Atrial Fibrillation Progression Research Articles

Structural phenotyping in atrial fibrillation with combined cardiac CT and atrial MRI: Identifying and differentiating individual structural remodelling types in AF.

Atrial remodelling (AR) is the persistent change in atrial structure and/or function and contributes to the initiation, maintenance and progression of atrial fibrillation (AF) in a reciprocal self-perpetuating relationship. Left atrial (LA) size, geometry, fibrosis, wall thickness (LAWT) and ejection fraction (LAEF) have all been shown to vary with pathological atrial remodelling. The association of these global remodelling markers with each other for differentiating structural phenotypes in AF is not well investigated. Patients referred for first-time AF ablation and controls without AF were prospectively recruited to undergo cardiac computed tomographic angiography (CCTA) and magnetic resonance imaging (MRI) with 3D atrial late-gadolinium enhanced (LGE) sequences. LAWT, atrial myocardial mass, LA volume and sphericity were calculated from CT. Biplane LA EF and LA fibrosis burden were derived from atrial MRI. Results were compared between patients with AF and controls. Forty two AF patients (64.3% male, age 64.6 ± 10.2 years, CHA2DS2-VASc 2.48 ± 1.5, 69.0% paroxysmal AF, 31% persistent AF, LVEF 57.9 ± 10.5%) and 37 controls (64.9% male, age 56.6 ± 7.2, CHA2DS2-VASc 1.54 ± 1.1, LVEF 60.4 ± 4.9%) were recruited. Patients with AF had a significantly higher LAWT (1.45 ± 0.52 mm vs 1.12 ± 0.42 mm, p = 0.003), tissue mass (15.81 ± 6.53 g vs. 12.18 ± 5.01 g, p = 0.011), fibrosis burden (9.33 ± 8.35% vs 2.41 ± 3.60%, p = 0.013), left atrial size/volume (95.68 ± 26.63 mL vs 81.22 ± 20.64 mL, p = 0.011) and lower LAEF (50.3 ± 15.3% vs 65.2 ± 8.6%, p < 0.001) compared to controls. There was no significant correlation between % fibrosis with LAWT (p = 0.29), mass (p = 0.89), volume (p = 0.49) or sphericity (p = 0.79). LAWT had a statistically significant weak positive correlation with LA volume (r = 0.25, p = .041), but not with sphericity (p = 0.86). LAEF had a statistically significant but weak negative correlation with fibrosis (r = -0.33, p = 0.008) and LAWT (r = -0.24, p = 0.07). AF is associated with significant quantifiable structural changes that are evident in LA size, tissue thickness, total LA tissue mass and fibrosis. These individual remodelling markers do not or only weakly correlate with each other suggesting different remodelling subtypes exist (e.g. fibrotic vs hypertrophic vs dilated). If confirmed, such a detailed understanding of the structural changes observed has the potential to inform clinical management strategies targeting individual mechanisms underlying the disease process.

Healthcare utilisation and quality of life according to atrial fibrillation burden, episode frequency and duration

BackgroundWe aimed to evaluate the association between atrial fibrillation (AF) burden, duration and number of episodes with healthcare utilisation and quality of life in patients with early paroxysmal AF without...

Sex Differences in Outcomes of an Intensive Risk Factor Modification Program in Patients With Atrial Fibrillation.

The outcomes of atrial fibrillation (AF) seem to be variable between males and females. We therefore aimed to determine sex differences in weight loss, cardiorespiratory fitness gain, and recurrence and progression of AF following risk factor management. Of 1415 consecutive patients referred for electrophysiology management of AF, 825 had a body mass index of ≥27 kg/m2; after exclusions, 355 (males, 234; females, 121) were offered risk factor management and participation in a tailored exercise program. Females were older than males (65.5±10.4 versus 62.5±10.6 years; P=0.013) with a higher body mass index (34.1±5.4 versus 32.6±4.1 kg/m2; P=0.003) and more commonly paroxysmal AF (67.8% versus 48.3%; P<0.001). There was no sex difference in clinic attendance (58.7% versus 60%; P=0.82), weight loss (P=0.86), fitness gain (P=0.44), or improvement in AF symptoms (P=0.35). Weight loss (≥10% compared with <10%) was associated with lower total AF recurrence in males (hazard ratio, 0.41 [95% CI, 0.23-0.73]) and females (hazard ratio, 0.41 [95% CI, 0.20-0.83]). Fitness gain (≥2 metabolic equivalents compared with <2 metabolic equivalents) was associated with lower total AF recurrence in females (hazard ratio, 0.13 [95% CI, 0.05-0.30]) but not in males (hazard ratio, 0.63 [95% CI, 0.38-1.04]; P=0.002). There was a trend toward more reversal from persistent to paroxysmal AF in males compared with females (21.8% versus 14.0%; P=0.079). Males and females with AF demonstrate a similar degree of weight loss and fitness gain through structured risk factor management. However, fitness had a much greater benefit for total arrhythmia recurrence in females compared with males, whereas there was a trend toward more AF reversal in males. URL: https://anzctr.org.au; Unique identifier: ACTRN12614001123639.

Impact of age-related gut microbiota dysbiosis and reduced short-chain fatty acids on the autonomic nervous system and atrial fibrillation in rats.

Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). Dysbiosis of gut microbiota has been implicated in age-related diseases, but its role in AF development remains unclear. This study aimed to investigate the correlations between changes in the autonomic nervous system, short-chain fatty acids (SCFAs), and alterations in gut microbiota in aged rats with AF. Electrophysiological experiments were conducted to assess AF induction rates and heart rate variability in rats. 16S rRNA gene sequences extracted from fecal samples were used to assess the gut microbial composition. Gas and liquid chromatography-mass spectroscopy was used to identify SCFAs in fecal samples. The study found that aged rats exhibited a higher incidence of AF and reduced heart rate variability compared to young rats. Omics research revealed disrupted gut microbiota in aged rats, specifically a decreased Firmicutes to Bacteroidetes ratio. Additionally, fecal SCFA levels were significantly lower in aged rats. Importantly, correlation analysis indicated a significant association between decreased SCFAs and declining heart rate variability in aged rats. These findings suggest that SCFAs, as metabolites of gut microbiota, may play a regulatory role in autonomic nervous function and potentially influence the onset and progression of AF in aged rats. These results provide novel insights into the involvement of SCFAs and autonomic nervous system function in the pathogenesis of AF. These results provide novel insights into the involvement of SCFAs and autonomic nervous system function in the pathogenesis of AF.

Inflammation Burden and Atrial Fibrillation Burden: A Bidirectional Relationship.

Atrial fibrillation (AF) burden is defined as the proportion of time the patient remains in AF over a given period of time; thus, it is theoretically highest in permanent AF and lowest in paroxysmal AF. Inflammation is associated with the initiation and maintenance of AF. However, the relationship between systemic immune-inflammation index (SII) and AF burden is unknown. In the present study, we investigated the relationship between SII and AF burden. The present study is a cross-sectional analysis of 453 patients (252 females and 201 males, aged 44 to 94 years) with AF (138 with paroxysmal AF and 315 with permanent AF) who visited the cardiology outpatient clinic between October 2022 and June 2023. SII was calculated as (neutrophils × platelets/lymphocytes). The predictive role of SII and other inflammatory markers in the likelihood of AF pattern was evaluated by logistic regression analyses, and p value < 0.05 was considered statistically significant. Age, diastolic blood pressure, heart rate, diabetes mellitus, neutrophil, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, SII, C-reactive protein, red blood cell distribution width, hemoglobin A1c, and left atrial diameter were significantly higher in the permanent AF group. According to the logistic regression analysis, age (p = 0.038), diabetes mellitus (p = 0.024), red blood cell distribution width (p = 0.023), C-reactive protein (p = 0.010), SII (p = 0.001), and left atrial diameter (p < 0.001) significantly contributed to the prediction of the likelihood of permanent AF. SII is independently associated with the AF burden. Prospective studies are needed to determine whether SII may be useful in identifying patients at high risk for AF progression.

Erythrocyte aggregability, and fibrinogen during atrial fibrillation

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Academician N. Kipshidze University Clinic - Republican Hospital; IVANE BERITASHVILI CENTER OF EXPERIMENTAL BIOMEDICINE, Department of rheology and diagnostic analytical services. Introduction Despite all biomedical efforts, the prevalence of atrial fibrillation and its associated morbidity and mortality are increasing globally year after year. The disease's unfavorable epidemiological picture determined the reality of the project. There are many hypotheses to explain the pathogenesis of atrial fibrillation. All the hypotheses are based on mechanisms at local points and microwaves (in whole or in part). None of them consider the role of hemodynamics and hemorheology in the formation and progression of atrial fibrillation. It is also unknown how atrial fibrillation affects intracardiac macro- and microcirculation. Purpose The goals of this project were to determine how hemodynamics and hemorheology change in patients with atrial fibrillation. In order to gain a better understanding of the pathological processes underlying AF, we sought to access the relationships between hemodynamics, rheological properties,and the coagulation system of blood. Methods The Erythrocyte (RBC) Aggregation Index (EAI) was monitored in the development and validation cohorts (90 patients and 20 healthy individuals) using the textural analysis system (Tas-Plus, Leitz, Germany) and an innovative "Georgian technique" with the unique function of a quantitative assessment of the EAI. The method was developed by Georgian scientists and is well-known around the world for being direct, numerical, and precise. In all patients Coagulogram and 12-lead standard ECG were performed. Results According to the data obtained, the patients' rheological and coagulation system conditions are the same, and they are distinct from the control group. During the statistical processing of the total amount of fibrinogen (Fib), the patients were divided into three categories. The average Fib in Category I patients was 336.40 ±27,77 mg/dl, and the average EAI-RBC value was 32.8± 9.4. Category II: FIB: 373.00±22.65mg/dl; EAI-RBC: 39.8±13.8 and Category III: FIB:471.27±21.58 mg/dl; EAI-RBC: 42.6±10.4. The control group: FIB: 301±18,1 mg/dl, EAI-RBC: 25.6±1.29. Fibrinogen and the Index of Erythrocyte Aggregation were found to have a linear relationship. The higher the concentration of fibrinogen, the more severe the hemorheological disorders. It should be noted that the categories were chosen without taking into account the forms of atrial fibrillation. Conclusions The findings clearly show the existence of two parallel mechanisms in the body. These are the coagulation systems, characterized by dynamic equilibrium, and the rheology systems, which lack a physiologically balanced opposing system. Coagulation control does not accurately describe hemorheological parameters, which are one of the most powerful mechanisms for atrial fibrillation formation In order to better understand the diseases' occurrence and progression, the simultaneous studies of fibrinogen concentration and rheological parameters are especially important for both fundamental and practical medicine.

Single-cell sequencing of immune cells from the coronary sinus reveals immune mechanisms of the progression of persistent atrial fibrillation

Identifying the atlas of immune cells from coronary sinus circulation (CSC) of patients with persistent atrial fibrillation (PerAF) may provide new insights into the role of immune cells in the progression of AF. Single-cell sequencing revealed substantial alterations in immune cells from CSCs of patients with PerAF, especially a markedly elevated abundance of Tcells, after which we identified a Tcell subset: FGFBP2(+)TRDC(-)CD4(-) Tcells (Ftc-T cells), which can promote the proliferation of cardiac fibroblasts (CFs),and the proportion of Ftc-T had a positive linear with AF recurrence post catheter ablation (CA). Moreover, IFI27 was found to be highly enriched in Ftc-T cells and promoted CFs proliferation and collagen expression. Altogether, our findings represent a unique resource providing in-depth insights into the heterogeneity of the immune cell from CSC of patients with PerAF and highlight the potential role of Ftc-T cells and IFI27 for AF progression.

Left atrial wall thickness measured by a machine learning method predicts AF recurrence after pulmonary vein isolation

Abstract Background Left atrial (LA) remodeling plays a significant role in the progression of atrial fibrillation (AF). Although LA wall thickness (LAWT) has emerged as an indicator of structural remodeling, its impact on AF outcomes remains unclear. We aimed to determine the association between LAWT and AF recurrence after pulmonary vein isolation (PVI). Methods Single-center registry of patients enrolled for radiofrequency PVI from 2016 to 2018. In all cases, a pre-ablation CT scan was performed within less than 48 hours. Mean LAWT was retrospectively determined by a semi-automated machine learning method with minimal human intervention (ADAS 3D®). Additionally, regional tissue thickness was assessed in four locations: roof and inferior, posterior, and anterior walls. In a subgroup of patients, a pre-ablation cardiac magnetic resonance (CMR) was also performed within the same week. LA functional parameters and fibrosis, using 3D delayed gadolinium enhancement, were analyzed. The primary endpoint was AF recurrence after a 3-month blanking period. Results A total of 439 patients (mean age 61±12years, 62% male, 78% with paroxysmal AF) were included. The mean LAWT was 1.4±0.2mm (ranging from 0.9 to 1.9mm). Software processing duration was 8.2±0.4 min, and the mean human input time was 1.3±0.1 min. There was no correlation between LAWT and CT-derived LA-indexed volume (Spearman –0.01, p=0.845). During a median follow-up of 5.8 (IQR 4.9–6.6) years, 238 patients (54%) had an AF relapse. LAWT was an independent predictor of recurrence, after adjusting for known confounders including age, non-paroxysmal AF, LA-indexed volume, and chronic kidney disease (adjusted HR 6.49 [95% CI 2.70-15.49], p&amp;lt;0.001). AF recurrence rates were 11%, 15%, and 21%/year across terciles of increasing LAWT (log-rank p&amp;lt;0.001) – Figure. The posterior LAWT revealed the strongest association with the study endpoint (HR 1.93 [95% CI 1.24-3.02], p=0.004). In the cohort of 62 patients with both CT and CMR, LAWT showed weak correlations with LA ejection fraction and LA coupling index (Spearman &amp;lt;0.25; p=0.054 and p=0.093, respectively), and a moderate correlation with LA fibrosis (Spearman 0.468; p&amp;lt;0.001). Conclusions Mean LAWT, easily assessed by commercially available machine learning software, is an independent predictor of AF recurrence after PVI in the long-term follow-up. This association is mainly driven by the posterior LAWT. Whether patients with increased LAWT should receive tailored therapy deserves further investigation.Figure

Application value of real-time 3D speckle tracking imaging in left atrial function evaluation of patients with paroxysmal atrial fibrillation.

To evaluate left atrial volume and function in patients with paroxysmal atrial fibrillation (AF) combined with left atrial appendage thrombosis and patients with paroxysmal AF without left atrial appendage thrombosis by 3-dimensional speckle tracking imaging (3D-STI), and to explore the application value of this set of parameters in the evaluation of left atrial function in patients with paroxysmal AF. A total of 40 patients with paroxysmal AF admitted from December 2018 to December 2020 were selected as the observation group. All patients with paroxysmal AF in the observation group underwent transesophageal echocardiography. According to the presence of left atrial appendage thrombosis, the patients were divided into the AF without thrombosis group (24 cases) and the AF with thrombosis group (16 cases). Thirty normal people were selected as control group who were chosen as having no heart-related disease. The left atrial volume parameters (Left atrial maximum volume LAVmax, Left atrial minimum volume LAVmin, Left atrial volume before atrial contraction LAVpre-A, Left atrial stroke volume LAEV), left atrial ejection fraction (LAEF) and left atrial strain parameters (Left atrial reservoir longitudinal strain LASr, Left atrial conduit longitudinal strain LAScd, Left atrial contraction longitudinal strain LASct, Left atrial reservoir circumferential strain LASr-c, Left atrial conduit circumferential strain LAScd-c, Left atrial contraction circumferential strain LASct-c) of the 3 groups were measured by 3D-STI. With the progression of paroxysmal AF, the left atrial volume increased, and the reservoir, conduit and contractile function were damaged. The left atrial volume continued to increase, and the reservoir, conduit and contractile function further decreased significantly in patients with AF combined with left atrial appendage thrombosis. LAEF was positively correlated with LASr and LASr_c. Real-time 3-dimensional spot tracking imaging (3D-STI) can evaluate the changes in left atrial volume and function in patients with paroxysmal AF, and has a certain reference value for clinical judgment of disease progression and prognosis.

Sex differences at diagnosis and in one-year outcomes in patients with early atrial fibrillation

Abstract Background Little is known about differences in clinical phenotype between men and women with atrial fibrillation (AF). Our aim was to explore phenotypical sex differences at diagnosis and at one-year follow-up, in patients with early AF. Methods We used data from 5,469 participants of the DUTCH-AF registry; a nationwide prospective registry of patients with early AF or atrial flutter (diagnosis ≤ 6 months before inclusion) in the Netherlands, aged ≥ 18 years. We describe sex differences in clinical phenotype at diagnosis and at one-year follow-up, including the following outcomes: i) ischemic and bleeding events, ii) all-cause mortality, iii) AF-related hospital admissions, including ablation and cardioversion, and iv) AF progression patterns. Results At inclusion, women were older than men (median 73 vs. 69 years, p&amp;lt;0.001), had more often paroxysmal AF (66% vs. 55%, p&amp;lt;0.001), and less often persistent AF (27% vs. 37%, p&amp;lt;0.001). They also had hypertension more often (59% vs. 53%, p&amp;lt;0.001), and less often vascular disease (12% vs. 21%, p&amp;lt;0.001, and reported more often symptoms at inclusion and in the month before follow-up; 56% vs. 46%, p&amp;lt;0.001, and 31% vs. 23%, p&amp;lt;0.001, respectively. Women underwent cardioversion and ablation procedures less often than men (14% vs. 21% p&amp;lt;0.001 and 3% vs. 5%, p&amp;lt;0.001, respectively). Moreover, for the combined rhythm control intervention cardioversion and ablation, women also underwent this rhythm control outcome less often than men (unadjusted odds ratio was 0.63 95% CI (0.55-0.73)), regardless of age, and the type of AF (i.e., paroxysmal or persistent AF) at inclusion (adjusted odds ratio 0.77 95% CI (0.62-0.92)). No differences were observed for ischemic and bleeding events, all-cause mortality, or AF progression patterns, but the number of these events was small. Conclusion Men and women with early AF differ in age, comorbidities, symptoms, and management. These findings are building blocks for individualized sex-specific AF care and research.

Association of Gut Dysbiosis with Potential Mechanisms Leading to Atrial Fibrillation: A Narrative Review

Atrial fibrillation stands as one of the deadliest forms of arrhythmia known to mankind due to its severe complication and co-morbidities. Its association with gut dysbiosis is profound. The gut microbiota hosts a diverse variety of microbes crucial for immune function and protection against cardiovascular and metabolic diseases. Poor lifestyle habits such as diet, decreased physical activity, and drug disrupt this gut homeostasis. Multiple studies have provided compelling evidence linking alterations in gut microbiota to the risk and progression of atrial fibrillation. Some proposed mechanisms involve key metabolites such as trimethylamine N-oxide (TMAO), lipopolysaccharides, short-chain fatty acids (SCFAs), bile acids, and tryptophan. These mechanisms encompass inflammation, oxidative stress, autonomic dysfunction, atrial remodeling, altered electrical activity, and calcium homeostasis. This review meticulously examines gut dysbiosis and its pivotal role in the progression of atrial fibrillation through diverse potential mechanisms, emphasizing the significance of dietary factors and potential interventions.

Conduction Velocity and Anisotropic Properties of Fibrillation Waves During Acutely Induced and Long-Standing Persistent AF

BackgroundQuantified features of local conduction heterogeneity due to pathological alterations of myocardial tissue could serve as a marker for the degree of electrical remodeling and hence be used to determine the stage of atrial fibrillation (AF). ObjectivesIn this study, the authors investigated whether local directional heterogeneity (LDH) and anisotropy ratio, derived from estimated local conduction velocities (CVs) during AF, are suitable electrical parameters to stage AF. MethodsEpicardial mapping (244-electrode array, interelectrode distance 2.25 mm) of the right atrium was performed during acute atrial fibrillation (AAF) (n = 25, 32 ± 11 years of age) and during long-standing persistent atrial fibrillation (LSPAF) (n = 23, 64 ± 9 years of age). Episodes of 9 ± 4 seconds of AF were analyzed. Local CV vectors were constructed to assess the degree of anisotropy. Directions and magnitudes of individual vectors were compared with surrounding vectors to identify LDH. ResultsCompared with the entire AAF group, LSPAF was characterized by slower conduction (71.5 ± 6.8 cm/s vs 67.6 ± 5.6 cm/s; P = 0.037) with a larger dispersion (1.59 ± 0.21 vs 1.95 ± 0.17; P < 0.001) and temporal variability (32.0 ± 4.7 cm/s vs 38.5 ± 3.3 cm/s; P < 0.001). Also, LSPAF was characterized by more LDH (19.6% ± 4.4% vs 26.0% ± 3.4%; P < 0.001) and a higher degree of anisotropy (1.38 ± 0.07 vs 1.51 ± 0.14; P < 0.001). Compared with the most complex type of AAF (type III), LSPAF was still associated with a larger CV dispersion, higher temporal variability of CV, and larger amount of LDH. ConclusionsIncreasing AF complexity was associated with increased spatiotemporal variability of local CV vectors, local conduction heterogeneity, and anisotropy ratio. By using these novel parameters, LSPAF could potentially be discriminated from the most complex type of AAF. These observations may indicate pathological alterations of myocardial tissue underlying progression of AF.

Structural, Functional, and Electrical Remodeling of the Atria With Reduced Cardiorespiratory Fitness: Implications for AF

BackgroundReduced cardiorespiratory fitness (CRF) is an independent risk factor for the progression of atrial fibrillation (AF). We hypothesized that reduced CRF is associated with structural, functional, and electrical remodeling of the left atrium. ObjectivesThis study sought to correlate objectively assessed CRF with functional and electrical left atrial (LA) parameters using invasive and noninvasive assessments. MethodsConsecutive patients with symptomatic AF undergoing catheter ablation were recruited. CRF was objectively quantified pre-ablation by using cardiopulmonary exercise testing. Using peak oxygen consumption, participants were classified as preserved CRF (>20 mL/kg/min) or reduced CRF (<20 mL/kg/min). LA stiffness was assessed invasively with hemodynamic monitoring and imaging during high-volume LA saline infusion. LA stiffness was calculated as ΔLA diameter/ΔLA pressure over the course of the infusion. LA function was assessed with echocardiographic measures of LA emptying fraction and LA strain. Electrical remodeling was assessed by using high-density electroanatomical maps for LA voltage and conduction. ResultsIn total, 100 participants were recruited; 43 had reduced CRF and 57 had preserved CRF. Patients with reduced CRF displayed elevated LA stiffness (P = 0.004), reduced LA emptying fraction (P = 0.006), and reduced LA reservoir strain (P < 0.001). Reduced CRF was also associated with reduced LA voltage (P = 0.039) with greater heterogeneity (P = 0.027) and conduction slowing (P = 0.04) with greater conduction heterogeneity (P = 0.02). On multivariable analysis, peak oxygen consumption was independently associated with LA stiffness (P = 0.003) and LA conduction velocities (P = 0.04). ConclusionsReduced CRF in patients with AF is independently associated with worse LA disease involving functional and electrical changes. Improving CRF may be a target for restoring LA function in AF.

ECG-based estimation of respiration-induced autonomic modulation of AV nodal conduction during atrial fibrillation.

Introduction: Information about autonomic nervous system (ANS) activity may offer insights about atrial fibrillation (AF) progression and support personalized AF treatment but is not easily accessible from the ECG. In this study, we propose a new approach for ECG-based assessment of respiratory modulation in atrioventricular (AV) nodal refractory period and conduction delay. Methods: A 1-dimensional convolutional neural network (1D-CNN) was trained to estimate respiratory modulation of AV nodal conduction properties from 1-minute segments of RR series, respiration signals, and atrial fibrillatory rates (AFR) using synthetic data that replicates clinical ECG-derived data. The synthetic data were generated using a network model of the AV node and 4 million unique model parameter sets. The 1D-CNN was then used to analyze respiratory modulation in clinical deep breathing test data of 28 patients in AF, where an ECG-derived respiration signal was extracted using a novel approach based on periodic component analysis. Results: We demonstrated using synthetic data that the 1D-CNN can estimate the respiratory modulation from RR series alone with a Pearson sample correlation of r = 0.805 and that the addition of either respiration signal (r = 0.830), AFR (r = 0.837), or both (r = 0.855) improves the estimation. Discussion: Initial results from analysis of ECG data suggest that our proposed estimate of respiration-induced autonomic modulation, a resp, is reproducible and sufficiently sensitive to monitor changes and detect individual differences. However, further studies are needed to verify the reproducibility, sensitivity, and clinical significance of a resp.

Environmental Exposome and Atrial Fibrillation: Emerging Evidence and Future Directions.

There has been increased awareness of the linkage between environmental exposures and cardiovascular health and disease. Atrial fibrillation is the most common sustained cardiac arrhythmia, affecting millions of people worldwide and contributing to substantial morbidity and mortality. Although numerous studies have explored the role of genetic and lifestyle factors in the development and progression of atrial fibrillation, the potential impact of environmental determinants on this prevalent condition has received comparatively less attention. This review aims to provide a comprehensive overview of the current evidence on environmental determinants of atrial fibrillation, encompassing factors such as air pollution, temperature, humidity, and other meteorologic conditions, noise pollution, greenspace, and the social environment. We discuss the existing evidence from epidemiological and mechanistic studies, critically evaluating the strengths and limitations of these investigations and the potential underlying biological mechanisms through which environmental exposures may affect atrial fibrillation risk. Furthermore, we address the potential implications of these findings for public health and clinical practice and identify knowledge gaps and future research directions in this emerging field.

Flecainide sebagai Antiaritmia untuk Fibrilasi Atrium dan Aritmia Lainnya

Atrial fibrillation (AF) is one of the most common arrhythmias globally, and its prevalence is projected to increase, including in Indonesia. AF progression is related to lower quality of life and less responsive to therapy or even becomes irreversible. The progression of AF is significantly slower with the rhythm control strategy than with the rate control strategy alone. The options for therapy in Indonesia are limited to amiodarone and propafenone. Amiodarone is one of the most common drugs prescribed for AF rhythm control, but associated with multiple organ toxicities, thus increasing the risk of multiple side effects, especially on long-term usage, potentially leading to drug discontinuation. Flecainide is an antiarrhythmia with a favourable effectiveness and safety profile, especially for AF management, used for acute cardioversion, long-term rhythm control, and as a therapeutic modality for AF with preexcitation syndrome. Flecainide is a potential drug to address the unmet needs of amiodarone as a long-term management for AF.

Usformer: A small network for left atrium segmentation of 3D LGE MRI

Left atrial (LA) fibrosis plays a vital role as a mediator in the progression of atrial fibrillation. 3D late gadolinium-enhancement (LGE) MRI has been proven effective in identifying LA fibrosis. Image analysis of 3D LA LGE involves manual segmentation of the LA wall, which is both lengthy and challenging. Automated segmentation poses challenges owing to the diverse intensities in data from various vendors, the limited contrast between LA and surrounding tissues, and the intricate anatomical structures of the LA. Current approaches relying on 3D networks are computationally intensive since 3D LGE MRIs and the networks are large. Regarding this issue, most researchers came up with two-stage methods: initially identifying the LA center using a scaled-down version of the MRIs and subsequently cropping the full-resolution MRIs around the LA center for final segmentation. We propose a lightweight transformer-based 3D architecture, Usformer, designed to precisely segment LA volume in a single stage, eliminating error propagation associated with suboptimal two-stage training. The transposed attention facilitates capturing the global context in large 3D volumes without significant computation requirements. Usformer outperforms the state-of-the-art supervised learning methods in terms of accuracy and speed. First, with the smallest Hausdorff Distance (HD) and Average Symmetric Surface Distance (ASSD), it achieved a dice score of 93.1% and 92.0% in the 2018 Atrial Segmentation Challenge and our local institutional dataset, respectively. Second, the number of parameters and computation complexity are largely reduced by 2.8x and 3.8x, respectively. Moreover, Usformer does not require a large dataset. When only 16 labeled MRI scans are used for training, Usformer achieves a 92.1% dice score in the challenge dataset. The proposed Usformer delineates the boundaries of the LA wall relatively accurately, which may assist in the clinical translation of LA LGE for planning catheter ablation of atrial fibrillation.

Clinical Predictors of Device-Detected Atrial Fibrillation During 2.5 Years After Cardiac Surgery: Prospective RACE V Cohort

BackgroundPostoperative atrial fibrillation (POAF) is a frequent complication after cardiac surgery that is associated with late atrial fibrillation (AF) recurrences (late-POAF) and increased morbidity and long-term mortality. ObjectivesThis study sought to determine device-detected POAF incidence and to identify clinical variables associated with POAF, both in patients with and without preoperative AF history. MethodsA total of 133 consecutive patients undergoing cardiac surgery were prospectively enrolled and continuously monitored with an implantable loop recorder for 2.5 years after surgery. Preoperative transthoracic echocardiography, 12-lead electrocardiogram, blood biomarkers, and clinical data were analyzed to develop prediction models for early- and late-POAF. ResultsIn patients without preoperative AF history, early-POAF within the first 90 postoperative days occurred in 41 (47.1%) of 87 patients. Late-POAF after the first 90 postoperative days occurred in 22 (25%) of 87 patients, and 20 of these patients also had early-POAF during the first 90 days (20 of 22 [91%]). Increased right atrial minimum volume indexed for body surface area (RAVImin) and early-POAF were independently associated with late-POAF. A prediction model for late-POAF, which included RAVImin >11 mL/m2, age >65 years, and early-POAF, achieved an area under the curve of 0.82 (95% CI: 0.72-0.92). For patients with preoperative AF-history, late-POAF recurrences were frequent (22 of 33 [67%]). Increased RAVImin was independently associated with a higher incidence of late-POAF. ConclusionsIn patients with and without AF history, late-POAF recurrences are frequent, including in patients undergoing surgical AF ablation. In patients with no history of AF, late-POAF might be predicted with excellent accuracy by using a combination of preoperative variables. In patients with a history of AF, signs of advanced AF substrate (eg, increased right atrial volumes) were associated with long-term AF recurrences. [Reappraisal of Atrial Fibrillation: Interaction Between Hypercoagulability, Electrical Remodeling, and Vascular Destabilisation in the Progression of AF; NCT03124576]

Possible risk factors for atrial fibrillation in patients with heart failure with mildly reduced ejection fraction

Aim. To study possible risk factors (RFs) for the development of paroxysmal and persistent atrial fibrillation (AF) in patients with heart failure with mildly reduced ejection fraction (HFmrHF).Material and methods. The study included 193 patients with chronic HFmrHF and non-valvular paroxysmal/persistent AF. Seventy-six comparable patients, but without AF, were studied as a control group. All patients underwent a detailed physical examination, including electrocardiography (ECG), echocardiography, ambulatory blood pressure monitoring, and Holter ECG monitoring. Levels of inflammatory markers, namely high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-a and fibrotic marker, transforming growth factor-b1 (TGF-b1) were measured using ELISA. The results obtained were analyzed using the method of binary logistic regression and odds ratio (OR), which allows us to assess the relationship of a specific outcome with possible risk factors and compare study groups according to the detection rate of risk factors.Results. A higher level of diastolic blood pressure (DBP) (OR=1,09, confidence interval (CI)=1,01-1,17, p=0,017) is a possible risk factor for paroxysmal AF in patients with CHF. Possible risk factors for paroxysmal and persistent AF in such patients are an increase in episodes of hypertensive crisis (OR=1,17, CI=1,071,43, p=0,001) and an increase in body mass index (BMI) (OR=1,13, CI=0,931,27, p=0,031). An increase in the OR index of left ventricular diastolic and systolic parameters was associated with significant atrial and ventricular remodeling, which contributes to AF progression from paroxysmal to persistent. Higher levels of inflammatory markers were observed in patients with AF compared with patients with HFmrHF without AF. The increase in the OR level of TGF-b1 (OR=3,84, CI=2,106,23, p=0,005) was significant in patients with persistent AF.Conclusion. Using the OR method, an increase in DBP, the prevalence of hypertensive crisis, BMI, left atrial and ventricular remodeling, an increase in markers of systemic inflammation and fibrosis are possible risk factors for AF in patients with HFmrHF.

Administration of USP7 inhibitor p22077 alleviates Angiotensin II (Ang II)-induced atrial fibrillation in Mice.

Atrial fibrillation (AF), the most common cardiac arrhythmia, is an important contributor to mortality and morbidity. Ubquitin-specific protease 7 (USP7), one of the most abundant ubiquitin-specific proteases (USP), participated in many cellular events, such as cell proliferation, apoptosis, and tumourigenesis. However, its role in AF remains unknown. Here, the mice were treated with Ang II infusion to induce the AF model. Echocardiography was used to measure the atrial diameter. Electrical stimulation was programmed to measure the induction and duration of AF. The changes in atrial remodeling were measured using routine histologic analysis. Here, a significant increase in USP7 expression was observed in Ang II-stimulated atrial cardiomyocytes and atrial tissues, as well as in atrial tissues from patients with AF. The administration of p22077, the inhibitor of USP7, attenuated Ang II-induced inducibility and duration of AF, atrial dilatation, connexin dysfunction, atrial fibrosis, atrial inflammation, and atrial oxidase stress, and then inhibited the progression of AF. Mechanistically, the administration of p22077 alleviated Ang II-induced activation of TGF-β/Smad2, NF-κB/NLRP3, NADPH oxidases (NOX2 and NOX4) signals, the up-regulation of CX43, ox-CaMKII, CaMKII, Kir2.1, and down-regulation of SERCA2a. Together, this study, for the first time, suggests that USP7 is a critical driver of AF and revealing USP7 may present a new target for atrial fibrillation therapeutic strategies.