Atrial Fibrillation Progression Research Articles

Aging-associated mechanisms of atrial fibrillation progression and their therapeutic potential

Atrial fibrillation (AF) is the most common sustained arrhythmia, with a particularly high prevalence in the elderly. As the global aging population rapidly expands, it is increasingly important to examine how alterations to the aging heart contribute to an increased AF susceptibility. This work critically reviews the key molecular mechanisms that may underpin the complex association between aging and AF. Moreover, we identify emerging novel opportunities for therapeutic intervention that may be able to prevent and/or improve the current treatment paradigms for age-related AF. This review contributes to a holistic understanding of the intricate relationship between aging and AF.

Left atrial functional changes associated with repeated catheter ablations for atrial fibrillation.

The impact of repeated atrial fibrillation (AF) ablations on left atrial (LA) mechanical function remains uncertain, with limited long-term follow-up data. This retrospective study involved 108 AF patients who underwent two catheter ablations with cardiac magnetic resonance imaging (MRI) done before and 3 months after each of the ablations from 2010 to 2021. The rate of change in peak longitudinal atrial strain (PLAS) assessed LA function. Additionally, a sub-study of 36 patients who underwent an extra MRI before the second ablation, gave us an additional time segment to evaluate the basis of change in PLAS. In the two-ablation, three MRI sub-study 1, the PLAS percent change rate was similar before and after the first ablation (r11 = -0.9 ± 3.1%/year, p = 0.771). However, the strain change rate from postablation 1 to postablation 2 was significantly worse (r12 = -23.7 ± 4.8%/year, p < 0.001). In the sub-study 2 with four MRIs, all three rates were negative, with reductions from postablation 1 to pre-ablation 2 (r22 = -13.3 ± 2.6%/year, p < 0.001) and from pre-ablation 2 to postablation 2 (r23 = -8.9 ± 3.9%/year, p = 0.028) being significant. The present study suggests that the more ablations performed, the more significant the decrease in the postablation mechanical function of the LA. The natural progression of AF (strain change from postablation 1 to pre-ablation 2) had a greater negative influence on LA mechanical function compared to the second ablation itself suggesting that second ablation in patients with recurrence after first ablation is an effective strategy even from the LA mechanical function aspect.

Integrating single-cell sequencing and genetic lineage tracing reveals endothelial plasticity during atrial remodeling

Abstract Background Atrial fibrillation (AF), as the most burdensome cardiac arrhythmia, could lead to the significant mortality and morbidity. Atrial fibrosis is a well-recognized pathophysiological factor of the development and progression of AF, which also hampers its treatment. However, the underlying mechanisms of this intricate process remain largely unknown. Purpose This study sought to reveal the cellular composition of AF substrate and investigate the vital contributors to atrial structural remodeling. Methods Left atrial appendages from three patients with AF undergoing surgical ablation and three individuals with sinus rhythm undergoing heart transplantation were subjected to 10X single-cell RNA sequencing (scRNA-seq). Another five public scRNA-seq or snRNA-seq datasets of potentially remodeled right or left appendages were retrieved across three publications. The vital contributors of atrial structural remodeling and their characteristics were identified by intercellular communication analysis and trajectory inference. Transverse aortic constriction (TAC) was used to induce atrial remodeling in Cdh5-CreERT2;RFP mice, followed by scRNA-seq of endothelial cells (ECs). Human primary atrial ECs and fibroblasts were isolated for cell-cell interaction experiments. ECs-specific mouse models of Transforming growth factor beta 1 (TGFB1) (knockout and overexpression) were generated. Electrophysiological and histology analyses were performed to determine the consequences of ECs-derived TGFB1 gain and loss of function in the atrium. Results The comprehensive analysis of different scRNA-seq datasets revealed that ECs played an important regulatory role in the homeostasis of atrial substrate and displayed remarkable mesenchymal activation during atrial remodeling, which was further confirmed by TAC mice. Immunofluorescence staining and high-content screening suggested that the complete transition from ECs to mesenchymal cells slightly contributed to atrial remodeling. However, TGFB1 secreted from mesenchymal activated ECs significantly promoted activation, proliferation, and collagen secretion of fibroblasts. We discovered that overexpression of TGFB1 in ECs of mice significantly increased atrial fibrosis, and thus prolonging AF duration. Besides, knockout of TGFB1 in ECs of mice underwent TAC significantly attenuated the atrial fibrosis and decreased the rate of AF. Conclusion Our work demonstrates that mesenchymal ECs-derived Tgfb1 plays an important role in atrial remodeling by regulating the fibroblast function. EC-specific interventions were suggested to facilitate the development of novel strategies for mitigating AF substrate remodeling.

Clonal haematopoiesis of indeterminate potential predicts recurrence of atrial arrhythmias after surgical ablation for atrial fibrillation

Abstract Background Clonal haematopoiesis of indeterminate potential (CHIP), characterized by the presence of somatic blood cell clone expanding without other haematological abnormalities, was recently shown to be significantly associated with the development and progression of atrial fibrillation (AF). However, the clinical relevance of CHIP in patients underwent surgical atrial ablation remained unexplored. Aims This study investigated the potential role of CHIP in the recurrence of atrial arrhythmias after surgical ablation in patients with AF. Methods Deep-target sequencing of 74 CHIP (a mean depth of coverage = 4051x) was performed in 132 patients with AF (mean age, 60 years; 75.8% male; mean left atrial diameter, 47mm) who underwent surgical ablation without previous atrial ablation between December 2014 and September 2021. Variant allele fraction (VAF) ≥ 2.0% of any targeted genes indicated the presence of CHIP mutations. The primary outcome is the recurrence of any atrial arrhythmias for &amp;gt;30s after a blanking period of 3 months within a year. The clinical significance of CHIP was determined by multivariable Cox proportional hazards regression. Results A total of 17.4% (23 of 132) patients with AF carried CHIP mutations (DNMT3A, 8.3% and TET2, 3.8%). CHIP prevalence varied among AF types, with paroxysmal, persistent, and long-lasting AF counting for 12.5%, 16.5%, and 36.4%, respectively. During one-year follow-up after blanking period, recurrent atrial arrhythmia was documented in 15 (65.2%) and 37 (33.4%) patients in the CHIP and non-CHIP groups, respectively (p = 0.005 for log-rank test). The association of CHIP with atrial arrhythmias recurrence remained significant after fully adjustment (hazard ratio, [95% confidence interval], 1.92 [1.02-3.63]). Conclusions CHIP mutations with a VAF ≥ 2.0% were identified in 17.4% AF patients undertaken surgical ablation and was associated with poor prognosis. CHIP assessment may be useful in the personalized management of patients who planned to perform surgical ablation for AF.

Altered fibrin clot properties and elevated von Willebrand Factors level are associated with progression to permanent atrial fibrillation during follow-up: a cohort study

Abstract Introduction Little is known about association of prothrombotic markers and atrial fibrillation (AF) progression to permanent arrythmia (PerAF). Formation of denser and poorly lysable fibrin clots have been observed in AF including patients with sinus rhythm in association with stroke and bleeding risk. We investigated whether altered fibrin clot properties and other prothrombotic state markers may contribute to AF transition to PerAF. Methods In the cohort study, in 226 anticoagulated AF patients (median age 69 years, median CHA2DS2-VASc of 3)with paroxysmal (n=83, 36.7%) or persistent (n=143, 63.3%) arrythmia we assessed at baseline plasma clot permeability (Ks), lysis time (CLT), and fibrinolysis involved proteins, including plasminogen activator inhibitor type 1 (PAI-1) along with von Willebrand factor (vWF) antigen. We recorded patients with PerAF during a median follow-up of 58 months. Results PerAF was documented in 62 (27.4%, 5.7%/year) subjects. These patients were older, with larger prevalence of heart failure (HF), higher body mass index by 9.6%, more often presented persistent AF and had longer history of arrythmia by 60%. We observed by 25.7% longer CLT and similar Ks, compared with the remainders, along with higher levels of vWF by 29% and PAI-1 by 21.3%. By multivariable analysis CLT, vWF and HF were independently associated with PerAF (R2=0.697, P&amp;lt;0.001). A cut-off CLT value of ≥105 min had a sensitivity of 88.7% and specificity of 78.7% in prediction of PerAF (area under curve 0.892, 95% confidence interval 0.848-0.935, P&amp;lt;0.001). Conclusion Impaired global fibrinolysis and elevated vWF levels are independently associated with faster progression to PerAF despite anticoagulation.Figure1

Left atrial and left ventricular positive and negative remodeling after catheter ablation of atrial fibrillation

Abstract Introduction Atrial fibrillation (AF) is associated with negative remodeling of left atrium (LA) and in later stages of diseases with negative remodeling of left ventricle (LV). Can radiofrequency ablation (RFA) of pulmonary veins cure AF and retain progression of arrhythmia? Purpose This study evaluated positive and negative remodeling of LA and LV after RFA of pulmonary veins and a 7-year follow-up. The patients were divided into 4 groups on the basis of Pulmonary Vein Isolation Outcome Degree (PVIOD 1-4), a new measure for the efficacy of catheter ablation of AF. Methods One hundred seventeen patients with symptomatic drug-refractory paroxysmal and persistent AF were treated with RFA. At baseline and after a 7 years of follow-up, 2-dimensional echocardiography was performed to assess LA diameter, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and left ventricular ejection fraction (LVEF). Results After a 7-year follow-up 32.5% patients with successful single RFA of AF (PVIOD 1) showed significant positive LA and LV remodeling: LA diameter 39.3±0.6 vs 36.5±0.6 mm, p=0.0007; LVEDD 53.1±0.6 vs 50.9±0.7 mm, p=0.008; LVESD 34.7±0.8 vs 32.0±0.1 mm, p=0.005 and LVEF 56.8±0.8 vs 62.1±1.1 %, p=0.000008. In 29.1% of patients with success after multiple procedures (PVIOD 2) occurred significant reverse LA remodeling: LA diameter 41.9±0.7 vs 40.2±0.6 mm, p=0.04. Clinical success (PVIOD 3) after RFA was defined as a significant reduction in the number and duration of AF episodes with or without previously ineffective antiarrhythmic drugs (AAD) class I and III. In 14.5% of subjects with long-term clinical success (PVIOD 3 and baseline LA diameter 43.2±1.0 mm) remodeling of LA and LV was not occurred. In 23.9% of patients with procedural and clinical failure after RFA (PVIOD 4) long-term follow-up showed significant negative remodeling of LA and LV: LA diameter 44.7±0.7 vs 47.4±0.7 mm, p=0.006; LVEDD 52.8±0.9 vs 57.1±0.6 mm, p=0.0006; LVESD 36.5±1.1 vs 40.7±1.2 mm, p=0.006 and LVEF 50.7±1.7 vs 43.8±1.8 %, p=0.004. Conclusions Single successful RFA of pulmonary veins in early stage of AF with normal LA diameter cure arrhythmia, which was proved with LA and LV positive remodeling after a 7-year follow-up. With increase of LA diameter, the success of RFA decrease. The multiple procedures slow the progression of AF, but are less effective because of long periods of time between them. Clinical success and role of AAD therapy are also important in AF management. If AF is not treated with RFA properly on time it becomes progressive disease.

Translation of pathophysiological mechanisms of atrial fibrosis into new diagnostic and therapeutic approaches.

Atrial fibrosis is one of the main manifestations of atrial cardiomyopathy, an array of electrical, mechanical and structural alterations associated with atrial fibrillation (AF), stroke and heart failure. Atrial fibrosis can be both a cause and a consequence of AF and, once present, it accelerates the progression of AF. The pathophysiological mechanisms leading to atrial fibrosis are diverse and include stretch-induced activation of fibroblasts, systemic inflammatory processes, activation of coagulation factors and fibrofatty infiltrations. Importantly, atrial fibrosis can occur in different forms, such as reactive and replacement fibrosis. The diversity of atrial fibrosis mechanisms and patterns depends on sex, age and comorbidity profile, hampering the development of therapeutic strategies. In addition, the presence and severity of comorbidities often change over time, potentially causing temporal changes in the mechanisms underlying atrial fibrosis development. This Review summarizes the latest knowledge on the molecular and cellular mechanisms of atrial fibrosis, its association with comorbidities and the sex-related differences. We describe how the various patterns of atrial fibrosis translate into electrophysiological mechanisms that promote AF, and critically appraise the clinical applicability and limitations of diagnostic tools to quantify atrial fibrosis. Finally, we provide an overview of the newest therapeutic interventions under development and discuss relevant knowledge gaps related to the association between clinical manifestations and pathological mechanisms of atrial fibrosis and to the translation of this knowledge to a clinical setting.

The spatial overlap between left atrial epicardial adipose tissue and fibrosis is not associated to clinical stage of atrial fibrillation

Left atrial (LA) epicardial adipose tissue (EAT) and wall fibrosis are both proven to contribute to the pathogenesis and progression of atrial fibrillation (AF). The theory of LA wall fibrosis induction by local EAT infiltration, paracrine secretions, and activation of the inflammatory process is strongly advocated, but the imaging evidence for anatomical proximity of the two tissue types and its association to AF stage is lacking. Accordingly, the aim of the study was to analyse the spatial overlap between LA EAT and adjacent wall fibrosis using 3D Dixon water-fat separated late gadolinium enhancement (LGE-Dixon) MRI and correlate the findings with the clinical AF stage. Forty-two AF patients (18 paroxysmal, 10 persistent, and 14 permanent) and nine non-AF patients were scanned. The permanent AF patients had greater LA volume and EAT than the paroxysmal group. The LA fibrosis area showed the same trend. The LA EAT-fibrosis overlap area was small and there was no significant difference between the three AF stages. There was no significant relationship between LA EAT- fibrosis overlap area and AF type. The findings shed light on the complex interplay between LA fibrosis and EAT during the progression from paroxysmal to permanent AF.

An international physician survey of current ablation practices in atrial fibrillation: An AIM-AF substudy

BackgroundPractice guidelines recommend ablation (ABL) in atrial fibrillation (AF) for rhythm control. Guidance for antiarrhythmic drugs (AADs) post-ABL is limited. ObjectiveThe purpose of this study was to determine AAD and ABL practices in the United States and Europe. MethodsAn online survey of experienced cardiologists (CDs) (n = 360) and interventional electrophysiologists (EPs) (n = 269) was conducted. AAD- and ABL-related survey questions and responses were analyzed. ResultsABL was preferred more often as first-line AF therapy (Rx) by US CDs/EPs (P ≤.001). ABL was selected to avoid AAD Rx by 46% (50% CDs, 40% EPs); to prevent AF progression by 41% (36% CDs, 47% EPs); and for superior efficacy by 28% (27% CDs, 30% EPs). ABL was used by 9% in asymptomatic AF (9% CDs, 10% EPs), by 14% in subclinical AF (13% CDs, 14% EPs), and by 17% for first AF event (15% CDs, 18% EPs). Primary ABL was preferred in heart failure by 38%. Comorbidities, age, and left atrial size were limitations for ABL by 48%, 40%, and 38%, respectively. AADs were used after ABL for AF/atrial tachycardia (AT) prophylaxis by 34% for 3–6 months and 29% for 1–2 months. AADs were given for a single AF recurrence by 34%, bridging to re-ABL by 32%, and long-term Rx by 34%. AF/AT post-ABL was most often managed with amiodarone (42%–48%). ConclusionABL was frequently preferred over AADs in symptomatic AF but notably also was used for asymptomatic and subclinical AF. Post-ABL AAD Rx for AF prophylaxis or recurrence was frequent, with empiric amiodarone being the most often selected AAD.

MCPIP1 promotes atrial remodeling by exacerbating miR‐26a‐5p/FRAT/Wnt axis–mediated atrial fibrosis in a rat model susceptible to atrial fibrillation

AbstractAtrial fibrosis plays a critical role in the pathogenesis of atrial fibrillation (AF). Monocyte chemotactic protein–induced protein‐1 (MCPIP1), recognized as a functional ribonuclease (RNase), exacerbates cardiac remodeling and contributes to a range of cardiovascular diseases. However, the involvement of MCPIP1 in atrial fibrosis and development of AF, along with its underlying biological mechanisms, remains poorly understood. This study demonstrated that knockdown of MCPIP1 significantly reduced AF inducibility, decreased left atrial diameter, and ameliorated atrial fibrosis, coinciding with reduced FRAT1/2/Wnt/β‐catenin signaling. Furthermore, the MCPIP1‐D141N mutation attenuated AF vulnerability and atrial remodeling compared to MCPIP1 overexpression in an acetylcholine and calcium chloride (ACh‐CaCl2)–induced rat model of AF. Conversely, overexpression of FRAT1/2 partially reversed the cardioprotective effects of MCPIP1‐D141N mutation. Using H9C2 cell lines, we observed that MCPIP1 may induce a transcriptional effect that downregulates miR‐26a‐5p expression, and luciferase and RNA immunoprecipitation (RIP) assays substantiated the direct interaction between miR‐26a‐5p and FRAT1/2. Moreover, overexpression of miR‐26a‐5p countered MCPIP1‐induced atrial remodeling and attenuated the progression of AF. In conclusion, these findings indicate that MCPIP1 facilitates atrial remodeling and the progression of AF by exacerbating miR‐26a‐5p/FRAT/Wnt axis–mediated atrial fibrosis through its RNase activity in an ACh‐CaCl2–induced rat model of AF.

Risk Factor Management for Patients with Atrial Fibrillation in Home Healthcare.

Atrial fibrillation (AF) is a common and persistent cardiac arrhythmia that impacts morbidity, mortality, disability, quality of life, and healthcare costs. Typically, AF is managed using a three-pillar approach of rate control, rhythm control, and anticoagulation. However, these interventions fail to address the underlying pathophysiological factors that contribute to AF. A compelling body of research expands traditional management by focusing on lifestyle modification to lower the risk of AF incidence, prevalence, progression, and severity. Home healthcare clinicians possess the knowledge and skills to examine and treat a wide range of risk factors that lead to AF, and therefore can substantially reduce incident and persistent AF and facilitate optimal outcomes. This perspective paper presents a clinical paradigm shift by proposing a five-factor Partner, Quantify, Recommend, Support, and Teach (PQRST) framework to support AF risk factor modification in home healthcare. The PQRST framework incorporates a greater focus on patient self-management through education and exercise to reduce incidence, prevalence, progression, and severity of AF.

Changes in epicardial adipose tissue volume before and after cryoballoon ablation in patients with atrial fibrillation: Supporting the “AF begets EAT” theory

BackgroundEpicardial adipose tissue (EAT) is closely associated with atrial fibrillation (AF), suggesting that it may be 1 of the causes of AF progression. However, it is unclear whether AF affects EAT. ObjectiveThis study aimed to demonstrate that sinus rhythm restoration reduces EAT volume (EATV) through left atrial reverse remodeling (LARR). MethodsWe analyzed data from 247 patients who underwent cryoballoon ablation for AF. EATV was assessed by contrast-enhanced computed tomography with a 3-dimensional analysis workstation, evaluating EATV surrounding the entire heart (total-EATV) and left atrium (LA-EATV) at baseline and 6 months after cryoballoon ablation. ResultsAt 6 months, all patients but 1 with persistent AF were in sinus rhythm. Total-EATV and LA-EATV were both significantly decreased in patients with persistent AF (n = 33; total-EATV: 148.8 ± 53.3 mL to 142.9 ± 53.5 mL [P = .01]; LA-EATV: 26.8 ± 11.3 mL to 25.2 ± 10.7 mL [P = .01]). No changes were observed in patients with paroxysmal AF (n = 214). Persistent AF was more strongly associated with LARR than paroxysmal AF (odds ratio, 2.34; 95% confidence interval, 1.01–5.44; P = .05). LARR showed an independent correlation with both total-EATV and LA-EATV reduction (odds ratio, 1.78 [P = .04] and 2.80 [P < .001], respectively). ConclusionThese findings suggest a novel “AF begets EAT” theory, complementing the previously accepted role of EAT as a cause of AF and supporting the “AF begets AF” mechanism.

A decade of follow-up: atrial fibrillation, pulmonary pressure, and the progression of tricuspid regurgitation.

Long-term data on atrial fibrillation (AF) impact on tricuspid regurgitation (TR) progression and its relation to pulmonary pressure are scant. We investigated this association in a study spanning over a decade. Adults with echocardiographic evaluation before 2014, free of significant TR, were included. Patients were dichotomized by baseline AF, followed by stratification according to systolic pulmonary artery pressure (sPAP). The development of new significant TR and its impact on mortality were studied. Study population included 21502 patients (median age 65, 40% female), 13% had baseline AF. During a median follow-up of 12 years, 11% developed significant TR. Compared with patients free of AF, patients with baseline AF were 3.5 and 1.3 times more likely to develop significant TR in a univariate and multivariate models, respectively (95% CI 3.27-3.91, 1.18-1.44, p<0.001 for both). The risk of TR progression was higher in patients with permanent AF and those treated with rate control strategy (HR 1.95 and 2.01, respectively; p<0.001 for both). The association of AF with TR progression was sPAP-related, being more pronounced among patients with normal sPAP than among those with elevated sPAP (HR 1.5vs. 1.18; p for interaction<0.001). TR progression was independently linked to a two-fold higher mortality risk, consistent regardless of baseline AF (p<0.001). AF is an independent predictor of TR progression, especially in patients with normal sPAP. Subsequent research on strategies to prevent TR progression in this patient population are warranted.This analysis investigated the association of AF with TR progression, and the interaction of pulmonary arterial pressure with this link. Among patients with AF (Left), progression to significant TR is highly prevalent, with higher risk among patients with permanent AF and lower risk in those treated with rhythm control strategy. Pulmonary arterial pressure interacts with this association (Right), such that among patients with normal sPAP, the link between AF and TR progression is stronger, suggesting that the importance of proactive AF management in this sugroup of patients. TR has important implications on mortality, regardless of AF status (Middle).AF=Atrial Fibrillation; A-STR=Atrial Secondary TR; CIED=cardiac implantable electronic device; TR=Tricuspid Regurgitation; V-STR=Ventricular Secondary TR.

Associations of ambient air pollution with incidence and dynamic progression of atrial fibrillation

The influence of air pollution on dynamic changes in clinical state from healthy to atrial fibrillation (AF), further AF-related complications and ultimately, death are unclear. We aimed to investigate the relationships between air pollution and the occurrence and progression trajectories of AF. We retrieved 442,150 participants free of heart failure (HF), myocardial infarction (MI), stroke and dementia at baseline from UK Biobank. Exposures to air pollution for each transition stage were estimated at the geocoded residential address of each participant using the bilinear interpolation approach. The outcomes were incident AF, complications, and death. Multi-stage models were used to evaluate the associations between air pollution and dynamic progression of AF. Over a 12.6-year median follow-up, a total of 21,670 incident AF patients were identified, of whom, 4103 developed complications and 1331 died. PM2.5, PM10, NOx and NO2 were differentially positively associated, while O3 was negatively associated with risks of progression trajectories of AF. PM2.5 exposure was significantly associated with an increased risk of progression. The associations of PM2.5, PM10, NOx, and NO2 on incident AF were generally more pronounced compared to other transitions. The cumulative transition probabilities were generally higher in individuals with higher exposure levels of PM2.5, PM10, NOx, and NO2 and lower exposure to O3. Air pollution could potentially have a role in increasing the risk of both the occurrence and progression of AF, emphasizing the significance of air pollution interventions in both the primary prevention of AF and the management of AF-related outcomes.

Clinical impact of atrial fibrillation progression in patients with heart failure with preserved ejection fraction: A report from the CHART-2 Study.

Atrial fibrillation (AF) frequently coexists with heart failure with preserved ejection fraction (HFpEF), and clinical outcomes of patients with AF vary depending on its subtype. While AF progression characterized by the transition from paroxysmal AF to persistent AF is sometimes observed, the incidence and clinical impact of AF progression in patients with HFpEF remain to be explored. We enrolled patients with HFpEF and paroxysmal AF from the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2) Study. AF progression was defined as the transition from paroxysmal AF to persistent AF. A total of 718 patients (median age: 72 years, 36% were female) were enrolled. For a median follow-up of 6.0 years (interquartile range: 3.0-10.2 years), AF progression occurred in 105 patients (14.6%), with a cumulative incidence of 16.7% at 10 years. In the multivariable Cox proportional hazards model, previous hospitalization for heart failure [hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.16-2.60; P = 0.007] and left atrial diameter (per 5-mm increase) (HR 1.37, 95% CI 1.20-1.55; P < 0.001) were significantly associated with AF progression. Furthermore, AF progression was significantly linked to worsening heart failure (adjusted HR 1.68, 95% CI 1.18-2.40; P = 0.004). Notably, 27 cases (26%) of worsening heart failure occurred within 1 year following AF progression. In patients with HFpEF, AF progression is significantly associated with adverse outcomes, particularly worsening heart failure. An increased risk is observed in the early phases following progression to persistent AF. Clinical Trials.gov Identifier: NCT00418041.

Exploring Diet-Based Treatments for Atrial Fibrillation: Patient Empowerment and Citizen Science as a Model for Quality-of-Life-Centered Solutions.

Atrial fibrillation (AF) is the most common heart rhythm disorder in the Western world. Between the years 2010 and 2019, the global prevalence of AF rose from 33.5 million to 59 million, highlighting the importance of developing equitable treatments for patients. The disease is associated with symptoms such as palpitations, dizziness, fatigue, shortness of breath, and cognitive dysfunction. In addition, AF increases the risk of developing a stroke and heart failure. Despite new insights into risk factors that can lead to the development of AF, the success of current treatments is suboptimal. Numerous risk factors, such as hypertension, diabetes, and obesity, have been associated with the development and progression of AF. As these can be lifestyle-related risk factors, lifestyle modification may be a solution to reduce AF-related symptoms as well as episodes. Research results show that certain dietary changes can reduce AF and numerous risk factors for AF. Increasing attention is being given to Mediterranean and whole, plant-based eating patterns, which emphasize eating grains, legumes, vegetables, fruits, and nuts, while excluding most-or all-animal products. Hence, what are the beneficial aspects of a Mediterranean and plant-based diet which consists mainly of unprocessed foods? In the current review, we discuss the outcomes of diet-based treatments. Moreover, other diet-related treatments, brought up by patient initiatives, are highlighted. These patient-initiated studies include L-glutamine and electrolytes as options to manage AF. Also, we highlight the emerging importance of valuing patient needs and a quality-of-life-centered approach to medicine. As indicated by recent studies and patient experiences, citizen science can create inclusive solutions that lead to patient empowerment and a holistic approach for AF management.

Long-Term Outcomes in Patients With Relatively High His-Bundle Capture Threshold After Permanent His-Bundle Pacing - A Multicenter Clinical Study.

Outcomes in patients with relatively high His-bundle (HB) capture thresholds at implantation are unknown. This study aimed to compare changes in the HB capture threshold and prognosis between patients with a relatively high threshold and those with a low threshold. Forty-nine patients who underwent permanent HB pacing (HBP) were divided into two groups: low (<1.25 V at 1.0 ms; n=35) and high (1.25-2.49 V; n=14) baseline HB capture threshold groups. The HB capture threshold was evaluated at implantation, and after 1 week, 1, 3, and 6 months, and every 6 months thereafter. HB capture threshold rise was defined as threshold rise ≥1.0 V at 1.0 ms compared with implantation measures. We compared outcomes between the groups. During a mean follow-up period of 34.6 months, the high-threshold group showed a trend toward a higher incidence of HB capture threshold of ≥2.5 V (50% vs. 14%; P=0.023), HBP abandonment (29% vs. 8.6%; P=0.091), lead revision (21% vs. 2.9%; P=0.065), and clinical events (all-cause death, heart failure hospitalization, and new-onset or progression of atrial fibrillation; 50% vs. 23%; P=0.089) than the low-threshold group. A baseline HB capture threshold of ≥1.25V was an independent predictor of clinical events. A relatively high HB capture threshold is associated with increased risk of HBP abandonment, lead revision, and poor clinical outcomes.

Early versus Late Radiofrequency Catheter Ablation in Atrial Fibrillation: Timing Matters.

Background: Despite the progressive course of atrial fibrillation (AF), the optimal timing of radiofrequency catheter ablation (RFCA) during disease course is still unknown. We aimed to investigate the impact of early RFCA within a year after AF diagnosis on procedural outcomes. Methods: A single-center retrospective study was conducted on symptomatic AF patients (n = 130) referred for RFCA with a 16-month median follow-up. Patients were stratified based on the diagnosis-to-ablation time (DAT) into early (≤1 year) and late (>1 year) RFCA groups. Atrial arrhythmia recurrence after single RFCA was the primary outcome. Secondary outcomes included cardiovascular hospitalizations, AF progression, and antiarrhythmic drug (AAD) use. Results: Within a year of AF diagnosis, 33 patients (25.4%) underwent RFCA. In the early-RFCA group, 84.4% of patients did not have recurrent atrial arrhythmia, in contrast to 60.8% in the late-RFCA group (p = 0.039). Late RFCA (HR = 2.74, 95% CI = 1.062-7.052, p = 0.037) and AF recurrence during the blanking period (HR = 4.57, 95% CI = 2.38-8.57, p < 0.0001) were independent predictors of atrial arrhythmia recurrence on multivariate analysis. Compared to the late-RFCA group, the early-RFCA group had significantly lower rates of cardiovascular hospitalizations (18% vs. 42%, p = 0.023), AF progression (0.0% vs. 11.3%, p = 0.044), and AAD use (45.4% vs. 81.4%, p < 0.001). Conclusions: Early RFCA within a year of AF diagnosis is associated with less atrial arrhythmia recurrence, fewer cardiovascular hospitalizations, less AF progression, and less AAD use. DAT of more than one year and AF recurrence during the blanking period are independent predictors of atrial arrhythmia recurrence after single RFCA.

Abstract Tu107: Decreased Mitochondrial Protein Expression Accompanies Atrial Hypertrophy but Precedes Atrial Fibrillation Onset in a Mouse Model of Spontaneous Atrial Fibrillation

Introduction: Atrial fibrillation (AF), characterized by episodes of rapid and irregular heart rate, increases left atrial (LA) demand for ATP. While the heart is metabolically flexible, able to use fatty acids, lactate, glucose, ketones, and amino acids to generate ATP, fatty acids are the primary fuel source. AF is associated with altered mitochondrial structure and function, but the role of energetic pathways in early stages of AF progression is not clear. Hypothesis: Decreased expression of mitochondrial proteins contributes to AF progression. Aim: Evaluate expression of proteins that influence mitochondrial structure and energetic capacity in AF onset and progression. Methods: AF burden was assessed weekly by electrocardiography (ECG) in male wild-type (WT) and cAMP responsive element modulator IbΔC-X heterozygous mice (CREM) (n=3). LA (4 - 9 mg) was obtained at 7 weeks and 16 weeks. Global proteomics was conducted, and 139,316 peptides were identified that mapped to 6000 robustly quantified proteins. Results: LA hypertrophy was evident in 7-week and 16-week CREM mice (Figure 1). We detected 2408 proteins differentially expressed in CREM compared to WT. At 7 weeks, Hallmark pathways adipogenesis, fatty acid metabolism, oxidative phosphorylation, and myogenesis were decreased in CREM (Table 1). These changes persisted at 16 weeks. We identified 740 differentially expressed mitochondrial proteins using MitoCarta 3.0 (552 decreased, 188 increased). Mitochondrial pathways associated with energy production, including branched chain amino acid metabolism, fatty acid transport and oxidation, carbohydrate metabolism, and tricarboxylic acid cycle were decreased (Table 1). Mitochondrial cristae organizing system (MICOS) and mitophagy, pathways that influence mitochondrial structure and content, were decreased. Terminal ECGs confirmed AF in 16-week CREM mice only. The coefficient of variation of RR intervals (CVRR), a measure of heart rate variability, was increased in 16-week CREM (Figure 2). These data suggest that decreased expression of mitochondrial proteins accompanies LA hypertrophy but precedes onset of AF. Conclusions: Decreased expression of proteins that regulate mitochondrial structure and energy production prior to AF onset suggests that these proteins play an important role in early LA changes that promote AF onset and progression. Future studies will examine how these changes in protein expression relate to alterations in atrial energy homeostasis.

Risk Factors for Treatment Transition in Patients with Low-Risk Atrial Fibrillation Patients Undergoing Anticoagulation Monotherapy: A Large Claims Database Study in Japan.

The global prevalence of atrial fibrillation (AF) is rising, paralleling increased life expectancy. Early rhythm control benefits AF management. However, in low-risk, often asymptomatic, AF patients, anticoagulant monotherapy is the selected treatment, aligning with current guidelines. However, early AF progression in these low-risk individuals is not well-understood. Thus, this study aims to: 1) determine the proportion of low-risk AF patients who worsen within a year of initial AF diagnosis and 2) identify risk factors such treatment transitions. We analyzed data from 18623 AF patients, spanning January 2005 to June 2017. Low-risk patients were those on anticoagulant monotherapy ± rate control, following the JCS/JHRS 2020 Guideline on Pharmacotherapy of Cardiac Arrhythmias. We defined 2 patterns of treatment transition for 1) initiating ablation or antiarrhythmic drug therapy and 2) solely using antiarrhythmic drugs. This retrospective cohort study was employed a 12-month study, following a 6-month screening period. We included 1874 patients for all rhythm control (analysis 1) and 1503 for only medication-based control (analysis 2). The primary endpoint, treatment transition of AF under monotherapy, occurred in 28.4% of patients in analysis 1 and 10.8% in analysis 2. Risk factors common to both scenarios were male gender, baseline rate control drug use, and rivaroxaban selection, as identified by multiple logistic regression. These findings suggest a higher AF treatment transition trend in patients starting rivaroxaban, calling for further research. The study highlights the importance of informed early rhythm control initiation decisions in clinical settings.