AbstractBackgroundAtrial Fibrillation Research Articles

Inflammatory-mediated atrial cardiomyopathy diagnosed using multimodality imaging and successfully treated with prednisolone: a case report

Abstract Background Atrial fibrillation is a common cardiac arrhythmia and often develops secondary to structural cardiac changes. Both the occurrence of atrial fibrillation and/or structural changes of the heart may lead to development of atrial cardiomyopathy and heart failure (HF). However, isolated atrial cardiomyopathy caused by focal atrial thickening is a rare condition, previously only described in case reports as a result of different aetiologies all linked to inflammation. Case summary A patient with inflammatory-mediated atrial cardiomyopathy causing atrial fibrillation and acute decompensated HF presented as isolated left atrial wall thickening on transoesophageal echocardiography. The diagnosis was confirmed using multimodality imaging with transthoracic and transoesophageal echocardiography, cardiac magnetic resonance imaging, positron emissions tomography/computer tomography scanning and intracardiac echocardiography-guided endomyocardial biopsy. Despite no specific histological aetiology, the observed atrial cardiomyopathy might be associated with type 1 diabetes mellitus. The patient in the present case was successfully treated with prednisolone. Discussion Diabetes mellitus is an important risk factor for developing atrial fibrillation and diabetic cardiomyopathy, due to reduced levels of anti-inflammatory and increased levels of proinflammatory cytokines causing cardiac inflammatory structural remodelling. The regression of the atrial thickening might be due to prednisolone’s anti-inflammatory effects and thereby ability to suppress atrial remodelling and reduce the occurrence of atrial fibrillation. However, the effect of prednisolone might only affect the non-manifested inflammatory-mediated atrial remodelling. Due to the rare occurrence of isolated atrial cardiomyopathy a multiple imaging approach during the diagnostic process and follow-ups are essential to determine the aetiology and effect of the treatment.

Assessing physicians’ knowledge, attitude, and practice on anticoagulant therapy in non-valvular atrial fibrillation: Syrian insights

BackgroundAtrial fibrillation (AF) is the most prevalent cardiac condition linked to increased mortality due to complications such as stroke. Oral anticoagulant (OAC) is the mainstay in preventing cerebrovascular accidents in patients with AF. Recent evidence identified gaps in physician’s knowledge in diagnosing and managing patients with AF. This study aims to assess Syrian physicians’ knowledge, attitude, and practices regarding the use of anticoagulant therapy in non-valvular AF (NVAF) patients. A cross-sectional study was conducted using a validated web-based questionnaire, which included 56 items separated into four sections that collected information about demographics, knowledge, attitude, and practices. Chi-square and Kruskal Wallis were performed to analyze the statistical relationships between the knowledge, attitude, practice, and demographic variables.ResultsA total of 497 participants completed the survey, of which 62.6% were between the ages of 25 and 35. The average participant scores for knowledge, attitude, and practices were (48.18 ± 21.57), (81.54 ± 9.26), and (62.83 ± 12.42), respectively. Participants who demonstrated good understanding, a positive attitude, and good practices were 22.3%, 87.3%, and 25.4%, respectively. The fear of bleeding was identified as the most significant barrier to initiating anticoagulant medication in AF patients (55.5%). Doctors who attended training had a better knowledge score than those who did not (mean ± S.D. = 57.24 ± 20.7). Participants who stated that over 70% of their AF patients use aspirin received the highest attitude score (mean ± S.D = 86.98 ± 21.17). PhD participants reported higher practice scores than those with other educational backgrounds (mean ± S.D = 73.96 ± 11.3).ConclusionThis research showed that primary care physicians in Syria had optimistic views regarding OAC therapy, suggesting that training interventions targeting physicians may lead to improvement in the treatment of patients with NVAF in Syria.

The use of percutaneous left atrial appendage occluder device in a patient with prior surgical ligation with incomplete exclusion: a case report

Abstract Background Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and the most common cause of cardioembolic stroke. The left atrial appendage (LAA) is the main source of thrombus formation in patients with AF. Therapies include use of percutaneous LAA closure devices, or surgical LAA occlusion (LAAO). Despite these options, complete closure of the LAA is not always achieved, and residual communication between the LAA and atrium may result in increased thrombus formation. Although studies have analysed the use of percutaneous measures such as coils, plugs, or second occluder device deployment in LAA with peri-device leak (PDL), use of percutaneous occlude devices in surgically occluded LAA is far less studied. Case summary We present a case of a 79-year-old female patient who underwent LAAO device deployment within a surgically occluded LAA with PDL. She underwent 27 mm LAAO device (WATCHMANTM) deployment and all the P.A.S.S. (Position, Anchor, Size, and Seal) criteria were satisfied. Only 1.4 mm PDL was present. She was continued on apixaban and aspirin post-operatively. Post-operative transoesophageal echocardiogram at 6 weeks demonstrated trivial PDL measuring 1.49 mm. Patient was continued on aspirin and clopidogrel, with discontinuation of apixaban. Discussion Percutaneous LAAO device deployment in previously surgically ligated LAA with incomplete exclusion is a potential therapeutic option for patients with AF and a high bleeding risk seeking a minimally invasive strategy, in an attempt to de-escalate anticoagulation therapy.

Atrial fibrillation diagnosed at different phases of myocardial infarction are all associated with excess risk

Abstract Background Atrial fibrillation (AF) in patients with myocardial infarction (MI) is associated with higher mortality and cardiovascular complications such as hospitalisation due to heart failure and ischaemic stroke. It is unknown whether the association with poor outcomes is general or specific for AF diagnosed before, at or during follow-up after an MI. Purpose The aim of this study was to investigate the occurrence of AF, and its clinical correlates at different stages in patients with acute MI. In addition, we also explored whether any association between AF and mortality, incident heart failure or stroke differed for AF diagnosed at these stages. Methods Patients attending cardiac rehabilitation after MI in Sweden 2006-2020 were identified in the Swedish registry for cardiac disease SWEDEHEART. The patients were divided into groups with sinus rhythm at hospitalisation and follow-up (reference group), AF at MI hospitalisation including prior and new-onset AF during MI hospitalisation, and late-onset AF diagnosed at cardiac rehabilitation follow-up visits during the first year post-MI. All patients were followed until 2020-12-31 and the groups were compared regarding overall mortality, hospitalisation due to heart failure, and stroke using log-rank test and Cox-regression adjusted for age in cubic splines and sex. Results Overall 104,325 patients (26% female) between 18-80 years old were investigated. 4731 patients presented with AF at admission for MI (4.5%) and 2,119 (2%) had a persistent AF at discharge. Out of these, 139 had new-onset AF at MI. STEMI was more common in patients with new onset AF compared to those with a history of AF before MI (40.3% vs 31.7%, p=0.013). During the one-year follow-up period after index MI 448 patients had a new-onset AF which was associated with older age, NSTEMI, reduced ejection fraction and more extensive coronary artery disease at the index MI. The association between AF diagnosed at the different phases of MI with outcomes are illustrated in figure 1. During a median follow-up of 7.0 years, patients with AF at MI had a higher mortality (33.3% vs 14.2%, p<0.001), more hospitalisations due to heart failure (25.6% vs 6.7%, p<0.001) and stroke (8.0% vs 3.9%, p<0.001) compared to patients with SR. Patients with new-onset AF at MI had a similar risk for these outcomes compared to patients with a history of AF at MI. Patients with late-onset AF during the one-year follow-up period after index MI also had higher mortality (28.3% vs 12.2%, p<0.001) and more hospitalisations for heart failure (21.9% vs 5.6%, p<0.001) but not stroke (4.2% vs 3.9%, ns) compared to patients that remained in SR. Conclusion In patients attending cardiac rehabilitation after MI, chronic AF, new-onset AF at MI and late-onset AF were associated with increased risk for mortality, heart failure hospitalisations and stroke. Hence, AF should be considered a severe risk factor in patients with MI irrespective of time of occurrence.AF at MI

Soluble ST2 biomarker utility in the comprehension of the clinical course of atrial fibrillation

Abstract Background Atrial fibrillation (AF) is the more frequent arrhythmia in clinical practice and probably one of the more analyzed. Despite this, the clinical pattern classification not always correlates with the clinical course of AF. There are still a lack of biomarkers to predict recurrence and the clinical course of this disease. Purpose ST2 soluble (ST2S) biomarker has being previously analyzed by our group in patients with AF and electrical cardioversion (ECV) demonstrating utility to predict recurrence. We sought to analyze the clinical outcome of patients with AF who underwent an ECV or pulmonary vein isolation (PVI) and its correlation with the ST2S biomarker at mid-term follow-up. Methods We performed a prospective, observational clinical trial that included 250 patients with AF who were referred to our hospital for a clinical procedure including ECV or PVI from September 2016 to 2019. A total of 40 matched controlled patients were also included for the initial analysis. ST2S was analyzed from blood samples at baseline, 3- and 6-months follow-up. Results From 250 patients with AF: 94 underwent an ECV and 156 patients an PVI. Mean age was of 58.5 ±10.4 years. From the 156 PVI: 68 had paroxysmal and 88 persistent AF. Clinical follow-up was continued for 1 year and recurrence was of 65.9% in ECV and 22.4% in PVI patients. Clinical and echocardiographic characteristic are described in table1. The initial value of the ST2S biomarker was higher in AF cases with respect to controls (p<0.001). The patients with paroxysmal AF had higher levels of ST2S.0 (12113.4 pg/mL) respect to control cases but with no significant difference (p=0.234). Comparing the values of ST2S in persistent AF patients (15634.8 pg/mL) with controls the value was higher with a significant difference. ST2S baseline values were compared according to the rhythm and patients in AF had significantly higher levels with respect to those in sinus rhythm (SR). ST2S baseline values were also compared according to heart rate (HR) and those in tachycardia had higher levels respect to those who didn't(Table2). When analyzing ST2S levels in the complete cohort of patients with AF according to recurrence, there were no significant differences (Figure1). In multivariant analysis only AF rhythm and LA index volume were significant predictors of recurrence at 3 months follow-up and AF rhythm and age were predictors at 6 months follow-up. Conclusions ST2S baseline values were higher in persistent AF with respect to paroxysmal AF and only persistent AF patients had higher levels compared with controls. Initial ST2S biomarker levels did not have a predictive value in the global cohort of AF but do correlate with the type of AF and AF rhythm. With these results we consider that even though there is an association with AF and ST2S biomarker levels, when analyzing independently to the type of procedure ST2S values were not predictive of recurrence at mid-term follow-up.

Incidence and types of significant tricuspid regurgitation in atrial fibrillation and sinus rhythm

Abstract Background Atrial fibrillation (AF) is associated with increased risk of incident tricuspid regurgitation (TR), but types of incident TR in AF versus sinus rhythm (SR) are not well-defined. Purpose We aimed to compare the risk of the different types of incident ≥moderate TR in AF and SR. Methods Adults first diagnosed with AF (2010-2021) who had a transthoracic echocardiogram (TTE) within 30 days after AF and adults with no diagnosis of AF who had a TTE in the same period were identified. Patients with previous cardiac surgeries, congenital heart disease, cardiomyopathy, cardiac devices, primary valve disease, previous or current ejection fraction (EF) <50%, severe diastolic dysfunction (SDD), ≥moderate left-sided valve disease (LVD), right ventricular systolic pressure (RVSP) ≥50 mmHg, ≥moderate TR, any tricuspid stenosis, or with no follow-up TTE ≥6 months from baseline were excluded. Patients were followed for the development of ≥moderate TR, the type of which was identified in a hierarchal order: 1) pacemaker-associated TR, 2) LVD-associated TR in the setting of ≥moderate LVD, 3) low EF or SDD-related TR, 4) pulmonary hypertension (PH)-associated TR if RVSP was ≥50 mmHg, 5) other ventricular functional TR (VFTR) if there was >mild RV enlargement or dysfunction, and 6) atrial functional TR (AFTR) when none of the previous was present. Patients were also followed for the occurrence of risk factors for TR (pacemaker insertion, ≥moderate LVD, low EF or SDD, PH, >mild RV enlargement or dysfunction) in a hierarchal order, and both the prevalence and future risk of the corresponding type of ≥moderate TR was determined at the onset of these conditions in AF and SR. Results Overall, 1,360 patients with new-onset AF (median age 67 years, 34% females) and 20,438 patients in SR (median age 60 years; 54% females) were included. Over median 3.8 (IQR 1.8-6.6) years, incident ≥moderate TR occurred in 110 patients with new-onset AF [2.13 per 100-person years] compared to 378 patients in SR [0.41 per 100-person years, p <.001]. All types of incident ≥moderate TR occurred more frequently in AF (p <.001 for all). The distribution and incidence of each type of TR in AF and SR are shown in Figure 1. The incidence of risk factors associated with the development of TR was higher in the AF group, except for pre-capillary PH, Figure 2A. At time of diagnosis or occurrence of these conditions, the prevalence of the corresponding TR types was higher in AF, except for pacemaker-TR, Figure 2B. The incidence of the corresponding TR type after occurrence of TR risk factors was higher in the AF group for LVD-TR and low EF/SDD-associated TR (p ≤0.03); although numerically higher in AF, the association was only borderline for PH-TR (p =0.05), Figure 2C. Conclusion Incident ≥moderate TR of all types occurred more frequently in patients with AF vs. SR and the distribution of TR types differed by rhythm. Patients with AF may benefit from a closer follow-up.Distribution and incidence rates of TRIncidence of TR risk factors & TR after

Mobile health technology integrated care in atrial fibrillation patients according to atrial fibrillation subtype: a subgroup analysis of the mAFA-II randomised trial

Abstract Background Atrial fibrillation (AF) is clinically categorised into different types (e.g. paroxysmal, persistent and permanent AF) according to the duration of the arrhythmia and whether it is accepted by physician and patient. These types of AF usually recognise different arrhythmic substrates, any may show different response to rate and rhythm control treatments. The Mobile Health Technology for Improved Screening and Optimized Integrated Care in AF (mAFA-II) prospective cluster randomised trial proved the efficacy of a mobile health (mHealth) implemented ‘Atrial fibrillation Better Care’ (ABC) pathway (mAFA intervention) for the integrated care management of patients with AF. Whether the effect of mAFA intervention could differ between different types of AF is still unknown. Purpose To assess the efficacy of mAFA intervention according to the type of AF. Methods mAFA-II was a cluster randomised trial which recruited 3,324 adults AF patients between June 2018 and August 2019 in 40 centres in China. Clusters were randomised in a 1:1 ratio to mAFA intervention or usual care. In this analysis, we included patients with either paroxysmal, persistent or long-standing/permanent AF; we then assessed the interaction between these three types of AF and the effect of mAFA intervention on the risk of major outcomes using multivariable Cox regression analysis. Results were expressed as adjusted Hazard Ratio (aHR) and 95% Confidence Intervals (95%CI). The primary outcome was the composite of ischemic stroke/thromboembolism, all-cause death, and rehospitalizations. Results 2,489 AF patients were included in this analysis (mean age: 69.6±13.2, females 37.8%). Of these, 1,333 had paroxysmal AF (673 allocated to mAFA intervention), 828 had persistent AF (380 allocated to mAFA intervention), and 328 had long-standing/permanent AF (104 allocated to mAFA intervention). Patients with long-standing/permanent AF were older and more likely burdened by several comorbidities. On multivariable Cox regression analysis, the efficacy of the mAFA intervention on the risk of the primary composite outcome was similar in the three groups, without statistically significant interaction (p for interaction=0.337), with the highest effect seen among patients with persistent AF (aHR: 0.27, 95%CI: 0.11-0.66). Conclusions A mHealth-technology implemented ABC pathway showed a similar effect on the reduction of the primary composite outcome among patients with different subtype of AF. These findings support the implementation of integrated care approach also in patients with more advanced form of AF.Cox-regression models for interaction

Elucidating the role of leukocyte telomere length in the risk of atrial fibrillation

Abstract Background Atrial fibrillation (AF) is strongly associated with older age. However, it is unclear whether, in addition to chronological age, more advanced biological ageing confers AF risk. Previous studies suggest AF and peripheral leukocyte telomere length (LTL, a measure of biological ageing) are associated, but this relationship and the causal relevance remains controversial. Purpose This study aims to explore the role of LTL in risk of AF through observational analyses and Mendelian randomisation (MR). Methods UK Biobank (UKB) is a large prospective study of individuals 40 to 69 years of age in which 393,018 participants have measured LTL and genetic data available. Observational associations between LTL and incident AF (ascertained in hospital admission data) were estimated using Cox proportional hazards models adjusted for potential confounders (age at LTL measurement, body mass index, physical activity, smoking status, alcohol intake, ethnicity, Townsend deprivation index, and sex). MR analyses included 195 SNPS previously shown to have conditionally independent genome-wide significant associations with measured LTL. In UKB, causal effects of genetically-predicted LTL for AF risk were estimated using the inverse-variance weighted approach. Validation was undertaken in independent data from the AFGen Consortium (Nielsen et al. 2015). Sensitivity analyses to consider the potential effects of pleiotropy were also conducted (weighted median MR, MR-Egger and Radial MR). Results Among 385,851 participants with available LTL measurements and without AF at baseline, 26,639 (6.9%) developed AF during follow-up. Longer measured LTL was associated with lower risk of AF (HR=0.98, 95%CI=0.97-0.99, p=0.002), with the cumulative incidence of AF by LTL quartile shown in Figure 1. However, MR analyses did not support a causal association between genetically-predicted LTL and AF (OR=1.04, 95%CI=0.96-1.14, p=0.36). Sensitivity analyses were consistent with the primary MR results, and did not suggest unbalanced pleiotropy (MR Egger intercept, p=0.54). Radial MR identified 4 outlier SNPs (associated with height, adiposity, and blood cell traits) but results remained consistent after exclusion of these variants (OR 1.00, 95%CI 0.93-1.08, p=0.90). Validation analyses in independent data were consistent with the non-significant association observed in UKB (OR=1.08, 95%CI=0.99-1.18, p=0.07; Figure 2). Conclusion This study combines conventional and genetic epidemiological approaches to explore the role of LTL in risk of AF. Large-scale observational analyses in UKB suggest an inverse association between LTL and AF. However, despite previous studies reporting associations between genetically-determined LTL and AF risk factors, our validated MR results do not support a causal relationship between LTL and AF, and potentially suggest observational associations are due to residual confounding.Figure 1Figure 2

Metabolomics to characterise adaptations in cellular metabolism for the stages of atrial fibrillation

Abstract Background Atrial fibrillation (AF) is a highly prevalent, progressive cardiac arrhythmia associated with high cardiovascular comorbidity. Current treatments targeting electropathophysiology have high recurrence rates, prompting researchers to uncover alternative molecular mechanisms underlying AF, aiming to find novel targets for diagnostics and treatment. Highly relevant to several cardiovascular diseases, adaptations in cellular metabolism have gained interest in AF. However, changes in the metabolome across various AF stages have not yet been studied. Aim The study aims to identify leads for potential biomarkers and treatment targets by gaining more insight in metabolic adaptation and mechanisms in atrial fibrillation. Methods From the HALT&REVERSE biobank, 60 atrial appendage samples were selected [controls (SR=21), paroxysmal (ParAF=16), persistent (PerAF=11) and longstanding-persistent AF (Ls-PerAF=12)]. Metabolomics, a large-scale semi-quantitative method based on mass-spectrometry, was performed. Comparisons were made SR vs. AF, and SR vs. AF stages by Mann-Whitney U and Kruskal Wallis statistical tests with a Benjamini-Hochberg correction (FDR=0,10) for multiple testing. Results Comparing SR and AF, fructose-1,6-diphosphate (F1,6DP) was decreased (p<0.001), whilst CDP (p<0.001) and UMP were increased (p<0.01). Comparing the AF stages, in SR vs. ParAF CDP was significantly increased. Regarding the AF stages, SR and LsperAF show the biggest differences in metabolites, presenting as decreases glycolysis and nicotinamide metabolites. Overall, metabolites associated with the glycolysis, nicotinamide, and carnitine metabolism show decreases in AF patients, whilst metabolites involved with pyrimidine metabolism are increased AF patients. Conclusion CDP, F1,6DP and UMP were strongly correlated with AF samples in univariate analyses and therefore should be further investigated in serum for their biomarker potential, specifically CDP which was already strongly increased in ParAF. F1,6DP and similar energy metabolites in the glycolysis and nicotinamide pathways are decreased in AF and therefore could be as a therapeutic target through supplementation. Leads from this analysis should be validated and further investigated in mechanistic studies of these metabolic pathways.

Inter-atrial block and atrial fibrillation predict cardiac adverse events in heart failure with preserved ejection fraction

Abstract Background Atrial fibrillation (AF) is a prognostic risk-factor in heart failure with preserved ejection fraction (HFpEF). Earlier stages of atrial dysfunction identified by the ECG, particularly inter-atrial block (IAB), may provide additional risk predictions in HFpEF patients in sinus rhythm. Purpose To assess the prevalence of IAB in patients diagnosed with HFpEF compared to non-HFpEF, and to evaluate the prognostic association of IAB and AF in patients diagnosed with HFpEF. Methods Consecutive symptomatic patients referred for a systematic diagnostic work-up to rule-in or rule-out HFpEF were included. The diagnosis of HFpEF was based on current guidelines (including HFA-PEFF and H2FPEF algorithms) and confirmed by consensus of multiple experienced HF specialists. Patients in whom HFpEF was ruled-out were included as non-HFpEF. We excluded patients with cardiac valve interventions before or up to 1 year after baseline, or with paced rhythm during IAB assessment. ECGs at baseline were assessed in detail for P-wave duration, morphology, and presence of IAB using digital calipers by investigators blinded to clinical data. IAB was defined based on a P-wave duration of >120ms. Patients with HFpEF and non-HFpEF were grouped into either i) AF based on ECG or medical history, ii) IAB based on ECG, or iii) no IAB or AF based on ECG. Adverse events were evaluated only in HFpEF patients and included HF hospitalization, cardiac or sudden death, and a composite of both. Results 372 patients with HFpEF and 68 non-HFpEF were included (females: 67.7% vs. 64.7%, p = 0.726; mean age: 75±7 vs. 67±10 years, p<0.001). AF was more common in HFpEF than non-HFpEF (64.8% vs. 23.5%, p<0.001). In sinus rhythm, presence of IAB was comparable between HFpEF and non-HFpEF (87.0% vs. 80.8%). During a mean follow-up of 3.2±1.6 years in HFpEF patients, more adverse cardiac events were observed when AF was present (23.7%, HR 10.6 [95%CI 1.5-1334.4]) compared to IAB (10.5%, HR 4.2 [95%CI 0.56-542.6]) and no IAB (0%), p = 0.0004 (Figure 1). Pairwise comparisons confirmed these observations: AF vs. IAB p = 0.006, AF vs. no IAB p = 0.031. In HFpEF patients with sinus rhythm, a trend was found for more adverse events when IAB was present versus no IAB (p = 0.06). Conclusion Patients with HFpEF have a higher prevalence of AF and similar prevalence of IAB compared to symptomatic patients ruled-out for HFpEF. Presence of IAB or AF in HFpEF may predispose to adverse cardiac events in patients without severe valve disease. IAB may enrich cardiac risk stratification in addition to AF in HFpEF.Survival curves for no IAB, IAB, and AF

Impact of atrial fibrillation burden on longitudinal changes in left ventricular structure and function: a post-hoc analysis of a randomized clinical trial

Abstract Background Atrial fibrillation (AF) is a well-established risk factor for heart failure (HF), stroke, and left ventricular (LV) dysfunction. However, only limited longitudinal data exist regarding the impact of AF burden on left ventricular (LV) structure and function. Purpose The aim of this study was to investigate the association between AF burden and longitudinal changes in LV structure and function in an older patient population with cardiac risk factors. Methods This study was a post-hoc analysis of a randomized clinical trial, which investigated whether AF screening with implantable loop recorders (ILRs) and subsequent initiation of anticoagulation could prevent stroke in high-risk individuals. As a substudy, a group of participants had extensive transthoracic echocardiography performed at baseline and a re-examination after ILR end-of-life. We included participants with available ILR data and echocardiographic data from both baseline and follow-up. We excluded participants with ongoing AF during the baseline echocardiogram. AF episodes were adjudicated by two cardiologists and AF burden was calculated as the percentage of time spent in AF during the total ILR monitoring period. Univariable and multivariable linear regression models were used to investigate the association between AF burden and changes in echocardiographic measures. The multivariable model was adjusted for age, sex, systolic blood pressure, diabetes, smoking status, previously acute myocardial infarction, previous coronary artery bypass grafting, prevalent HF, body mass index, estimated glomerular filtration rate, number of days monitored by ILR, and the number of days between the two echocardiographic examinations. Both models included adjustment for the baseline value of the echocardiographic measure. Results The study population consisted of 640 participants with available baseline and follow-up echocardiograms. Mean age was 73.6 years (±3.4 years) and 278 (43.4%) were women. AF was documented in 188 (29.4%) participants during a median ILR monitoring period of 3.2 years (IQR 2.9-3.4 years). The mean timespan between the echocardiographic examinations was median 5.0 (IQR 4.6-5.2) years. Among participants with AF, the median AF burden was 0.098% (IQR 0.026-0.758%). Over the course of echocardiographic follow-up, mean ∆GLS was -0.59% (±3.49%), mean ∆LVEF was -1.44% (±8.5%), and mean ∆E/e’ was -1.12(±3.23) in those with AF. Increasing AF burden was significantly associated with an accelerated decline in absolute global longitudinal strain in both univariable (ß= -0.12, p=0.002) and multivariable (ß= -0.11, p=0.003) models (Table 1/Figure 1). Conclusions In an older at-risk population, AF was frequent, and increasing AF burden was found to be independently associated with an accelerated decline in LV function. These findings support AF as an independent risk factor in the development of HF.

Pulmonary hypertension is an adverse risk factor for patients admitted with atrial fibrillation

Abstract Background Atrial Fibrillation (AF) poses a significant burden on the resources of the American Healthcare system. Heart failure and AF commonly coexist in patients. Elevated left ventricular and atrial pressures result in progressive left atrial dilation and remodeling which in turn predisposes to the generation of AF. Many of these patients develop pulmonary hypertension (PHT) due to the remodeling and elevated left-sided pressures. Since many who have AF could have PHT, we aimed to assess outcomes in this population. Methods We utilized the National Inpatient Sample from 2016-2019 to identify roughly 16,500,000 hospitalized adults who had AF. These hospitalizations were further stratified based on the presence of PHT. A multivariate regression model was used to adjust for confounders and analyze the variables. Results Of those with AF, 1,855,020 (11.2%) had PHT. In-hospital mortality was higher in those with PHT (5.6% vs 4.9%; p<0.001). Figure 1 shows the Forrest plot for multivariate analysis of in-hospital outcomes when adjusted for patient demographics, comorbidities, and hospital characteristics. When adjusted similarly, patients with AF and PHT had longer length of stay (LOS) by 0.92 days (p<0.001) and had additional hospital costs (HC) of $9,463 (p<0.001). Conclusion In this study, patients admitted with AF with co-existing PHT had significantly worse outcomes in terms of in-hospital mortality, LOS, HC, cardiac arrest, pulmonary embolism, atrial flutter, AKI, blood transfusions, pneumonia, and endotracheal intubation. One major limitation of our study is the lack of outpatient follow up. Given that overall outcomes are worse in the setting of PHT, potential strategies for early rhythm control for AF should be pursued to avoid negative cardiac remodeling that would predispose to the development of PHT. AF patients with co-existing PHT should be aggressively monitored during hospitalizations as they have the potential to have worse outcomes.

The assessment of left atrial and left atrial appendage mechanics in patients with different stages of atrial fibrillation

Abstract Background Atrial fibrillation (AF) is associated with left atrial (LA) mechanical dysfunction, which predisposes to stasis of blood within the LA and thus increases the risk of stroke. However, limited is known about the mechanical functional alterations of left atrial appendage (LAA) in relation to stages of AF. Here, we sought to analyse LA and LAA mechanics during different stages of AF in detail. Methods A total of 92 patients with AF referring for radiofrequency ablation were consecutively enrolled. Patients were categorized according to rhythm and stages of AF:sustained AF(SAF) (n=31), paroxysmal AF with sinus rhythm(PAF-SR)(n=30) andAF rhythm(PAF-AF)(n=31)at the time of echocardiography. Twenty-seven patients without a history of AF were included as controls. Using speckle-tracking echocardiography, LA and LAA global peak positive longitudinal strain (GLS) and mechanical dispersion (MD) were measured in all patients. Mechanical dispersion was defined as the standard deviation of the time to peak of the regional strain corrected by R-R interval. Results Patients with PAF-AF and SAF displayed prominently impaired LA and LAA mechanics(all P < 0.01 vs. PAF-SR and no AF). In the presence of SR, only LAA mechanical function were lower in PAF patients than patients without AF(LAA GLS 20.5±5.7%(no AF) vs 15.9±5.4%(PAF-SR); LAA MD 6.9±3.8%(no AF) vs 9.4±3.9(PAF-SR),both P<0.01). AF stages were independent determinants of LA and LAA mechanics after adjusting for age and comobidities. Conclusions AF affected mechanical function of LA and LAA on their own, and more so if stage of AF has advanced to more persistent forms. In addition, LAA mechanical dysfunction occurred earlier than that of LA.fig 1fig 2

High levels of intermediate cd14++cd16+ monocytes predict incident atrial fibrillation in the general population

Abstract 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

The risk and cause of death according to prevalent atrial fibrillation and the role of CHA2DS2-VASc score to stratify the risk of all-cause and cardiovascular death

Abstract Background Atrial fibrillation (AF) is the most common cardiac arrhythmia, and its prevalence is rapidly increasing. AF is associated with increased risks of stroke and all-cause death. Understanding the causes of death (COD), the relative risks of each cause in AF patients compared to non-AF population, and finding out modalities to stratify the risk of death among AF patients is essential to plan optimal care of AF patients. Purpose We aimed to analyze the COD of AF patients and the relative risk of death from specific causes in AF patients compared to non-AF population using a nationwide population based cohort. Also, we identified the role of CHA2DS2-VASc score to stratify the risk for all-cause death and death from cardiovascular causes in AF patients. Methods Using the Korean nationwide claims database, subjects who received nationwide health screening examination at 2009 and aged 40 or older were included (n=7,240,800). Patients with missing values in health examinations were excluded. Finally, 6,87,929 patients were included: 40,585 patients with AF and 6,837,344 subjects without AF. COD were classified by diagnostic codes. Results A total of 490,807 deaths were reported during follow-up (incidence rate of all-cause death: non-AF group, 19.1 and AF group, 34.2 per 1000 person-years). In AF group, cardiovascular diseases were the most common COD occupying 39.8% of all-death, whereas only 19% of non-AF subjects died due to cardiovascular diseases (Figure A). The proportion of death from cerebrovascular diseases in the AF group was two times higher than that of the non-AF group (15.1% vs. 7.5%, respectively). Compared to non-AF group, AF group was associated with a significantly higher risk of all-cause death (hazard ratio [HR] 1.739, 95% confidence interval [CI] 1.708-1.771, p <0.001) (Figure B). AF group was associated with higher risks of death from cardiovascular diseases and death from cerebrovascular diseases by almost 3-fold than non-AF group (HR [95% CI], 2.899 [2.814-2.985] for death from cardiovascular diseases; 2.899 [2.814-2.985] for death from cerebrovascular diseases, all p <0.001) (Figure B). Among AF patients, the risks of all-cause, cardiovascular, and cerebrovascular death were well-stratified by CHA2DS2-VASc scores (Figure C). The increases of HRs by increases of CHA2DS2-VASc score were more prominent in the risk of death from cerebrovascular diseases, followed by death from cardiovascular causes, and all-cause death. Conclusions Compared to non-AF subjects, AF patients showed higher risks of death from cardiovascular and cerebrovascular diseases. The risks of death from cardiovascular and cerebrovascular diseases were clearly stratified according to CHA2DS2-VASc score. Integrated management for AF patients should be focused on to prevent death from cardiovascular and cerebrovascular causes. CHA2DS2-VASc score could help to stratify the risk of all-cause death and death from specific causes in AF patients.

Interventional rhythm control is associated with an improved long-term prognosis of patients with atrial fibrillation undergoing transcatheter edge-to-edge mitral valve repair

Abstract Background Atrial fibrillation (AF) is the most common concomitant disease in patients undergoing transcatheter edge-to-edge repair (TEER) for severe mitral regurgitation (MR) and detrimentally affects their long-term survival. While the prognostic improvement of catheter ablation (CA) of AF in the overall cohort of heart failure (HF) patients as well as that of surgical ablation of AF with concomitant MR surgery are well established, data on the outcomes of CA of AF in TEER patients are lacking. Methods In a multicenter retrospective observational cohort study, consecutive patients undergoing TEER were enrolled and long-term survival of patients receiving catheter ablation (CA) for AF was compared with that of patients on pharmacological AF treatment and with that of patients without a history of AF, using propensity score matching and multivariable Cox regression analyses. Results A total of 821 patients were identified who successfully underwent TEER procedure. Within this cohort, 608 (74.1%) had concomitant AF, of which 48 patients received CA. Patients with CA of AF showed significantly higher cumulative survival 5 years after the TEER procedure compared with propensity score-matched patients on pharmacological rhythm control of AF (64.6% [31/48] vs. 33.3% [64/192], p=0.01) or on rate control of AF (64.6% [31/48] vs. 25.0% [24/96], p=0.0015). Multivariable Cox regression analysis confirmed that CA of AF was independently associated with significantly better long-term outcome than pharmacological rhythm control and rate control of AF (hazard ratio [HR] 0.4, 95%-confidence interval [CI] 0.2-0.9, p=0.02 and HR 0.4, 95%-CI 0.2-0.7, p=0.004, respectively). CA even offsets the prognostic disadvantage of coexisting AF, as the cumulative survival 5 years after TEER intervention is not significantly different from propensity score-matched TEER patients without a history of AF (64.6% [31/48] vs. 38.9% [56/144], p=0.3). Conclusion Using established statistical methods of propensity score matching and multivariable Cox regression, we demonstrate a significantly improved long-term outcome of TEER patients undergoing CA of concomitant AF compared with pharmacological AF management. CA even offsets the prognostic disadvantage of coexisting AF, as the outcome is not significantly different from that of TEER patients without a history of AF. In light of the growing evidence of prognostic benefit and safety of CA of AF in the overall cohort of HF patients, our data, albeit not randomized, provide strong evidence for interventional rhythm control of AF as an essential part of a modern and holistic management of TEER patients. We alert to the importance of treating concomitant AF, as this is a very promising approach to improve the prognosis of this unique and continually growing HF population.Flow chart of the study designSurvival analyses of PSM cohorts

Factors associated with delayed treatment initiation of oral anticoagulants among Medicare patients with atrial fibrillation

Abstract Background Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in the United States (US) and is associated with increased risk of stroke.1 Oral anticoagulants (OACs) are the primary treatment to reduce stroke risk in patients with AF.2,3 However, there is recent evidence of underuse of OAC in AF patients.4 Purpose To identify factors associated with delayed OAC treatment initiation among AF patients in the US clinical practice. Methods Medicare beneficiaries aged ≥65 years with a new diagnosis of AF without moderate-to-severe mitral stenosis or a mechanical heart valve after 1 Oct 2015 were included. Additional inclusion criteria included ≥1 claim for an OAC on or after 1st diagnosis of AF, ≥12 months of continuous Medicare Parts A, and D enrollment, and CHA2DS2-VASc score of ≥2 for males/≥3 for females. Time from 1st AF diagnosis to OAC initiation (index OAC), and demographic, sociodemographic, clinical and index OAC formulary characteristics were described. Delayed initiation was defined as OAC initiation >3 months after and early initiation as OAC initiation 0-3 months after 1st AF diagnosis. Factors associated with delayed OAC initiation were assessed using multivariable logistic regressions. Results A total of 446,441 patients met the inclusion criteria. Time from 1st AF diagnosis to OAC initiation was <1 month for 52.4% of patients, 1–≤3 months for 18.1%, >3–≤6 months for 7.1%, >6–≤12 months for 6.8%, and >12 months for 15.7%. Accordingly, 30% had delayed vs. 70% had early OAC initiation. Median age was 78 years (both), 48% and 47% were male, 87% and 89% were White, and median CHA2DS2-VASc score was 4 (both), respectively, for the delayed and early OAC initiation cohorts (Table 1). Factors associated with delayed OAC initiation included Black race (odds ratio [OR]: 1.29, 95% confidence interval [CI]: 1.25–1.33), South and West US census regions (OR: 1.22, 95%CI: 1.19–1.24 and OR: 1.29, 95%CI: 1.26–1.32, respectively), dementia (OR: 1.27, 95%CI: 1.23–1.30), congestive heart failure (OR: 1.20, 95%CI: 1.26–1.32), bleeding hospitalization ≤3 months before 1st AF diagnosis (OR: 1.22, 95%CI: 1.18–1.27), prior authorization (OR: 1.69, 95%CI: 1.66–1.71), and tier 4 formulary for index OAC at AF diagnosis (OR: 1.26, 95%CI: 1.22–1.30). Additionally, having low-income subsidy or dual eligibility (for Medicare and Medicaid) was associated with increased odds of delayed OAC initiation (OR: 1.06, 95%CI: 1.02–1.10 and OR: 1.09, 95%CI: 1.05–1.14, respectively; Figure 1). Conclusions In this study on Medicare patients with AF, Black race, low-income subsidy, and dual eligibility were found to be associated with delayed OAC initiation, suggesting potential disparities in the care of AF with timely OAC treatment. Moreover, OAC requiring prior authorization (the strongest predictor) or being on formulary tier 4 were associated with delayed initiation, indicating formulary restrictions may create barriers to timely OAC access for AF patients.Table 1.Patient characteristicsFigure 1.Factors of delayed initiation

A systematic review and meta-analysis reveals a consensus transcriptional signature highlighting neutrophil degranulation as a preserved and critical biological process in atrial fibrillation

Abstract Background Atrial fibrillation (AF) is the most frequent persistent arrhythmia, and is associated with a high burden of disease, especially when co-occurring with other cardiovascular pathologies. Despite significant advances in the understanding of its pathophysiology through transcriptomic studies, there are marked differences in the identified key AF genes between studies, potentially due to specific sociodemographic and clinical characteristics of the populations evaluated. Therefore, the transcriptional signature that is common to AF, regardless of the specific context, is currently unclear. Purpose To provide a consensus transcriptional signature of AF by comprehensively analyzing the studies comparing the gene expression patterns in patients with AF and controls in Sinus Rhythm (SR). Methods Four literature databases were searched to identify studies reporting gene expression patterns in atrial myocardial tissue from patients diagnosed with AF and comparing them with those of controls reportedly in SR. We excluded studies reporting results from in vitro experiments or those that provided incomplete information regarding the methodology for sample collection of bioinformatic analysis. After an initial descriptive analysis of the included studies, we manually curated and processed all the available datasets. At first, gene coverage was evaluated to assess the comparability of the included data, followed by meta-analysing the suitable datasets to obtain the consensus gene signature. Finally, we estimated the activities of relevant transcription factors and pathways by using biological prior knowledge bioinformatic tools (DoRothEA, and PROGENy, respectively). Results 38 studies were included, from which seven related datasets consisting of 262 AF and 86 SR control samples fulfilled the selection criteria for meta-analysis (Figure). We observed a high heterogeneity in the marker genes reported across the studies, however, disease signatures were conserved across the included studies. Gene ranking revealed a significant enrichment of fibrosis and myocyte degeneration-related gene sets; however, enriched pathways, transcription factors, and microRNAs related to neutrophil activity gene signatures, specifically those related to the degranulation process, occupied an outstanding position in the top positions of the ranking (Table). Conclusion Despite high heterogeneity amongst studies, a conserved and identifiable molecular signature in AF is present. The high relevance of neutrophil activity in this signature is consistent with previous studies performed in AF and other cardiovascular diseases, such as ischemic heart failure. The identification of a consensus transcriptional footprint is a feasible approach that provides valuable information to better understand the common molecular mechanisms underlying the different disease patterns in AF.Figure.Table.

Left atrial glucose metabolism by 18F-FDG PET/CT in persistent atrial fibrillation and after return to sinus rhythm

Abstract Background Atrial Fibrillation (AF) is strongly associated with the development of Left Atrial (LA) remodeling. Animal studies pointed to an important role of metabolic deregulation in AF, yet few studies have assessed LA myocardial metabolism in vivo in patients with AF. 18-fluorodeoxyglucose (FDG) Positron Emission tomography (PET) has been widely used for evaluation of left ventricular (LV) metabolism, but its application to study metabolism of LA has not yet been explored. Purpose The aim of this study was to evaluate LA glucose metabolism and contractile efficiency in patients with persistent AF, following our successful implementation of a protocol enabling the acquisition of high-resolution PET images of the LA. Methods 36 nondiabetic patients (64±7 years, 29 men) with persistent non valvular AF (peAF) undergoing a first AF ablation and 5 healthy age matched volunteers (69±5 years, 3 men, p=0.114) without AF underwent FDG PET, speckle tracking echocardiography (STE) and cardiac MRI (cMR). PET was performed after overnight fasting and after administration of a nicotinic acid derivative (Acipimox 250 mg) to maximally stimulate myocardial glucose uptake. The 3 tests were repeated 3 months later in 26 patients in whom return to permanent sinus rhythm (SR) could be obtained after the ablation procedure. PET images were registered with cMR LA angiography, and the mean partial volume and spillover corrected standardized FDG uptake (SUV) in the whole LA, the left atrial appendage (LAA), and the left ventricle (LV) were computed. Measurements were compared to global Peak Atrial Longitudinal Strain (GPALS) and to left atrial ejection fraction (LAEF) measured by STE and LA contractile efficiency was computed as the ratio of LA SUV to LAEF. Results Hemodynamics (syst. BP mmHg: 128±11 vs 129±5 mmHg, p=0.663) and metabolic parameters (glycemia: 99±14 vs 96±7 mg/dl, p=0.480) were similar in peAF patients and healthy controls. While 18F-FDG SUV in the LV was comparable between pEAF patients and healthy controls, patients in peAF exhibited significantly increased SUV in LA and LAA compared to controls. Following a return to SR, LA-SUVmean and LAA-SUVmean in patients peAF decreased significantly after 3 months (20.3%, p<0.002 and 34.1%, p<0.001), whereas the LV-SUVmean remained unchanged (p=0.847). The Global Peak Atrial Longitudinal Strain (GPALS) increased by 54.2%(p<0.001), and the Left Atrial Ejection Fraction (LAEF) by 39.2% (p<0.001), post-restoration of SR. (Figure 1). Accordingly contractile efficiency of LA SUV/LAEF in peAF patients improved significantly upon their return to SR (47%, p<0.001). Conclusion LA glucose metabolism is significantly increased in peAF and return after restoration of SR. This could indicate oxygen wasting and reduced contractile efficiency of AF or metabolic shift towards preferred glucose metabolism in AF. These findings support the notion that LA glucose metabolism plays a role in the pathophysiology of AF.Figure 1Figure 2

Prevalence and incidence of diastolic dysfunction in new-onset atrial fibrillation: implications for clinical and preclinical HFpEF

Abstract Background Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are closely associated diseases that frequently coexist. However, due to the overlapping symptoms, the diagnosis of HFpEF can be overlooked with symptoms being attributed to AF. Purpose We aimed to investigate the prevalence of diastolic dysfunction (DD) in patients with new-onset AF compared to sinus rhythm (SR), study changes in diastolic function parameters over time in the two groups and compare the incidence of DD at follow-up. Methods Adults with new diagnosis of AF and adults in SR were identified. Patients with previous cardiac surgeries, congenital heart disease, hypertrophic or infiltrative cardiomyopathy, primary mitral disease, left-sided valve disease, low ejection fraction, enlarged left ventricle, or with no 6-month follow-up echocardiogram were excluded. Diastolic function was assessed through 4 components: mitral medial e’ <0.07 m/sec, mitral medial E/e’ >15 in SR and >11 in AF, TR velocity >2.80 m/sec, and left atrial volume index >34 ml/m2, with severe DD (SDD) defined by ≥3/4 findings and moderate DD (MDD) by ≥2/4 abnormal diastolic function parameters. Annualized changes were calculated as the difference between follow-up and baseline values divided by years in between. In a secondary analysis, patients with new-onset AF were propensity score-matched to patients with SR in a 3:1 ratio based on age, sex, body mass index, and comorbidities. Results Overall, 1,747 patients with incident AF (median age 67 years; 34% females) and 29,623 in SR (median age 59 years; 51% females) were included. New-onset AF was independently associated with the presence of SDD vs SR (8% vs 2%) and MDD (25% vs 11%, p<.001 for both in adjusted analysis). Over median follow-up of 3.2 (IQR 1.6-5.8) years, annualized severity progression in each of the 4 diastolic function parameters was greater in the AF group (p<.001 for all), Table. The incidence rates of SDD and MDD were 3.7 and 8.8 per 100-person year, respectively, in AF versus 1.1 and 3.6 per 100-person years, respectively, in SR (p<.001 for both at univariate and multivariable analysis), Figure. Results were similar in the propensity-score matched analysis. Conclusions Patients with new-onset AF more commonly have moderate or severe diastolic dysfunction that indicates the presence of potentially overlooked clinical HFpEF (when symptoms exist) or preclinical HFpEF (when symptoms are absent) compared to patients in SR. In long-term follow-up, patients with AF display accelerated progression in DD; suggesting that therapies to prevent progression to symptomatic HFpEF may be highest value in this patient population.