiarrhythmic therapy of tachyarrhythmias (n=40, control group).

Results
Both groups were comparable by mean age of pregnant (28.2±4.2 vs. 27.3±3.9 years, p=0.093) and mean duration of gestation (24 ±3.4 vs. 23.8 ±3.2 weeks, p=0.123). New onset arrhythmia prevailed in both groups (64% vs. 55%, p=0,280). Supraventricular tachycardia was the most common arrhythmia during gestation (81,8% vs. 52,5%, p=0,005), which was followed by premature contraction (13,6% vs. 40%, p=0,007). Cases of ventricular tachycardia were rare (4,6% vs. 7,5%, p=0,665). Ablation was performed under the guidance of CARTO (45%) and Ensite Precision systems (55%) without using fluoroscopy in all cases. Acute procedural success of zero-fluoroscopy ablation was in 100% with mean procedural time 71±17 minutes without any complication. Outcomes: further course of gestation characterized by increased incidence of uterine contractile activity and placental abruption only in main group (4,54%, p=0.464 and 2.3%, p=642 respectively). There were no differences in the rate of other complication: uterine blood flow violation (15.9% vs 12.9%, p=0.234) and preeclampsia (4.55% vs 5%, p=0.237). Vaginal type of delivery was in the majority of cases in both groups (82% vs 83%, p=0.242). Neonatal outcomes characterized with normal range of fetal birth weight (median 3207,39±485,61 vs. 3312,3±234,1 grams, p=0.709) and 5 minute Apgar score (median 8,4±1,6 vs. 8,7±1,2, p=0.921). There was no incidence of maternal and fetal mortality. In 12 month, follow-up all there was no arrhythmia recurrence.

Conclusions
Zero-fluoroscopy ablation of tachyarrhythmias in pregnant is feasible and can be safety performed during gestation in cases of drug refractory with benign outcomes.
Macrophage heterogeneity in cardiometabolic disease
Authors: Zurke Y , Dib L , Park I , Cole J , Berthold D B , Udalova I A , Sansom S N , Monaco C 
Published: October 2024

Abstract
Metabolic diseases such as obesity and atherosclerosis are characterised by chronic inflammation that leads to the accumulation of immune cells in affected organs. Macrophages in the obese adipose tissue and the atherosclerotic plaque show transcriptional, phenotypic and functional heterogeneity. The accumulation of CD11c+ macrophages in atherosclerosis and obesity suggests the presence of conserved macrophage phenotypes in metabolic tissues.
We aimed to characterise shared and distinct features of monocytes and macrophages in the aorta and adipose tissue in the context of metabolic disease using single-cell techniques.
Single-cell RNA sequencing of the blood, aorta and visceral adipose tissue during a time course of metabolic disease progression (steady state, 12w western diet, 18w western diet) and data integration with murine aortic and adipose tissue community datasets revealed conserved and tissue specific features of metabolic disease. Resident macrophages in the aorta and adipose tissue displayed tissue specific transcriptional programs, highlighting that cell maintenance and function of tissue resident macrophages differ between metabolic tissues. Further, macrophages in the aorta and adipose tissue undergo disease associated compositional changes. For example, we uncovered distinct CD11c+ macrophage subsets that are conserved in the aorta and adipose tissue across multiple metabolic disease models and share core transcriptional signatures between both metabolic tissues. However, CD11c+ macrophage subsets showed tissue specific dynamics during metabolic disease progression. Overall, our analysis underscores that tissue niche affects macrophage composition as well as activation and transcriptional regulation patterns. Understanding similarities and differences between the two tissues will be important to inform identification of new therapeutic targets for cardiometabolic diseases.
Novel computational approach enables tailoring catheter ablation to a patient and evaluating the role of reverse remodelling in atrial fibrillation recurrence
Authors: Obada G , Ogbomo-Harmitt S , Deprez M , Aslanidi O 
Published: October 2024

Abstract

Background
Atrial Fibrillation (AF) is the most common cardiac arrhythmia affecting up to 2.5% of the population, decreasing the quality of life and increasing the chances of stroke five-fold. Radiofrequency Catheter Ablation (RFCA) is an emerging technique that warrants long-term curative treatment of AF. However, its success rate remains sub-optimal, with 50% of the arrhythmias recurring at 1-year follow-up. AF is a self-sustained condition that perpetuates by altering the atrial structure and cellular electrophysiological properties, the process referred to as remodelling. However, these changes can be reversible after successful AF treatment.

Aim
This study aims to create a novel, patient-tailored RFCA technique that targets re-entrant activity in the left atrium (LA), to test the technique in-silico, and to investigate the importance of reverse remodelling in AF recurrence after RFCA.

Methods
LA meshes with fibrosis were segmented from Late Gadolinium Enhanced Magnetic Resonance (LGE MR) images of AF patients (n = 13) and combined with the Courtemanche-Ramirez-Nattel (CRN) atrial electrophysiology model to create patient-specific 3D LA models. AF was initiated through the pacing at the end of effective refractory period (PEERP) protocol. The first ablation was automated to target the cores of re-entrant drivers. If this led to AF termination, recurrence was tested by pacing in the same 3D LA models with two variants of CRN electrophysiology: (i) AF-remodelled model, and (ii) healthy, i.e. reverse-remodelled model. If recurrence was present in either case, the second ‘redo’ ablation was performed using the same technique targeting the new re-entrant drivers. AF recurrence was then tested again (Figure).

Results
The first ablation terminated AF in all 13 patient-specific models. In the following PEERP test, AF recurrence rate was (i) 51.92% in the AF-remodelled cases (out of which, 37.04% of new drivers originating in the anterior wall, and 62.96% in the posterior wall). AF recurrence rate was only (ii) 5.77% in the reverse remodelled cases (all drivers originating in the posterior wall). The second ‘redo’ ablation was performed for all recurrent cases and terminated AF with 92.31% success rate. The second procedure also increased the freedom from AF after the PEERP test: (i) 37.5% recurrence for the remodelled cases (44.44% anterior, 55.56% posterior) and (ii) no recurrence in the reverse-remodelled cases.

Conclusion
This study shows the importance of reverse remodelling in the success of RFCA treatment for AF. In-silico ablation of patient-specific 3D LA models shows that AF recurrence drops to 5.77% and 0% after the first and second procedure, respectively, if the LA is reverse-remodelled. Our novel approach can be used to help improve clinical RFCA therapy.Computational pipeline for AF Treatment
Protamine administration after catheter ablation of atrial fibrillation using electroporation: a randomized controlled trial
Authors: Moravec O , Skala T , Vacha J , Klimes D , Seidler D , Stanke L , Klementova O , Taborsky M 
Published: October 2024

Abstract

Background
Safety of protamine administration after catheter ablation of atrial fibrillation (AF) using pulse-field system has not been previously described in a prospective randomized trial.

Methods
Consecutive patients with paroxysmal, persistent or long-standing persistent AF undergoing catheter ablation of AF using Farapulse system were randomly assigned in 1:1 ratio for protamine administration before sheaths removal. All vascular punctions were navigated using a direct ultrasound control. Right femoral vein was used for FaraDrive (16 F) sheath and left femoral vein for ICE (11 F) and decapolar diagnostic catheter (7 F). All sheaths were removed immediately at the end of procedure with subsequent local haemostasis with figure-of-eight suture. Primary endpoint was early and late access site complications. Secondary endpoints were significant bleeding, thromboembolic events and duration of hospital stay.

Results
428 consecutive patients were enlisted into the study (213 in protamine group; 215 in control group). Baseline and procedural characteristics were similar between both groups. ACT before venous sheath removal was higher in patients not receiving protamine (330.1 ± 38.6 vs. 189.3 ± 44.7 seconds, P &lt; 0.001). There were no significant differences in both primary and secondary endpoints between both groups: groin hematoma (5 vs 5; p = NS); there were no thromboembolic complications in both groups and no significant differences of hospital stay duration.

Conclusion
Protamine administration after atrial fibrillation ablation using Farapulse system is not necessary when using ultrasound navigated vascular access and haemostasis with figure of eight suture.
Incidence of systolic heart failure and need for implantable cardiac defibrillators in patients with atrial fibrillation who had catheter ablation versus antiarrhythmic medical therapy
Authors: Ali B , Deluca M , Verma B , Yu E , Patel D , Patel R , Hassan A , Karim S 
Published: October 2024

Abstract

Background
The CASTLE-AF trial demonstrated that patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) who underwent catheter ablation (CA) showed improved patient outcomes. These outcomes included a reduction in all-cause mortality and heart failure hospitalizations along with an improvement in left ventricular ejection fraction, when compared to those receiving medical therapy alone. However, there is no data regarding development of novel HFrEF and the need for implantable cardiac defibrillator (ICD) in patients with AF who underwent CA vs. those on antiarrhythmic therapy (AAD).

Purpose
This study aims to assess if there is a difference in the development of HFrEF and the need for ICD intervention amongst AF patients who underwent CA vs. those on AAD. We hypothesize that patients with AF who underwent CA will have a decrease in the development of HFrEF and mitigation in the need for ICD intervention compared to AAD alone.

Methods
A large retrospective, multicentre database was utilized to identify patients aged 18-80 with AF from 2017-2023. Two cohorts were subsequently established based on treatment received: 1) CA vs. 2) AAD (amiodarone, flecainide, dronedarone, dofetilide, propafenone, sotalol). Patients with crossover between the groups were excluded. Student’s t-test was performed to compare baseline characteristics between cohorts. Relevant comorbidities, atrial fibrillation types, and cardiovascular medications were used for propensity matching. Kaplan Meier curves were calculated to compare outcomes at 5 years such as HFrEF development, ICD implantation, mortality, and hospitalizations.

Results
Patients that underwent CA (n=32,774) and AAD (n=345,882) were propensity matched yielding 32,670 patients per cohort. CA demonstrated a significantly decreased need for ICD intervention compared to AAD (1.69% vs. 3.28%; HR=0.559; 95% CI [0.503, 0.621], log rank p&lt;0.0001). Secondary outcomes showed significant reduction in development of systolic heart failure (4.83% vs. 10.60%; HR=0.499; 95% CI [0.467, 0.533], log rank p&lt;0.0001), overall hospitalizations (12.03% vs. 27.32%; HR=0.440; 95% CI [0.420, 0.461], log rank p&lt;0.0001), and all-cause mortality (2.38% vs. 14.19%; HR=0.188; 95% CI [0.174, 0.203], log rank p&lt;0.0001) with catheter ablation.

Conclusions
Patients that underwent CA had a significant reduction in development of systolic heart failure and mitigation in the need for ICD implantation when compared to those on AAD alone. Randomized clinical trials are needed to better understand this relationship and to further define which subpopulation of atrial fibrillation patients would derive the most benefit from CA.
Ablation strategy for patients with atrial fibrillation and heart failure - a Danish nationwide cohort study
Authors: Riis-Vestergaard L , Huth Ruwald M , Gislason G , Loch Hansen M 
Published: October 2024

Abstract

Introduction
Atrial fibrillation (AF) patients with heart failure (HF) face increased risks of AF recurrence and HF admission. Catheter ablation (CA) is a recognized treatment option. Due to observed atrial remodelling and fibrosis associated with ventricular remodelling in HF patients, it could be suggested that a more comprehensive ablation strategy should be applied for these patients.

Purpose
To examine the risk of AF recurrence and HF admission by ablation strategy for patients with AF and HF.

Method
This nationwide cohort study was conducted using real-life data from Danish healthcare registries. All patients above 18 years of age, with a diagnosis of AF and HF that underwent first-time CA from January 1st 2010 to December 31st 2018, were identified and included at the date of ablation. Exposure of interest was ablation strategy - pulmonary vein isolation (PVI) or additional ablation to PVI (PVI plus). PVI plus was defined as either roofline, mitral linear ablation, posterior wall isolation, complex fractionated atrial electrograms or ganglionated plexi ablation. Primary endpoint was HF admission and AF recurrence after a 3-months blanking period. AF recurrence was defined by a composite endpoint of first-reached endpoint of either use of antiarrhythmic drugs, AF admission, electrical cardioversions, or AF re-ablation. The relative rates of recurrent AF and HF admission by ablation strategy (PVI or PVI plus) were examined by Cox proportional models using PVI as reference. The analyses were adjusted for clinically important baseline characteristics including age, sex, AF type (paroxysmal or persistent), diagnosis-to-ablation time, procedural year, body mass index, size of left atrium, as well as co-morbidities such as ischemic heart disease, chronic obstructive pulmonary disease, chronic kidney disease, hypertension, and diabetes.

Results
The study cohort consisted of 1,270 patients diagnosed with AF and HF undergoing first-time CA, of which 1,119 (88%) received PVI and 151 (12%) received PVI plus. 80% where males in both groups. Median age was 62 for the PVI group and 64 for the PVI plus group. Severely enlarged left atrium, ischemic heart disease and use of amiodarone were more prevalent in the PVI plus group compared to the PVI group (Table 1). The relative risk of recurrent AF showed a hazard ratio of 1.02 (95% CI: 0.77-1.37) for the PVI plus group compared to the PVI group, and for HF admission the hazard ratio was 0.95 (95% CI: 0.55-1.65) for the PVI plus group compared to the PVI group (Figure 1).

Conclusion
No significant differences in AF recurrence and HF admission were observed between PVI and PVI plus strategy in AF and HF patients in this observational study. With a diagnosis-to-ablation time exceeding 3 years, it could be argued that advanced atrial remodelling may diminish the impact of reverse atrial remodelling after catheter ablation, irrespective of the ablation strategy employed.Table 1Figure 1
Clinical findings from a large endo-epicardial atrial arrhythmia ablation registry
Authors: Manoharan K , Julia Calvo J J C , Mann I M , Amin R A , Mccready J M C , Silberbauer J S 
Published: October 2024

Abstract

Background
Despite advances, catheter ablation success rates for persistent AF remain at 50-60%. The approach for recurrent persistent AF, beyond pulmonary vein isolation, remains contentious. Surgical maze procedures have demonstrated superior outcomes compared to catheter ablation. Catheter-based linear lesions sets have failed to demonstrate efficacy, perhaps due to a lack of consistent transmurality with endocardial radiofrequency.

Objective
We report our safety and clinical data of an endo-epicardial approach using high-power radiofrequency ablation for atrial arrhythmias.

Methods
126 patients (80% male; mean age 65 years [43-81]) underwent redo ablation, between August 2020 and February 2024, for recurrent symptomatic atrial arrhythmias using an endo-epicardial approach. We used a standardised linear lesion set (posterior wall isolation and anterior mitral line) for recurrent persistent AF.

Results
Utilising an intentional coronary sinus exit and C02 insufflation technique, we achieved epicardial access in 121 anti-coagulated patients. 5 patients were found to have pericardial adhesions, prohibiting access. There were 2 LIMA punctures which were coiled, 2 cases of excess pericardial bleeding (not access related), that settled conservatively, and no surgery or death. 92% of patients received epicardial ablation. 86 anterior mitral lines (95% acute block, 79% with epi ablation), 88 roof lines (92% blocked, 50% with epi ablation) and 81 floor lines (98% blocked, 36% with epi ablation) were undertaken. 106 posterior wall isolations were performed (94% isolated, 51% epi ablation). 75 patients had a standardised lesion set and were included for recurrence analysis. 49 had persistent AF (71% male, mean age 65 years, mean LAVI 38 ml/m2, 26 PVI at baseline and 23 PV reconnections) and 26 longstanding persistent AF (92% male, median age 64 years, mean LAVI 37.1 mls/m2, 16 PVI at baseline and 10 PV reconnections). 82% with persistent AF (median follow up time 11 months) and 38% with longstanding persistent AF (median follow up time 10.1 months) maintained sinus rhythm. The submitted image demonstrates the freedom from persistent AF, for the cohort who are beyond the 3-month blanking period, as per classification of atrial arrhythmia.

Conclusion
In one the largest cohorts to date, we have shown that endo-epicardial atrial ablation is feasible and safe with epicardial ablation allowing improved transmurality and thus acute linear block. Clinical outcomes, using a posterior wall isolation and anterior mitral line, were favourable for persistent but not longstanding persistent AF.