bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smooth muscle cell-specific deletion of S100A4 modifies smooth muscle cell fate and inflammation in murine atherosclerotic lesions
Authors: Azar P , Cardoso Dos Santos L M , Correia De Sousa M , Foti M , Bochaton-Piallat M L 
Published: October 2024

Abstract

Background
S100A4, a calcium-binding protein, is crucial in smooth muscle cell (SMC) phenotypic switch, yet its role in atherosclerotic plaque development and SMC plasticity remains unclear. Our previous experiments using an S100A4 neutralizing antibody approach in ApoE-/- atherosclerotic-prone mice showed reduced atherosclerotic burden but did not establish a direct link between the various S100A4-expressing cells and atherosclerosis.

Methods/Results
Herein, we show that aortic Oil RedO staining in ApoE-/-; S100A4-/- mice subjected to a 12-week high-cholesterol-diet (HCD) revealed reduced lesion areas compared to ApoE-/- mice (Figure 1, from 21.29% of the total aorta in ApoE-/-; S100A4+/+ mice to 13.27% in ApoE-/-; S100A4-/- mice), highlighting a pivotal role for S100A4 in atherosclerotic plaque development.
We then used a lineage tracing ApoE-/- mouse model, in which we induced an SMC-specific deletion of S100A4 (SMC-S100A4Δ/Δ). After 12 weeks of HCD, SMC-S100A4Δ/Δ and control mice (SMC-S100A4wt/wt) were sacrificed, and aortas were processed for en face Oil Red O staining, immunohistochemistry, and single-cell RNA sequencing (scRNA-seq). SMC-specific deletion of S100A4 reduced the necrotic core area (from 29.75% of total plaque area in SMC-S100A4wt/wt to 18.23% in SMC-S100A4Δ/Δ mice) without affecting total atherosclerotic plaque size suggesting a more potent impact on plaque composition. ScRNA-seq analysis from SMC-S100A4Δ/Δ and SMC-S100A4wt/wt mice showed that the inflammatory macrophage-like SMC phenotype was highly suppressed in the plaque and associated with increased SMC repair phenotypes as well as a global reduction of myeloid inflammatory cells. SMCs also retained specific contractile SMC markers, namely Acta2 and Myh11 (fold change of 2.285 and 2.492, respectively) hinting towards a more stable fibrous cap. Immunofluorescence staining on aortic roots plaque (Figure 2) confirmed those results with an increase of SMCs (from 11.02% to 16.18%) as well as a-smooth muscle actin (a-SMA, Acta2)-positive SMCs (from 3.25% to 5.1%) in SMC-S100A4 Δ/Δ mice.
Furthermore, the Gene Set Enrichment Analysis (GSEA) of scRNAseq data revealed that, in SMC-S100A4Δ/Δ mice, genes related to mitochondrial metabolism and oxidative respiration were highly downregulated in all SMC clusters. We investigated SMC mitochondrial fitness in vitro and showed that S100A4-/- SMCs have an increased basal oxygen consumption rate and an increased proton leak (fold change of 1.37 and 1.96 respectively) suggestive of differences in cellular metabolic adaptability.

Conclusion
Our research emphasizes the significant role of S100A4 in plaque development, demonstrating how SMC-derived S100A4 knockdown affects plaque evolution, reducing inflammation, and promoting stability likely through influencing SMC phenotypic switch through metabolic pathways.
Real world data on SVT ablation in Denmark Higher risk of need for reablation in todays patient population a Nationwide registry based Danish study
Authors: Middelfart C , Toennesen J , Lock Hansen M 
Published: October 2024

Abstract

Introduction
Supraventricular tachycardias (SVTs) are a common reason for healthcare contacts and can have significant impact on patient’s quality of life. Today, ablation therapy is considered the treatment of choice for many cardiac tachyarrhythmias, and it is increasingly utilized to treat SVT-patients with chronic symptoms. Ablation therapy for SVTs is considered a safe procedure with high periprocedural success rates. However, recent studies on today’s patient population have shown a tendency towards higher age and more comorbidity, which might affect these success rates. Therefore, there is a need to explore more real-world data on long-term outcomes of catheter ablations in today’s population.

Purpose
To examine the long-term success rates of ablation therapy by investigating risk of reablation in patients treated for either an accessory pathway (AP), atrioventricular nodal re-entry tachycardia (AVNRT) or ectopic atrial tachycardia (EAT).

Methods
Using Danish nationwide registries, patients of 18 years or older who underwent RFA for AP, AVNRT or EAT between January 1st 2010 and January 1st 2019 were included. Comorbidities and use of antiarrhythmic drugs were analyzed. The cumulative incidences of reablation for either AP, AVNRT or EAT were estimated at 5-year follow-up.

Results
Figure 1 shows the baseline characteristics of the study population. A total of 5.905 patients were included in the study, with a median age of 52 [38, 65], and 47% were male. Among them, the AP group comprised 1.575 patients, with a mean age of 42 [29, 55], and 61% were male. The AVNRT group consisted of 3.598 patients, with a mean age of 56 [43, 67], and 42% were male. In the EAT group, there were 732 patients, with a mean age of 57 [42, 67], and 44% were male. The comorbidity burden was generelly higher in EAT patients, who also had the highest use of antiarrhythmic drugs.
Figure 2 shows the 5-year cumulative incidence of reablation for AP, AVNRT or EAT-patients. Risk of reablation after 5 years was 12%, 5% and 12% for AP-, AVNRT- and EAT patients respectively. After 1 year the risk was 9%, 3% and 9% for AP-, AVNRT- and EAT patients respectively.

Conclusion
Despite the generally safe nature of ablation therapy with high periprocedural success rates, our findings highlight a notable risk of reablation, particularly for AP and EAT patients, after 5 years of follow-up.Baseline Characteristics5year cumulative incidence of reablation
A prospective study of a novel pocket compression device to reduce pocket hematoma after cardiac implantable electronic device implantation in a high bleeding risk population
Authors: Tijskens M , De Schouwer K , Thoen H , Strazdas A , Wolf M , De Greef Y , Schwagten B 
Published: October 2024

Abstract

Background
Pocket hematoma (PH) is one of the most common complications after cardiovascular implantable electronic device (CIED) implantation resulting in an up to 9 times higher risk for CIED infections.(1) Different preventive strategies have been proposed with mixed results. Current standard of care consists of preventive elastic adhesive tape leaving 2 major disadvantages: unpredictable pressure on the pocket and inability to visually assess the pocket with the bandage applied.

Aim
To evaluate the safety and effectiveness of a novel pocket compression device in patients undergoing CIED implantation in a high bleeding population.

Material and methods
This randomized controlled trial included 32 patients in the study group (pocket compression device) and 33 in the control group (elastic adhesive tape). The studied pocket compression device contains an inflatable compartment to modify the degree of pocket compression which is transparent facilitating pocket evaluation. The primary outcome was the incidence of various grades of PH. The secondary outcomes comprised the incidence of pressure lesion, pain score (0-10) and endocarditis during follow-up.

Results
There were no clinical or procedural differences between groups (age 78.01±9.71, heart failure 53.8%, kidney failure 20.0% and on antithrombotic drugs 49.2%). There were significantly less pocket hematomas in the study group (1/32 (3.1%) vs 20/33 (60.6%), P&lt;0.001). Most pocket hematomas were grade I for which watchful waiting was applied (1/32 (3.1%) vs 17/33 (51.6%), P&lt;0.001). Grade II and grade III PH only occurred in the control group (respectively 1/33 and 2/33) resulting in hospitalization prolongation and longer interruption of antithrombotic drugs &gt;24hours. Two control patients eventually received the study device to control PH. None underwent reoperation. Pressure lesions did not occur. Patients in the study group had lower pain scores at application (0.75±1.12 vs 1.80±1.38, P=0.009), after 2 hours (0.81±1.36 vs 1.94±1.50, P=0.002) and the next day (0.38±0.91 vs 1.06±1.634, P=0.042). None of the patients experienced endocarditis during mean follow-up of 1 year.

Conclusion
The use of a pocket compression device in patients undergoing CIED implantation in a high bleeding population leads to less PH and postoperative pain in comparison to conventional elastic adhesive tape.bandage study
Novel parameters for micra transcatheter pacing system implantation on the right ventricular mid-septum
Authors: Pak M , Kakita K , Yamasaki T , Hattori T 
Published: October 2024

Abstract

Background
No procedural parameters for Micra transcatheter pacing system (Micra TPS) implantation on the right ventricular mid-septum have been established though it is encouraged for safety.

Purpose
We aimed to investigate procedural predictors for Micra TPS implantation on the ventricular mid-septum.

Methods
This is a single-center, retrospective and observational study. Eighty-two patients who underwent Micra TPS implantation were enrolled. The implantation sites of the ventricular septum were classified into basal, mid and apical-septum in the right anterior oblique 35° image. Predictors for mid-septal implantation were evaluated using univariable and multivariable logistic regression analysis which involved explanatory variables considered clinically important. The explanatory variables included the angle between the axis of a device cup of a delivery catheter and the tangent of the ventricular septum in the left anterior oblique 45° image (defined as angle θ). The diagnostic cut-off value of the significant predictor for mid-septal Micra implantation was assessed using receiver operating characteristic (ROC) curve analysis.

Results
Micra TPS was implanted on the ventricular mid-septum in 61 patients (74.4%), the apical-septum in 21 patients (25.6%), and the basal-septum in no patients. In univariable logistic regression analysis, each angle θ and α-loop shape appearance of a delivery catheter was significantly associated with mid-septal implantation (Odds ratio [OR], 1.1; 95% confidential interval [CI], 1.02-1.10; P=0.002, and OR, 4.6; 95% CI, 1.63-13.6; P=0.005, respectively). After multivariable adjustment, both angle θ and α-loop shape appearance were independently associated with mid-septal implantation (adjusted OR, 1.1; 95% CI, 1.01-1.09; P=0.010, and adjusted OR, 3.3; 95% CI, 1.01-11.4; P=0.048, respectively). Because no Micra TPS was implanted on the basal-septum, an ROC curve for binary outcome of mid-septal and apical-septal implantation was drawn. The ROC curve showed a cut-off value of angle θ for Micra TPS implantation on the ventricular mid-septum was 22° with high sensitivity and specificity at 80.0% and 70.0% (area under the curve= 0.781).

Conclusion
The angle θ ≧ 22°and the α-loop shape appearance of a delivery catheter may be useful predictors for Micra TPS implantation on the ventricular mid-septum.
Risk of embolic events in patients with Chagasic Cardiomyopathy and Atrial Fibrillation despite antithrombotic therapy: is anticoagulation enough?
Authors: Echeverria L E , Sanchez-Garcia R , Mantilla A F , Pizarro M P , Jimenez O , Rojas L Z , Gomez-Ochoa S A 
Published: October 2024

Abstract

Background
Chagasic cardiomyopathy (CC) differs from other heart failure causes in multiple aspects, highlighting the risk of systemic embolisms. However, few studies have evaluated the risk of embolic events in anticoagulated patients with CC compared to other cardiomyopathies.

Objective
We aimed to analyze the incidence of systemic embolisms in a cohort of anticoagulated patients diagnosed with atrial fibrillation (AF) with and without CC.

Methods
A retrospective cohort study was conducted at a fourth-level hospital from 2014-2020. All patients diagnosed with cardiomyopathy of any etiology and AF on an anticoagulation regimen were included. The primary outcome was the incidence of embolic events. A survival analysis was performed using adjusted Cox proportional hazard models. A p-value of &lt;0.05 was considered significant. All statistical tests were two-tailed.

Results
149 anticoagulated patients with cardiomyopathy were evaluated (median age: 71 years; women: 30.20%). The cumulative incidence of embolic events was significantly higher in patients with CC (17.50%) compared to those with other cardiomyopathies (4.95%), despite that the latter had a substantially higher CHA2DS2-VASc score (p=0.013). After multivariate analysis, patients with CC had a significantly higher risk of embolic events regardless of the CHA2DS2-VASc score and the anticoagulant prescribed (HR 5.65. 95% CI 1.46-21.83; p=0.012).

Conclusions
CC was associated with a significantly higher risk of embolic events despite anticoagulation therapy in both groups. More research is required to understand the origin of this risk observed to translate this knowledge into specific indications for anticoagulation for patients with CC.Cumulative incidence of embolic events
Stratification of residual thromboembolic risk among anticoagulated atrial fibrillation patients: a hierarchical cluster analysis from a global, real-world population
Authors: Ishiguchi H , Abdul-Rahim A H , Huang B , Lam H M , Liu Y , Olshansky B , Chao T F , Huisman M V , Lip G Y H 
Published: October 2024

Abstract

Background
Assessment of residual thromboembolic risk among atrial fibrillation (AF) patients despite being on oral anticoagulants (OACs) poses a significant challenge. This study utilises a hierarchical cluster analysis approach to identify risk phenotypic profiles in a global prospective AF registry.

Methods
Data were drawn from recently diagnosed non-valvular AF patients receiving OACs, as recorded in phases II and III of the GLORIA-AF (Global Registry on Long-Term Oral Anti-thrombotic Treatment in Patients With Atrial Fibrillation) registry. A hierarchical cluster analysis based on patient demographics was performed to identify distinct phenotypes. The incidence and risks of thromboembolic events (ischaemic stroke, transient ischaemic attack, or systemic embolism) and relevant events (major bleeding and all-cause death) were compared across clusters.

Results
The study included 22,410 patients (mean age 70±8 years; 56% male), from which 5 phenotypes were delineated: Cluster 1 ("uncontrolled hypertension"), Cluster 2 ("young with a history of coronary artery disease"), Cluster 3 ("young and obese"), Cluster 4 ("frailty"), and Cluster 5 ("non-paroxysmal AF with tachycardia"). Cluster 4 was associated with the highest rates of thromboembolic events (1.66/100 person-years), major bleeding (1.92/100 person-years), and all-cause mortality (6.02/100 person-years). Conversely, Cluster 3 showed the lowest risk profiles across all outcomes (thromboembolic events: 0.64 events/100 person-years, major bleeding: 0.83 events/100 person-years, and all-cause death: 1.44 events/100 person-years). Cluster 1 displayed a moderate thromboembolic event rate (1.04/100 person-years), although lower rates were observed in Clusters 2 and 5 (Figure 1).

Conclusions
Hierarchical cluster analysis effectively identified distinct phenotypes within a global AF population, offering valuable insights for stratifying the risks of residual thromboembolic events and other significant outcomes in anticoagulated AF patients (Figure 2).Figure 1Figure 2
Strategy optimization for the combined procedure of left atrial appendage occlusion plus catheter ablation in patients with atrial fibrillation (COMBINATION): a multi-center, randomized study
Authors: Du X F , Chu H M , Yang B , Zhong J Q , Ruan Z B , Chen Q , Tao S M , Lai H L , Liang J Q , Xie R Q , Ye P , Zhou X H , Li Y D , Li J P , Zhao Y J 
Published: October 2024

Abstract

Background
The long-term efficacy and safety of combining left atrial appendage closure (LAAC) plus catheter ablation (CA) in patients with atrial fibrillation (AF) in a single procedure have been established. However, the optimal combining strategy has not been well elucidated.

Objective
To determine the impact of different combining strategies on long-term clinical outcomes.

Methods
In this prospective multicenter study, patients with non-valvular AF referred for the combining procedure were randomly assigned to the ablation-first or occlusion-first groups at a 1:1 ratio. We evaluated the outcomes of LAAC with a Watchman device and CA using a contact-force sensing catheter during long-term follow-up.

Results
Of the 202 randomized patients, 194(96.0%) completed the trial with 97 patients in each group. Baseline characteristics were comparable between groups. All procedures were accomplished with acute successful LAAC and restoration of sinus rhythm. Incidences of periprocedural complications were similar. Higher chronic peri-device leak (PDL, 15.5% vs 5.2%, P=0.031) and device-related thrombus (DRT, 8.2% vs 1.0%, P=0.035) rates were observed in the ablation-first group. The event-free survival rate of the primary endpoint (composite of stroke/transient ischemic attack, thromboembolism, clinically-relevant bleeding, cardiovascular rehospitalization/death) was significantly higher in the occlusion-first group (83.5% vs 71.1%, log-rank P=0.036, HR 0.53, 95%CI 0.29-0.95) during a median 2.5-year follow-up. Patients with male gender and higher CHA2DS2-VASc score were at lower risk in the subgroup analysis. Long-term freedoms from AF (77.3% vs 63.5%, log-rank P=0.039) and atrial tachyarrhythmias (70.1% vs 55.7%, log-rank P=0.044) were higher in the occlusion-first group, respectively.

Conclusions
The occlusion-first approach is recommended for combined procedures where a plug-like device is implanted due to its superior long-term clinical benefits.Flowchart of the COMBINATION trialIncidences of primary endpoint
Elucidating the mechanism of rapid functional recovery following atrial fibrillation ablation in patients with left ventricular systolic dysfunction
Authors: Okada M , Koyama Y , Tanaka K , Hirao Y , Harada S , Miyazaki N , Iwasa K , Watanabe H , Iwanaga Y , Okamura A , Tanaka N 
Published: October 2024

Abstract

Introduction
Successful sinus rhythm restoration by catheter ablation (CA) of atrial fibrillation (AF) rapidly improves cardiac function in patients with left ventricular (LV) systolic dysfunction. However, the underlying mechanism of this recovery remains unknown.

Purpose
To elucidate the mechanism of the functional recovery after CA of AF and systolic dysfunction.

Methods
We retrospectively examined 4001 consecutive patients who underwent first-time CA of AF between 2012 and 2021 at our institution. Of them, 505 patients had baseline LV ejection fraction (LVEF) of &lt;50%. Among them, we enrolled 454 patients who received electrocardiogram-gated contrast-enhanced 256-slice multi-detector computed tomography (MDCT) (Brilliance iCT, Philips Medical Systems, Cleveland, Ohio) both at baseline and 3 months after CA. Changes in LV measures, wall thickness, and LV mass were examined based on MDCT data.

Results
A reduction of LV end-systolic volume (LVESV) (from 71 ± 37 ml to 46 ± 34 ml, p &lt;0.001) and improvement of LVEF (from 39 ± 9% to 62 ± 14%, p &lt;0.001) were observed after CA. However, there was no significant change in LV end-diastolic volume (LVEDV) (from 118 ± 49 ml to 116 ± 46 ml, p = 0.13). Mean wall thickness during diastole did not change (from 7.1 ± 1.4 mm to 7.1 ± 1.4 mm, p = 0.94), either. However, wall thickness during systole significantly changed after CA (from 10.0 ± 1.7 mm to 12.7 ± 2.8 mm, p &lt;0.001). As a result, there was no significant change in LV mass after CA (from 84.3 ± 28.7 g to 84.4 ± 28.1 g, p = 0.88). A regression analysis revealed a significant inverse correlation between the delta LVEF and delta LVESV (r = -0.59, p &lt;0.001). However, the delta LVEF was not correlated with the delta LVEDV and delta LV mass.

Conclusions
The rapid improvement of LVEF after CA of AF was attributed to a decrease in the LVESV. Unchanged LV mass indicated that this functional recovery was solely a mechanical issue, without evidence of myocyte regression.
Impact of conduction velocity in left atrium assessing with omnipolar technology in patients with atrial fibrillation
Authors: Enomoto Y , Yamamoto J , Hara H , Hiroi Y 
Published: October 2024

Abstract

Background
There is increased interest in exploring substrate of atrial fibrillation (AF) and recent studies have shown that atrial conduction velocity (CV) reflects the electrophysiological phenomena and plays key role in perpetuating AF. The novel omnipolar technology (OT) use three unipolar and two orthogonal bipolar signals allow us to analyze the voltage, activation direction, and CV independent of catheter position.

Objective
The purpose of the present study was to evaluate if the left atrium (LA) CV which assessed by OT predict the any atrial tachy-arrhythmia (AT) recurrence after initial AF ablation.

Methods
We enrolled 58 consecutive patients who underwent initial pulmonary vein isolation (PVI) for drug refractory AF. (mean age: 68.2±10.2 years old, 32 male(55.1%), 32 persistent AF(55.1%), CHADS2 score:1.6±0.6). After electrical PVI was achieved and remained in sinus rhythm, the LA was mapped with high density mapping catheter (Advisor HD Grid, Abott USA) utilizing with the novel OT combined with Ensite X system (Abott, USA). The conduction distance and conduction times were measured from the earliest activation site to the latest activation site in LA (Figure 1). Each conduction velocity in anterior, posterior, and septal area were also calculated as conduction distance divided by conduction time. The LA voltage was also measured.

Results
During a mean follow up period of 316±143 days, the recurrence of AT after initial PVI was observed in 9 (15.5%) patients. There were no significant differences in baseline demographics between AT recurrence and non-recurrence group (mean age:66±13.3 vs 68.5±10.5 years old P=0.66, CHADS2 score: 1.5±0.57 vs 1.68±0.62 P=0.59, proportion of persistent AF: 15.4% vs 15.5% P=0.82, LA volume: 102±35.9 vs 93.6±37.3ml P=0.63). The earliest activation site in LA were identified in 3 areas including anterior site of right pulmonary vein (51.7%), Bachmann bundle area (41.4%), and antero-septal area (6.89%) (Figure 2). In patients with AT recurrence, the CV in LA was significantly slower than those without AF recurrence(0.61±0.21 vs 0.81±0.16 m/s, P=0.036) whereas the whole LA voltage was not (1.52±0.75 vs 2.22±1.06 mv, P=0.28). The CV in each LA portion are similar between recurrence and non-recurrence AT group. (anterior:0.57±0.24 vs 0.81±0.23 m/s, P=0.18, posterior: 0.87±0.18 vs 1.2±0.49 m/s P=0.36, septal: 0.89±0.76 vs 1.15±0.39 m/s, P=0.41).

Conclusion
The earliest activation site in LA was varied in each case. The whole CV in LA is a predictor of AF recurrence after PVI whereas the CV of each LA portion and LA voltage was not.