bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and predictors of asymptomatic cerebral infarction following radiofrequency catheter ablation for atrial fibrillation
Authors: Watanabe T , Yamada T , Morita T , Kawasaki M , Kikuchi A , Kondou T , Kawai T , Nishimoto Y , Seo M , Nakamura J , Kayama K , Fujita T , Tamura Y , Fukunami M
Published: November 2023

Backgrounds

Left atrial catheter ablation has been established as an important treatment option for atrial fibrillation (AF), but it carries the risk of periprocedural thromboembolism. Periprocedural major stroke is rare, but silent stroke does not appear to be rare. Accurate risk stratification for stroke and appropriate anticoagulation management are essential.

Purpose

We aimed to investigate the incidence and predictors of silent cerebral infarction (CI) associated with AF catheter ablation, detected by diffusion-weighted magnetic resonance imaging (DW-MRI).

Methods and Results

We performed a retrospective analysis of 618 consecutive patients (age 72±10 years, persistent atrial fibrillation (PEF) 45%, CHA2DS2-VASc score 2.6±1.4) with persistent or paroxysmal AF that underwent pulmonary vein (PV) or additional ablation and post-procedural cerebral MRI 1 day after ablation. During the ablation procedure, activated clotting time (ACT) was checked every 20 minutes, and additional heparin boluses were administered as needed to maintain ACT >320 seconds. Patients were analyzed for possible demographical, medical, echocardiographic, and procedural predictors of infarction events. Post-procedure DW-MRI detected new infarction lesions in 83 patients (13.4%:CI-group). There were no differences between the CI and non-CI groups with respect to age, type of anticoagulant and complex fractionated atrial electrogram ablation. Body weight, brain natriuretic peptide and left atrial diameter were significantly higher in the CI group. Left ventricular ejection fraction (LVEF) was significantly lower in the CI than non-CI group (58.6±12.6 vs. 64.2±11.8, P<0.001). PEF was more frequent in patients with CI than non-CI group (63.9 vs. 42.1%, P<0.001). In a multivariate regression model revealed only EF was a significant predictor for the occurrence of new asymptomatic lesions on post-procedural DW-MRI (OR 0.949, 95% CI 0.92-0.98, P=0.001).

Conclusions

This study shows a high incidence of silent micro-embolic events after AF ablation. Lower LVEF were potential predictors of this complication.
Catheter ablation of atrial fibrillation: three-dimensional transesophageal echocardiography versus magnetic resonance imaging for pre-interventioal pulmonary vein imaging (8-year follow-up)
Authors: Kettering K
Published: November 2023

Catheter ablation has become the first line of therapy in patients with symptomatic, recurrent, drug-refractory atrial fibrillation (AF). However, it is still challenging because of the high degree of variability of the pulmonary vein (PV) anatomy. Three-dimensional transesophageal echocardiography (TEE) is a promising new technique for cardiac imaging. Therefore, we have evaluated the usefulness of 3-D TEE for analysing the left atrial anatomy prior to an ablation procedure in comparison to magnetic resonance imaging (MRI).

Methods

In 240 patients, 3-D TEE and cardiac MRI were performed immediately prior to an ablation procedure (paroxysmal AF: 110 patients, persistent AF: 130 patients). The image quality provided by 3-D TEE and by cardiac MRI was compared in all patients. Two different ablation strategies were used. In patients with paroxysmal AF, the cryoablation technique was used. In the other patients, a circumferential pulmonary vein ablation was performed using a three-dimensional mapping system.

Results

A 3-D TEE and a cardiac MRI could be performed successfully in all patients prior to the ablation procedure. Several variations of the PV anatomy could be visualized precisely by 3-D TEE and cardiac MRI (e.g. accessory PVs, common PV ostia, varying diameter of the left atrial appendage and its distance to the left superior PV). The image quality was good in the majority of patients even if AF with rapid ventricular response was present during the examination. The image quality provided by 3-D TEE was acceptable in 230/240 patients (95.8 %). The TEE findings correlated well with the PV angiographies performed using cardiac MRI. There was a good correlation with regard to the diameter of the PV ostia assessed by these two imaging techniques. All ablation procedures could be performed successfully (mean number of completely isolated PVs: 3.9 (cryo group), 3.9 (radiofrequency catheter ablation group)). At 96-month follow-up, 64.6 % of all patients were free from an arrhythmia recurrence (cryo group: 70.0 %, Carto group: 60.0 %). There were no major complications.

Conclusions

AF ablation procedures can be performed safely and effectively based on prior 3-D TEE imaging. The image quality was acceptable in the vast majority of patients.
Comparison of myocardial injury and inflammation between ablation index-guided and conventional contact force-guided ablation in atrial fibrillation patients
Authors: Yano M , Egami Y , Kawanami S , Sugae H , Ukita K , Kawamura A , Nakamura H , Yasumoto K , Tsuda M , Okamoto N , Matsunaga-Lee Y , Nishino M , Tanouchi J
Published: November 2023

Background

Ablation index (AI)-guided ablation improves the incidence of arrhythmia recurrence as compared to conventional contact force (CF)-guided ablation.

Purpose

The aim of this study was to elucidate the differences in the biomarkers associated with myocardial injury and inflammation between conventional CF-guided and AI-guided ablation.

Methods

Atrial fibrillation (AF) patients who underwent pulmonary vein isolation (PVI) from the Osaka Rosai Atrial Fibrillation ablation (ORAF) registry were enrolled. We divided the patients into two groups: conventional CF-guided PVI (CF group) and AI-guided PVI (AI group). The differences in biomarkers associated with myocardial injury and inflammation, and long-term durability of PVI between the two groups were evaluated.

Results

This study population included a total of 794 patients (CF-guided, 241 patients; AI-guided, 553 patients). Total application time was significantly shorter, and total application number was significantly smaller in AI than CF group. High-sensitive troponin I (hs-TnI) post-ablation was significantly higher in AI than CF group (p<0.001), even after taking the total application number and total application time into consideration. No significant differences in inflammatory markers changes from pre- to post-ablation were observed between the two groups. Multiple regression analysis showed that age, AF type, AI-guided ablation and creatinine were significantly associated with the acute myocardial injury (hs-TnI value) after catheter ablation (standardized beta-coefficient=-0.096, p=0.013, standardized beta-coefficient=0.159, p<0.001, standardized beta-coefficient=0.078, p=0.031 and standardized beta-coefficient=0.118, p=0.003, respectively). AI-guided ablation was significantly associated with the hs-TnI post-ablation by multiple regression analysis. The PV reconnection ratio was significantly smaller in AI than CF group (p=0.037).

Conclusion

According to the results of the biomarkers during AF ablation, AI-guided ablation had the ability to create larger lesions than CF-guided ablation, but had an equivalent inflammatory status to CF-guided ablation. The differences in myocardial injury and inflammation could be the mechanism of the better durability of PVI for AI-guided ablation.
Risk of complications in patients undergoing pulmonary vein antrum isolation: a single centre experience
Authors: Khaykin Y , Azizi Z , Alipour P , Gao-Kang J , Pirbaglou M , Falvey G , Khaykin M , Mooring A , Jasrai A , Zarifian Kamyab S , Narbonne M , Malcolm R , Timajchi E , Pantano A , Sadek M M
Published: November 2023

Background

Pulmonary vein antrum isolation (PVAI) is the gold standard approach to treat symptomatic atrial fibrillation (AF) refractory to medical therapy. While PVAI may result in a number of potential complications, there is a growing body of literature supporting safety of same day discharge post-PVAI.

Purpose

To retrospectively evaluate the incidence of post-procedure acute adverse events (AE), and elucidate factors associated with increased risk of such complications in patients undergoing PVAI.

Methods

Patients underwent PVAI between 2004-2021 at a tertiary care centre, and were followed-up at 3, 6 and 12 months post-PVAI. All procedures were performed utilizing intra-cardiac echocardiography. Baseline characteristics of patients who experienced acute AE were compared with those in patients who did not. Univariate and multivariate logistic regression models adjusted for age, sex, type of AF, left atrial size, and comorbidities were employed to evaluate risk factors for acute AE.

Results

2829 patients (mean age: 61.5±10.4 years, 33.7% female, 64.1% paroxysmal AF) were included in this study. Overall incidence of acute AE was 92 (3.3%), which included: 60 (2.1%) patients with access site hematoma, 20 (0.7%) patients with hematoma requiring treatment, and 12 (0.4%) patients with cardiac tamponade. Other complications included: 5 (0.18%) strokes or transient ischemic attacks (TIA), 3 (0.10%) esophageal fistulas, and 1 (0.03%) phrenic nerve injury. Females (4.2% vs 2%, P=0.001), patients older than 75 years (3.3% vs 2.7%, P=0.8), non-paroxysmal AF (3.4% vs 2.4%, P=0.1), body mass index ≥ 35 kg/m2 (3.6% vs 2.7%, p=0.04), those with an implanted device (6.7% vs 2.3%, p=0.004), and sinus node dysfunction (SND) (6.6% vs 2.5%, p=0.001) had a greater rate of acute AEs. Patients with comorbidities, including hypertension (3.4% vs 2%, P=0.04), Type 2 diabetes ( 3.2% vs 2.7%, p=0.7), congestive heart failure (5.6% vs 2.5%, P=0.008), and coronary artery disease (3.9% vs 2.6%, p=0.1) also manifested higher rate of acute AE. In the multivariate logistic regression model, female sex (OR= 2.5 [1.4, 4.4]), CHF (OR= 2.6 [1.3, 4.9]) and SND (OR=2.6 [1.1, 5.5] were associated with increased AE risk when adjusted for age, AF type, and other comorbidities.

Conclusion

In the multivariate model, female sex, a history of congestive heart failure, and SND were independently associated with a greater risk of AE following PVAI.
Effect of pre-procedural anticoagulation in patients undergoing ablation: a meta-analysis of randomized controlled trials
Authors: Duhan S , Taha A , Keisham B , Badu I , Faisaluddin M , Patel H , Sandhyavenu H
Published: November 2023

Background

Atrial fibrillation (AF) is the most common type of arrhythmia seen in a clinical setting. Patients have a high risk of stroke, especially in the first two years of diagnosis. Anticoagulation therapy is prescribed to patients with a high CHAD2S2-VASc score. Based on recent evidence, catheter ablation (CA) is emerging as the preferred first-line treatment of modality. The benefit of interruption of anticoagulation before CA is unclear. Interruption of anticoagulation and insertion of a foreign body during CA can lead to an increased risk of thromboembolism (TE). Anticoagulation is interrupted before the procedure to balance the risk of TE and bleeding.

Objective

To assess the risk of bleeding and TE in patients undergoing CA with uninterrupted versus interrupted anticoagulation.

Methods

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) strategy to search PubMed/MEDLINE, EMBASE, and Cochrane databases from inception till January 2023. We included randomized controlled trials and excluded observational studies. The data was extracted from full texts. Data Random effects model and Mantel-Haenszel method were used to calculate pooled risk ratio and 95% confidence interval.

Results

A total of 10 studies were included, with 4,584 participants. The risk of TE [1.76; 95% confidence interval (CI): 0.33, 9.46] and bleeding [1.10; 95% CI: 0.59, 2.05] did not change significantly with the interruption of all anticoagulation agents. Similarly, interruption of individual anticoagulants such as heparin [0.81, 95% CI: 0.19, 3.39], vitamin K antagonists (VKA) [9.21, 95% CI: 0.02, 5627.42], and direct oral anticoagulants (DOAC) [1.36, 95% CI: 0.26, 7.23] did not show any change in the risk of TE. There was no significant change in the risk of bleeding with heparin discontinuation (Figure 1).

Conclusion

Our study supports recent trials such as Randomized Evaluation of Long-term Anticoagulant Therapy (RE-LY) and emerging data that support uninterrupted anticoagulation prior to ablation as there is no increased risk of bleeding or TE.
Long-term stability of atrial sensing in implantable cardioverter-defibrillators with floating atrial dipole leads
Authors: Ferreira Neves I , Lacerda Teixeira B , Portugal G , Silva Cunha P , Valente B , Lousinha A , Osorio P , Santos H , Monteiro A , Covas S , Contins R , Cruz Ferreira R , Martins Oliveira M
Published: November 2023

Introduction

To maintain the advantages of having atrial sensing without the need to implant an additional lead, a single-lead ICD system with a floating atrial dipole (VDD DX ICD, Biotronik) with active fixation to the right ventricle has been developed. In this generation of ICDs, specially filtered atrial signs may be high enough to allow early detection of atrial arrhythmias and improve discrimination between atrial and ventricular tachycardias. However, maintaining reliable and stable atrial sensing via the floating dipole could be a concern regarding this technology. We aimed to determine the long-term stability of atrial sensing in patients (P) with this type of device.

Methods

All P implanted with ICDs with an active fixation DX lead at our centre between 2013 and 2021 were included. Atrial sensing and ventricular or supraventricular arrhythmic events were recorded during follow-up. We retrospectively analysed the atrial sensing evolution and compared it with a control group that had been implanted with a VDD pacemaker (PM).

Results

Seventy DX ICD P (82.9% males, age 69±14 years [between 19 and 86], 81.4% implanted as primary prevention) with > 1-year follow-up were included. The control group included 52P (age 82±6.3 years) who underwent PM implantation due to an advanced atrioventricular block. The mean P-wave amplitude at implantation was 4.85±2.44 mV in the DX ICD group and 1.54±0.89 mV in the VDD PM group. At one year after implantation, P-wave amplitude was 4.26±2.68 mV in the DX ICD group and 1.20±1.16 mV in the control group. From the control group, 7P (15,6%) lost atrial sensing after one year of follow-up, having their PM programmed as VVI after that. None of the P in the ICD group had lost atrial sensing in the same time period. After one year of follow-up, the P-wave amplitude had a mean reduction of 41.3% in the DX ICD group and of 65% in the control group (P=0.05).

Conclusions

Atrial signals can be reliably sensed by the floating dipole rings of a DX ICD in a long-term follow-up. This technology resulted in a higher stability of atrial sensing when compared with that obtained in P with a VDD PM. Additionally, a noteworthy number of P with a VDD PM lost atrial sensing, which did not happen in the group with the DX ICD.Results
HIPSC model reveals M1 macrophages cause atrial arrhythmia correlated to electrophysiological remodelling of atrial cardiomyocytes in 2D and 3D engineered heart tissue
Authors: Hutschalik T , Schotten U , Matsa E
Published: November 2023

Atrial fibrillation (AF) is the most common sustained arrhythmia with an estimated prevalence of 1.5–2%. Current treatments lack effectiveness and do not prevent recurrence. Inflammation is reported in AF patients, however, a causal connection remains elusive.

In this study, we investigated the arrhythmic effects of pro-inflammatory macrophages (M1) on human induced pluripotent stem cell (hiPSC)-derived atrial cardiomyocytes (aCM), to better understand their role in AF. Macrophages are known to play a role in cardiac electrophysiology, but their role in arrhythmia is unclear.

Three healthy hiPSC lines were differentiated to aCM and M1. Multi-electrode array recordings of isogenic, 2D cocultures of M1 and aCM showed a significant increase in beat rate irregularity compared to control conditions (P<0.001). Furthermore, spike amplitude of aCM and M1 cocultures was significantly decreased (P<0.001). Arrhythmias occurred only after activation of macrophages in the coculture. Addition of anti-inflammatory glucocorticoids significantly reduced beat irregularity in aCM and M1 cocultures compared to vehicle (1.9-fold decrease for Hydrocortisone, P<0.005) further supporting macrophage mediated inflammation to be the cause of the arrhythmia. RNA sequencing of aCM and M1 cocultures revealed aberrant expression of arrhythmia associated cardiac sodium and atrial potassium ion channels (SCN5A, KCNA5). Normal expression was restored through hydrocortisone addition.

In addition, inflammation-induced arrhythmia was observed in 3D engineered heart tissues containing hiPSC derived aCM, M1 and cardiac fibroblasts. Tissues showed a significant increase in beating irregularity (P<0.005) compared to controls and had a significant, median reduction (>30%) of contraction amplitude (P<0.05).

Our findings suggest a causal relationship between M1 and the occurrence of atrial arrhythmia. The reduction of arrhythmia using glucocorticoids correlates to clinical observations, that show their use being linked to reduced post operative AF burden. These results strongly support the relevance of the proposed hiPSC coculture model and elucidate a new potential AF mechanism.
Effect of epigenetic regulation on left atrial function and recurrence after catheter ablation in patients with atrial fibrillation
Authors: Choi J I , Han M R , Yang H H , Kim Y G , Jeong J H , Lee H S , Choi Y Y , Shim J , Kim Y H
Published: November 2023

Background

Genetic variation and modifiable risk factors play a significant role in the pathogenesis of atrial fibrillation (AF). However, the influence of epigenetic modification on AF remains to be elucidated.

Methods

Epigenetic evaluation was performed in 115 AF patients who underwent radiofrequency catheter ablation (RFCA) in a single institution. We measured methylation at approximately 850,000 bp cytosine-phosphate-guanine (CpG) sites in the 115 samples.

Results

The degree of methylation was compared across seven classification criteria: type of AF, late recurrence, impaired left atrium (LA) function, late gadolinium enhancement, LA diameter, LA volume, and flow velocity of the LA appendage. The four most significantly methylated genes in our cohort were DEFB104B, C3, TANC1, and TMEM9B. The DEFB104B gene (cg20223677 in the transcription start site), which encodes β-defensin 104B, was hypomethylated in three groups: those with late recurrence, impaired LA function, and impaired LAA flow velocity. Enriched functional annotation of the differentially methylated datasets revealed that five out of the seven AF groups in this cohort were associated with genes involved in the cell movement of endothelial cell lines, sprouting angiogenesis by endothelial cell lines, or migration of endothelial cell lines.

Conclusion

In this study, epigenetic profiling revealed that epigenetic modification might affect crucial traits of AF, such as the degree of atrial myopathy and treatment effects after RFCA, suggesting the hypothesis that the pathogenesis of AF might be affected by not only genetic variation or modifiable factors but also by epigenetic modulation. The identified methylation-susceptible loci can be used in targeting for epigenetic-based therapeutic agents.
Association of atrial fibrillation symptom with clinical outcomes: a prospective multicenter registry study
Authors: Lee S , You S C , Bae H J , Park J B , Park J K , Kang K W , Kim J , Park H W , Choi E K , Kim J B , Lee Y S , Shim J M , Joung B Y
Published: November 2023

Background and Objectives

Atrial fibrillation (AF) is usually classified on the basis of the disease subtype. However, this characterization does not capture the full heterogeneity of AF. This study was performed to evaluate whether the remodeling of heart, treatment of AF, and clinical outcome is different according to the symptom of AF.

Patients and Methods

In the prospective, multicenter study of AF registry, we identified 10,210 patients with non-valvular AF (mean age, 66.7 years; 35.3% were women) enrolled between June 2016 and March 2022 with eligible follow-up visits. The patients were classified into two groups according to the presence of AF symptoms. Clinical factors related with AF symptoms were analyzed. The primary outcome was defined as a composite of all cause death, ischemic stroke, transient ischemic attack, systemic embolism, myocardial infarction, and hospitalization for heart failure.

Results

Among 10,210 patients, 4,327 (42%) were symptomatic AF, and 5,883 (58%) were asymptomatic AF. The asymptomatic group had older age, more male sex, comorbidities such as hypertension and diabetes mellitus, larger LA AP diameter (43.6 vs. 42.2, P <0.001), and higher E/E’(10.4 vs. 10.0, P <0.001). During median follow-up of 32.9 (29.5 ∼ 36.4) months, incidence of the primary outcome in Asymptomatic vs. Symptomatic were 1.44 and 1.45 per 100 person-year, respectively. In multivariable Cox regression analysis, AF symptoms were not associated with an increased risk of the primary outcome (HR 1.02; 95% CI, 0.81 ∼ 1.29, P = 0.871). In linear regression, symptom of AF was negatively associated with LA AP diameter (β coefficient -0.43, 95% CI -0.76 ∼ -0.11, P = 0.009).

Conclusions

In the multicenter prospective AF registry, the presence of AF symptoms was not related to cardiovascular outcomes. However, AF symptoms were related to LA remodeling.Cumulative incidence for primary outcomeLinear regression for LA AP diameter
Coffee consumption and adverse outcome events in patients with atrial fibrillation
Authors: Iten V , Coslovsky M , Hennings E , Reichlin T , Rodondi N , Mueller A , Beer J , Conte G , Chocano P , Bonati L , Kuehne M , Osswald S , Aeschbacher S , Zuern C
Published: November 2023

Background/Introduction

Moderate coffee consumption has been associated with a lower risk of major adverse cardiovascular events (MACE) in the general population. However, there are some concerns that coffee consumption might be harmful for patients with atrial fibrillation (AF).

Purpose

The aim of this study was to investigate the association of coffee consumption with MACE and other adverse outcome events in AF patients.

Methods

Data of AF patients from two large prospective, multicenter cohort studies (yearly based follow-up data from Swiss-AF and Beat-AF) were used for this analysis. Coffee consumption was assessed and categorized into two main groups "not-daily" and "daily" consumers and subcategories (<1, 1, 2-3 and ≥4cups/day). The primary endpoint was defined as a composite of stroke or systemic embolism, myocardial infarction, hospitalization for acute heart failure and cardiovascular death (MACE). We performed time-updated multivariable adjusted Cox regression analyses to investigate the association of coffee consumption with MACE and other adverse outcome events.

Results

Among 3,835 patients (mean age 71.4 years, 28.0% females), 3,095 (80.7%) reported daily coffee consumption. The incidence rate for MACE was 5.09 in daily and 7.49 per 100py in not-daily consumers. Cumulative incidence curves are presented in Figure 1. After comprehensive multivariable adjustment, daily coffee consumption was associated with a 23% relative risk reduction for MACE compared to not-daily consumption (hazard ratio (HR) (95% confidence interval (CI)) 0.77 (0.67-0.89), p<0.001;). Compared to patients with not-daily coffee consumption, patients with moderate coffee consumption (2-3 cups/day) had the lowest hazard for MACE (HR (95%CI) 0.73 (0.62; 0.85), p<0.001). The associations between coffee consumption and all adverse outcome events are presented in Figure 2.

Conclusion

In a population of AF patients, daily coffee consumption was associated with a lower risk of MACE and other adverse outcomes. These findings seem to be similar to those in the general population.
Risk differences between atrial fibrillation patients with different clinical phenotypes: insights from the French population
Authors: Fawzy A M , Bisson A , Bentounes S A , Bodin A , Herbert J , Lip G Y H , Fauchier L
Published: November 2023

Background

Atrial fibrillation (AF) patients represent a clinically complex, heterogeneous population comprising multiple homogeneous cohorts.

Purpose

We aimed to identify the common clinical phenotypes of AF patients and compare clinical outcomes between these subgroups.

Methods

A 1% representative sample of all AF patients hospitalized between 2010 and 2019 was identified from the French national database. Agglomerative hierarchical cluster analysis was performed using Ward’s method and squared Euclidian distance , to derive 4 distinct clusters of patients (Figure 1) using 31 clinical variables. Cox regression analyses were used to evaluate outcomes including all-cause death, cardiovascular death, non-cardiovascular death, ischaemic stroke, hospitalisation for heart failure (HF) and composite of ventricular tachycardia, ventricular fibrillation and cardiac arrest (VT/VF/CA).

Results

Four clusters were generated from the 12,688 patients included. Cluster 1 (n=2375) was younger, with a low risk of cardiovascular disease (CVD) and risk factors such as hypertension, dyslipidaemia and diabetes, but had the highest cancer prevalence. Clusters 2 (n=6441) and 3 (n=1639) depicted moderate-risk groups for CVD, with the female majority and high rates of lung conditions being the distinct features respectively. Cluster 3 also had the highest degree of frailty, with clusters 2 and 4 following closely. Cluster 4 (n=2233) represented a high-risk cohort for CVD with a high prevalence of coronary artery and vascular disease. Over a follow-up period of 2.0±2.3 years (median 1.1, interquartile range 0.1-3.4), cluster 3 had the highest cumulative incidence of all outcomes except for cardiovascular death which was highest in cluster 4. Compared to cluster 1, cluster 3 had the highest risk for all-cause death, HR 1.24 (1.09-1.41), cardiovascular death, HR 1.56 (1.19-2.06), non-cardiovascular death, HR 1.20 (1.04-1.38), hospitalisation for HF, HR 2.07 (1.71-2.50) and VT/VF/CA, HR 1.74 (1.20-2.53).

Conclusion

Four main clusters of AF patients were identified, discriminated by the differential presence of comorbidities. Our findings suggest that AF patients with moderate CVD-risk may have a poorer prognosis compared to AF patients with high CVD-risk in the presence of lung pathology. Therefore, this subgroup of patients may require more stringent management of existing comorbidities such as chronic obstructive pulmonary disease and sleep apnoea, alongside their AF.
High levels of intermediate cd14++cd16+ monocytes predict incident atrial fibrillation in the general population
Authors: Sveen K A , Smith G , Goncalves I , Edsfeldt A , Engstrom G , Bjorkbacka H , Bengtsson E
Published: November 2023

Background

Atrial fibrillation (AF) is associated with increased inflammation and recent evidence also links inflammation to the pathogenesis of AF. However, studies of circulating immune cells and their contribution to AF are sparse. In particular, prospective studies of monocyte subsets and risk of developing AF are lacking. These studies are important to identify individuals at high risk of AF and further understanding of the pathogenesis of the disease.

Purpose

In the current study we compared differences in circulating monocyte subsets and incidence of AF in a large community-based cohort.

Methods

The study included 666 randomly selected individuals from the cardiovascular arm of the Malmö Diet and Cancer study. Among these, 145 individuals experienced incident AF during the follow up of 18.6 (11.5-21.7) years. To enumerate monocyte subsets (classical CD14++CD16-, intermediate CD14++CD16+, and non-classical CD14+CD16++) mononuclear leukocytes frozen at baseline were analyzed with flow cytometry. Monocyte subsets were determined as total numbers and percentages of total monocytes.

Results

Percentages of classical CD14++CD16- monocytes or non-classical CD14+CD16++ monocytes did not differ in subjects who developed AF compared to subjects without AF. However, intermediate monocytes displayed a trend towards increased percentages in subjects with incident AF. In addition, the number of intermediate CD14++CD16+ monocytes and classical CD14++CD16- monocytes were increased in subjects with incident AF. Both percentages and numbers of intermediate monocytes were associated with increased risk of developing AF during follow-up after adjustment for common risk factors.

Conclusions

This study shows that intermediate CD14++CD16+ monocytes are associated with incident atrial fibrillation independently of other common risk factors in the general population, supporting a role of inflammatory cells in AF.Figure 1
A multiple cut-off diagnostic meta-analysis to identify the atrial high-rate episodes threshold that better relates to thromboembolic events
Authors: Ballatore A , Saglietto A , Griffith Brookles C , Xhakupi H , De Ferrari G M , Anselmino M
Published: November 2023

Background

Despite the high prevalence of atrial high-rate episodes (AHRE) detected by cardiac implantable electronic devices (CIED), clinical guidelines and consensus documents have failed to agree on a universal AHRE definition. Clear evidence on the best management strategy is lacking.

Purpose

The present is a diagnostic test accuracy meta-analysis aiming to derive from available literature the optimal AHRE threshold to predict thromboembolic events.

Methods

PubMed/MEDLINE and EMBASE databases were screened for studies on CIED patients reporting incidence of thromboembolic events referred to at least one AHRE definition. A random-effect diagnostic test accuracy meta-analysis with multiple cut-offs was performed: duration of AHRE was the "diagnostic test" (positive test if the patients experienced an AHRE lasting at least as long as the time cut-off under examination) whose performance in predicting the "disease" (thromboembolic events) was evaluated across multiple cut-offs. Two analyses, according to AHRE definition (longest episode vs. cumulative burden), were performed.

Results

23 studies were included in the analyses (Fig. 1 Panel A), encompassing 46,189 patients: 19 considering the longest single AHRE and 4 the AHRE burden, respectively. Median follow-up was 40.75 (IQR 28.25-52.80) months. The analysis on the longest single AHRE indicated 0.07 minutes as the optimal cut-off to differentiate AHRE associated or not to thromboembolic events [sensitivity 65.4% (95% CI 48.8-79.0%), specificity 52.7% (95%CI 46.0-59.4%), area under the summary receiver operating characteristic curve (AUC-SROC): 0.62; Fig. 1 Panel B]. The analysis on AHRE burden indicated, instead, 1.4 minutes as the optimal cut-off [sensitivity 58.2% (95%CI 25.6-85.0%), specificity 57.5% (95% CI 42.0-71.7%), AUC-SROC 0.60; Fig. 1 Panel C]. PPV and NPV for 6 minutes and 24 hours cut-offs were similar in each analysis (Figure 2). Sensitivity analyses exclusively considering studies reporting data on patients without previous AF diagnosis and high-quality studies only yield similar results.

Conclusion

The present evidence-based approach suggests the presence (or not) of AHRE, rather than a specific duration, relates to an increased thromboembolic risk in CIED patients. A linear relationship between AHRE duration (both in terms of single longest episode than cumulative burden) and thromboembolic events was not observed.
Clinical characteristics of apixaban prescription in AF patients with single dose-reduction criterion: ASPIRE (efficacy and safety of apixaban in real-world practice in Korean frail patients with AF)
Authors: Choi J , Lee S R , Choi E K , Choi J I , Han S W , Oh S I
Published: November 2023

Background/Introduction

Previous observational studies reported that off-label underdosed apixaban might be associated with a higher risk of stroke. However, the real-world clinical practice data on the off-label underdosed apixaban in patients with atrial fibrillation (AF) who meet single dose reduction criteria remains scarce.

Purpose

This study aimed to evaluate the apixaban dosing pattern in patients with AF who met a single dose reduction criterion. The difference in clinical characteristics underlying the on-label and off-label underdose prescription of apixaban was also assessed.

Methods

The efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE) study is a multicenter, prospective cohort study. This study included patients with AF having a single dose reduction criterion of apixaban. Study subjects were categorized into two groups according to apixaban dose (on-label 5 mg twice daily [on-label], or off-label underdose 2.5 mg twice daily [off-label]). We evaluated the difference in the clinical characteristics were evaluated. Additionally, the ‘marginal zone’ was defined as age between 75 and 80 years, weight between 60 and 65kg, and creatinine level between 1.2-1.5mg/dL.

Results

A total of 1997 patients were included in this analysis (mean age 74.3±7.8 years, women 55.8%); 591 (29.7%) patients were 80 years or older, 1250 (62.6%) patients had body weight 60 kg or below, and 156 (7.8%) patients had serum creatinine 1.5mg/dL or higher. Of these patients, 1022 (51.2%) patients were prescribed off-label underdose apixaban. The off-label group was older and had higher mean CHA2DS2-VASC score, Charlson Comorbidity Index, and HAS-BLED scores than the on-label group. Hypertension, heart failure, prior bleeding history, chronic kidney disease, anemia, and concomitant antiplatelet agent usage were more prevalent in the off-label group, but prior stroke history was more common in on-label group. In the age ≥ 80 years group, the marginal zone serum creatinine was more prevalent in off-label group (p=0.011). In the body weight ≤ 60 kg group, the prevalence of marginal zone bodyweight and serum creatinine were higher in off-label group (p<0.001 and p=0.02, respectively). In creatinine ≥ 1.5 mg/dL group, the proportion of marginal zone body weight were more common in off-label underdose group (p=0.001) (Figure).

Conclusions

Among AF patients with a single dose reduction criterion for apixaban, almost half of the patients were prescribed off-label underdose apixaban. Physicians were more likely to prescribe off-label underdose apixaban in patients with more frail characteristics, whereas on-label apixaban was preferred in patients with prior history of stroke. The clinical outcome of off-label underdose apixaban would be compared with the on-label standard dose in a future study.
Sleep apnea independently predicts incident atrial fibrillation in the young - Implications for targeted screening
Authors: Deb B , Vasireddi S K , Bhatia N K , Rogers A J , Clopton P , Narayan S M
Published: November 2023

Background

The risk factors predisposing to AF and ischemic stroke are not well defined in the younger population. That said, routine screening for neither obstructive sleep apnea (OSA) nor atrial fibrillation (AF) is recommended, although these risk factors comigrate. We hypothesized that OSA independently predicts AF in the young.

Methods

We mined electronic data from 2008 to 2022 from a large suburban academic and community healthcare system, for the endpoint of incident AF in 20-50Y adults. We related the endpoint to covariates including CHADSVASC components, OSA, race and socioeconomic factors prior to the diagnosis of AF, excluding patients with existing (prevalent) AF, hemorrhagic stroke, hypercoagulability and central sleep apnea.

Results

From an overall population of 1.7MM, we identified 765,645 aged 20-50Y. Of these, 7500 had OSA. In the follow-up period, 4833 young individuals (45 per 100K person-years) experienced incident AF. Sleep apnea [HR:5.16; (4.68, 5.68)] was the non-CHADSVASC strongest risk factor for incident AF, other than CKD [HR:3.74 (3.20,4.38)], Black race [HR:1.30 (1.16,1.46)], Hispanic ethnicity [HR:1.20; (1.10, 1.32)] and smoking [HR:1.32; (1.24, 1.41)] (Figure 1A). Within CHADSVASC, other than heart failure [HR:10.23; (8.94,11.80)], all the other components had lower hazards than sleep apnea (Figure 1B). The C-index of CHADSVASC score is 0.51 which is augmented to 0.65 (P<0.05) with addition of OSA, CKD, race, ethnicity and smoking.

Conclusions

In a population of over 700 thousand 20–50-year-old adults, sleep apnea is a strong independent predictor for incident AF. This has implications for screening and therapy of young patients.
Relationship between corrected QT prolongation and new-onset atrial fibrillation in the general Japanese population
Authors: Ninomiya Y , Kawasoe S , Kubozono T , Tokushige A , Ichiki H , Kamada H , Yoshimoto I , Ikeda Y , Miyahara H , Tokushige K , Ohishi M
Published: November 2023

Background

The QT interval, an electrocardiogram (ECG) parameter, can be corrected for heart rate, giving the QTc. The QTc is an indicator of ventricular repolarisation and is widely used as a predictor of ventricular arrhythmia. Recent studies have reported a relationship between prolonged QTc and atrial fibrillation (AF) development.

Purpose

We investigated whether a relationship between QTc prolongation and new-onset AF could be identified in the general Japanese population.

Methods

This retrospective study evaluated the annual health check-up data of 103,304 adults (50,438 males; age, 54±15 years) that did not have AF at baseline, from April 2005 to October 2018. Most participants underwent annual health examinations as recommended by the Japanese health welfare policy. The QTc times were calculated with the Bazett formula (QTc=QT/√RR), using the mean QT and RR intervals. Participants were grouped according to QTc time: long-QTc group (males, >440 ms; females, >460 ms) and normal-QTc group. AF was diagnosed using a 12-lead surface ECG. Logistic regression analyses were performed to determine the strength of the association between prolonged QTc and new-onset AF. Multivariate analyses were adjusted for clinical variables (age, sex, obesity, hypertension, dyslipidaemia, diabetes, estimated glomerular filtration rate, and habitual drinking).

Results

The median follow-up time for the total study population was 6 years. During follow-up, 341 (0.3%) new cases of AF were recorded. Univariate analysis revealed a significant increase in new-onset AF in the long-QTc group (odds ratio [OR], 2.80; 95% confidence interval [CI], 1.85–4.25; p<0.001). After adjusting for clinical variables, multivariate analysis revealed that a long QTc was significantly associated with new-onset AF (OR, 1.71; 95% CI, 1.12–2.61; p=0.013). In the multivariate analysis, age (OR, 1.06; 95% CI, 1.05–1.07; p<0.001), sex (OR, 2.55; 95% CI, 1.95–3.33; p<0.001), obesity (OR, 1.46; 95% CI, 1.16–1.84; p=0.001), and habitual drinking (OR, 1.90; 95% CI, 1.50–2.41; p<0.001) were also significant predictors of new-onset AF.

Conclusions

Prolonged QTc is associated with an increased risk of new-onset AF in the general Japanese population. The mechanism of this causal relationship requires further investigation.
Repeated measurement of the novel atrial biomarker BMP10 improves risk stratification in anticoagulated patients with atrial fibrillation: Insights from the ARISTOTLE trial
Authors: Gkarmiris K I , Lindback J , Alexander J , Granger J , Kastner P , Lopes R , Ziegler A , Oldgren J , Siegbahn A , Wallentin L , Hijazi Z
Published: November 2023

Background

Atrial fibrillation (AF) increases the risk of stroke, heart failure, and death. Biomarkers provide important prognostic information about these complications in AF. Recently, bone morphogenic protein 10 (BMP10), a protein mainly expressed in atrial tissue, was identified as a novel marker in AF for the risk of ischemic stroke.

Purpose

To assess the association between baseline characteristics with BMP10 concentrations, and if repeated BMP10 measurements at 2 months improve the prognostication of ischemic stroke or systemic embolism and other cardiovascular events in patients with AF.

Methods

BMP10 was measured in plasma samples collected at randomization and at 2 months in patients with AF who were randomized to apixaban or warfarin in the ARISTOTLE trial (n = 2878) with a median follow-up time of 1.8 years. BMP10 was analyzed with a prototype Elecsys immunoassay. The association of baseline variables with BMP10 at 2 months was evaluated with linear regression analysis. Cox-regression models adjusted for baseline characteristics and comorbidities including kidney function and BMP10-level at baseline were used in order to evaluate associations with outcomes.

Results

Median age was 70 (63.0-76.0) and 63% were male. The events during the follow up period were 34 ischemic strokes, 155 deaths and 99 hospitalizations for heart failure. Median concentration of BMP10 was 2.4 ng/mL at inclusion and 2.6 ng/mL at 2 months (median increase 7.8%, p<0.001). The Spearman correlation for BMP10 at baseline and 2 months was 0.71. The baseline variables most strongly associated with higher BMP10 levels at 2 months, in descending order of importance, were: higher BMI, female sex, worse kidney function, older age, AF-rhythm, diabetes, and randomized treatment. BMP10 levels at 2 months improved the risk stratification in models adjusted for clinical variables including baseline levels of BMP10. For ischemic stroke and death, the estimated associations were nonlinear (Figure) with increased risk with higher BMP10 levels (p=0.037 and p<0.001, respectively), whereas the association with HF hospitalization was linear with HR of 1.91 (p=0.012) comparing the third and first sample quartiles. Patients randomized to apixaban had approximately 2.2% lower BMP10 levels at 2 months compared to those randomized to warfarin (p<0.001).

Conclusions

In patients with AF, the level of the atrial biomarker BMP10 is consistently associated with the risk of stroke at baseline and after 2 months of treatment with warfarin or apixaban. Repeated compared to only one measurement of BMP10 further improves risk stratification. Apixaban as compared to warfarin is associated with a reduction in the BMP10 level, which is in accordance with the lower risk of stroke with apixaban as compared to warfarin.
Predictors of left ventricular reverse remodeling after catheter ablation for atrial fibrillation: sub analysis of a randomized controlled EARNEST-PVI trial
Authors: Sunaga A , Hikoso H , Tanaka N , Masuda M , Watanabe T , Inoue K , Matsuoka Y , Kida H , Sotomi Y , Dohi T , Okada K , Nakatani D , Sakata Y
Published: November 2023

Background

Atrial fibrillation (AF) is widely known to cause heart failure. The catheter ablation for AF improves left ventricular function in many patients with heart failure. However, the predictors of left ventricular reverse remodeling are not well established.

Purpose

The purpose of this study was to examine the predictor of left ventricular reverse remodeling in patients with persistent AF.

Methods

The predictors of left ventricular reverse remodeling was examined using data from EARNEST-PVI trial which compared 12-month rhythm outcomes between persistent AF patients allocated to pulmonary vein isolation (PVI) alone and those allocated to PVI followed by left atrial linear ablation or complex fractionated electrograms ablation. Left ventricular reverse remodeling in this study was defined as a 15% reduction of left ventricular systolic diameter at transthoracic echocardiogram 12 months after initial ablation compared to preoperative echocardiogram.

Results

Of the 512 patients enrolled in the EARNEST-PVI trial, 453 patients with preoperative and 12-month postoperative echocardiogram data were analyzed. Median age was 67 [60. 73] years and 75.7% were male. Recurrence of AF was observed in 106 patients (23.4%) during 12 months after the ablation. LVEF before the initial ablation was 44 [39, 47]% and LVEF 12 months after the initial ablation was 60 [55, 63]% (P<0.001), and LVDs before the initial ablation was 30 [27, 34] mm and LVDs after the initial ablation was 29 [27, 31] mm (P<0.001). Left ventricular reverse remodeling was observed in 78 patients (17.2%). Multivariate linear regression analysis showed age (Odds ratio 0.967 [95%CI=0.939-0.996], P=0.025), preoperative hear rate (Odds ratio 1.032 [95%CI=1.018-1.047], P<0.001) and the use of β-blocker (Odds ratio 2.119 [95%CI=1.235-3.638], P=0.006) were independently associated with left ventricular reverse remodeling but AF recurrence was not (Odds ratio 0.532 [95%CI=0.425-1.561], P=0.538).

Conclusion

Patients with persistent AF showed improvement of LVEF and left ventricular reverse remodeling 12 months after the catheter ablation. Age, heart rate before the initial ablation and the use of β-blocker were predictive factors for the left ventricular reverse remodeling after the ablation regardless of AF recurrence.
Influence of heart failure and chronic kidney disease on cardiovascular outcome in patients with atrial fibrillation - insights from a cohort study of 7,412 patients
Authors: Baumer U , Pedarnig L , Hammer A , Steinacher E , Kazem N , Koller L , Hengstenberg C , Sulzgruber P , Niessner A , Hofer F
Published: November 2023

Background

Heart failure (HF) and chronic kidney disease (CKD) form a vicious circle, reinforcing each other’s disease development and progression and causing higher rates in both morbidity and mortality. Here, we aimed to investigate the relationship between these two prevalent and interrelated diseases in an unselected patient population with AF.

Methods

This analysis includes patients with known AF, treated at a tertiary center between 07/2000 and 07/2019. The primary combined endpoint was hospitalization for heart failure (HHF) or cardiovascular (CV) death. We used cox regression models adjusted for age, sex, diabetes, coronary artery disease, hypertension, BMI and CRP-levels.

Results

We examined 7412 patients with AF and followed them over a median of 5.3 years. The median age was 70 years (IQR 61 to 78 years) and 2,945 (39.7%) were female. 434 (5.0%) patients had known CKD, 1,296 (17.5%) patients had HF, and 372 (5.4%) patients had both CKD and HF. There was a significant stepwise increase in event rates for the composite of CV death/HHF among patients without CKD or HF (KM event rate at 5 years: 23%), patients who had HF but no CKD (KM event rate at 5 years: 61%), patients with CKD but no HF (KM event rate at 5 years: 63%), and those who had both, HF and CKD (KM event rate at 5 years: 82%; P-logrank <0.001; Figure 1A). After multivariable adjustment, both CKD (with an adjusted hazard ratio of 2.22 and a 95% confidence interval of 1.87 to 2.63) and HF (with an adjusted hazard ratio of 2.53 and a 95% confidence interval of 2.26 to 2.84) were significantly associated with CV death/HHF and exerted a similar magnitude of the relationship. Patients with concomitant disease had the highest risk of the primary endpoint (with an adjusted hazard ratio of 3.96 and a 95% confidence interval of 3.34 to 4.68; Figure 1B).

Conclusion

AF patients with CKD and HF are at very high risk of CV death/HHF. Commonly used risk scores usually focus on stroke as the most dreaded complication in patients with AF. These findings suggest that the influence of CKD and HF expand beyond the risk of stroke to CV death/HHF in an unselected AF patient population.Figure 1