Persistent AbstractBackgroundAtrial Fibrillation Research Articles

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

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

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.

Predictors of left ventricular reverse remodeling after catheter ablation for atrial fibrillation: sub analysis of a randomized controlled EARNEST-PVI trial

Abstract 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.

Left atrial stiffness and sex differences in atrial fibrillation recurrence after catheter ablation

Abstract Background Atrial fibrillation (AF) occurs more frequently in men, but women suffer more AF recurrence; mechanisms are not completely understood. Purpose To explore whether sex related differences in LA stiffness (LAstiffn) in patients with AF ablation could potentially explain differences in AF recurrence. Methods We screened patients with catheter ablation for AF, in sinus rhythm at 3 months post-ablation, with no significant mitral valve disease (< moderate), and with prospectively measured LA volumes [maximum (LAVI) and minimum volume index] by echocardiography. LAStiffn index was estimated as (E/e’)/LA emptying fraction. Outcome endpoint was AF recurrence up to 14 years post ablation. Results A total of 591 patients with AF ablation were studied (mean age 60±10 years; 25% women; Table1). At 3 months post-ablation, LAVI was 36±10 mL/m2 and LAstiffn was 0.31±0.21 1/%. Compared to males, female patients were slightly older, had more frequently hypertension, congestive heart failure, prior stroke/TIA, higher CHA2DS2-VASc score; they less often had persistent AF, coronary artery disease, or dilated cardiomyopathy. Women also had higher LAstiffn (0.37±0.24 vs. 0.29±0.19, P <.0001, Figure 1), despite similar indexed LA volumes (Table1). Rates of AF recurrence at follow-up (median 7.5 years; 347 patients with events) were higher in women vs. men (Figure 2, left; log-rank P<.001) and persisted after adjustment for age, type and duration of AF, body mass index, cardiovascular risk factors and comorbidities, CHA2DS2-VASc score ≥2, LV ejection fraction, and LAVI (adjusted HR 1.58 [1.20-2.08], P=.001). Overall, LA volumes and LAstiffn were higher in patients with older age and more comorbidities (hypertension, congestive heart failure, coronary artery disease, persistent AF, CHA2DS2-VASc score ≥2, etc; P<.01 for all). At multivariable regression analysis, LAVI and LAstiffn correlated with E/e’, LV size and mass, degree of mitral/tricuspid regurgitation, and LV stroke volume index (only LAVI). In addition, LAstiffn was higher in patients with elevated right ventricular systolic pressure (RVSP) >35 mmHg and increase in RVSP more than 10 mmHg from pre-ablation (P<.0001) (correlation R=0.44, P<.0001). At follow-up, after adjusting for age and LAVI, higher LAstiffn remained associated with AF recurrence in women (P=.02, HR 2.82 per unit change, 95% CI, 1.08-6.72; Figure 2, right), but not in men (P=.30). Conclusions LAStiffn is higher in women vs. men and correlates with burden of comorbidities, aging, diastolic dysfunction and pulmonary hypertension, possibly reflecting more extensive LA myopathy, and potentially contributing to sex differences in AF recurrence.Figure 1Table 1

Metabolomics and frailty: a "from bench to bedside" approach to atrial fibrillation in older patients

Abstract Background Atrial fibrillation (AF) is the most common sustained arrhythmia diagnosed at an advanced age. The most important complications of AF are stroke, heart failure and dementia. The pathophysiology of the arrhythmia is complex and multifaceted and several aspects are still not completely understood. Purpose Our project aimed at exploring the molecular characteristics of AF in older patients using an untargeted metabolomics approach, an analytical technique that provides an insight of the global metabolic profile at an individual level. As secondary endpoints, we evaluated the association between metabolomics and acylcarnitines, which are mediators of myocyte electrical instability, and difference in metabolomics profile between healthy controls (C) and AF patients (AF-P). Method We evaluated 50 consecutive older AF-P with persistent AF, waiting to be treated with elective electrical cardioversion of the arrhythmia, and 22 healthy controls (C). In all patients, the cardiological evaluation was integrated with tools of the Geriatric Multidimensional Assessment (GMA) to describe neurocognitive function (Mini-Mental State Examination, MMSE), depressive symptoms (15-item Geriatric Depression Scale, GDS), and physical performance (Short Physical Performance Battery, SPPB). Interleukin-6 (IL-6), a marker of low-grade inflammation, was measured with ELISA assays. Metabolomics analysis and acylcarnitine measurements were carried out using gas chromatography coupled with mass spectrometry (GC-MS). Results AF-P and C did not differ by age (76 ± 6 vs. 70 ± 14 years, p = 0.055); patients had a lower proportion of women (AF-P: 32% vs. C: 64%, p = 0.012). Cluster analysis applied to metabolomic data in all population identified two subset of subjects, characterized by a different body mass index (BMI; 23.57 vs. 32.53 Kg/m², p = 0.046). When studying only the AF-P group, the simultaneous presence of a higher CHA2DS2-VASc score (4.17 ± 1.32 vs. 2.88 ± 1.83, p = 0.007), a lower physical function (SPPB; 8.97± 2.22 vs. 10.75 ± 1.13, p = 0.009), and higher IL-6 levels (4.42 vs. 2.39 pg/mL, p = 0.002) described the cluster with a worse clinical phenotype and a specific metabolomics pattern. Furthermore, an association between IL-6 and medium- long-chain acylcarnitines emerged (acylcarnitine 12:1, β = 31.7 ± 9.4, R = 0.446, p = 0.001). Conclusions Present analysis demonstrated that a specific metabolomics profile was characteristic of older AF patients with a frail phenotype, identified by higher CHA2DS2-VASc score and IL-6 concentration, and lower physical performance. Future studies are needed to reveal the single molecular pathways responsible of these behaviour, potentially useful to guide a targeted therapy. Last, inflammation per se could contribute to electrical instability in AF, while body mass index, a surrogate measure of undernutrition, could identify different metabolic pathways in controls and in patients with the arrhythmia.Metabolomics by clinical phenotypes

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

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.

Early pulmonary vein isolation in patients with heart failure

Abstract Background Atrial fibrillation (AF) and heart failure (HF) are often present simultaneously, leading to worse outcomes compared to the respective morbidity alone. Pulmonary vein isolation (PVI) is the most effective treatment modality and should be considered as first-line therapy, however, the optimal timing of the procedure is still unknown. Purpose We aimed to investigate the effect of early PVI on all-cause mortality and AF recurrence in patients with HF. Methods The data of 334 patients with symptomatic paroxysmal (n=118, 35.5%) or persistent (n=212, 63.5%) AF and HF with LVEF < 50% were analyzed, who underwent PVI using radiofrequency energy between 2010 and 2022. All available medical data of the patients were collected in a structured registry. Early PVI was defined as catheter ablation performed within 12 months of AF diagnosis. The median follow-up was 1524.5 [365.0-3939.0] days with a minimum of 365 days. Our primary endpoints were all-cause mortality and AF recurrence following 3-months blanking period. Results During the follow-up of the 334 patients, 164 (49.1%) experienced AF recurrence and 86 (25.8%) patients died. The median age was 64 [56.1-69.9] years. The median LVEF was 40% for early PVI and 38% for deferred PVI (p=0.057). Out of the 139 (41.6%) patients who underwent early PVI, 36 (25.9%) had AF recurrence and 83 (59.7%) were taking amiodarone. Patients who underwent early PVI had longer freedom from recurrence (median 1042.5 [474.8-1921.0] days for early PVI, median 424 [134.5-1153.0] days for deferred PVI). Early PVI predicted lower rate of AF recurrence (HR: 0.29, p<0.0001). Early ablation was not associated with mortality benefit. Among those who experienced AF recurrence, a repeat ablation was associated with better survival (HR: 0.29, p<0.0001). Conclusions Our study shows that early rhythm control therapy with catheter ablation may be more beneficial compared to deferred PVI in patients with AF and HF. A repeat ablation may be considered in case of arrhythmia recurrence in patients with AF and HF to reduce mortality.

Atrial fibrillation organisation correlates with ventricular response regularity in patients with persistent atrial fibrillation

Abstract Background Atrial fibrillation (AF) is characterised by an irregularly irregular ventricular rhythm. However, the mechanisms by which the regularity of ventricular response is influenced by AF dynamics is yet to be understood. In AF, there is a spectrum of organisation of atrial electrical activity; from organised AF sustained by focal drivers through to disorganised AF sustained by multiple wavelet re-entry. We aimed to investigate whether the ventricular response in AF was associated with the organisation of atrial electrical activity, with the hypothesis that AF organisation correlates with ventricular response regularity. Methods We retrospectively reviewed data from 239 patients with persistent AF undergoing pulmonary vein isolation (PVI). In each patient both before and after ablation, AF organisation and measures of ventricular variability and irregularity were evaluated in 50s segments. Shannon entropy (ShEn) and Sample entropy (SampEn) derived from coronary sinus (CS) atrial electrograms were used to assess AF organisation. RR interval (RRI) metrics derived from the surface ECG were used to determine ventricular variability and irregularity. RRI variability was evaluated using the time-domain measures: normalised mean RRI difference, standard deviation of RRIs (SD RRI), normalised SD RRI, root mean square of successive RRI differences (rMSSD) and percentage of successive RR intervals that differ from each other by more than 50ms (pNN50). RRI irregularity was measured using SampEn and normalised SampEn. Results A significant decrease in atrial ShEn and SampEn was observed following PVI across all CS channels (e.g. SampEn CS 3-4: pre-ablation=0.907±0.512 vs post-ablation=0.790±0.447, p<0.0001). Both ShEn and SampEn from CS atrial electrograms were significantly correlated with the RRI variability and irregularity measures from surface ECG (pNN50, normalised mean RRI difference, normalised SD RRI and normalised SampEn) both pre- and post-ablation (pNN50: r=0.0771, p=0.00838, Figure 1; normalised mean RRI difference: r=0.144, p<0.0001; normalised SD RRI: r=0.175, p<0.0001; normalised SampEn: r=0.168, p<0.0001; correlations with SampEn CS 3-4 pre-ablation shown). Conclusion The reduction in atrial ShEn and SampEn following PVI suggests that an increase in AF organisation occurs with PVI. The significant correlations between atrial entropy and measures of RRI variability and irregularity suggest that AF organisation impacts ventricular response regularity. Therefore, interpretation of the RRI variability and irregularity from the surface ECG may give some insight, non-invasively, into the level of AF organisation.Figure 1

975 SIMPLY-DETECTED INFLAMMATORY BLOOD MARKERS PREDICT INDEXED LEFT ATRIAL VOLUME AMONG PATIENTS UNDERGOING ATRIAL FIBRILLATION CATHETER ABLATION

Abstract Background atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. Predisposing factors for priming and maintenance of AF include increased left atrial (LA) size, which correlates with LA disease and is a major risk factor for recurrence after AF catheter ablation (CA). The role of inflammation in the pathogenesis of AF and the associated atrial cardiomyopathy has been ill-defined Objective we hypothesized that simply-detected inflammatory blood markers could correlate with left atrial volume, and thus with the severity of AF-associated atrial cardiomyopathy. Methods we conducted a retrospective, observational study enrolling 472 consecutive patients (male gender, n= 357, 76%; mean age, 61±11 years) who underwent paroxysmal (n=318) or persistent (n=154) AF CA at our institution. In each patient, widely available laboratory markers of inflammation (C-reactive protein (PCR), uric acid, and red blood cells distribution width [RDW]) were measured prior to CA and correlated to LA volume, using univariable and stepwise multivariable linear regression. Results the mean left ventricular ejection fraction (EF) was 57,4±7,6%, whereas the mean indexed LA volume was 35,3±11,9 ml/m2. The mean RDW measured 13,5±1,3, the mean PCR value was 0,5±1 mg/L, and the mean uric acid value was 5,2±1,4 mg/dl. In univariable linear regression analysis, RDW (β 2.65; 95% CI [1.81-3.49]; p=0.0002), PCR (β 1.2; 95% CI [0.02-2.38]; p=0.047), CHA2DS2VASc (β 2,17; 95% CI [1.42-2.94]; p 0.001), uric acid (β 0.85; 95% CI [0.01-1.69]; p=0.05), EF (β -0.37; 95% CI [-0.51-0.23]; p=0.002) and age (β 0.35; 95% CI [0.25-0.45]; p=0.00004) were significantly related to LA volume. In multivariable linear regression model, EF (β -0.24; 95% CI [-0.39- -0.09]; p 0.002), age (β 02; 95% CI [0.08-0.32]; p 0.0017) and RDW (β 1.5; 95% CI [0.62-2.38]; p 0.00093) retained their independent association with LA volume. Conclusion RDW, a simple-detected blood marker, proved to be an independent predictor of LA size, suggesting a mechanistic link between inflammation and the severity of atrial cardiomyopathy. These observations may allow a very simple and low-cost identification of AF patients at higher risk of adverse outcomes and recurrences after CA, facilitating treatment plan decisions (e.g., rate vs. rhythm control).

Baseline profile and results of atrial fibrillation ablation in patients with arrhythmia-induced cardiomyopathy

Abstract Background Atrial fibrillation (AF) is known to trigger a reversible dilated cardiomyopathy referred as arrhythmia-induced CM (AiCM). However, it remains unclear why some patients are more prone to develop AiCM than others and there is scarce information about their clinical outcomes after AF ablation. Purpose We ought to find clinical and analytical predictors for the development of AiCM and recovery of LVEF in patients referred for AF ablation. Methods A prospective multicenter study of consecutive patients undergoing point-by-point radiofrequency (RF) catheter ablation between September 2016 and November 2021 was conducted. The low voltage areas and left atrial (LA) volume were analyzed offline on high density electroanatomical maps collected prior to RF ablation. Peripheral blood sample for biomarker analysis (Gal-3, FABP4 and sRAGE) were obtained at the time of the procedure. Results 803 consecutive patients were included, median age was 61 and 240 (30,81%) were women. AF pattern was paroxysmal in 254 (32,60%) and persistent in 534 (68,55%; of whom, long-standing persistent in 113 (14,51%) patients). The median follow-up period was 23.83 months [IQR 9 to 36]. The multivariate analysis revealed LA area, width of QRS segment, persistent AF and chronic kidney disease (CKD) as independent predictors for AiCM. Recurrence-free survival was not different amog both cohorts (Figure 1). The median increase in LVEF from baseline to the 6-month follow-up visit in patients with AiCM was 16% (CI 14.31–18.47) without changes in the non-AiCM group. The median LVEF previously to CA from patients in the AiCM group was 38% (IQR 30–45%) and after the procedure 57% (IQR 50–60%) [see figure 2]. Conclusions AiCM is characterized to have a particularly complex pathophysiology not fully understood thus far. Pulmonary vein isolation in patients is safe and suitable for patients that suffered from tachycardiomyopathy. We found that persistent AF and chronic kidney disease play a key role in its development. Neither peripheral blood biomarkers nor left atrial samples showed relevant association with its occurrence. Funding Acknowledgement Type of funding sources: None.

Left atrial vorticity is independently associated with embolic brain infarcts and represents a promising imaging biomarker of cardioembolism in sinus rhythm and atrial fibrillation

Abstract Background Atrial fibrillation (AF) is associated with embolic stroke, but risk scores such as CHA2DS2-VASc perform only modestly (C statistics 0.6–0.7). Meanwhile, up to 25% of embolic strokes in patients without AF have no identifiable cause, and occult left atrial (LA) thromboembolism may be a relevant mechanism in such cases. Purpose We hypothesised that imaging of left atrial blood flow could improve embolic risk prediction in patients with and without AF. We used 4D flow magnetic resonance imaging (MRI) to identify a biomarker that is: (a) independently associated with embolic brain infarction by brain MRI, (b) able to stratify blood flow characteristics both during AF and in sinus rhythm (SR), and (c) reproducible. Methods We recruited 3 patient cohorts to respectively address each aim. Firstly, to assess the association between LA flow parameters and embolic brain infarcts, we recruited cohort A, consisting of 134 patients (41% female; age 70±9 years) with a history of ischaemic stroke (N=44) or no history of stroke but with CHA2DS2VASc score ≥1 (N=90). Next, the sensitivity of 4D flow parameters to rhythm change was assessed in cohort B: 37 patients with persistent AF studied before and after cardioversion, whose results were compared with those of 23 healthy controls in SR [CHA2DS2-VASc = 0.0 (0.0–0.0)]. Finally, scan-rescan coefficients of variation (CV) and interval-scan CV at 30 days were determined in Cohort C (86 subjects; 64 in SR, 22 in AF). Brain MRI was used to identify large non-cortical or cortical brain infarcts (LNCCI) – i.e. infarcts likely to be embolic in origin. Results At least one LNCCI was present in 39 of 134 patients in cohort A. Lower LA vorticity was significantly associated with higher risk of prevalent LNCCIs (Figure 1), after adjustment for AF, age, and CHA2DS2VASc score [OR=2.10 (95% CI 1.12–3.92) per SD, P=0.02]. This association remained significant after further adjustment for other cardiac parameters (all P<0.05, Figure 1). By contrast, there was no significant association between peak velocity and LNCCIs (P=0.21). LA vorticity was sensitive to rhythm change, improving significantly in patients in cohort B in SR at ≥4 weeks after cardioversion (CV) of persistent AF (Figure 2A, paired P<0.001 vs pre-CV), but remained impaired compared to healthy controls (Figure 2B, P<0.01). Finally, reproducibility studies in cohort C showed that LA vorticity had a same-day scan-rescan CV of 7% without significant differences between SR and AF subjects (P>0.05), and also showed no significant temporal variability on interval scanning (P>0.05). Conclusions LA vorticity is reproducible, sensitive to changes in heart rhythm, and independently associated with embolic brain infarcts, suggesting a promising imaging biomarker of cardioembolism in SR and AF. LA blood flow imaging could improve stroke prediction and the personalisation of decisions about anticoagulation, regardless of heart rhythm. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Oxford BRC, BHF

The impact of right atrium and left atrium reverse remodeling for functional regurgitation of atrioventricular valve among patients who were underwent ablation for atrial fibrillation

Abstract Background Atrial fibrillation (AF) is a risk factor of Regurgitation of Atrioventricular Valve and Regurgitation of Atrioventricular Valve is improved after ablation for AF. However, Mechanism of improvement of Tricuspid regurgitation (TR) and Mitral regurgitation (MR) after ablation for AF were unclear. Methods The one hundred fifty-seven cases consecutive patients who were underwent ablation for persistent AF were examined in this study. These patients were performed Holter ECG and Echocardiography 6 months after ablation for persistent AF. The area of the Right Atrium (RA), Left Atrium (LA), diameter of the tricuspid valve anulus and Mitral valve annulus, were measured by echocardiography at before and 6 months after ablation for AF. The reverse remodeling index (RRI) was defined as divided post area of RA and LA by pre area of RA and LA. The Improved group was defined as one or more than regurgitation grade improvements. Results TR improved in 56 cases (35.7%) of 157 cases and MR improved in 25 (16.6%) cases of 157 cases. The ratio of improved TR was significantly higher than ratio of improved MR (p<0.01). The difference in tricuspid annulus diameter before and after ablation for AF was significantly longer in TR improved group than in TR non-improved group. (4.9±5.3 mm vs 1.6±5.4 mm, p<0.01). The RRI of RA in TR improved group was significantly smaller than in TR non-improved group (0.73±0.19 vs 0.89±0.26 p<0.01). The difference in mitral annulus diameter before and after ablation for AF was not significant differences between MR improved group and MR non-improved group. The RRI of LA in MR improved group was significantly smaller than in MR non-improved group (0.79±0.22 vs 0.90±0.25 p<0.01). The RRI of RA was significantly smaller than RRI of LA among patients who were able to maintain sinus rhythm after ablation for persistent AF (0.79±0.23 vs 0.85±0.24 p=0.04). Conclusion Reverse remodeling of RA was higher than Reverse remodeling of LA among patients who were able to maintain sinus rhythm after ablation for persistent AF and Reverse remodeling of RA and LA were important factors of improvement of TR and MR after ablation for persistent AF. These results considered to be the cause why the improvement rate of TR was higher than the Improvement rate of MR after persistent AF. Funding Acknowledgement Type of funding sources: None.

Prevalence of modifiable risk factors and related poor cardiovascular outcomes following atrial fibrillation ablation

Abstract Background Atrial fibrillation (AF) has become a global epidemic. Early catheter ablation and therapies modifying risk factors (RF) have been shown to improve outcomes of AF ablation. However, the time invested in pursuing risk factor modification may delay ablation, which could negate the procedural benefit. Purpose This study sought to investigate the prevalence and impact of potentially modifiable RF among AF patients undergoing catheter ablation in clinical practice. Methods This retrospective study included 724 consecutive patients undergoing AF ablation at a tertiary care center from 2012–2019. Pre-specified modifiable risks were examined, including the time from AF diagnosis to ablation, fluctuation/increase in BMI >5% prior to ablation, mean systolic/diastolic blood pressure >125/80 mmHg, obstructive sleep apnea with CPAP noncompliance, hyperlipidemia without statin therapy, tobacco use, excessive alcohol use, and diabetes mellitus with hemoglobin A1c (HbA1c) >6.5%. The primary outcome was a composite of recurrent atrial arrhythmias, cardiovascular (CV) hospitalizations and mortality following AF ablation. A multivariate analysis was performed. Results The mean age was 61±10 years old, 32.5% were female and 72.2% had persistent AF. Many study patients had modifiable RF, ranging from 4.7% with excessive alcohol use to 64.0% experiencing delayed AF ablation. The mean time from AF diagnosis to ablation was 4.7 years. During a mean follow-up of 1.6 years after ablation, 467 (64.5%) patients met the primary outcome. Independent RF for the primary outcome were an increase/fluctuation in BMI >5% (adjusted hazard ratio [AHR] 1.31, 95% confidence interval [CI] 1.07–1.60; P=0.008), diabetes with HbA1c >6.5% (AHR 1.50, 95% CI 1.09–2.03; P=0.014) and hyperlipidemia without statin therapy (AHR 1.30, 95% CI 1.08–1.57; P=0.005). Delayed AF ablation over 1.5 years did not alter the outcome, Figure 1. Conclusion Substantial portions of patients undergoing AF ablation have potentially modifiable RF. Increased or fluctuating BMI, diabetes with HbA1c >6.5%, and hyperlipidemia not treated with statin therapy portend an increased risk of recurrent atrial arrhythmia, CV hospitalizations and mortality. These findings underscore an importance pursuing RF management in patients with AF to reduce adverse outcomes after ablation. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The Jensen Family Research Sponsorship at the University of Nebraska Medical Center

C1 THE ROLE OF ATRIAL ELECTRO–MECHANICAL COUPLING AS PREDICTOR OF CATHETER ABLATION EFFICIENCY

Abstract Background Atrial fibrillation (AF) results in electrical and structural remodeling of the atria, and the extent of remodeling has already been found to be associated with higher AF recurrence rate after catheter ablation (CA). Recently, a novel echocardiographic parameter derived from tissue Doppler imaging (TDI), called PA–TDI, has been introduced to assess the total atrial activation time, as a non–invasive surrogate of fibrosis and atrial cardiomyopathy. The aim of the study was to investigate the role of PA–TDI interval as predictor of AF ablation efficacy. Methods Consecutive patients with persistent or paroxysmal symptomatic AF referred to our Center to perform radiofrequency ablation or cryoablation procedures were prospectively enrolled. In these patients, a complete transthoracic echocardiographic examination was performed before and after the ablation procedure, including assessment of the PA–TDI interval. Results From October 2018 to May 2020, 221 consecutive patients (mean age 61 ± 9 years, 74% male, mean BMI 26.5 ± 3.6, mean Ejection Fraction 61 ± 6%) symptomatic for AF, undergoing the procedure ablation (first procedure or re–do) were enrolled. Out of the blanking period, 25% of patients experienced recurrence of arrhythmia during follow–up (mean 16 months). Compared to patients who did not relapse, patients with AF recurrence have a generally longer post–procedural PA–TDI interval (139.6 ± 22.1 msec vs 153.9 ± 33 msec, respectively). In the multivariable analysis only post–procedure PA–TDI and re–do interventions were found to be independent predictors of AF recurrence. A PA–TDI cut–off> 144msec identifies patients at risk of post ablation AF recurrence with sensitivity 58.7% and specificity 73.5% (AUC 0.697). Conclusions The PA–TDI interval is an independent predictor of AF recurrence after catheter ablation. This echocardiographic parameter is easily obtainable, low–cost, reproducible, and accessible even in peripheral centers.

Impact of low-dose or under-dose direct oral anticoagulant on coagulation and fibrinolytic markers in patients with atrial fibrillation

Abstract Background Atrial fibrillation (AF) is known to increase the risks of cerebral and systemic embolism. Apart from vitamin K antagonists, edoxaban, a direct oral anticoagulant (DOAC), has been approved for oral anticoagulation in patients with non-valvular AF. On the other hand, DOACs are sometimes prescribed at off-label under-doses for patients who have undergone ablation for AF. Prothrombin fragment F1+2 is an activation peptide released from prothrombin during thrombin formation. The purpose of this study is to compare the effects of DOAC doses on coagulation and fibrinolytic markers. Methods and results A total of 88 patients with AF (age: 68±11 years, male:45%, paroxysmal AF n=49, persistent AF n=39) were recruited. All patients were received edoxaban (60mg or 30mg) once a day. For the purpose of the study, patients were divided into three groups according to whether they had been treated before the ablation procedure under an appropriate standard dose group (n=30 [34.1%]), appropriate low-dose group (n=35 [39.8%]), or off-label under-dose group (n=23 [26.1%]). We examined the coagulation and fibrinolytic markers, and echocardiographic parameters before ablation. All patients were followed up for 12 months after AF ablation. Creatinine clearance was significantly higher in appropriate standard-dose group than in appropriate low-dose or off-label under-dose group (101.1±38.4, 57.1±15.9 and 73.2±14.6 mL/min, respectively; P<0.001). There were no significant baseline differences in AF type, history of stroke/transient ischemic attack (TIA), plasma B-type natriuretic peptide, protein C, fibrinogen, D-dimer level, left ventricular ejection fraction or left atrium dimension among the three groups. Prothrombin fragment F1+2 level was significantly lower in the appropriate standard-dose group than the appropriate low-dose and off-label under-dose groups (105.9±29.4, 142.6±41.3 and 142.8±84.9 pmol/L, respectively; P=0.011, Figure). One patient in the appropriate low-dose group had a TIA and 1 patient in the off-label under-dose group had a bleeding event during the follow up period after ablation. Conclusion Our results suggest that an appropriate standard dose of edoxaban is needed to suppress hypercoagulability in patients with AF. Funding Acknowledgement Type of funding sources: None. Prothrombin fragment F1+2 level

Same day discharge after atrial fibrillation ablation is feasible and safe. Results of a prospective study in 1015 patients

Abstract Background Atrial fibrillation (AF) ablation is the standard treatment for symptomatic paroxysmal and persistent AF. It is a common practice for patients to stay overnight after the ablation for observation of possible complications. Thus, increasing volume of procedures places a significant strain on institutions. To tackle this issue, our institution developed a same-day discharge (SDD) protocol for AF ablation. Purpose To assess the feasibility and safety of the SDD protocol after at least four-hour observation in patients undergoing radiofrequency ablation (RFA) for AF. Methods A SDD protocol was implemented in our institution in March 2019. We conducted a prospective observational study that included all consecutive patients who underwent ablation for AF until January 2021. A detailed workflow setup provided in the figure. To compare means the Mann Whitney U test, and for categorical variables – χ2 test were used. The difference was significant when p<0.05. Results A total of n=1015 patients underwent RFA in the study period. Of those, same-day discharge was feasible in n=751 (74.1%) and n=264 stayed overnight. The mean age (SDD 62.5 SD 8.8 years vs overnight-stay 64.1 SD 9.2 years, p=0.105) and gender distribution (males SDD 46.8% vs overnight-stay 39.8%, p=0.265) did not differ between the two groups. In the SDD group no patients were readmitted for complications within 24 hours after the ablation. A severe complication was defined as pericardial effusion with drainage, pulmonary oedema, thromboembolic event and vascular complication needing surgical intervention. In total 3.0% of all patients experienced a severe complication. The main reasons for staying overnight were small groin hematoma without intervention (18.9%), nausea (14.4%) and logistic issues (32.2%). The 30-day hospital readmission rate was insignificantly higher in the overnight-stay group (19.4% vs 28.0%, p=0.113). The most common reasons for readmission were arrhythmias (SDD 10.1% vs overnight-stay 20.5%) and chest pain (SDD 7.6% vs overnight-stay 2.4%). One late pericardial effusion with drainage on day 10 after the ablation was noted in the SDD group. Conclusion Same-day discharge in patients after RFA for AF is feasible and safe with an observational period of at least four hours and immediate transthoracic echocardiography after the procedure. Funding Acknowledgement Type of funding sources: None.

Declined ELABELA plasma levels in hypertension patients with atrial fibrillation: a case control study

BackgroundAtrial fibrillation (AF) is a common arrhythmia in patients with hypertension. ELABELA, which has cardioprotective effects, is decreased in the plasma of patients with hypertension and might be associated with AF in the hypertensive population. This study aims to measure the ELABELA plasma levels in hypertension patients with and without AF and to analyse the related factors.MethodsA total of 162 hypertension patients with or without AF were recruited for our monocentric observational study. Subjects were excluded if they had a history of valvular heart disease, rheumatic heart disease, cardiomyopathy, thyroid diseases, or heart failure. The patients’ histories were recorded, and laboratory examinations were conducted. Plasma ELABELA was detected by immunoassay. Echocardiographs were performed, and parameters were collected by two experienced doctors. Binary logistic regression analysis was used to identify the association between ELABELA plasma level and AF in patients with hypertension.ResultsPlasma ELABELA levels were lower in hypertension patients with AF than in those without AF (2.0 [1.5, 2.8] vs. 4.0 [3.4, 5.0] ng/ml, P < 0.001). ELABELA levels were correlated with age, heart rate, BNP levels and left atrial dimension. In addition to the left atrial dimension, ELABELA plasma levels were associated with AF in patients with hypertension (OR 0.081, 95% CI 0.029–0.224, P < 0.001). ELABELA levels were further decreased in the persistent AF subgroup compared with the paroxysmal AF subgroup (1.8 [1.4, 2.5] vs. 2.2 [1.8, 3.0] ng/ml, P = 0.012) and correlated with HR, BNP and ESR levels.ConclusionsELALABELA levels were decreased in hypertension patients with AF and further lowered in the persistent AF subgroup. Decreased ELABELA plasma levels were associated with AF in hypertension patients and may be an underlying risk factor.

Cardiac autonomic function and cognitive performance in patients with atrial fibrillation

BackgroundAtrial fibrillation (AF) is associated with loss of cognition and dementia. Cardiac autonomic dysfunction has been linked to cognitive decline. We aimed to investigate if reduced cardiac autonomic function (CAF) is associated with cognitive impairment in AF patients.MethodsPatients with paroxysmal, persistent and permanent AF were enrolled from a multicenter cohort study if they had AF (“AF group”) or sinus rhythm (“SR group”) on a baseline 5 min ECG recording. Parameters quantifying CAF (heart rate variability triangular index (HRVI), mean heart rate (MHR), RMSSD, SDNN, total power and power in the VLF, LF, HF ranges) were calculated. We used the Montreal Cognitive Assessment (MoCA) to assess global cognitive function.Results1685 AF patients with a mean age of 73 ± 8 years, 29% females, were included. MoCA score was 24.5 ± 3.2 in the AF group (N = 710 patients) and 25.4 ± 3.2 in the SR group (N = 975 patients). After adjusting for multiple confounders, lower HRVI was associated with lower MoCA scores, both in the SR group [β = 0.049; 95% confidence interval (CI) 0.016–0.081; p = 0.003] and in the AF group (β = 0.068; 95% CI 0.020–0.116; p = 0.006). In the AF group, higher MHR was associated with a poorer performance in the MoCA (β = − 0.008; 95% CI − 0.014 to − 0.002; p = 0.014). We found no convincing evidence of association for other CAF parameters with cognition.ConclusionOur data suggest that impaired CAF is associated with worse cognitive performance in patients with AF. Among standard HRV parameters, HRVI might be the most promising ECG index.Trial registrationClinicalTrials.gov Identifier: NCT02105844.Graphic abstract