bluuebunny/crossref_metadata_2025_split huggingface dataset:
High glucose enhanced lipoprotein(a) [Lp(a)] oxidation in a manner inhibited by eicosapentaenoic acid (EPA) in vitro
Authors: Sherratt S , Libby P , Dunbar R L , Bhatt D L , Mason R P 
Published: October 2024

Abstract

Background
Elevated lipoprotein(a) (Lp(a)) levels are causally and independently associated with increased cardiovascular (CV) risk. Targeted molecular therapies are in development. Levels of oxidized Lp(a) were more predictive of CV events and endothelial dysfunction in type 2 diabetes than non-oxidized forms. EPA administered as icosapent ethyl (IPE) reduced CV events in statin-treated patients (REDUCE-IT) with diabetes and high CV risk. As a fatty acid with multiple conjugated double bonds, EPA inhibits lipoprotein oxidation by a potent lipid-centric scavenging mechanism. We therefore tested the effects of EPA on oxidation of Lp(a) and non-modified LDL under conditions of high glucose to mimic aspects of hyperglycemia in vivo.

Methods
Lp(a) was enriched to 41% of total ApoB-containing particles from patients with elevated levels by isopycnic centrifugation. Samples of Lp(a) and non-modified LDL were incubated under high glucose (200 mg/dL) conditions at 37°C for 30 min with EPA (50 µM). Samples were then subjected to copper sulfate-induced oxidation (20 µM) monitored by formation of malondialdehyde (MDA) via a colorimetric assay.

Results
Lp(a) enriched plasma underwent increased oxidation, peaking at 4 hr by 32-fold compared to baseline (0.37 ± 0.04 vs 12.27 ± 0.61 µM, p&lt;0.001) under conditions of high glucose. Non-modified LDL also underwent oxidation in the presence of high glucose with a distinct rate compared to Lp(a), peaking after 3 h (0.28 ± 0.09 vs 10.91 ± 0.93 µM, p&lt;0.001). EPA significantly inhibited both Lp(a) and LDL oxidation in a time-dependent manner. After peak oxidation was achieved in Lp(a) (4 h) and LDL (3 h), EPA inhibited oxidation by 57% (5.29 ± 0.25 µM, p&lt;0.001) and 81% (2.12 ± 0.09 µM, p&lt;0.001), respectively.

Conclusions
Under hyperglycemic conditions, EPA inhibited oxidation of Lp(a)-enriched plasma and non-modified LDL in a time-dependent manner. The activity of EPA may arise from its lipophilic properties and highly conjugated structure that scavenges free radicals in lipid-concentrated environments. The potent antioxidant activity of EPA may contribute to reduced CV risk in patients with diabetes and elevated Lp(a).
PI3 kinase delta governs regulatory T-cell biology and thus confers protection against atherosclerosis progression in mice
Authors: Zierden M , Berghausen E M , Gnatzy-Feik L , Millarg C , Picard F S R , Kiljan M , Geissen S , Polykratis A , Zimmermann L , Pasparakis M , Baldus S , Winkels H , Vantler M , Rosenkranz S 
Published: October 2024

Abstract

Introduction and Purpose
Atherosclerosis is a chronic inflammatory disease of arteries, critically involving innate and adaptive immune cells like macrophages as well as T and B lymphocytes. Macrophages are major drivers of disease through the ingestion of lipoproteins, foam cell formation, and secretion of inflammatory mediators. Although macrophages outnumber other leukocytes in atherosclerotic plaques, T and B cells can shape the course of disease by promoting or mitigating inflammatory responses. The phosphoinositide 3-kinase delta (PI3Kd) exerts a key role in the regulation of immune responses including activation, proliferation, differentiation, and effector function of lymphocytes. Therefore, PI3Kd may represent a promising target for the modulation of inflammatory diseases. Consequently, we aimed to analyse the role of PI3Kd during atherogenesis.

Methods and Results
To investigate the role of haematopoietic PI3Kd in atherosclerosis, bone marrow from PI3Kd-/- or PI3Kd+/+ mice was transplanted into Ldlr-/- mice. After a 6-weeks-challenge by high fat diet, PI3Kd-/- recipient Ldlr-/- mice displayed profoundly impaired CD4+ and CD8+ T-cell numbers, CD4+ T-cell activation, CD4+ effector T-cell differentiation, and proatherogenic CD4+ T-helper (Th) 1 responses in para-aortic lymph nodes and spleen compared with PI3Kd+/+ transplanted controls. Surprisingly, the net effect of PI3Kd deficiency was a substantial increase of aortic inflammation and atherosclerosis in Ldlr-/- mice. Whereas plaque content and functions of macrophages including foam cell formation, efferocytosis, and cytokine secretion remained largely unaffected, haematopoietic PI3Kd ablation strongly reduced mature B cells and serum immunoglobulins in Ldlr-/- mice. Importantly, PI3Kd deficiency severely impaired numbers, proliferation, immunosuppressive functions, and stability of regulatory CD4+ T cells (Tregs). Consequently, adoptive transfer of PI3Kd+/+ Tregs fully restrained the atherosclerotic plaque burden in PI3Kd-/- transplanted Ldlr-/- mice without affecting B-cell numbers and serum immunoglobulins, whereas transferred PI3Kd-/- Tregs failed to relieve atherosclerosis progression.

Conclusions
Here, we demonstrate that PI3Kd plays a crucial role in Tregs, Th1 cells, and B cells during atherogenesis. Lack of PI3Kd signalling specifically in atheroprotective Treg responses outplays its impact on B-cell and proatherogenic Th1 responses, thus leading to aggravated atherosclerosis. Hence, PI3Kd is a key regulator of Treg biology and thereby protects against atherosclerosis, suggesting that fine-tuning PI3Kd signalling may represent a promising target for Treg-directed therapy.
Inhibition of fractalkine signalling in patients with acute myocardial infarction - First results from the FRACTAL trial
Authors: Loh S , Ekinci Y , Bennaceur K , Ogundimu E , Bigirumurame T , Maier R , Jeyalan V , Egred M , Mcdiarmid A , Maredia N , Plein S , Olin T , Richardson G , Austin D , Spyridopoulos I 
Published: October 2024

Abstract

Background
We have previously demonstrated a strong association between expression of the fractalkine receptor CX3CR1 on lymphocytes and microvascular obstruction (MVO) in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction. Our pre-clinical studies also found an improvement in infarct size, inflammation and intramyocardial haemorrhage (IMH) when rats were pre-treated with the fractalkine inhibitor KAND567.

Purpose
FRACTAL (FRACTalkine inhibition in Acute myocardial infarction) study was a phase IIa, pilot, randomized, 2-arm parallel group, placebo-controlled, double blinded, multi-centre trial. Its primary aim was to assess the safety and tolerability of intravenous and oral administration of the fractalkine inhibitor KAND567 as well as reducing signs of reperfusion injury in STEMI patients undergoing PPCI.

Methods
Patients with a new diagnosis of anterior STEMI, who had index chest pain within 5 hours and angiographic occlusion of the LAD, were randomised on a 1:1 basis to receive either KAND567 or placebo over a period of 72 hours. All patients then underwent a baseline MRI scan at 3 days with a follow-up scan at 3 months, paralleled by longitudinal deep immuno­phenotyping over 9 time points.

Results
A total of 71 patients were enrolled into the study with 64 (90.1%) being male patients. The mean age of patients was 59.2 years. 37 patients received KAND567, whilst 34 received placebo over 72-hour period. Throughout the 3-month follow-up period, 23 (62%) patients from the KAND567 arm as compared to 24 (71%) patients in the placebo arm had reported adverse events. There was no statistical difference in serious adverse events (SAEs) between both arms with 9 documented in the placebo arm and 12 in the KAND567 arm. Safety bloods also demonstrated no significant differences between the two groups across all time points. There was a higher incidence of left ventricular (LV) thrombus in the placebo arm as compared to the KAND567 arm (17.6% vs. 2.7%; p=0.049). Additionally, the study also demonstrated a lower occurrence of IMH in the KAND567 arm compared to the placebo arm (35.5% vs. 55.2%; p=0.19). Deep immunephenotyping suggested clear target engagement in the KAND567 arm in natural killer cells as well as in cytotoxic T-lymphocytes.

Conclusion
This first in-man study demonstrates that inhibition of the fractalkine pathway in STEMI patients appears safe and well-tolerated, while demonstrating a promising potential in preventing LV thrombus and IMH. The results suggest a new mechanism and class of drug to target reperfusion injury, clearly warranting a larger phase III study.LV thrombus and IMH
Long-term efficacy and safety of ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy
Authors: Wang Gottlieb A , Edner J , Gottlieb-Vedi E , Yacoub N , Shahim A , Schwieler J , Bastani H , Drca N , Saluveer O , Jensen-Urstad M , Braunschweig F , Haugaa K , Shahim B 
Published: October 2024

Abstract

Background
Hypertrophic cardiomyopathy (HCM) is often accompanied by atrial fibrillation (AF) but data on safety and long-term outcomes after catheter ablation for AF in HCM are scarce.

Purpose
To investigate safety, long-term efficacy and clinical outcomes following AF ablation in patients with HCM and in matched controls.

Methods
Patients with HCM (n=76) undergoing a first catheter ablation for AF or atrial flutter between 1999 and 2022 at a University Hospital in Sweden were included (age 64±12 years, 43% female). Diagnosis of HCM was based on the European Society of Cardiology definition (left ventricular wall thickness ≥15 mm or ≥13 mm not solely explained by abnormal loading conditions, and combined with family history, genetic components and/or electrocardiogram abnormalities). Patients with HCM were matched with controls (n=152) based on age, gender, ablation type and intervention-year. Patients were followed for a mean of 5 years and study endpoints included heart failure hospitalization (HFH), stroke and mortality. Cox regression analyses were performed for the association between HCM and the endpoints.

Results
Among the overall population, 121 (53%) underwent pulmonary vein isolation (PVI), 62 (27%) isthmus ablation and 45 (20%) His-Bundle ablation. Patients with HCM had a shorter mean duration of AF before ablation (48 months vs. 66 months; p=0.047) and more severe symptoms as indicated by a higher EHRA class (EHRA class IV: 30% vs. 10%; p&lt;0.01). Procedural success rate of PVI and isthmus ablation was lower in patients with versus without HCM (88% vs. 97%; p=0.02). Procedure related complications (vascular complications, tamponade) were overall similar in both groups (9% in HCM vs. 5% in controls, p=0.17) except for higher rates of pulmonary oedema in patients with HCM (7% vs 1%, p=0.03). There was a nearly two-fold increase in risk of AF recurrence after PVI or isthmus ablation in patients with HCM compared to controls (OR 1.95; 95% CI 1.06-3.58; p=0.03). During follow-up, patients with HCM had an increased risk of HFH (HR 2.55, 95% CI 1.21-5.36, p=0.01) but not of stroke or mortality (Figure 1).

Conclusion
AF ablation was overall safe in patients with HCM but less effective. Patients with HCM had an increased risk of the individual endpoint of HFH after AF ablation but not stroke or mortality during long-term follow-up.
Effect of selective renal denervation guided by renal nerve stimulation on atrial remodeling
Authors: Li D , Long Y X , Zhou H , Yin Y H 
Published: October 2024

Abstract

Background
The renal nerves play a crucial role in regulating blood pressure (BP), and the parasympathetic nervous has been confirmed as one of the components of the renal nerves, with close connections to the central solitary nucleus. Renal nerve stimulation (RNS) can activate not only the sympathetic nerves, leading to an elevation in BP, but also the parasympathetic nerves, resulting in a reduction in BP. Multiple clinical studies have demonstrated that compared to pulmonary vein isolation (PVI), renal denervation (RDN) combined with PVI significantly increased the likelihood of freedom from atrial fibrillation, but its mechanism remains unclear.

Purpose
Exploring the effects of renal sympathetic denervation and renal parasympathetic denervation on atrial neural remodeling and structural remodeling from a histological perspective of atrial myocardium.

Methods
24 adult healthy Kunming dogs were randomly divided into three groups: (1) RNS-guided reduced BP response sites ablation (RRA group, n=8), (2) RNS-guided elevated BP response sites ablation (ERA group, n=8), and (3) RNS only, no ablation (RSC group, n=8). Left atrial samples were obtained after a 4-week follow-up period.

Results
Compared to the RSC group, the ERA group showed a significant decrease in tyrosine hydroxylase (TH), while the RRA group showed a significant decrease in choline acetyltransferase (CHAT) and muscarinic acetylcholine receptor 2 (CM2) (Fig. 1A-1C). Histological results indicated that compared to the RSC group, the ERA group exhibited orderly arrangement of myocardial cells, with a significant reduction in the degree of mitochondrial swelling and a decrease in average myocardial cell area. In contrast, the RRA group showed disordered arrangement of myocardial cells, with some myofibril dissolution, noticeable swelling of cell nuclei and mitochondria, and an increase in average myocardial cell area (Fig. 1D). Further evaluation of left atrial fibrosis degree revealed that compared to the RSC group, the ERA group showed a significant decrease in Collagen I, with a reduction in interstitial fibrosis degree, while the RRA group showed a significant increase in Collagen I expression, with an increase in myocardial interstitial fibrosis degree (Fig.2).

Conclusion
Renal sympathetic denervation can reduce atrial sympathetic nerve, improve atrial macrostructure, ultrastructure, and fibrosis levels, which may be one of the reasons why RDN combined with PVI is more effective in maintaining sinus rhythm compared to PVI. Renal parasympathetic denervation can decrease atrial parasympathetic nerve, leading to deterioration of atrial tissue structure and exacerbation of fibrosis. This emphasizes the importance of electrical stimulation guidance during the RDN procedure to avoid "side effects" caused by renal parasympathetic nerves ablation.Figure 1Figure 2
Significant reduction of complications applying an optimized vascular access and post-interventional groin-site management during electrophysiology procedures
Authors: Obergassel J , Schenker N , Asbeck C , Lemoine M D , Ismaili D , My I , Moser F , Riess J , Nies M , Kirchhof P , Ouyang F , Reissmann B , Rillig A , Metzner A , Rottner L 
Published: October 2024

Abstract

Background
Catheter ablation of cardiac arrhythmias is an established treatment strategy. However, the optimal femoral vascular access strategy and post-interventional management in the electrophysiology (EP) setting is still under debate.

Purpose
To assess the impact of ultrasound-guided versus conventional femoral vascular puncture and of a modified post-interventional groin-site management strategy on complication rates.

Method
Patients undergoing EP procedures at the our university heart and vascular center are included in an institutional prospective registry. Conventional vascular access as well as post-interventional groin site pressure-bandage and bed rest of 6 hours (group I) was compared to a new strategy including ultrasound-guided vascular access, venous closure by a Z-suture and groin site pressure-bandage for only 2 hours plus additional 4 hours bed rest (group II). Incidences of minor and major groin site complications for both groups were compared. Hematoma, bleeding, arteriovenous fistula or pseudoaneurysm of the femoral artery without need for intervention (e.g. transfusion, thrombin injection, surgery) were classified as minor complications. Complications requiring intervention or retroperitoneal hematoma were defined as major complications.

Results
A total of 1535 procedures in 1381 patients (779 (51 %) procedures in 705 (51%) patients in group I and 756 (49%) procedures in 676 (49%) patients in group II) were analyzed. In group I and group II, respectively, 39%/44% procedures were index pulmonary vein isolations, 30%/29% repeat atrial fibrillation, 16 %/15% supraventricular tachycardia, 12%/11% PVC or VT ablations, and 4%/2% left atrial appendage occlusions. The total groin site complication rate was 9% (70/779 procedures) for group I, and 5% (38/756 procedures) for group II (OR 0.54 [95%-CI 0.35-0.82], p=0.003). Major groin site complications occurred in 2% (19/779 procedures) in group I and were reduced to 1% (10/756 procedures) in group II (OR 0.53 [95%-CI 0.22-1.22], p=0.156).

Conclusion
The overall groin site complication rate in EP-procedures was significantly reduced by implementing a novel institutional standard for vascular access management including ultrasound-guided puncture and a modified post-interventional groin site management.
Improved clinical outcome by means of three-dimensional electroanatomically- guided slow pathway elimination with irrigated, contact- force sensing catheter
Authors: Doundoulakis I , Tsiachris D , Antoniou C K , Kordalis A , Tsioufis P , Laina A , Botis M , Bartsioka L I , Kotoulas S , Sakalidis A , Gatzoulis K , Tsioufis K 
Published: October 2024

Abstract

Background
Slow pathway (SP) ablation, in the context of atrioventricular node reentrant tachycardia (AVNRT) treatment could result in either complete elimination or only modification of the SP with ambiguity regarding associated benefits.

Purpose
Three-dimensional electroanatomical mapping (3D-EAM) with irrigated, contact-force sensing may be used adjunctively aiming to complete SP elimination. Our purpose was to compare a 3D-EAM based strategy targeting SP elimination to the conventional fluoroscopic approach with respect to clinical outcome.

Methods
Eighty-four consecutive AVNRT patients (33 males, mean age 50.1±11.7 years) underwent a conventional fluoroscopic ablation approach (N=42) or a 3D-EAM-guided ablation irrigated, contact-force sensing catheter (ThermoCool SmartTouch ST, Biosense Webster, Inc.) focusing on complete SP elimination (N=42).

Results
Several procedural parameters improved with 3D-EAM use, including fluoroscopy time (2.0±4.3min vs 11±4.0min) and slow pathway elimination frequency (100% vs 50%, all p&lt;0.001). Altogether, over a mean follow-up of approximately 2.0 years, recurrence occurred in 6 of 42 (14.3%) in the conventional group as compared to 1 of 42 (2.4%) in the EAM-based group (P =0.04).

Conclusions
The present study showed that an EAM-based SP elimination strategy is not only feasible and safe but it is also accompanied by improved clinical outcome in the setting of AVNRT ablation.
Digital health in the EP lab: routine implementation of remote access and technical support for complex ablation procedures
Authors: Popescu S S , Heeger C H , Vogler J , Eitel C , Botezat B I , Duta A I , Feher M , Phan H L , Mamaev R , Kuck K H , Tilz R R 
Published: October 2024

Abstract

Background
Complex electrophysiological procedures are performed using three-dimensional (3D) electroanatomical mapping (EAM) systems, which are usually operated on site, by field technical engineers (FTE). Due to a lack of skilled personnel, the engineers usually must travel between different hospitals and the procedures have to be planed in advance. Remote access (RA) technologies were recently implemented in clinical practice, aiming to increase the flexibility in the EP lab and maximise healthcare resources use.

Methods
Electroanatomical mapping was performed remotely by means of an integrated audio-visual solution for RA. The operator and the FTE communicated exclusively using the RA system, while the latter worked only in home office. Consecutive procedures were prospectively enrolled and analysed in terms of indication, procedural characteristics, feasibility and saved travelled time by the FTA.

Results
Between September 2022 and July 2023, a total of 133 EP procedures were performed in a high volume, tertiary electrophysiological centre in Germany. The mean age was 67 (57.5, 75.5) years. Women represented 39.8% of the population. The median BMI was 26.2 (23.1, 30.3) Kg/m2. A total of 56 (42.1%) patients underwent an atrial fibrillation ablation procedure (37.5% paroxysmal), 22 (16.5%) an atrial tachycardia ablation, 13 (9.8%) cavotricuspid isthmus ablation, 15 (11.3%) supraventricular tachycardia ablation, 14 (10.5%) a premature ventricular contraction ablation, 12 (9%) ventricular tachycardia ablations and 1 patient an electrophysiological diagnostic study. The median time length of procedure was 130 (96.5, 168) minutes. The median number of radiofrequency applications was 63.5 (22.3, 109.5), while the median RF time was 14.2 (6.9, 25.1) minutes. The fluoroscopy time was 9.2 (6.5, 12.6) minutes, with a median radiation dose of 408.5 (233.0, 631.8) cGy x cm2. The median amount of contrast media was 40 (8.75, 50.0) ml and the median amount of heparin administered was 12000 (8000, 16000) UI. Protamine was used in 9 cases, with a median of 7000 (5000, 7000) UI.
Except for one supraventricular procedure, where no arrhythmia induction was possible, all procedures were successful. One major complication was observed. In one case, the internet-based headphone connection was not stable. Therefore, the communication was established via a conventional smartphone. No change to on-site support was needed.
The travel time reduction was available in 130 cases. In total, 290 travel hours could be saved.

Conclusion
The routine implementation of RA for complex EP procedures proved to be safe and efficient. This approach has the potential to increase the feasibility in case of emergency procedures, reduce travel times for FTE and streamline healthcare resources allocation.
Sex differences in shocks and device-related complications in subcutaneous implantable-cardioverter defibrillator patients
Authors: De Veld J , Sivanesan S , Pepplinkhuizen S , Smeding L , Knops R E 
Published: October 2024

Abstract

Background
The use of implantable cardioverter-defibrillators (ICDs) improves the life expectancy of patients at risk of sudden cardiac death. However, ICD treatment comes with the risk of device-related complications. As the lead is the Achilles heel of the transvenous ICD (TV-ICD), the subcutaneous ICD (S-ICD) was developed to overcome the risk of lead-related complications. It is reported for TV-ICDs that women receive less appropriate therapy, but are more likely to experience ICD-related complications than men. It is unclear whether these differences also exist among S-ICD recipients.

Purpose
This study investigates the differences in appropriate shocks (AS) and device-related complications in men and women implanted with an S-ICD.

Methods
Retrospective data was collected of all patients implanted with an S-ICD between 2009 and 2022 in our tertiary center. Propensity score matching was used to create two comparable groups that differed by sex. The numbers of patients with an AS and device related-complication requiring intervention were compared between men and women. Differences between the groups were tested using a Fisher’s exact or X2-test.

Results
A total of 108 men and 108 women were included in this analysis. The median age was 40 years in men and 41 years in women (p=0.747), 61% had a primary prevention indication, and the median follow-up duration was 8 years. AS were seen in 15 women versus 24 men (p=0.156). There were 6 women versus 12 men with a device-related complication requiring intervention (p=0.218) (figure). The most common complication in men was infection (4/12) whereas in women erosion of the pocket occurred most frequently (2/6).

Conclusions
In this study, there was no significant difference in the number of patients with AS or complication between men and women with an S-ICD. However, a trend was seen towards more shocks and complications in men. The S-ICD may be a more suitable device for women, but further research with a larger sample size is needed.sex differences in S-ICD recipients