bluuebunny/crossref_metadata_2025 huggingface dataset:
Ablation of right ventricular endocavitary arrhythmias
Authors: Haq I , Ezzedine F , Sugrue A , Asirvatham S J , Killu A M
Published: October 2024

Background

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

Purpose

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

Methods

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

Results

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

Conclusions

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

Background

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

Purpose

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

Methods

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

Results

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

Conclusion

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

Introduction

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

Aim

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

Methods

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

Results

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

Conclusion

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

Introduction

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

Purpose

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

Methods

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

Results

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

Conclusion

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

Conclusion

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

Aim

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

Methods and Results

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

Conclusions

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

Introduction

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

Methods

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

Results

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

Conclusion

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

Background

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

Purpose

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

Methods

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

Results

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

Conclusion

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

Background

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

Methods

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

Results

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

Conclusion

Randomized trials have shown clear benefits with catheter ablation compared to medical management for AFIB in heart failure. Ablation has demonstrated significantly lower all-cause mortality, reduced CV mortality, HF hospitalizations, AFIB recurrence rate, and improvement in LVEF. Patients who underwent catheter ablation showed improvement in functional outcomes like 6MWT and MLHFQ scores. There was no difference in the incidence of cerebrovascular events compared to medical management. This study adds to the growing evidence in the literature for ablation therapy; however, more trials are needed to identify patients for optimal benefits across the spectrum of heart failure patients.Forest PlotsForest Plots
Antithrombotic therapy and the risk of pocket hematoma after subcutaneous implantable cardioverter-defibrillator implantation
Authors: Pepplinkhuizen S , Kors N , De Veld J A , Dijkshoorn L A , Bijsterveld N R , De Weger A , Smeding L , Wilde A A M , Olde Nordkamp L R A , Knops R E
Published: October 2024

Introduction

The PRAETORIAN trial, which randomized S-ICD versus TV-ICD in patients with a class I or IIa indication for ICD therapy, showed that clinically significant pocket hematomas were more frequent following S-ICD implantation. Many ICD recipients have comorbidities requiring anticoagulant (AC) and/or antiplatelet (AP) therapy, which increase the risk for hematoma formation post implantation. In contrast to TV-ICD implantation, little data exists regarding the optimal AC and AP strategy during S-ICD implantation to prevent pocket hematomas.

Methods

All patients who underwent de novo S-ICD implantations between February 2009 and January 2023 at our tertiary center were included. Data was collected retrospectively from electronic patient records. Clinically significant pocket hematomas were defined as an accumulation of blood at the pocket site within 30 days after S-ICD implantation, necessitating actions including applying a pressure bandage, surgical evacuation, drain insertion, a change in medication or an extended hospital stay or blood transfusion.

Results

A total of 348 patients were included of which 224 (64.4%) patients used antithrombotic therapy pre-implantation. Median age at implantation was 50 years (IQR: 36-61 years), 33.4% of the patients were female and the vast majority of implants were intermuscular (90.2%). Eighteen (5.2%) patients developed a clinically significant pocket hematoma. A total of 94 (27%) patients used AC therapy prior to the implantation of which 73 (21%) patients used a vitamin K antagonist (VKA). A total of 130 (37.4%) patients used AP therapy at baseline of which 49 (14.1%) patients were on dual AP therapy (DAPT). Continuation of VKA and continuation of DAPT with ticagrelor were independent predictors for pocket hematoma formation (p<0.001, and p<0.001 respectively). There were significantly more pocket hematomas in patients with continued VKA compared to patients with interrupted VKA (27.3 % (6/22) vs. 4.3% (2/47), respectively, p=0.011). Moreover, continuation of DAPT with ticagrelor was associated with significantly more pocket hematomas post implantation compared to continuation of DAPT with clopidogrel (4/12 vs 1/28, respectively, p=0.022).

Conclusion

This study showed that continuation of VKA during S-ICD implantation was associated with an increased risk of pocket hematoma formation compared to interruption of VKA. The continuation of DAPT with ticagrelor was an independent predictor of pocket hematoma formation and showed significantly more pocket hematomas compared to continuation of DAPT with clopidogrel. These findings support the need for specific peri-operative thrombotic therapy guidelines for S-ICD implantations to reduce the risk of pocket hematomas.
Altered fibrin clot properties and elevated von Willebrand Factors level are associated with progression to permanent atrial fibrillation during follow-up: a cohort study
Authors: Nowak K , Zabczyk M , Natorska J , Polak M , Zalewski J , Undas A
Published: October 2024

Introduction

Little is known about association of prothrombotic markers and atrial fibrillation (AF) progression to permanent arrythmia (PerAF). Formation of denser and poorly lysable fibrin clots have been observed in AF including patients with sinus rhythm in association with stroke and bleeding risk. We investigated whether altered fibrin clot properties and other prothrombotic state markers may contribute to AF transition to PerAF.

Methods

In the cohort study, in 226 anticoagulated AF patients (median age 69 years, median CHA2DS2-VASc of 3)with paroxysmal (n=83, 36.7%) or persistent (n=143, 63.3%) arrythmia we assessed at baseline plasma clot permeability (Ks), lysis time (CLT), and fibrinolysis involved proteins, including plasminogen activator inhibitor type 1 (PAI-1) along with von Willebrand factor (vWF) antigen. We recorded patients with PerAF during a median follow-up of 58 months.

Results

PerAF was documented in 62 (27.4%, 5.7%/year) subjects. These patients were older, with larger prevalence of heart failure (HF), higher body mass index by 9.6%, more often presented persistent AF and had longer history of arrythmia by 60%. We observed by 25.7% longer CLT and similar Ks, compared with the remainders, along with higher levels of vWF by 29% and PAI-1 by 21.3%. By multivariable analysis CLT, vWF and HF were independently associated with PerAF (R2=0.697, P<0.001). A cut-off CLT value of ≥105 min had a sensitivity of 88.7% and specificity of 78.7% in prediction of PerAF (area under curve 0.892, 95% confidence interval 0.848-0.935, P<0.001).

Conclusion

Impaired global fibrinolysis and elevated vWF levels are independently associated with faster progression to PerAF despite anticoagulation.Figure1
Invasive haemodynamic assessment shows the obesity-HFpEF phenotype is common amongst patients with symptomatic AF
Authors: Ariyaratnam J , Elliott A D , Mishima R S , Emami M , Kadhim K , Middeldorp M E , Sanders P
Published: October 2024

Background

The obesity-HFpEF phenotype is a unique form of heart failure associated with elevated LA and RA pressures, cardiac remodelling and poor exercise capacity. The influence of this HFpEF phenotype amongst patients with AF is unknown.

Objective

We sought to determine the influence of the obesity-HFpEF phenotype amongst patients with symptomatic AF, using invasive testing, imaging and cardiopulmonary exercise testing to assess haemodynamics, cardiac remodelling and exercise capacity in patients undergoing AF ablation.

Methods

Consecutive patients with symptomatic AF due to undergo an AF ablation procedure were recruited. Participants were grouped according to the presence of obesity if body mass index (BMI) exceeded 30kg/m2. Mean LA pressure (mLAP) and mean RA pressure (mRAP) were measured invasively at AF ablation and HFpEF was defined as mLAP>15mmHg at rest or after infusion of 500mls saline. Cardiac remodelling was assessed using transthoracic echocardiography. Exercise capacity was evaluated using cardiopulmonary exercise testing and AF symptoms and quality of life were assessed using the AF Symptom Severity Questionnaire.

Results

Of 120 participants, 44 (36.7%) were obese and 76 (63.3%) were non-obese (Table 1). Despite younger age (p=0.003), obese participants were more likely to have a coexistent diagnosis of HFpEF (84.1% vs 67.1%, p=0.043). In addition to higher mLAP (p<0.001), obesity was associated with higher mRAP (p<0.001) compared to non-obese patients. Obesity was not associated with differences in LV volume (p=0.559) or function (p=0.381) but was associated with larger LA volumes (p=0.032). On functional assessment, obese participants demonstrated a higher burden of AF symptoms (p=0.049), poorer quality of life (p=0.017) and a trend towards reduced exercise capacity (p=0.068).

Conclusion

Obese patients with AF demonstrate characteristic features of the obesity-HFpEF phenotype, including elevated LA and RA pressure, left atrial enlargement and poorer functional capacity. Novel treatments for the obesity-HFpEF phenotype, such as GLP-1 inhibitors, may be useful in obese patients with AF.
Contractile reserve is associated with response to catheter ablation in patients with atrial fibrillation and left ventricular systolic dysfunction
Authors: Ahluwalia N , Batay M , Dane R , Abbass H , Joshi A , Honarbakhsh S , Hunter R J , Lloyd G , Schilling R J
Published: October 2024

Background

Although patients with atrial fibrillation (AF) and left ventricular systolic dysfunction (LVSD) can benefit from catheter ablation, some patients do not respond. Prospectively identifying responders is challenging. Contractile Reserve (CR) on Exercise Stress Echocardiography (ESE) has demonstrated stratifying value before cardiac resynchronisation therapy but has not been evaluated in the setting of AF.

Objective

To evaluate whether CR on ESE was associated with response to CA in patients with LVSD.

Methods

Patients with persistent AF and LVSD (LVEF <50%) undergoing first-time catheter ablation were enrolled in the AFHF study. Patients underwent trans-thoracic echocardiography at rest and maximum exertion using a recumbent cycle ergometer. CR was the difference in LVEF at maximum exertion versus rest. Echocardiography was repeated six months after successful catheter ablation to determine Response based on the Universal Definition of Heart Failure improvement (LVEF +10%, or if baseline LVEF >40% then LVEF>50%).

Results

52 patients were enrolled with baseline demographics in Table 1. 39 patients completed follow-up with 32 (82%) being responders. Responders had greater CR than non-responders (+10% (+5, +12) vs 3% (0, +4), (p=0.008)). A CR ≥ 5% had a positive predictive value of 0.96 for Response in this cohort. The AUROC was 0.83 with a specificity of 0.86. This was also associated with significant improvement in reported Minnesota living with HF scores (p<0.01).

Conclusion

CR was associated with response to CA in patients with persistent AF and LVSD in this exploratory analysis. Validation in an external cohort is needed to evaluate fit before prospective evaluation of its clinical utility.Baseline CharacteristicsROC curve for response to ablation
Circulating ketone bodies, genetic predisposition, and incident atrial fibrillation
Authors: Wang N , Sun Y , Li J , Yu B , Zhou Y , Wang B , Tan X , Lu Y
Published: October 2024

Background

Ketone bodies (KB) are essential alternative fuel sources for the myocardium. However, the evidence on the level of circulating KB and heart disorders is inconsistent. Whether the total and individual KB are associated with risk of onset atrial fibrillation (AF) in the general population and in individuals with different genetic susceptibilities to AF are still unclear.

Purpose

To examine the association between circulating KB and AF risk and to further test whether genetic risk could modify the above association.

Methods

In the UK Biobank, 247,304 participants (mean age 56.5, 45.3% men) with available data on KB and without baseline AF were included. The concentrations of KB, including β-hydroxybutyrate (β-OHB), acetoacetate, and acetone, were measured using nuclear magnetic resonance, and the values of KB were increased by one and then log10-transformed for analyses. The genetic risk of AF was based on the standard polygenic risk score. The definitions of AF were based on the ICD-10 code I48, which was linked to primary care, hospital admission electronic health records and death records. Cox proportional hazard model was used to estimate the hazard ratio (HR) with 95% confidence interval (CI).

Results

During a median follow-up of 13.8 years, 16,936 cases of onset of AF were recorded. After adjusting for age, sex, race, Townsend index, education, alcohol intake frequency, smoking status, healthy diet, metabolic equivalent, body mass index, systolic blood pressure (SBP), total cholesterol, estimated glomerular filtration rate, cardiovascular diseases, and diabetes, elevated total KB, β-OHB, acetoacetate, and acetone were all with the risk of AF (HR, 95% CI per 10-fold increase: 1.20, 1.13-1.28; 1.13, 1.07-1.19; 1.12, 1.06-1.18; and 1.78, 1.57-2.01, respectively). The highest risk of AF was observed among individuals at high genetic risk to AF and had the highest quartile of total KB (HR 2.91, 95% CI 2.66-3.19). Participants who had low genetic risk were more susceptible to high total KB for incident AF (p for interaction = 0.036). The associations of total KB, β-OHB, and acetone with AF risk were more prominent for men (HR, 95% CI per 10-fold increase: 1.32, 1.22-1.44; 1.22, 1.14-1.31; 2.01, 1.72-2.36) than for women (p for interaction <0.05). The association between total KB and AF risk was strengthened in individuals <60 years, current smokers, and those with SBP<130 mmHg (p for interaction = 0.033, 0.021, and 0.017, respectively).

Conclusions

Circulating KB concentrations were associated with AF risk, with acetone showing the strongest relationship with AF. Individuals at low genetic risk were more susceptible to the level of total KB for incident AF. Our findings suggest that KB may be a biomarker, particularly for identifying individuals without AF at baseline who are at low genetic risk. The additive value of plasma KB to a risk prediction score warrants further investigation.
Adherence to the ABC pathway improves prognosis in patients with AF: preliminary findings from an updated meta-analysis of 360,000 patients
Authors: Romiti G F , Corica B , Lip G Y H , Proietti M
Published: October 2024

Background

With the increasing complexity of patients with Atrial Fibrillation (AF), the ‘Atrial Fibrillation Better Care’ (ABC) pathway was proposed to streamline a holistic approach for the comprehensive management of patients with AF. The ABC pathway is based on three main pillars: ‘A’ Avoid stroke (through optimal anticoagulant use); ‘B’ Better symptom control; and ‘C’ Cardiovascular and Comorbidity management optimization. Such a holistic and integrated approach is currently recommended by international guidelines, including the ones from the European Society of Cardiology (ESC); a previous meta-analysis showed sub-optimal adherence to such approach in real-world cohorts, with an overall reduction in the risk of major outcomes in patients treated according to the ABC pathway. We hereby performed an updated systematic review and meta-analysis of the current evidence on the implementation of the ABC pathway in patients with AF.

Methods

We performed a systematic review and meta-analysis according to PRISMA Guidelines. MEDLINE and EMBASE were searched for all studies reporting data on the prevalence of ABC pathway adherent management in patients with AF, and/or the association between ABC pathway management and the incidence of major outcomes, including all-cause death, cardiovascular death, thromboembolism, and major bleeding. Data on the prevalence of ABC pathway management were pooled using a generalized linear mixed model; number of events and total number of patients were pooled using a random-effect model. Pooled estimates were reported as odds ratios (OR) and 95% Confidence Intervals (95%CI); heterogeneity was estimated using the restricted maximum-likelihood estimator, and the Inconsistency index (I2) was also reported.

Results

4,059 articles were retrieved from the literature search; after duplicates removal, title and abstract screening and full-text evaluation, 16 studies were included, for a total of more than 360,000 patients. Pooled prevalence of adherence to the ABC pathway was 28.5% (95%CI: 21.1-37.3%, I2=100%; Figure 1). Adherence to the ABC pathway was associated with a significant lower risk of all-cause death (pooled OR: 0.47, 95%CI: 0.40-0.56, I2=97%), cardiovascular death (pooled OR: 0.43, 95%CI: 0.33-0.56, I2=95%) and stroke (pooled OR: 0.61, 95%CI: 0.47-0.79, I2=91%; Figure 1). Patients treated adherent to the ABC pathway also showed a lower risk of major bleeding (pooled OR: 0.77, 95%CI: 0.66-0.90, I2=85%).

Conclusions

In this updated systematic review and meta-analysis, adherence to the ABC pathway was found in less than one-third of patients with AF. Implementation of the ABC pathway was associated with lower risk of all major adverse events in patients with AF, including all-cause death, and thromboembolic and bleeding events. These data further reinforce the need for routine implementation of the ABC pathway for the management of AF in clinical practice.Figure 1
Procedural findings and follow-up results of catheter ablation of atrial fibrillation in patients after radiation therapy for breast cancer
Authors: Tydecks M , Krafft H , Iamanidze L , Bahlke F , Englert F , Erhard N , Syvaeri J , Milz S , Hess S , Abdiu E , Popa M , Telishevska M , Lengauer S , Hessling G , Deisenhofer I
Published: October 2024

Backround

Data on breast cancer radiation therapy (RT) associated atrial cardiomyopathy and its potential role in the pathophysiology of atrial fibrillation (AF) is very limited.

Objectives

To investigate the effect of breast cancer radiotherapy (RT) on atrial cardiomyopathy and its possible role in the pathophysiology of atrial fibrillation. What is the therapeutic success of antral pulmonary vein isolation (PVI) with possible substrate modifications (CFAE) in patients with breast cancer radiation therapy and paroxysmal or persistent atrial fibrillation.

Methods

We searched the institution’s data base for patients who received RT for breast cancer and underwent subsequently 3D mapping guided AF ablation. Intraprocedural mapping data and short- and long-term results of ablation were evaluated according to "no low voltage" and "low voltage" present. Low voltage amplitudes in bipolar electrograms were defined as <0.5 mV for endocardial maps created during SR and <0.3mV during AF. Ablation strategy comprised pulmonary vein isolation (PVI) ± additional substrate modification according to the mapping results. Follow Up (FU) was evaluated using repetitive 7-days Holter ECG and clinical visits.

Results

We included 45 patients (all female, 70.9±7.2 years) with paroxysmal or persistent AF (n=18 and n=27). In 3D mapping, 60% of the patients (27/45) showed left atrial low voltage (LV group) with the majority showing low voltage in the anterior wall of the left atrium (LA) in 18 of 45 patients (40%). PVI with ablation of complex fractionated signals (CFAE) was predominantly performed (18/27). After one ablation, 33.3% (9) of the patients in the LV group were recurrence-free and after an average of 1.9 ablations, freedom from recurrence was achieved in 21 patients with low voltage (77.8%). In 18 patients, no low voltage was detected (NLV group) and PVI only was performed in the majority (14/18). In this NLV group, 61.1% (11) of the patients were recurrence-free after one ablation and freedom from recurrence was achieved in 72.2% (13) after an average of 1.2 ablations.

Conclusion

Thoracic radiation therapy in patients with breast cancer can lead to low voltage in the LA with the predominant low voltage location being the anterior wall of the LA. An extended ablation strategy (PVI & CFAE) can show good treatment options in these patients with atrial fibrillation, with high freedom from recurrence after a mean of two ablation procedures.Freedom from recurrence after ablationCharacteristics of left atrium (LA)
Artificial intelligence-enabled electrocardiogram for left ventricular diastolic dysfunction and long-term risk of new-onset atrial fibrillation
Authors: Tsaban G , Lee E , Wopperer S , Abbasi M , Yu H T , Kane G , Lopez-Jimenez F , Deshmukh A , Asirvatham S , Noseworthy P , Friedman P , Attia Z I , Oh J
Published: October 2024

Background

Heart failure (HF) and atrial fibrillation (AF) are intertwined, sharing common risk factors and influencing each other in a reciprocal manner. While left ventricular diastolic dysfunction (LVDD) stands as a hallmark of HF's hemodynamic profile, its direct correlation with heightened AF risk remains uncertain. Our recent validation of an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm for LVDD detection has opened new avenues. Yet, whether AI-ECG-detected LVDD correlates with long-term AF risk remains unexplored.

Methods

We performed a retrospective study among all patients with a comprehensive LVDD assessment from the test population of the AI-ECG LVDD study between September 2001 and June 2022. Patients with prior documented AF according to health records or previous ECG were excluded. Patients were classified by AI-ECG as normal diastolic function (DF), grade 1 (G1), grade 2 (G2), or grade 3 (G3) LVDD. We assessed the risk of AF across AI-ECG LVDD grade, with normal DF as reference, with competing risk models.

Results

Of 97,023 patients free of AF at baseline, 63,533 (65.4%), 10,776 (11.1%), 18,940 (19.5%), and 3,774 (3.9%) were classified as normal DF, G1-LVDD, G2-LVDD, and G3-LVDD, respectively. Worse AI-ECG LVDD was associated with older age, lower left ventricular ejection fraction (LVEF), and higher rates of HF, diabetes, hypertension, chronic pulmonary disease, renal failure, and cardiovascular disease (p-of-trend<0.001 for all). Over a median follow-up of 4.8 years (interquartile range 1.8-9.2 years), new-onset AF occurred in 6,795 (7.0%) patients. In multivariable survival analysis, adjusted to multiple risk factors including LVEF and clinical HF, G2 and G3 LVDD, representing patients with high filling pressures, were independently associated with a higher AF-risk [G2-LVDD: adjusted hazard ratio (aHR) 1.64 (95% confidence interval (95%CI) 1.52-1.73), G3-LVDD: aHR 2.24 (95%CI 2.02-2.48)].

Conclusion

The AI-ECG LVDD algorithm independently predicts long-term AF risk, regardless of LVEF and clinical HF status, highlighting its potential for identifying high-risk populations and guiding proactive monitoring and management.
Effect of the longitudinal change in anemia status on clinical outcomes for patients with nonvalvular atrial fibrillation: analysis from the Hokuriku-Plus AF registry
Authors: Tsuda T , Hayashi K , Kato T , Kusayama T , Nakagawa Y , Nomura A , Tada H , Usui S , Sakata K , Fujino N , Takamura M
Published: October 2024

Background

Anemia is a common comorbidity in older patients with heart failure (HF)1 and atrial fibrillation (AF)2, associated with an increased risk of adverse events. This study evaluated the prognostic effects of longitudinal changes in anemia status on clinical outcomes in patients with AF, as limited data are available on this aspect.

Methods and Results

We prospectively evaluated data of 1,388 patients with AF obtained from the Hokuriku-Plus AF registry (1,010 men, 72.3±9.7 years) and recorded the incidence of cardiovascular death (CVD), HF, thromboembolism, and major bleeding. Finally, 1,233 patients with AF with baseline and first year of follow up hemoglobin levels were evaluated. Patients were categorized into 3 groups based on the longitudinal changes in 1-year anemia status: AF without anemia (group 1), AF with improved anemia (group 2), and AF with sustained or new-onset anemia (group 3). During 1–5-year follow up, the incidences of CVD, HF, thromboembolism, and major bleeding were significantly higher in patients with AF and anemia than in those without (Figure1). Additionally, the incidence of CVD or HF was significantly higher in group 3 than in groups 1 and 2 (Figure 2). Multivariate analysis revealed no anemia or improvement from anemia in 1 year as an independent predictor for reducing CVD and HF.

Conclusions

Recovery from anemia may be associated with a favorable clinical course in AF.
Sex-specific prognostic implications of new-onset atrial fibrillation in patients treated with dual chamber pacemakers
Authors: Marinko S , Farouq M , Platonov P G , Borgquist R
Published: October 2024

Background

Right ventricular pacing induces ventricular dyssynchrony, which over time may result in left ventricular dysfunction, increased left ventricular filling pressures, and ensuing left atrial dilatation, with increased risk of atrial arrhythmias. Atrial fibrillation (AF) prior to device implant is associated with worse prognosis, but the prognostic effects of new-onset AF during pacemaker treatment are less well described.

Purpose

To describe risk factors, incidence, and prognostic effects of new-onset AF after treatment is initiated with a dual chamber pacemaker. To evaluate mortality and risk of heart failure diagnosis or hospitalisation for heart failure in patients who develop AF, compared to those who do not develop AF.

Methods

All patients without pre-existing heart failure or atrial fibrillation, who received a dual chamber pacemaker at a large-volume tertiary care center during the period 2005–2020 were included. Data was crossmatched between the national pacemaker registry, the population registry and national disease registries. The primary outcome was 10-year mortality, and the secondary outcome was new-onset heart failure.

Results

37127 patients were included in the study, of which 14760 (30%) were female. Median age was 76.4 years [interquartile range, IQR, 68.0–83.1] and the most common indication for pacemaker implant was AV block (57.7%), see Table 1. Overall, 10-year survival was higher for female patients, compared to male patients, p<0.0001 (see Kaplan-Meier curve in Figure 1A). Patients who developed new-onset AF had more comorbidities, were slightly older and a higher percentage were men. During follow-up 3661 (9.9%) developed atrial fibrillation within two years (9.1% of female and 10.3% of male patients, p<0.001), at a median of 291 [88–461] days after implant. In multivariable Cox regression analysis with new-onset AF as time dependent covariable and adjusted for clinically relevant covariables, AF was an independent predictor of higher all-cause mortality (HR 1.43 [1.37–1.49], p<0.0001). Risk factors for new-onset AF included increasing age, male sex, hypertension, malignancy, diabetes, chronic obstructive lung disease, chronic renal disease, and sick sinus syndrome indication (all p<0.01). In separate analyses for men and women, the risk factors and magnitude of odds ratios were the same.

Conclusion

In patients treated with dual chamber pacemakers due to bradycardia or AV block, development of new-onset AF within two years was associated with a higher 10-year mortality. The risk of developing AF was higher for men, but the negative prognostic effect was more pronounced for women.Figure 1A.-B. K-M survival curves