bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelial insulin-like growth factor-1 signaling regulates vascular barrier function and atherogenesis
Authors: Drozd M , Bruns A , Yuldasheva N , Maqbool A , Viswambharan H , Skromna A , Makava N , Eades L , Watt N , Haywood N , Bridge K , Beech D , Wheatcroft S , Kearney M , Cubbon R
Published: October 2024

Background

Progressive deposition of cholesterol in the arterial wall characterizes atherosclerosis, which underpins most cases of myocardial infarction and stroke. Insulin-like growth factor-1 (IGF-1) is a hormone that regulates systemic growth and metabolism and possesses anti-atherosclerotic properties. However, the role of IGF-1 in the endothelium remains unexplored.

Purpose

To study the effect of increased endothelial IGF-1 receptor (IGF-1R) expression on atherogenesis using in vivo and in vitro models.

Methods

We generated atherosclerosis prone ApoE-/- transgenic mice with endothelium restricted overexpression of human IGF-1R (hIGFREO-ApoE-/-) or signalling defective K1003R mutant IGF-1R (mIGFREO-ApoE-/-). ApoE-/- littermates were controls. Following 12 weeks of western diet, we assessed atherosclerosis, systemic metabolism, leukocyte homeostasis and vascular permeability using histology, flow cytometry, metabolic testing, bone marrow transplantation and in vivo perfusion with either VE-Cadherin, Evans blue or BODIPY-LDL. For in vitro studies, human umbilical vein endothelial cells were transduced with custom-made lentivirus particles allowing doxycyline-inducible wild-type or mutant K1003R IGF-1R overexpression; with transduced cells not exposed to doxycycline as controls. Confluent cells were exposed to 100mM hydrogen peroxide to model the permeability-inducing conditions observed in atherosclerosis. In vitro, we assessed junctional proteins, FITC-dextran permeability and transcellular BODIPY-LDL uptake.

Results

We show that mice with endothelial overexpression of IGF-1R have less atherosclerosis, arterial cholesterol uptake, and vascular leakage of multiple organs. Conversely, mice with endothelial overexpression of signalling defective IGF-1R did not exhibit these phenomena. We found no differences in systemic metabolism or growth. In complementary in vitro studies, overexpressing wildtype IGF-1R altered the localization of some tight junction proteins (VE-Cadherin and Claudin 5) and reduced leakage across human endothelial monolayers; this was not observed with signalling defective IGF-1R. Moreover, it reduced endothelial cell internalization of cholesterol-rich lipoproteins and increased the association of these particles with clathrin, but not caveolin-1, both of which participate in vesicular uptake of lipoproteins.

Conclusion

Overall, our findings indicate that endothelial IGF-1 signalling modulates both para- and trans-cellular vascular barrier function. This is particularly relevant to the phenomenon of atherosclerosis and suggests that increased vascular IGF-1 signalling reduces atherosclerosis. Beyond this, our data are potentially relevant to many disease processes associated with altered vascular barrier function. This discovery could lead to novel therapeutics to normalise vascular barrier function.
Vitamin K2 and the Vitamin-K-Cycle-Enzyme VKORC1L1 improve endothelial regeneration by inhibiting endothelial-mesenchymal transition, inflammatory cell activation and ferroptosis
Authors: Al Zaidi M , Repges E , Tiyerili V , Oldenburg J , Jansen F , Nickenig G , Zimmer S , Aksoy A
Published: October 2024

Introduction

Vascular inflammation is a crucial contributor to atherosclerosis, in which oxidative stress, endoplasmic reticulum (ER) stress and transition of endothelial to mesenchymal cells (EndMT) are of critical importance.

Vitamin-K-antagonists (VKA) promote vascular dysfunction, while dietary vitamin K intake was proposed to reduce incidence of coronary artery disease, but the mechanisms remain unresolved. Key enzyme for regeneration of vitamin K is the Vitamin K epoxide reductase complex subunit 1 (VKORC1), which also represents the pharmacological target of VKA. VKOR-like1 (VKORC1L1) is an isoenzyme of VKORC1, which resides at the ER-membrane, exerts antioxidative properties and is involved in vitamin K maintenance.

Aim of this study was to investigate the role of Vitamin K2 and the VKOR-enzymes in endothelial cell inflammation.

Methods and Results

In human coronary artery endothelial cells (HCAEC), Vitamin K2 improves endothelial regeneration by increasing proliferation and cell viability and by reducing both apoptosis and ferroptosis (relative viability: RSL3 0.11 ± 0.01 vs 0.32 ± 0.05 RSL3+K2-1µM vs. 0.44 ± 0.11 RSL3+K2-10µM, p<0.001). Moreover, Vitamin K2-supplementation inhibits EndMT by reducing expression of mesenchymal markers (Calponin, SM22; Fig.1).

In silico analyses of the proteome of human coronary atherosclerosis revealed increased expression of VKORC1L1, but not of VKORC1. In vitro induction of oxidative stress and ER-Stress promoted time- and dose-dependent enhanced expression of VKORC1L1, without altering VKORC1 expression (H2O2: 2.3-fold vs. 0.8-fold after 40 minutes, p=0.04; tunicamycin: 1 μg/ml: 1.43-fold vs. 0.8-fold, p<0.01). Likewise, siRNA-mediated VKORC1L1 knockdown induces an inflammatory gene signature with upregulation of NFkB-signalling and endoplasmic reticulum stress (NF-κB: 1.95-fold ± 0.13, GRP78: 1.32-fold ± 0.04 vs. control, p<0.01). Furthermore, VKORC1L1 downregulation increased formation of reactive oxygen species (ROS) and reduced proliferation (EdU signal: 0.56 ± 0.02 vs. control, p < 0.01). In contrast, VKORC1-knockdown does not impair endothelial regeneration and function (Fig.2). Vitamin K2 reduces vascular inflammation and endoplasmic reticulum stress in the case of VKORC1-, but not VKORC1L1-knockdown. In addition, inducing EndMT resulted in a reduction of VKORC1L1, but not of VKORC1, while VKORC1L1-knockdown aggravates EndMT.

Conclusion

VKORC1 and its isoenzyme VKORC1L1 exhibit divergent effects on endothelial cell inflammation. Further studies are warranted to shed light on the regulation of the enzymes to improve our understanding regarding vascular side effects of VKA treatment and beneficial effects of vitamin K supplementation.
Association of telomeres length with cardiovascular risk factors and arterial stiffness
Authors: Sagris M , Theofilis P T , Oikonomou E O , Toupance S T , Benetos A B , Vlachopoulos C V , Tsioufis K T , Tousoulis D T
Published: October 2024

Background

Leukocyte telomere length (LTL) has been explored as a marker of biological aging, with connections established to age-related diseases like atherosclerosis. Studies have particularly associated telomeres with conditions such as peripheral vascular disease, coronary heart disease, and cardiovascular mortality.

Methods

In this cross-sectional analysis we enrolled individuals from "Corinthia" study which was conducted in the homonym region in Greece. We measured LTL in individuals to obtain comparative metrics on the prevalence of cardiovascular risk factors as well as arterial stiffness. Carotid-femoral pulse wave velocity (cfPWV) was used to evaluate arterial stiffness.

Results

Our analysis included 419 individuals aged 62.4 ± 11.8 years with a median LTL at 6.78 (IQR: 5.08-8.72) bp. Using the median LTL as a cutoff, the cohort was divided into two groups, Group A: 208 patients with low LTL, Group B: 211 patients with high LTL. Group A exhibited a significantly higher proportion of males (52.4% vs. 34.1%, p < 0.01), higher body mass index (BMI) (29.3 ± 4.7 kg/m2 vs. 28.5 ± 4.4 kg/m2, p <0.05), and a higher prevalence of hypertension (78.8% vs. 67.8%, p = 0.01) and dyslipidemia (51% vs. 38.9%, p = 0.014). No significant difference was observed regarding the prevalence of diabetes mellitus, smoking habits, and established cardiovascular disease. In the analysis of the whole cohort, cfPWV was found significant higher in Group A (9.61 ± 3.46 m/s vs. 8.38 ± 2.49 m/s, p <0.01) compared to group B (Figure, Panel A). This association remained significant (β = -0.096, p = 0.038), even after adjustment for confounders in the multivariate regression analysis. Finally, a statistically significant negative correlation between LTL and cfPWV was observed (Figure, Panel B).

Conclusion

LTL plays a pivotal role in cardiovascular health, and lower LTL is associated with impaired cfPWV values and a heightened prevalence of obesity, hypertension, and dyslipidemia.Asociation of LTL with cfPWV values.
Beyond LDL-cholesterol: effects of alirocumab on the human apolipoproteome
Authors: Schmidt L , Theofilatos K , Losdat S , Lang I , Raeber L , Mayr M
Published: October 2024

Introduction

The PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction) trial enrolled 300 participants with longitudinal plasma samples available at four time points (enrollment, 24 hours, 4 weeks, 52 weeks), of which 266 completed the 52-week follow-up.

Purpose

Expanding on a previous investigation employing apolipoprotein proteomics in patients with coronary heart disease, the current study aimed to evaluate the impact of the monoclonal antibody alirocumab on apolipoprotein and proprotein convertase subtilisin/kexin type 9 (PCSK9) levels.

Methods

A mass spectrometry assay was employed to quantify 15 apolipoproteins. Linear mixed-effects models assessed the impact of timepoints and treatments (alirocumab: n = 131, placebo: n = 135, in addition to statins) on apolipoprotein levels.

Results

Alirocumab led to a fast rise in PCSK9 levels, with a marked increase [inter-quartile range] of 262% [207%] as early as 24 hours after treatment initiation, followed by more pronounced elevations at 4 weeks and 52 weeks, reaching 1575% [813%] and 1480% [747%], respectively (P < 0.001 for all comparisons). At 52 weeks, the ApoB reduction compared with enrollment was -75% [10%] with alirocumab vs. -43% [19%] with placebo (P < 0.001, between groups), while the change in LDL-C was -88% [9%] with alirocumab vs. -54% [19%] with placebo (P < 0.001). Alongside significantly greater reductions in ApoC2 (P = 0.0041) and ApoC3 (P < 0.001) with alirocumab, ApoE changed by -41.6% [21.1%] with alirocumab compared to -15.4% [24.5%] with placebo (P < 0.001). Overall, there was no impact on Apo(a) levels compared to baseline.

Conclusion

The rapid increase in PCSK9 levels after 24 hours suggests immediate immunocomplex formation. A compensatory rise in PCSK9 production may contribute to later elevations. Alirocumab not only lowered LDL-C but also achieved a sustained reduction in very low-density lipoprotein-associated apolipoproteins (ApoC2, ApoC3, and ApoE), indicating additional benefits of PCSK9 inhibitors.
Macrophages overexpressing interleukin-10 target and prevent atherosclerosis: regression of plaque formation and reduction in necrotic core
Authors: Wang M , Zhou S , Zhang L , Chen Y
Published: October 2024

Background

Atherosclerosis, a slowly progressing inflammatory disease, is characterized by the presence of monocyte-derived macrophages. Interventions targeting the inflammatory characteristics of atherosclerosis hold promising potential. Although interleukin (IL)-10 is widely acknowledged for its anti-inflammatory effects, systemic administration of IL-10 has limitations due to its short half-life and significant systemic side effects.

Purpose

We aimed to investigate the effectiveness of an approach designed to overexpress IL-10 in macrophages and subsequently introduce these genetically modified cells into ApoE-/- mice to promote atherosclerosis regression.

Methods

We engineered RAW264.7 cells to overexpress IL-10 (referred to as IL-10M) using lentivirusvectors. The ApoE-/- mice were divided into two groups based on the timing of the intervention. The early intervention group (n = 45) received intravenous tail injections from the beginning of Western diet (WD) at six weeks old. The late intervention group (n = 45) started receiving injections at 16 weeks old, 2 months after being fed the WD. Both the early and late intervention group stopped receiving injections after 5 months of being fed the WD.

Results

The IL-10M exhibited robust IL-10 secretion, maintained phagocytic function, improved mitochondrial membrane potentials, reduced superoxide production and showed a tendency toward the M2 phenotype when exposed to inflammatory stimuli. IL-10M can selectively target plaques in ApoE-/- mice, and oil red staining of the entire aorta unequivocally demonstrated that intervention with IL-10M elicited a substantial reduction in plaque area. H&E staining revealed that mice treated with IL-10M in the early intervention group showed a significant reduction in the ratio of plaque area to lumen area. However, the late intervention group did not exhibit statistically significant differences. Notably, mice treated with IL-10M exhibited significantly smaller necrotic cores and reduction in matrix metalloproteinase 9 within the aortic plaques in both the early and late intervention groups. Additionally, the administration of IL-10M showed no obvious side effects.

Conclusion

We developed an anti-inflammatory protein delivery system based on engineered macrophages that can target atherosclerotic plaques and reduce the plaque area and necrotic core. This approach has a promising safety profile and has the potential to be a therapeutic strategy for the intervention of atherosclerosis.
Valvular leaflets and epicardial fat have a significant effect on lesion size in RF ablation
Authors: Colling C C , Reents T R , Kottmaier M K , Englert F , Bahlke F , Deisenhofer I , Bourier F
Published: October 2024

Introduction

Radiofrequency (RF) current is the classic ablation technology in the EP lab. Underlying RF ablation parameters, such as RF power, impedance, duration and contact force are used to calculate expected lesion size. Furthermore, lesion indices (LSI, AI) are applied to estimate expected lesion durability and contiguity.

Purpose

The aim of this ex-vivo study was to assess the influence of valvular tissue and epicardial fat on RF lesion creation.

Methods

An ex-vivo porcine model was created to create RF lesions under standardized conditions. Temperature was constantly kept at 37°C using a thermostat and a circulation pump was used to imitate blood flow. A contact force sensing ablation catheter (ST SF) was used to create RF lesions using predefined RF parameters (30W/50W, CF 10g, 30sec). Lesions using the same RF parameters were created above and right next to mitral valve leaflets as well as on epicardial fat tissue (figure 1). Lesions were then dissected, and lesion depths and diameters were measured using a digital precision caliper.

Results

A total of 210 lesions were created. RF lesions ablated on valvular leaflets showed significantly smaller lesion depth and lesion diameter when compared to RF lesions ablated right next to valvular (diameter 8.0±2.0mm vs 10.8±1.8mm; depth 4.4±1.2 vs 7.7±1.6mm, p<0.01). Lesions ablated on epicardial fat were significantly smaller in diameter (9.2±1.5) and depth (6.5±1.8) than purely endocardial lesions (p<0.01). Examples are depicted in figure 1.

Conclusions

Valvular leaflets as well as epicardial fat tissue have a significant influence on RF lesion creation. RF ablation performed on valvular leaflets or epicardial fat results in significantly (p<0.01) smaller lesions when compared to RF ablations directly on endocardial tissue. This should be considered in ablations of accessory pathways and epicardial procedures.Figure 1
Left atrial substrate modification for persistent atrial fibrillation and left atrial macro or microreentrant tachycardia using a single-shot pulsed field ablation system - a single centre case series
Authors: Lustig P , Lee J , Sponder M , Stix G , Hengstenberg C , Schoenbauer R , Stojkovic S
Published: October 2024

Background

Pulsed field ablation (PFA) is a novel ablation technique for pulmonary vein isolation (PVI) in patients with paroxysmal and persistent atrial fibrillation. However, data for efficacy and safety of PFA for left atrial substrate modification in patients with long-standing persistent atrial fibrillation (AF) and macro- as well as microreentrant atrial tachycardia (AT) is scarce.

Aim

Here we provide a retrospective, single-centre case series regarding efficacy and safety of left atrial substrate modification, using a single-shot PFA system.

Methods and Results

Over a period of 6 months, 8 patients with long-standing persistent AF and AT underwent Re-PVI with left atrial substrate modification using a single-shot PFA system. Median age was 63 years (IQR 58 - 75), and 4/8 of patients were female. Time from first diagnosis of AF was 7 years (IQR 4 –10). All but 1 patient underwent previous PVI (IQR 1-3) with (5/7) or without (2/7) prior substrate modification using radiofrequency ablation. On transthoracic echocardiography, all patients showed severe left- and right-atrial enlargement, with LA volume of 58 ml/m2 (IQR 49.7–72) and RA diameter of 62 mm (IQR 55-75). In 8 patients, 9 ATs and 2 typical flutters were treated with PFA. Following PVI, additional posterior wall isolation was performed in 6/8 patients, roof in 6/8, and anterior wall (between superior mitral anulus and RSPV) in 4/8 patients. In addition, 2/8 patients had cavotricuspid isthmus ablation for typical atrial flutter. All patients received atropine prior to PVI, as well as bolus of nitro-glycerine prior to PFA of anterior wall and/or cavotricuspid isthmus. Acute success rate was 100% and all ATs as well as typical flutter terminated with PFA. After median follow-up time of 88 days (IQR 61-112), 3 patients had a documented recurrence of AF/AT, in 2 of which electrical cardioversion was necessary. We observed no acute and/or chronic complications following PFA, i.e. no pericardial effusion/tamponade, TIA/stroke, myocardial infarction, coronary artery spasm, AV-block, bleeding, or atrioesophageal fistula.

Conclusion

In this small, single-centre case series, left atrial substrate modification for long-standing persistent AF and AT using a single-shot PFA system was safe and showed an excellent acute success rate.
Association between preprocedural thromboembolic or bleeding events under oral anticoagulation therapy and mid-term outcomes after percutaneous left atrial appendage closure
Authors: Sumiyoshi H , Fujita M , Nishiura N , Mushiake K , Chatani R , Ono S , Tasaka H , Maruo T , Kadota K , Kubo S
Published: October 2024

Background

Currently, no consensus has been established on the most effective antithrombotic therapy to prevent thromboembolic and bleeding events in patients undergoing percutaneous left atrial appendage closure (LAAC).

Methods

We retrospectively investigated the incidence of device-related thrombosis (DRT), thromboembolic events, and bleeding events in patients who underwent LAAC from September 2019 to October 2022. After categorizing patients into groups based on preprocedural thromboembolic or bleeding events under oral anticoagulation (OAC) therapy, we compared the incidence of DRT and prognosis according to the postprocedural antithrombotic therapy.

Results

In patients who received the conventional antithrombotic therapy (OAC with and without single antiplatelet therapy for 45 days after LAAC and dual-antiplatelet therapy from 45 days to 6 months followed by single antiplatelet therapy), preprocedural thromboembolic events despite OAC were independently associated with DRT or postprocedural thromboembolic events at the 3-year follow-up (hazard ratio [HR] 4.55; 95% confidence interval [CI] 1.32–15.6; P = 0.016), whereas preprocedural bleeding events were independently associated with postprocedural bleeding events (HR 8.01, 95% CI 1.45–58.3; P = 0.036). Continuation of OAC for 12 months among patients who developed preprocedural thromboembolic events during OAC significantly decreased the incidence of DRT or postoperative thromboembolic events (P = 0.002) with no increase in the bleeding events (P = 0.522).

Conclusions

Preprocedural thromboembolic and bleeding events can predict adverse events after LAAC with conventional antiplatelet-based antithrombotic therapy. Patients who develop thromboembolic events under continuous OAC may benefit from continuous OAC for 1 year after LAAC.
Remote monitoring of cardiac implantable electronic devices using smart device interface versus radiofrequency-based interface: a systematic review
Authors: See Tow H , Fong K Y , Wang Y , Yeo C , Ching C K , Lim T W , Tan V H
Published: October 2024

Background

Guidelines recommended remote monitoring (RM) in managing patients with Cardiac Implantable Electronic Devices (CIED). In recent years, smart device (phone or tablet) monitoring-based RM (SM-RM) was introduced. SM-RM is a specifically developed application (app) which can be downloaded from app stores using smart devices. The app uses Bluetooth low-energy to communicate automatically and securely with the patient’s CIED. The app then uses a cellular or Wi-Fi internet connection to transfer the data securely to the manufacturer’s repository.

Purpose

This study aims to systematically review SM-RM versus bedside monitor RM (BM-RM) using radiofrequency in terms of compliance, connectivity, and episode transmission time.

Methods

We conducted a systematic review, searching three international databases from inception until July 2023 for studies comparing SM-RM (intervention group) versus BM-RM (control group).

Results

Two propensity score-matched studies with a total of 21978 patients were retrieved (9642 patients in the SM-RM arm and 12336 patients in the BM-RM arm) (1, 2). There is significantly higher compliance among patients using SM-RM compared with patients using BM-RM in both pacemaker and defibrillator patients. There were higher enrolment rates and completed scheduled transmissions among SM-RM compared to BM-RM. Higher connectivity was also seen in patients with SM-RM, and more SM-RM patients transmitted at least once compared to BM-RM patients. Additionally, SM-RM patients had more patient-initiated transmissions compared to BM-RM patients. Younger patients (aged <75) had more patient-initiated transmissions, and a higher proportion had ≥10 such transmissions compared with older patients (aged ≥75) in both SM-RM and BM-RM groups. The episode transmission time of SM-RM patients was also shorter than that of BM-RM patients.

Conclusion

SM-RM is a step in the right direction, with good compliance, connectivity, and shorter episode transmission time. It allows patients to feel empowered and in control of their health. Further research on cost-effectiveness and long-term clinical outcomes can be carried out in the future.
Eight year Follow-Up Data on a Leadless Pacing System Real life experience in comparison to data of the prospective trial
Authors: Winter S , Nguyen Q , Tuscher T , Fischer S , Sinning J M
Published: October 2024

Introduction

The Micra leadless intracardiac pacing system has been introduced and implemented into clinical routine in 2015, with its next generation MICRA AV in 2020. Feasibility, implantation safety, and acute success have been proven in the setting of controlled studies. Even apart from controlled studies, this new technology was beneficial for the individual patient. We aimed to report our single center follow-up (FU) data with a follow-up of up to six years.

Methods

In 292 patients (146 men; age: 81±5,7 y), Micra implantation was performed.

Pacemaker interrogation was performed one to seven days after implantation and during FU (1; 3; 6, then every 6 month) up to 84 months. Data were assessed in a real-life setting and compared with existing data of a controlled prospective trial.

Results

The implantation was successful in all 292 attempts with only one pericardial effusion as major complication. During follow up there were two patients developing severe heart failure symptoms resulting in an implantation of a CRT-device and switching of the leadless pacemaker system.

The average acute thresholds, sensing and impedance after system release were: 0.57±0.34V@0.24ms; 10,02±3,96mV and 752±1201Ohm. During follow up of up to 8 years neither, pacemaker failure, nor infections were reported. Measurements were reevaluated for long-term thresholds, sensing and impedance: 0.75 ± 0.38V @ 0.24 ms; 18,38 ±2,75 mV and 525 ± 102 Ohm. During eight years, no significant changes from acute to long-term measurements were detectable. In comparison to the controlled trial, our measurements of this real-life cohort were very similar.

Conclusion

In a real-life setting, the implantation of the leadless Micra system demonstrates a high rate of implantation success without major complications. We were also able to show stable long-term system parameters in the clinical setting of up to seven years of follow up with a very good battery longevity of about 12,3 years.
Equal performance of the subcutaneous and transvenous implantable cardioverter defibrillator across all age groups in the PRAETORIAN trial
Authors: Pepplinkhuizen S , Olde Nordkamp L R A , Kuschyk J , Bonnemeier H , El-Chami M F , De Weger A , Van Der Stuijt W , Smeding L , Bijsterveld N R , Richter S , Boersma L V A , Betts T R , Wilde A A M , Knops R E
Published: October 2024

Introduction

The subcutaneous ICD (S-ICD) is developed to overcome lead-related complications and systemic infections, inherent to transvenous ICD (TV-ICD) therapy. In the PRAETORIAN trial the S-ICD proved to be non-inferior to the TV-ICD with regard to inappropriate shocks (IAS) and complications. However, the S-ICD is still mainly the preferred choice in young patients with a long life expectancy and therefore higher risk for lead-related complications. We aimed to evaluate the impact of age on complications and IAS between the S-ICD and TV-ICD.

Methods

The PRAETORIAN trial is an investigator-initiated, international, multicenter, randomized, two-arm noninferiority trial that was conducted in the United States and Europe. In total 849 patients with a class I or IIa indication for ICD therapy and no pacing indication were randomized to receive an S-ICD (N=426) or TV-ICD (N=423) and followed for a median of 49 months. We compare the occurrence of complications and IAS between increasing quartiles of age.

Results

Quartile 1 (Q1) consisted of 203 patients aged <55 (109 S-ICD, 94 TV-ICD), Q2 of 199 patients aged 55-62 (100 S-ICD, 99 TV-ICD), Q3 of 232 patients aged 63-69 (111 S-ICD, 121 TV-ICD) and Q4 of 215 patients aged ≥70 (106 S-ICD, 109 TV-ICD). Between the quartiles, there were no significant differences in occurrence of device-related complications (P = 0.32) or IAS (P = 0.66). In Q1, there were 15 (7.4%) complications (5 S-ICD, 10 TV-ICD) and 13 (6.4%) IAS (7 S-ICD, 6 TV-ICD), compared to 20 (10.1%) complications (7 S-ICD, 13 TV-ICD) and 17 (8.5%) IAS (9 S-ICD, 8 TV-ICD) in Q2, 22 (9.5%) complications (12 S-ICD, 10 TV-ICD) and 19 (8.2%) IAS (11 S-ICD, 8 TV-ICD) in Q3 and 18 (8.4%) complications (7 S-ICD, 11 TV-ICD) and 21 (9.8%) IAS (14 S-ICD, 7 TV-ICD) in Q4 (Figure 1.). Figure 2. shows forest plots of the hazard ratios per quartile.

Conclusions

The S-ICD performed equal to the TV-ICD with regard to IAS and complications between quartiles of age, making the S-ICD a good alternative across all age groups.
Permanent and persistent atrial fibrillation are independent risk factors of mortality after severe COVID-19
Authors: Zajac A , Kasprzak J D
Published: October 2024

Background

New coronavirus disease (COVID-19), pandemic infection caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), had a deep global influence on morbidity and mortality profile. Comorbidities, especially cardiovascular diseases were identified to strongly modify the clinical course of COVID-19. However, the prognostic role of incident or prevalent atrial fibrillation has not been fully explained.

Purpose

The aim of this study was to evaluate the association between atrial fibrillation and outcomes following hospitalization in patients with severe COVID-19.

Methods

We analyzed 199 patients (72 female, median age 70 years) with severe COVID-19 hospitalized between November 2020 and February 2021, due to SARS-CoV-2 infection. Study cohort included 68 patients with a history of AF (34 patients with paroxysmal AF, 19 with permanent AF, 15 patients with persistent AF) and 51 patients presented with AF during hospitalization.

Results

Overall mortality during 90 days from the admission to hospital was 41% (n=82). Non-survivors were older, had significantly elevated inflammation markers (CRP, WBC, procalcitonin, IL-6), NT-proBNP and D-dimer on the first day of hospitalization, lower left ventricular ejection fraction and worse kidney function as compared to those who stayed alive during the follow-up. Among the hospitalized patients with COVID-19, a history of AF and the presence of AF during hospitalization contributed to higher mortality, p=0.001. The patients with permanent and persistent AF were at the greatest risk of death, p<0.001. In multivariate analysis, taking into account whether the patients had a history of AF, the subtypes of AF (paroxysmal, permanent, persistent) and whether the AF was present during hospitalization to identify the independent risk factors of death in the study period, we found that AF was related to worse prognosis and persistent or permanent form represented an independent predictor of mortality, p=0.035.

Conclusions

Different clinical presentations of AF have varying impact on survival in severe COVID-19. Mortality in hospitalized patients with severe COVID-19 was higher among patients with history of AF, especially with persistent and permanent type of AF, and with AF present during hospitalization.Figure.Survival depending on the type o.
Postoperative atrial fibrillation following noncardiac surgery is associated with long-term heart failure: insights from a nationwide cohort
Authors: Karacan M , Yafasova A , Fosboel E L , Tas A , Gundlund A , Gustafsson F , Stahl A , Schou M , Wolsk E , Dridi N P , Koeber L , Butt J H
Published: October 2024

Background

Atrial fibrillation (AF) is associated with the development of heart failure (HF). Whether postoperative AF (POAF) also confers a greater risk of HF is unclear.

Purpose

To investigate the long-term rate of incident HF in patients developing new-onset POAF after noncardiac surgery relative to patients who did not develop POAF after noncardiac surgery.

Methods

In this cohort study, the Danish nationwide registries were used to identify all patients aged ≥30 years who developed POAF following noncardiac, nonobstetric surgery from 1996 to 2020. These patients were matched in a 1:3 ratio by age, sex, type of surgery, selected comorbidities, and year of inclusion with patients without POAF after noncardiac surgery. The primary outcome was incident HF. Secondary outcomes were HF hospitalization and all-cause mortality.

Results

A total of 2,270 patients with POAF were matched with 6,810 patients without POAF (median age: 75 years [25th-75th percentile: 67-82 years]; 53.5% females). The median follow-up was 7.2 years. Compared with patients without POAF, those with POAF had a higher associated long-term rate of incident HF (2.6 versus 1.2 events per 100 person-years; HR 2.39 [95% CI 2.06-2.78]]), HF hospitalization (2.2 versus 1.0 events per 100 person-years; HR 2.33 [95% CI 1.97-2.74]), and all-cause mortality (9.8 versus 7.4 events per 100-person-years; HR 1.55 [95% CI 1.45-1.66]) (Figure 1).

Conclusions

Patients with new-onset postoperative atrial fibrillation following noncardiac surgery had a higher associated long-term rate of incident heart failure compared to those without postoperative atrial fibrillation following noncardiac surgery. These findings highlight the importance of increased awareness among physicians of the risk of adverse outcomes, including heart failure, in patients with postoperative atrial fibrillation after noncardiac surgery. Closer postoperative follow-up and monitoring, as well as aggressive treatment of cardiovascular risk factors, may be warranted to reduce the risk of adverse outcomes in these patients.
The association of NT-proBNP levels in atrial fibrillation patients and 3-year risk of heart hospitalization and death
Authors: Szummer K , Lindeberg F , Mazhar F , Carrero J J
Published: October 2024

Background

NT-proBNP-levels are often elevated in patients with atrial fibrillation (AF), but their clinical use and interpretation for predicting subsequent cardiovascular events has not been explored in an all-comers setting.

Aim

To determine whether NT-proBNP levels are associated with the risk of subsequent heart failure (CHF) and/or death in patients with AF and its relation to prior CHF diagnosis

Method

All patients with new-onset AF (defined by ICD-code I48) who had an NT-proBNP-level within +/- 14 days of the date of the AF date measured in a regional laboratory repository between 2000-2021 were included in the analysis cohort. Patients were categorized into NT-proBNP level (pg/mL) <1000, 1000-1999, ≥2000. If several NT-proBNP-levels were measured, the maximal value was used. The association between NT-proBNP level and the outcome CHF hospitalization and/or death within 3 years of diagnosis was assessed in Cox regression analyses adjusted for baseline characteristic and medications. Since there was an interaction (p<0.001) between Nt-proBNP-level and prior/new-onset CHF at time of AF diagnosis and no known CHF, two separate analyses were performed in patients with or new-onset CHF and those without prior CHF.

Results

There were 10559 patients with AF and no CHF, and 11 257 with AF and CHF. There were 14% of patients with new-onset CHF at time of new-onset AF diagnosis. These were grouped together with patients with known CHF. Patients with no prior CHF were younger (76 years (95% CI 68-83) vs 80 (72-87), p<0.001), and healthier with less often diabetes (18.4% vs 24.5%, p<0.001), prior myocardial infarction (12.0% vs 24.3%), a lower CHA2DS2-VASc score (3.0 vs 5.0, p<0.001) and a lower median NT-proBNP level (1650 pg/mL (95% CI 702-3549) vs 4240 pg/mL (2160-8860), p<0.001).

Among patients with AF and no prior CHF, the incidence rate in the lowest NT-proBNP level was low, but increased with higher levels (Table). Adjusting for covariates and medications, the risk of both CHF hospitalization and CHF/death compared to the reference category NTproBNP< 1000 pg/mL was nearly 2 and 3 times higher among those who with initial NT-proBNP level 1000-1999 and ≥ 2000.

Among patients with AF and known CHF, the incidence rate of CHF hospitalization or CHF hospitalization/death at the same NT-proBNP-strata was several times higher compared to patients without known CHF. Adjusting for covariates, the risk increased for CHF hospitalization or CHF/hospitalization similarly for each strata as for patients without known CHF.

AF patients without known HF but with the highest elevation of NTproBNP-level had a risk of subsequent hospitalization of heart failure which was higher than those with known heart failure and lowest NTproBNP-level.

Conclusion

A higher NTproBNP-level in patients with AF identifies patients at higher risk of CHF hospitalization and/or death in both patients with no and prior CHF.Table
Screening for Atrial Fibrillation (AF) by handheld single-lead ECG and risk of all-cause mortality stratified by non-AF cardiovascular disease
Authors: Sun W , Yan B
Published: October 2024

Purpose

Screening for Atrial fibrillation (AF) has been suggested as a strategy to increase early detection of silent AF. We aimed to evaluate all-cause mortality between patients with screen-detected and clinically-diagnosed AF, and the effect of oral anticoagulation therapy (OAC) on mortality.

Methods

We prospectively enrolled and performed AF screening using handheld single-lead ECG(AliveCor) on consecutive patients who attended medical outpatient clinics during December 2014 and December 2017. Repeat screening was performed among patients who had >1 clinic visits. All participants were divided into 5 cohorts: (i) previously known AF at baseline (kAF); (ii) initial screen-detected AF (S1-AF); (iii) subsequent screen-detected AF (FU-sAF); (iv) clinically-diagnosed AF during follow-up (FU-cAF); and (v) no AF. Risk of all-cause mortality was estimated by adjusted hazard ratio (HR) using COX proportional hazards regression, adjusting for age, gender, co-morbidities, concurrent chronic use of medications including OAC, with AF detection or clinical diagnosis and OAC therapy handled as time-varying variable. Subgroup analysis was conducted to identify heterogeneity of effect across with or without non-AF cardiovascular disease (CVD).

Results

Of 11,972 subjects (mean age 76.6±7.8, female 49.2%), 18.7% (n=2,236) had previously kAF, 1.9% (n=223) S1-AF, 0.6% (n=71) FU-sAF, 7.3% (n=867) FU-cAF, and 71.6% (n=8,559) no AF. During a median FU duration of 6.8(IQR: 5.2-8.1) years, patients with kAF (HR=1.8(1.6-2.0)), S1-AF (HR=1.6(1.3-1.9)) and FU-cAF (HR=1.6(1.4-1.8)) were at higher risk of all-cause mortality, compared to individuals without AF, whereas FU-sAF (HR=1.0(0.7-1.4)) had similar low risk of death as no AF. Heterogeneity of effect was detected in subgroup analysis. Among patients without non-AF CVD, FU-sAF (HR=6.0(1.8-19.8)) and FU-cAF (HR=4.7(3.3-6.7)) were at markedly higher risk of all-cause mortality. DOAC (HR=0.57(0.38-0.87)) but not VKA (HR=0.72(0.43-1.15) reduced mortality. However, in patients with CVD other than AF, risk of FU-sAF (HR=1.1(0.8-1.6)) decreased to as low as individuals without AF (P for interaction =0.0039).Both DOAC (HR=0.51(0.46-0.58)) and VKA (HR=0.87(0.78-0.98) were beneficial.

Conclusion

Likely delayed AF detection suggested by groups of FU-cAF and FU-sAF may be associated with significant rise in risk of mortality among patients without non-AF CVD. The effect diminished when non-AF CVD as potential competing risk existed. The role of VKA in reducing all-cause mortality warrants more studies.
Colchicine prevents post-ablation atrial fibrillation recurrence: a systematic review and meta-analysis
Authors: Jain H , Odat R , Jain J , Saleem M , Passey S , Patel N , Goyal A , Gole S , Verma A
Published: October 2024

Background

Catheter ablation for atrial fibrillation (AF) is a commonly performed procedure with appreciable effectiveness; however, post-AF ablation recurrence is often observed. The pathophysiology behind this recurrence is often inflammation and oxidative stress triggered during the ablation procedure. Colchicine is a potent anti-inflammatory agent that has emerged as a promising therapeutic for preventing post-ablation AF recurrence; however, the data available on its efficacy are limited.

Purpose

This meta-analysis aimed to investigate the outcomes of post-ablation AF patients who received colchicine in the postoperative period.

Methods

A comprehensive literature search spanning major bibliographic databases was conducted to retrieve studies comparing outcomes in post-ablation AF patients who received colchicine versus those who did not. The outcomes of interest included AF recurrence, pericarditis, gastrointestinal side effects, and hospitalization. AF recurrence was determined with a 12-lead electrocardiogram and/or Holter monitoring. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were pooled from all studies using the DerSimonian and Laird random-effects model. Statistical significance was set at p ≤ 0.05.

Results

Six studies were included with 1791 patients (721 in the colchicine group and 1070 in the placebo group). Patients who received colchicine had significantly lower odds of AF recurrence on follow-up [OR: 0.62; 95% CI: 0.48, 0.79; p=0.0001] but had higher gastrointestinal side effects [OR: 2.67; 95% CI: 1.00, 7.12; p=0.05]. There were no statistically significant differences in acute pericarditis [OR: 0.54; 95% CI: 0.27, 1.05; p=0.07] or hospitalization [OR: 1.03; 95% CI: 0.73, 1.45; p=0.87].

Conclusion

Prophylactic use of colchicine after catheter ablation in patients with AF leads to a reduction in AF recurrence, albeit with increased gastrointestinal side effects such as diarrhea and nausea. Colchicine use did not lead to a reduction in the rates of pericarditis and hospitalization after ablation. Large randomized controlled trials are necessary to evaluate the efficacy of colchicine in the prevention of AF recurrence, particularly focusing on the dose and duration of treatment to optimize the side effect profile.
Left atrial and left ventricular positive and negative remodeling after catheter ablation of atrial fibrillation
Authors: Jurcevic R , Angelkov L , Jakovljevic V , Grujic Milanovic J , Tomovic M , Kojic D , Ristic V , Vukajlovic D , Grbovic A , Babic M , Susic M , Otasevic P , Tasic N , Bojic M
Published: October 2024

Introduction

Atrial fibrillation (AF) is associated with negative remodeling of left atrium (LA) and in later stages of diseases with negative remodeling of left ventricle (LV). Can radiofrequency ablation (RFA) of pulmonary veins cure AF and retain progression of arrhythmia?

Purpose

This study evaluated positive and negative remodeling of LA and LV after RFA of pulmonary veins and a 7-year follow-up. The patients were divided into 4 groups on the basis of Pulmonary Vein Isolation Outcome Degree (PVIOD 1-4), a new measure for the efficacy of catheter ablation of AF.

Methods

One hundred seventeen patients with symptomatic drug-refractory paroxysmal and persistent AF were treated with RFA. At baseline and after a 7 years of follow-up, 2-dimensional echocardiography was performed to assess LA diameter, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and left ventricular ejection fraction (LVEF).

Results

After a 7-year follow-up 32.5% patients with successful single RFA of AF (PVIOD 1) showed significant positive LA and LV remodeling: LA diameter 39.3±0.6 vs 36.5±0.6 mm, p=0.0007; LVEDD 53.1±0.6 vs 50.9±0.7 mm, p=0.008; LVESD 34.7±0.8 vs 32.0±0.1 mm, p=0.005 and LVEF 56.8±0.8 vs 62.1±1.1 %, p=0.000008. In 29.1% of patients with success after multiple procedures (PVIOD 2) occurred significant reverse LA remodeling: LA diameter 41.9±0.7 vs 40.2±0.6 mm, p=0.04. Clinical success (PVIOD 3) after RFA was defined as a significant reduction in the number and duration of AF episodes with or without previously ineffective antiarrhythmic drugs (AAD) class I and III. In 14.5% of subjects with long-term clinical success (PVIOD 3 and baseline LA diameter 43.2±1.0 mm) remodeling of LA and LV was not occurred. In 23.9% of patients with procedural and clinical failure after RFA (PVIOD 4) long-term follow-up showed significant negative remodeling of LA and LV: LA diameter 44.7±0.7 vs 47.4±0.7 mm, p=0.006; LVEDD 52.8±0.9 vs 57.1±0.6 mm, p=0.0006; LVESD 36.5±1.1 vs 40.7±1.2 mm, p=0.006 and LVEF 50.7±1.7 vs 43.8±1.8 %, p=0.004.

Conclusions

Single successful RFA of pulmonary veins in early stage of AF with normal LA diameter cure arrhythmia, which was proved with LA and LV positive remodeling after a 7-year follow-up. With increase of LA diameter, the success of RFA decrease. The multiple procedures slow the progression of AF, but are less effective because of long periods of time between them. Clinical success and role of AAD therapy are also important in AF management. If AF is not treated with RFA properly on time it becomes progressive disease.
Impact of left atrial stiffness measurement as a pre-procedural predictor of an extensive left atrial low-voltage area
Authors: Hasegawa Y , Wada R , Sekiya Y , Akagawa R , Suzuki N , Ikami Y , Otsuki S , Kashimura T , Chinushi M , Inomata T
Published: October 2024

Background

The presence of a left atrial (LA) low-voltage area (LVA) after pulmonary vein isolation for atrial fibrillation (AF) is a strong predictor of recurrence and LVAs are often an additional ablation target. However, predicting the presence of an LVA before the procedure remains challenging.

Purpose

To assess the LA stiffness index as a preprocedural predictor of an extensive LVA.

Methods

We prospectively evaluated 74 patients who underwent catheter ablation for AF and high-density bipolar LA voltage mapping during sinus rhythm or high right atrial pacing. "LVA" was defined as an area with bipolar electrograms (<0.5 mV), while "extensive LVA" was defined as the presence of an LVA that covered more than 15% of the LA surface. Echocardiographic measurements, including the LA volume index (LAVi), E/e' ratio, LA reservoir strain (LASr), and LA stiffness index, calculated as the ratio of E/eʹ to LASr, were performed prior to catheter ablation in all patients.

Results

Overall, 17 patients (23.0%) had an extensive LVA. Patients with extensive LVAs were older (73 ± 7 vs. 66 ± 8 years; P=0.003), predominantly female (59% vs. 23%; P=0.01), and more frequently showed persistent AF (59% vs. 30%; P=0.04) in comparison to patients without extensive LVAs. According to a receiver operating characteristic curve analysis, the LA stiffness index was more accurate than the LAVi or LASr for predicting extensive LVAs (Figure), allowing using a cutoff value ≥0.6 with 73% sensitivity and 91% specificity. A multivariate logistic regression analysis revealed that the LA stiffness index was an independent predictor of an extensive LVA (odds ratio [OR], 44.11; 95% CI 3.83–507.47, P=0.002).

Conclusion

The LA stiffness index was a robust predictor of the extent of LVAs in AF patients and thus could be useful for the preprocedural selection of candidates for catheter ablation and to determine the most effective ablation strategies.
Incidence of acute pericarditis after pulsed-field ablation for the treatment of atrial fibrillation
Authors: Isenegger C , Arnet R , Jordan F , Salis M , Knecht S , Krisai P , Voellmin G , Spreen D , Osswald S , Sticherling C , Kuehne M , Badertscher P
Published: October 2024

Introduction

Pulsed-field ablation (PFA) has emerged as a novel treatment strategy for patients with atrial fibrillation (AF). While traditional thermal ablation modes such as radiofrequency energy or cryoballoon energy showed an acute pericarditis rate of 0.5 – 4%, little is known about the incidence of acute pericarditis after PFA.

Purpose

To assess the incidence of acute pericarditis using PFA for the treatment of AF.

Method

Patients undergoing catheter ablation for AF using PFA were consecutively enrolled in a prospective registry in a tertiary referral center between January 2022 and January 2024. After PFA, all patients received a clinical assessment for cardiothoracic symptoms including cardiac auscultation, 12-lead ECG and transthoracic echocardiography. A clinical diagnosis of acute pericarditis was established according to the 2015 European Society of Cardiology (ESC) guidelines by the presence of at least 2 of the following criteria within 90 days after PFA: 1) pleuritic chest pain; 2) friction rub; 3) new widespread ST-elevation or PR depression on ECG; 4) pericardial effusion. Suspected acute pericarditis was diagnosed if 1 criterion was fulfilled.

Results

A total of 388 patients with AF (median age 67.5 years, 32% female) underwent pulmonary vein isolation using PFA. 0 (0%) patients fulfilled ≥ 2 ESC criteria required for diagnosis of acute pericarditis. Suspected acute pericarditis within 90 days after the procedure was found in 17 (4.4%) patients. 29 (7.5%) patients reported some sort of cardiothoracic symptoms (chest pain, chest tightness, chest discomfort, shortness of breath or pleuritic chest pain). Among them, 6 (1.5%) patients received anti-inflammatory drug treatment due to suspected pericarditis. 0 (0%) patients had a friction rub, 6 (1.5%) patients showed PR depression (no ST-elevation) and 5 (1.3%) patients demonstrated pericardial effusions. None of the pericardial effusions required drainage.

Conclusion

In this large cohort of patients undergoing PFA for AF, no patients suffered acute pericarditis according to current ESC criteria. Any type of cardiothoracic symptoms after PFA were noted in 7.5% of patients with 1.5% of patients requiring drug therapy.Graphical Abstract