Early detection of atrial fibrillation (AFib) is crucial for altering its natural progression and complication profile. Traditional demographic and lifestyle factors often fail as predictors of AFib. This study investigated pre-operative, circulating microRNAs (miRNAs) as potential biomarkers for post-operative AFib (POAF) in patients undergoing coronary artery bypass grafting (CABG). We used an array polymerase chain reaction method to detect pre-operative, circulating miRNAs in seven patients who subsequently developed POAF after CABG (cases) and eight patients who did not develop POAF after CABG (controls). The top 10 miRNAs from 84 candidates were selected and assessed for their performance in predicting POAF using machine learning models, including Random Forest, K-Nearest Neighbors (KNN), XGBoost, and Support Vector Machine (SVM). The Random Forest and XGBoost models showed superior predictive performance, with test area under the curve (AUC) values of 0.76 and 0.83, respectively. Differential expression analysis revealed four upregulated miRNAs-hsa-miR-96-5p, hsa-miR-184, hsa-miR-17-3p, and hsa-miR-200-3p-that overlapped with the POAF-miRNA signature. The POAF-miRNA signature was significantly associated with various cardiovascular diseases, including acute myocardial infarction, hypertrophic cardiomyopathy, and heart failure. Biological pathway analysis indicated these miRNAs target key signaling pathways involved in cardiovascular pathology, such as the MAPK, PI3K-Akt, and TGF-beta signaling pathways. The identified miRNAs demonstrate significant potential as predictive biomarkers for AFib post-CABG, implicating critical cardiovascular pathways and highlighting their role in POAF development and progression. These findings suggest that miRNA signatures could enhance predictive accuracy for POAF, offering a novel, noninvasive approach to early detection and personalized management of this condition.

Atrial fibrillation (AF) is increasingly recognized as the clinical manifestation of an underlying atrial disease process rather than a purely electrical disorder. This evolving paradigm has given rise to the concept of atrial cardiomyopathy (AtCM), encompassing structural, electrical, contractile, and molecular remodeling of the atrial myocardium that contributes to AF initiation, maintenance, and progression. Although consensus definitions of AtCM now exist, its integration into clinical practice remains limited, with AF management still largely guided by arrhythmic patterns rather than substrate characterization. This review synthesizes current diagnostic strategies for AtCM within the context of AF, emphasizing a multimodal approach. We outline advances in cardiac imaging-including echocardiography, cardiac magnetic resonance, and computed tomography-for detailed assessment of atrial morphology, function, and fibrosis. Electroanatomic mapping is discussed as a key invasive tool for substrate localization, while electrocardiographic indices such as P-wave morphology and dispersion serve as accessible surrogates of electrical remodeling. In parallel, we examine the role of circulating biomarkers and emerging genomic, transcriptomic, and epigenomic markers in refining disease phenotyping. Despite promising progress, significant challenges remain. Standardization of imaging protocols, validation of biomarker thresholds, and integration of artificial intelligence tools are needed to enhance clinical utility. A diagnostic framework informed by atrial substrate assessment may support more tailored therapeutic decision-making in AF. Future research should prioritize the harmonization of diagnostic criteria and explore how substrate profiling in AF may refine risk stratification and improve clinical outcomes.

Left atrial appendage thrombus (LAAT) is the predominant etiology of ischemic stroke in patients with atrial fibrillation (AF), and LAAT is optimally demonstrated by transesophageal echocardiography (TEE). The study aimed to assess patients with nonvalvular atrial fibrillation (NVAF) identified with thrombus using TEE compared to those without thrombus, utilizing the C-reactive protein/albumin ratio (CAR) as a sensitive biomarker.

This study was conducted retrospectively at a single center with 668 patients with NVAF who underwent TEE. Patients were divided into two groups based on the presence or absence of LAAT on TEE. The levels of CAR, C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were compared.

CAR was identified as an independent variable in patients with thrombus detected on TEE. (OR: 12.773, CI: 6.669-24.464, p < 0.001) Albumin was shown to have the highest area under the curve (AUC) value for thrombus prediction, followed by CAR, CRP, NLR, and PLR, in that order. (AUC: 0.999 CI: 0.993-1.000; 0.977 (0.962-0.987); 0.931 (0.909-0.949); 0.600 (0.562-0.937) p < 0.001, AUC: 0.574 CI: 0.535-0.612 p: 0.014).

Our study demonstrates that CAR serves as an independent predictor of LAAT and shows more dependability than other biomarkers such as NLR, CRP, and PLR.

Inflammasomes are multiprotein complexes of the innate immune system that mediate inflammatory responses to infection and to local and systemic stress and tissue injury. The principal function is to facilitate caspase-1 auto-activation and subsequently maturation and release of the effectors interleukin (IL)-1β and IL-18. The atrial-specific NLRP3 inflammasome is a unifying causal feature of atrial fibrillation (AF) development, progression and recurrence after ablation. Many AF-associated risk factors and co-morbidities converge mechanistically on the activation of this central inflammatory signaling platform. This review presents the historical conceptual development of a distinct atrial inflammasome and its potential causal involvement in AF. We follow the early observations linking systemic and local inflammation with AF, to the emergence of an atrial-intrinsic NLRP3 inflammasome operating within not just immune cells but also in resident atrial fibroblasts and cardiomyocytes. We outline the key developments in understanding how the atrial NLRP3 inflammasome and its effector IL-1β contribute causally to cellular and tissue-level arrhythmogenesis in different pathological settings, and outline candidate therapeutic concepts verified in preclinical models of atrial cardiomyopathy and AF.

Sleep architectural disruption is associated with atrial fibrillation (AF); however, associated autonomic influences remain unclear and it is unknown if this detriment persists during wakefulness. We hypothesize sleep disruption and autonomic dysfunction have diurnal patterning in patients with paroxysmal AF.

We analyzed data from the Sleep Apnea and Atrial Fibrillation Biomarkers and Electrophysiologic Atrial Triggers (SAFEBEAT) study designed to examine paroxysmal AF and sleep apnea, including simultaneous collection of continuous electrocardiogram monitoring (Heartrak Telemetry®) and actigraphy (Actiwatch GTX) for 7-21 days. Heart rate variability (HRV) measures in time-domain (standard deviation of normal-to-normal (NN) intervals (SDNN), coefficient of variation (CV)) and frequency-domain (low frequency power (LFP), high frequency power (HFP)) were used as surrogates of autonomic function and averaged per sleep/wake per day. A linear mixed-effects model assuming compound symmetry correlation structure was used to assess the relationship of HRV with actigraphy-derived sleep data.

The analytic sample (age 60.1 ± 12.0 years, body mass index 32.6 ± 6.7 kg/m2, 36% female, 75% White) included 100 participants with paroxysmal AF. Longer sleep latency was associated with lower HFP during wakefulness (coefficient - 0.0501, p = 0.031). Higher sleep efficiency was associated with increased SDNN (coefficient 0.0007, p = 0.014) and CV (coefficient 0.0167, p = 0.047). Higher arousal index was associated with increased CV (coefficient 0.0166, p = 0.007) and LFP (coefficient 0.0232, p = 0.003). During sleep, longer average awakenings duration was associated with increased LFP/HFP ratio (coefficient 0.1977, p < 0.001) and reduced HFP (coefficient - 0.1338, p < 0.001). Significant sleep-wake interactions were observed for sleep latency with HFP (p = 0.024), sleep efficiency with SDNN and CV (both p < 0.01), WASO with SDNN, CV, and LFP (all p < 0.05), and frequency of awakenings with CV and LFP (both p < 0.05).

Actigraphy-based measures of sleep disruption were associated with autonomic function alterations exhibiting diurnal variability in paroxysmal AF. Greater overall HRV and parasympathetic modulation were related to better sleep quality. Increased sympathetic activation was associated with sleep fragmentation. Results provide insights into differential autonomic dysfunction related to sleep disruption that may contribute to atrial arrhythmogenesis.

ObjectiveThe coronavirus disease 2019 (COVID-19) pandemic illustrated the relationship between cardiac arrhythmias and pro-inflammatory states. Pro-inflammatory cytokines, including interleukin-6 (IL-6), have significant effects on cardiac conduction. Atrial or ventricular arrhythmias occurring while infected results in a doubling of mortality. Tocilizumab, a monoclonal antibody that blocks the IL-6 receptor, is associated with improved mortality and is believed to be related to immune modulation of the COVID-19-related hyperinflammatory state.MethodsA single-center retrospective review of all patients with severe COVID-19, defined as admission to an intensive care unit or requirement of respiratory or circulatory support, from March 2020 through March 2022, was conducted. Patients who received or did not receive tocilizumab were grouped into the treatment and control groups, respectively.ResultsFour hundred seventy-three patients were reviewed and 400 met the criteria for inclusion in our study. There were 305 patients (age, 63 ± 13 years, 58% male) in the control group and 95 (age, 57 ± 15 years, 51% male) in the treatment group. In-hospital mortality was greatly reduced with tocilizumab compared with controls (44.2% vs 85.9%, p < 0.001) and new-onset atrial fibrillation (AF) showed a statistically significant reduction (17.8% vs 29.5%, p = 0.019). New-onset wall motion abnormalities, potentially related to myocarditis or acute coronary syndrome, also trended toward significance with tocilizumab (7.7% vs 15.7%, p = 0.10). Deep vein thrombosis, pulmonary embolism, stroke, and sustained ventricular arrhythmias did not meet statistical significance.ConclusionAs expected, tocilizumab did show significant improvement in mortality. Tocilizumab also showed a significant reduction of new-onset AF. Other cardiac structural endpoints did not reach statistical significance.Abstract PresentationsA preliminary version of this research was presented during a regional conference at the Mid-Atlantic Capital Cardiology Symposium (MACCS) on 19 November 2023.

Enhanced inflammatory signalling causally contributes to atrial fibrillation (AF) development. Gasdermin D (GSDMD) is an important downstream effector of several inflammasome pathways. However, the role of GSDMD, particularly the cleaved N-terminal (NT)-GSDMD, in non-immune cells remains elusive. This study aimed to elucidate the function of NT-GSDMD in atrial cardiomyocytes (ACMs) and determine its contribution to atrial arrhythmogenesis.

Human atrial appendages were used to assess the protein levels and localization. A modified adeno-associated virus 9 was employed to establish ACM-restricted overexpression of NT-GSDMD in mice.

The cleavage of GSDMD was enhanced in ACMs of AF patients. Atrial cardiomyocyte-restricted overexpression of NT-GSDMD in mice increased susceptibility to pacing-induced AF. The NT-GSDMD pore formation facilitated interleukin-1β secretion from ACMs, promoting macrophage infiltration, while up-regulating 'endosomal sorting complexes required for transport'-mediated membrane-repair mechanisms, which prevented inflammatory cell death (pyroptosis) in ACMs. Up-regulated NT-GSDMD directly targeted mitochondria, increasing mitochondrial reactive oxygen species (ROS) generation, which triggered proarrhythmic calcium-release events. The NT-GSDMD-induced arrhythmogenesis was mitigated by the mitochondrial-specific antioxidant MitoTEMPO. A mutant NT-GSDMD lacking pore-formation capability failed to cause mitochondrial dysfunction or induce atrial arrhythmia. Genetic ablation of Gsdmd prevented spontaneous AF development in a mouse model.

These findings establish a unique pyroptosis-independent role of NT-GSDMD in ACMs and arrhythmogenesis, which involves ROS-driven mitochondrial dysfunction. Mitochondrial-targeted therapy, either by reducing ROS production or inhibition of GSDMD, prevents AF inducibility, positioning GSDMD as a novel therapeutic target for AF prevention.

Atrial fibrillation (AF) is a prevalent arrhythmia in hypertensive patients and significantly increases mortality. Chronic inflammation plays a critical role in the pathophysiology of AF.

This study aimed to evaluate the prognostic value of systemic immune-inflammation index (SII) in predicting AF recurrence after catheter ablation in hypertensive patients.

This retrospective cohort study included 418 hypertensive patients with paroxysmal AF who underwent catheter ablation between January 2019 and January 2023. Cox proportional hazards models, restricted cubic spline (RCS) analysis, and receiver operating characteristic (ROC) curves were used to evaluate the association between SII and AF recurrence. The predictive performance of SII was compared with that of C-reactive protein (CRP) and high-sensitivity C-reactive protein (hsCRP). Sensitivity analyses were performed to assess the robustness of findings.

AF recurrence occurred in 17.94% of patients. SII was an independent predictor of recurrence (HR 1.13, 95% CI 1.09-1.19; P < .001). RCS analysis revealed a nonlinear relationship with a threshold of 457.41 × 109/L, above which the risk of recurrence increased markedly. ROC analysis demonstrated that SII had superior predictive performance compared to CRP and hsCRP (AUC 0.688 vs 0.510 and 0.542). Sensitivity analyses confirmed the robustness of SII across subgroups.

SII is a valuable marker for predicting AF recurrence postablation in hypertensive patients. It supports inflammation-based risk assessments and should be considered in clinical risk stratification. Further research is needed to explore inflammation-targeted therapies.

This review critically examines the evolving role of C-reactive protein (CRP) in cardiovascular disease (CVD), addressing its pathogenesis and relationship with various CVDs including coronary artery disease (CAD), heart failure, and atrial fibrillation.

CRP is mechanistically implicated in endothelial dysfunction, oxidative stress, and plaque destabilization. Recent studies demonstrate that lipid-lowering agents (statins, bempedoic acid) and anti-inflammatory therapies (canakinumab, colchicine) reduce CRP levels and improve outcomes in CAD. In heart failure, elevated CRP predicts adverse events, though evidence on phenotypes varies, and novel therapies (glucagon-like peptide-1 agonists, sodium-glucose cotransporter-2 inhibitors) lower CRP independently of weight loss. For atrial fibrillation, CRP correlates with postoperative incidence and recurrence postablation, though data remain inconsistent. Guidelines offer differing opinion with the American College of Cardiology and the American Heart Association (ACC/AHA) guidelines cautiously endorsing CRP for risk stratification in intermediate-risk individuals, while European guidelines advise against its routine use for primary prevention, reflecting unresolved questions about CRP's additive value.

CRP remains a pivotal inflammation biomarker in CVD, yet its causal role and clinical applicability require clarification. While CRP-guided therapies show promise, discrepancies in guidelines highlight the need for robust trials to determine whether targeting CRP directly improves outcomes. Future research should focus on CRP's pathophysiological mechanisms and validate its utility in personalized CVD management.

Decreased left atrial appendage emptying velocity (LAAV) is a marker for thrombus formation. This study evaluates the association between LAAV and inflammatory indices in non-valvular atrial fibrillation (AF) patients.

The study population was 1428 patients with AF, 875 of whom enrolled. Based on the LAAV, patients were divided into three groups of 262 patients with a velocity of <25 cm/s, 360 patients with a velocity of 25 to 55 cm/s, and 253 patients with a velocity of >55 cm/s to assess and compare in terms of inflammatory indices, including the platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, systemic immune inflammation index, neutrophil - to - platelet ratio and white blood cell-to-platelet ratio (WPR).

There was no statistical difference in the level of inflammatory indices between the three groups, and none of them were related to LAAV (p > .05) except WPR with a weak negative correlation (p = 0.01, r = -0.10). Patients with lower LAAV were found to have a higher age (p = 0.001), decreased left ventricular ejection fraction (p = 0.001) and greater left atrial volume index (p = 0.001).

This study did not show any association between inflammatory indices and LAAV in non-valvular AF patients except for the WPR.

Atrial fibrillation (AF) is a common arrhythmia in critically ill patients. The objective of this narrative review is to evaluate the characteristics of patients who develop new-onset atrial fibrillation (NOAF) because of sepsis, current management of NOAF in sepsis patients, special consideration in different populations that developed NOAF, health economic and quality of life of patients. We conducted a literature search on PubMed to find research related to NOAF, sepsis and critical illness. Nineteen studies were analyzed for risk factors and outcomes. The incidence rate ranges from 0.53% to 43.9% among these studies. There were numerous risk factors that had been reported from these articles. The most reported risk factors included advanced age, male sex, White race, and cardiovascular comorbidities. The management of septic patients is significantly challenging because of the unfavorable cardiovascular consequences and thromboembolic hazards associated with NOAF. There are comprehensive guidelines available for managing AF, but the effectiveness and safety of therapies in patients with sepsis are still uncertain. Various approaches for managing newly diagnosed AF have been explored. Sinus rhythm can be restored through either pharmacological or non-pharmacological intervention or combination of both. In addition, thromboembolism is a complication that can occur in patients with AF and can have a negative impact on the prognosis of sepsis patients. The use of anticoagulation to prevent stroke after NOAF in sepsis patients is still controversial. Extensive prospective investigations are required to have a deeper understanding of the necessity for anticoagulation following NOAF in sepsis. Beside the treatment of NOAF, early detection of NOAF in sepsis plays a critical role. The prompt initiation of rhythm control medication following a clinical diagnosis of AF can enhance cardiovascular outcomes and reduce mortality in patients with AF and cardiovascular risk factors. Additionally, NOAF in the intensive care unit can prolong hospital stays, increasing hospitalization costs and burdening the hospital. Therefore, preventing and managing NOAF effectively not only benefit the patients but also the hospital in financial aspect. Lastly, to address the existing gaps in knowledge, future research should focus on developing machine learning models that can accurately anticipate risks, establish long-term follow-up protocols, and create complete monitoring systems. The focus is on early intervention and personalized approaches to improve outcomes and quality of life.

The relationship between gastroesophageal reflux disease (GERD) and atrial fibrillation (AF) has been increasingly recognized, but its nature and strength remain unclear. We conducted a systematic review and meta-analysis of studies from January 2010 to November 2024 using PubMed, Excerpta Medica Database (EMBASE), and Web of Science databases. Seven studies were included: three cohort studies, two Mendelian randomization studies, one case-control study, and one cross-sectional study. Meta-analysis revealed that GERD was associated with a significantly increased risk of AF (RR: 1.27, 95% CI: 1.15-1.40). This association remained robust in sensitivity analyses. The two Mendelian randomization studies provided genetic evidence supporting a potential causal relationship. The proposed mechanism involves inflammatory pathways extending from the esophagus to the left atrium. The analysis was constrained by the small number of studies, methodological heterogeneity (I-Square: 81%), and limited ability to perform subgroup analyses. The findings suggest that GERD patients may benefit from AF screening, and GERD management could potentially modify AF risk. Future research should focus on prospective studies examining the impact of GERD treatment on AF prevention and progression, as well as identifying high-risk subgroups who might benefit most from targeted interventions.

Colchicine is an anti-inflammatory herbal medicine with a history stretching back thousands of years. It is a cornerstone in the acute and prophylactic treatment of gout and has secured a permanent place in the standard pharmacological repertoire for familial Mediterranean fever, pericarditis, neutrophilic dermatoses, Behçet's disease and severe aphthous ulcers refractory to oral treatment. The US Food and Drug Administration (FDA) has recently approved colchicine to reduce the risk of myocardial infarction, stroke, coronary revascularization and cardiovascular death in adult patients with established atherosclerotic disease or with multiple risk factors for cardiovascular diseases. The recommendation level for cardiovascular prophylaxis was raised from IIb to IIa in the current European Society of Cardiology (ESC) guidelines from 2024. Clinical studies in recent years also demonstrated an effect for acute coronary syndrome and atrial fibrillation. This review article highlights the efficacy and safety profile of colchicine and provides insights into recent and potential future evidence-based fields of application.

New Onset Atrial Fibrillation (NOAF) is the most common arrhythmia in intensive care. Complications of NOAF include thromboembolic events such as myocardial infarction and stroke, which contribute to a greater risk of mortality. Inflammatory and coagulation biomarkers in sepsis are thought to be associated with NOAF development. The aim of this systematic review and narrative synthesis is to identify inflammatory and coagulation biomarkers as predisposing risk factors for NOAF in sepsis.

Three databases (Medline, Cochrane Library, and Scopus) were searched using a predefined search strategy. Inclusion / exclusion criteria were applied, and quality assessments were performed using the Newcastle Ottawa Scale (NOS).

We identified 1776 articles; and 12 articles were included in this review. 8 articles were retrospective observational studies and 4 were prospective observational studies. There was considerable heterogeneity between studies regarding outcomes, methodological design, quality, definitions and reported biomarkers of interest. There is evidence that C-reactive protein (CRP) is associated with NOAF, with hazard ratios 3.33 (3.32-3.35) p = 0.001 and odds ratios of 1.011 (1.008-1.014) p<0.001. International Normalised Ratio (INR) and fibrinogen may be associated with NOAF with odds ratios reported as 1.837 (1.270-2.656) p = 0.001 and 1.535(1.232-1.914) p<0.001 respectively.

Further research is required to confirm the association between inflammatory and coagulation biomarkers and the development of NOAF in sepsis. A broader evidence base will guide treatment strategies, improving the standard of care for patients who develop NOAF in sepsis. Furthermore, given the heterogeneity between studies consideration should be given to inclusion of immune biomarkers in future core outcome sets for trials investigating NOAF.

Although atrial fibrillation is the most common rhythm problem, the results of treatment to restore sinus rhythm are still not satisfactory. Nearly half of patients undergoing ablation relapse within one year. Therefore, triggered activities may not be the only cause. Inflammation is quite common in AF. In this study, we investigated the effect of PIV, an inflammatory marker, on recurrence.

A total of 157 patients who underwent ablation with cryo balloon were included in the study. One-year follow-up was evaluated for causes of recurrence.

When the inflammatory parameters between the two groups are analyzed, CRP (5.9 [5.0-6.9] vs 9.7 [7.6-11.9], p < 0.001), NL ratio (2.8 [2.5-3.0] vs 6.4 [5.0-6.8], p < 0.001), SII2 (618.5 [557.1-679.9] vs 1798.9 [1305.8-2292.1], p < 0.001), PIV (355.9 [313.4-398.4] vs 1832 [1317.8-2347.1], p < 001) were significantly higher in the AF recurrence group. ROC analysis showed that PIV had the best sensitivity and specificity.

Inflammation has been found to be a cause of AF recurrence and PIV is one of the best markers for this.

Preventing postoperative atrial fibrillation (POAF) as one of the most significant complications of cardiovascular surgeries remains a major clinical challenge. We conducted a systematic review with network meta-analysis of randomized controlled trials, to identify the most effective and safe anti-inflammatory drugs to prevent new-onset POAF.

MEDLINE, Embase, Web of Science, and Cochrane Library were searched without language or publication-date restriction on August 8, 2022 (updated on August 8, 2023). We assessed the risk of bias of included trials using the Cochrane risk-of-bias 2.0 tool. We conducted a frequentist random-effects network meta-analysis in R, and we assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach.

A total of 85 trials reported the incidence of new-onset POAF, including 18,981 patients. Use of nonsteroidal anti-inflammatory drugs (relative risk [RR] 0.37 [95% confidence interval [CI] 0.23-0.59]) and statins (RR 0.56 [95% CI 0.45-0.7]) potentially reduced the risk of POAF compared with placebo (both with a moderate certainty level). Use of fish oil in combination with vitamins C and E (RR 0.30 [95% CI 0.13-0.68]) may reduce the risk of POAF, compared with placebo (low level of certainty). Use of colchicine (RR 0.62 [95% CI 0.45- 0.85]), corticosteroids (RR 0.70 [95% CI 0.59-0.82]), and N-acetylcysteine (RR 0.69 [95% CI 0.49- 0.98]) may reduce the risk of POAF (all with a low level of certainty). None of the interventions had a significant effect on mortality rate or risk of serious adverse effects.

Use of nonsteroidal anti-inflammatory drugs and statins probably are effective in preventing new-onset POAF, with a moderate level of certainty, compared to placebo.

The effectiveness of statin use in preventing adverse cardiovascular events in individuals with atrial fibrillation (AF) has remained uncertain. This study aimed to assess whether statin use could lead to better outcomes among individuals with AF.

We enrolled 397 787 patients with AF from January 1, 2012 to December 31, 2020. Patients with AF were divided into 2 groups (statin user and statin nonuser), and the risks of composite outcomes (including ischemic stroke, hemorrhagic stroke, and transient ischemic attack), all-cause death, and major adverse cardiovascular events (which encompassed cardiovascular death, myocardial infarction, stroke, and heart failure hospitalization) were analyzed. We analyzed 288 958 patients with newly diagnosed AF (mean age, 73 years; 44% women; mean CHA2DS2-VASc score, 3.5). Compared with patients without statin use, statin users had lower risks of composite end points (adjusted hazard ratio [HR], 0.91 [95% CI, 0.87-0.94]; P<0.01). In regard to all-cause death, statin users exhibited a 67% risk reduction compared with statin nonusers (adjusted HR, 0.33 [95% CI, 0.32-0.33]; P<0.01). Statin use was also associated with reduced incidence of major adverse cardiovascular events (adjusted HR, 0.64 [95% CI, 0.63-0.66]; P<0.01). In the subgroups stratified by CHA2DS2-VASc score, statin therapy was particularly effective for patients with CHA2DS2-VASc scores 0 to 3 for composite end points but consistently reduced all-cause mortality and major adverse cardiovascular events across all score categories.

Among patients with newly diagnosed AF, statin use was associated with lower risk of ischemic stroke, hemorrhagic stroke, transient ischemic attack, all-cause mortality, and major adverse cardiovascular events.

The confirmed benefits of regular moderate exercise on cardiovascular health have positioned athletes as an illustration of well-being. However, concerns have arisen regarding the potential predisposition to arrhythmias in individuals engaged in prolonged strenuous exercise. Atrial fibrillation (AF), the most common heart arrhythmia, is typically associated with age-related risks but has been documented in otherwise healthy young and middle-aged endurance athletes. The mechanism responsible for AF involves atrial remodeling, fibrosis, inflammation, and alterations in autonomic tone, all of which intersect with the demands of endurance sports, cumulative training hours, and competitive participation. This unique lifestyle requires a tailored therapeutic approach, often favoring radiofrequency ablation as the preferred treatment. As the number of professional and non-professional athletes engaging in high-level daily sports activities rises, awareness of AF within this demographic becomes imperative. This review delivers the etiology, pathophysiology, and therapeutic considerations surrounding AF in endurance sports.

Left atrial epicardial adipose tissue (LA-EAT) is associated with the recurrence of atrial tachyarrhythmias (AF/AT) after catheter ablation for atrial fibrillation (AF). However, no previous studies have assessed the predictive value of segment-specific LA-EAT volumes for AF/AT recurrence. This study aimed to assess the relationship between segmental LA-EAT volume and AF/AT recurrence.

This study included 350 consecutive patients who underwent initial AF ablation (53.7 % paroxysmal AF (PAF)). Preoperative multidetector row computed tomography assessed LA-EAT, categorized into three segments: anterior-EAT, posterior-EAT, and interatrial septal adipose tissue (IAS-AT).

During a mean follow-up period of 351 ± 109 days, 56 patients (16.0 %) experienced AF/AT recurrence. The mean LA-EAT volume was 20.7 ± 11.1 ml and LA-EAT ≥26.8 ml was an independent risk factor for AF/AT recurrence (HR 2.21, 95 % confidence interval (CI): 1.24-3.93, P = 0.007). Receiver operating characteristic analyses revealed the area under the curve for IAS-AT was 0.669 (95 % CI: 0.596-0.743) with an optimal cut-off point of 1.3 ml (sensitivity 76.8 %; specificity 50.0 %), significantly outperforming the anterior- and posterior-EAT in predicting recurrent AF/AT. Multivariate analysis indicated IAS-AT was an independent predictor of AF/AT recurrence in patients with persistent AF (PeAF) (HR 3.52, 95 % CI: 1.52-8.13, P = 0.003), but not in patients with PAF.

LA-EAT predicts AF/AT recurrence after AF ablation, with IAS-AT proving significantly more effective than other LA-EAT segments in predicting recurrence. Notably, IAS-AT emerged as an independent predictor of AF/AT recurrence in patients with PeAF but not in those with PAF.

This study aimed to evaluate the ability of selected microRNAs as biomarkers of atrial fibrillation (AF) in ischemic stroke patients in comparison with other established biochemical biomarkers. A prospective case-control study of consecutive ischemic stroke patients with AF admitted to a comprehensive stroke center was conducted. The control group consisted of patients with ischemic stroke with no AF detected on prolonged (at least 3 weeks) Holter ECG monitoring. As potential biomarkers of AF, we analyzed the plasma levels of microRNAs (miR-21, miR-29b, miR-133b, miR-142-5p, miR-150, miR-499, and miR-223-3p) and 13 biochemical biomarkers at admission. The predictive accuracy of biomarkers was assessed by calculating the area under the receiver operating characteristic curve. The data of 117 patients were analyzed (61 with AF, 56 with no AF, 46% men, median age 73 years, median National Institutes of Health Stroke Scale 6). Biochemical biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP], high-sensitivity cardiac troponin I, fibrinogen, C-reactive protein, eGFR, and total triglycerides) were significantly associated with AF. NT-proBNP had the best diagnostic performance for AF with area under the receiver operating characteristic curve 0.92 (95%, CI 0.86-0.98); a cutoff value of >528 ng/L had a sensitivity of 79% and a specificity of 97%. None of the other biomarkers, including microRNAs, was associated with AF. Conventional biochemical biomarkers (NT-proBNP, high-sensitivity cardiac troponin I, fibrinogen, C-reactive protein, eGFR, and triglycerides), but not microRNAs (miR-21, miR-29b, miR-133b, miR-142-5p, miR-150, miR-499, and miR-223-3p) were significantly associated with AF in our ischemic stroke cohort.

Previous studies have found that inflammatory proteins are involved in the pathogenesis of atrial fibrillation (AF). We used mendelian randomization to explore the potential pathogenic inflammatory proteins of AF.

This study adopts a Mendelian randomization design to primarily assess causal associations using the Wald ratio and the inverse variance weighting method. It leverages protein quantitative trait locus (pQTL) data encompassing 91 types of inflammatory proteins from 14,824 participants of European ancestry. The primary analysis phase utilizes AF GWAS data from 55,106 participants, with an additional 237,690 participants included in the validation stage. Sensitivity analyses, including reverse causality analysis, Bayesian colocalization analysis, and phenotype scanning, were conducted. Finally, the study explores potential targeted drugs.

The findings highlight a causal link between 7 inflammatory proteins and AF, with 2 showing positive correlations and 5 exhibiting negative correlations. Among these, fibroblast growth factor 5 (FGF5) emerges as particularly robust in sensitivity analysis. Colocalization analysis indicates a shared genetic variation between FGF5 and AF, supporting its potential as a targeted therapy for AF. Importantly, this causal relationship remains unaffected by reverse causality. Furthermore, significant pleiotropic effects were observed in phenotype scanning. Finally, the causal association between FGF5 and AF was successfully replicated during the validation phase.

FGF5 may become an intervention target for AF targeted therapy.

Heart failure and chronic kidney disease are common and clinically important conditions that regularly coexist. Electrophysiologic changes of advanced heart failure often result in abnormal conduction, causing dyssynchronous contraction, and development of ventricular arrhythmias, which can lead to sudden cardiac arrest. In the last 2 decades, implantable cardioverter-defibrillator and cardiac resynchronization therapy devices have been developed to address these complications. However, when the coexisting chronic kidney disease is advanced, the associated pathophysiologic cardiovascular changes can alter the efficacy and safety of those interventions and complicate the management. This review explores the impact of comorbid advanced heart failure and advanced chronic kidney disease on the efficacy and safety of implantable cardioverter-defibrillator and cardiac resynchronization therapy, the currently available evidence, and potential future directions.

Atrial fibrillation (AF) is one of the most prevalent cardiac arrhythmias and has a significant economic and social burden. Whether it is associated with lifestyle behaviors and socioeconomic status is currently poorly understood. This study aimed to explore the relationship among these factors and determine the role of inflammatory cytokines.

We investigated the causal effects of lifestyle behaviors and socioeconomic status on AF using bidirectional two-sample Mendelian randomization (MR). Instrumental variables were obtained from a publicly available genome-wide association study. A two-step MR was conducted to determine the mediating role of 91 inflammatory cytokines. Inverse variance weighted was used as the main method with four supplementary MR methods. To obtain more robust results, several sensitivity analyses were conducted.

The results indicated that seven of the lifestyle behaviors [smoking initiation, vegetable intake, coffee consumption (cups/day), dozing, lifetime smoking index, napping, and alcohol abuse] were potential risk factors for AF. One socioeconomic status, education attainment (years of education), was causally associated with a decreased risk of AF. Moreover, we found that thymic stromal lymphopoietin, CD40l receptor, C-X-C motif chemokine 6, and C-X-C motif chemokine 11 levels mediated the causal effect, at proportions of 13.6%, 4.1%, 4.3%, and 6.9%, respectively.

Our findings provide insight into the relationship between lifestyle behaviors, socioeconomic status, and AF. Inflammatory cytokines are potential mediators of this relationship.

Sleep apnea is a widespread and yet still underdiagnosed condition. Various studies from the past have provided evidence that there is a link between sleep apnea and various cardiovascular diseases, including arrhythmias.

The aim of this article is to provide an overview of the current study situation and to point out possible consequences relevant to everyday life.

A systematic search was carried out in various databases using the keywords sleep apnea (OSAS/SA) and arrhythmias/dysrhythmias.

There are several pathophysiological links between sleep-related breathing disorders and cardiac arrhythmias, the most important of which appear to be intrathoracic pressure, increased adrenergic tone as well as recurrent hypoxia and hypercapnia. This results in an increased occurrence of clinically relevant arrhythmias, such as atrial fibrillation, symptomatic bradycardia, high-grade atrioventricular (AV) blocks as well as ventricular arrhythmias in patients with untreated sleep apnea. These pathologies also appear to be positively influenced by the treatment of sleep apnea.

A close correlation between sleep apnea and cardiac arrhythmias is undisputed. Large randomized studies in this respect are so far rare but it is undisputed that a thorough search should be carried out for sleep apnea and consistently treated in patients with a history of cardiac disease as this can have a relevant influence on the treatment and ultimately the prognosis of the patient.

The concept of "atrial cardiomyopathy" (AtCM) had been percolating through the literature since its first mention in 1972. Since then, publications using the term were sporadic until the decision was made to convene an expert working group with representation from four multinational arrhythmia organizations to prepare a consensus document on atrial cardiomyopathy in 2016 (EHRA/HRS/APHRS/SOLAECE expert consensus on atrial cardiomyopathies: definition, characterization, and clinical implication). Subsequently, publications on AtCM have increased progressively.

The present consensus document elaborates the 2016 AtCM document further to implement a simple AtCM staging system (AtCM stages 1-3) by integrating biomarkers, atrial geometry, and electrophysiological changes. However, the proposed AtCM staging needs clinical validation. Importantly, it is clearly stated that the presence of AtCM might serve as a substrate for the development of atrial fibrillation (AF) and AF may accelerates AtCM substantially, but AtCM per se needs to be viewed as a separate entity.

Thus, the present document serves as a clinical consensus statement of the European Heart Rhythm Association (EHRA) of the ESC, the Heart Rhythm Society (HRS), the Asian Pacific Heart Rhythm Society (APHRS), and the Latin American Heart Rhythm Society (LAHRS) to contribute to the evolution of the AtCM concept.

Neutrophil-activating peptide 2 (NAP-2, CXCL7), a platelet-derived neutrophil chemoattractant, is involved in inflammation. We investigated associations between NAP-2 levels, neutrophil extracellular traps (NETs) formation, and fibrin clot properties in atrial fibrillation (AF). We recruited 237 consecutive patients with AF (mean age, 68 ± 11 years; median CHA2DS2VASc score of 3 [2-4]) and 30 apparently healthy controls. Plasma NAP-2 concentrations were measured, along with plasma fibrin clot permeability (Ks) and clot lysis time (CLT), thrombin generation, citrullinated histone H3 (citH3), as a marker of NETs formation, and 3-nitrotyrosine reflecting oxidative stress. NAP-2 levels were 89% higher in AF patients than in controls (626 [448-796] vs. 331 [226-430] ng/ml; p < 0.0001). NAP-2 levels were not associated with demographics, CHA2DS2-VASc score, or the AF manifestation. Patients with NAP-2 in the top quartile (> 796 ng/ml) were characterized by higher neutrophil count (+ 31.7%), fibrinogen (+ 20.8%), citH3 (+ 86%), and 3-nitrotyrosine (+ 111%) levels, along with 20.2% reduced Ks and 8.4% prolonged CLT as compared to the remaining subjects (all p < 0.05). NAP-2 levels were positively associated with fibrinogen in AF patients (r = 0.41, p = 0.0006) and controls (r = 0.65, p < 0.01), along with citH3 (r = 0.36, p < 0.0001) and 3-nitrotyrosine (r = 0.51, p < 0.0001) in the former group. After adjustment for fibrinogen, higher citH3 (per 1 ng/ml β = -0.046, 95% CI -0.029; -0.064) and NAP-2 (per 100 ng/ml β = -0.21, 95% CI -0.14; -0.28) levels were independently associated with reduced Ks. Elevated NAP-2, associated with increased oxidative stress, has been identified as a novel modulator of prothrombotic plasma fibrin clot properties in patients with AF.

Atrial fibrillation (AF) is characterized by the absence of p-waves on ECG and irregular rhythm. It often presents with palpitations either palpitations may occur acutely over a short period or intermittently over several years. Other cardinal symptoms of atrial fibrillation include fatigue, dyspnea, and lightheadedness; it is important however to note that most affected individuals are asymptomatic. Concurrently, sleep disorders such as obstructive sleep apnea (OSA), insomnia, narcolepsy, and circadian rhythm disorders which are a group of conditions associated with the body's internal clock that affect the timing of sleep and alertness, are raising concerns due to their potential associations to arrhythmias. This review explores the bidirectional relationship between AF and sleep disorders, highlighting their implications for risk stratification and management strategies.

The narrative approach of this review synthesizes evidence from numerous studies obtained through meticulous literature searches. Specific sleep disorders with a bidirectional relationship with AF are the focus, with scrutiny on the prevalence of this connection. The examination delves into the pathophysiology of sleep-related autonomic dysregulation and inflammation, emphasizing potential management modalities. Various meta-analysis cohorts have highlighted a strong connection between sleep disorders and atrial fibrillation (AF). Patients with sleep disorders, especially OSA, have a higher likelihood of developing AF, and conversely, those with AF are more prone to sleep disorders. This impact is not limited to development, as sleep disorders also contribute to the progression of AF, with AF, in turn, negatively impacting sleep duration and quality. Sleep disorders may play an important role in atrial remodeling as well as electrophysiological abnormalities, rendering the atrial tissue more susceptible to arrhythmogenesis. The narrative review suggests that treating sleep disorders could not only improve sleep quality but also reduce risk factors associated with atrial fibrillation. The effective management of sleep disorders emerges as a potential challenge in preventing and treating atrial fibrillation.

In conclusion, this narrative study highlights the bidirectional relationship between sleep disorders and atrial fibrillation. There is a positive correlation, affecting the development, progression, and management of atrial fibrillation. The detrimental impact of sleep disorders on atrial remodeling and electrophysiological abnormalities underscores the significance of their diagnosis and treatment. Education about the importance of sleep and the benefits of sleep disorder treatment becomes imperative for patients with AF and sleep disorders.

Rate control (RC; meanHRHolter ≤ 125 bpm) increases survival in dogs with atrial fibrillation (AF). The mechanisms remain unclear.

Investigate echocardiographic and biomarker differences between RC and non-RC (NRC) dogs. Determine if changes post-anti-arrhythmic drugs (AAD) predict successful RC in subsequent Holter monitoring. Evaluate if early vs late RC affects survival.

Fifty-two dogs with AF.

Holter-derived mean heart rate, echocardiographic and biomarker variables from dogs receiving AAD were analyzed prospectively at each re-evaluation and grouped into RC or NRC. The primary endpoint was successful RC. Between group comparisons of absolute values, magnitude of change from admission to re-evaluations and end of study were performed using Mann-Whitney tests or unpaired t-tests. Logistic regression explored variables associated with inability to achieve RC at subsequent visits. Kaplan-Meier survival analysis was used to compare survival time of early vs late RC.

At visit 2, 11/52 dogs were RC; at visit 3, 14/52 were RC; and at visit 4, 4/52 were RC. At the end of study, 25/52 remained NRC. At visit 2, both groups had increased cardiac dimensions, but NRC dogs had larger dimensions; biomarkers did not differ. At the end of study, RC showed decreased cardiac dimensions and end-terminal pro-brain natriuretic peptide (NT-proBNP) compared with NRC. No variables were useful at predicting RC success in subsequent visits. Survival analysis found no differences between early vs late RC.

The RC dogs had decreased cardiac dimensions and NT-proBNP, suggesting HR-mediated reverse-remodeling might benefit survival, even with delayed RC achievement. Pursuit of RC is crucial despite initial failures.

Atrial fibrillation (AF) is the most common rhythm disturbance seen in clinical practice. Evidence emerged that suggested inflammation was associated with risk of AF. Helicobacter pylori (HP) cause gastric and esophageal inflammation, as well as systemic and vascular inflammation. These local and systemic inflammatory effects may increase the risk of AF. The pathogenesis of atrial fibrillation (AF) remains unknown. However, many recent studies point to an association between AF and inflammation because of a demonstrable significant correlation between the dysrhythmia and various biomarkers of inflammation. Given the suggested involvement of inflammation with this dysrhythmia, an initiating factor for inflammation has been sought. Chronic bacterial infection is the most likely event to initiate and maintain an inflammatory process. Recently, bacterial infections have been hypothesized to be involved in the pathogenesis of AF, and Helicobacter pylori and Chlamydia pneumoniae are two bacteria that have aroused interest. The aim of this study was to compare the prevalence of H. Pylori infection, proven by gastric biopsy, between AF patients and control group and the role of CRP, MPV, age and sex in patients with HP associated AF.

We investigated one hundred eighty patients with HP in whom gastroscopy was done and/or urea breathe test because of dyspepsia and epigastric discomfort for eventual detecting the presence of H. pylori infection, and the prevalence of fibrillation in patients with HP, and whether age, sex, inflammatory markers are different in the two groups. The study was enrolled in the Department of Internal Medicine, Ziv Medical Center, Safed, Israel, from 2015 until 2019.

The prevalence is more pronounced in men with both atrial fibrillation and H. pylori, in terms of age we see that the incidence of atrial fibrillation is more relative in the older age P<0.001. There is no statistically significant difference in the inflammatory marker MPV between the two groups P<0.005. The levels of high-sensitivity C-reactive protein (hs-CRP) have been shown to be higher among patients with H. pylori with AF compared with the control group HP without AF statistically significant P<0.001.

There is a correlation between HP and AF, AF is more related to age and to an increased inflammation marker CRP in patients diagnosed with HP.

Aim: The index study aimed to investigate the clinical impact of initial high-sensitivity C-reactive protein (hs-CRP) on outcomes in nonvalvular atrial fibrillation (AF). Methods: Single-center, prospective, observational study recruiting all recently diagnosed treatment-naive AF patients. Hs-CRP was measured at baseline and patients were followed for 24 months. Results: A total of 126 patients with a mean age of 66.2 (±12.0) years were enrolled. The composite outcome of major adverse cardiac or cerebrovascular events (MACCE) occurred in 19 (17.7%) at 24 months. Raised initial hs-CRP emerged as an independent predictor of MACCE on regression analysis (OR: 1.569, 95% CI: 1.289-1.912; p < 0.001). Conclusion: Raised hs-CRP was an independent predictor of MACCE at 24 months. It allows for early identification of high-risk patients.

Obesity increases the risk of atrial fibrillation (AF), potentially through proteins secreted by adipose tissue (AT) that affect atrial electrical and structural remodeling. We aim to give a comprehensive overview of circulating AT proteins involved in inflammation and fibrosis, that are associated with prevalent AF (paroxysmal or persistent) and the risk on developing new-onset AF. These include adipokines, defined as proteins enriched in AT as adiponectin, but also proteins less specific to AT. We systematically performed an explorative search for studies reporting associations between proteins secreted from cells residing in the AT and AF, and additionally assessed the effect of obesity on these proteins by a secondary search. The AT proteins involved in inflammation were mostly increased in patients with prevalent and new-onset AF, and with obesity, while the AT enriched adipokines were mostly not associated with AF. This review provides insight into circulating adipose tissue proteins involved in AF substrate formation.

Recent studies suggest that bioactive mediators called resolvins promote an active resolution of inflammation. Inflammatory signalling is involved in the development of the substrate for atrial fibrillation (AF). The aim of this study is to evaluate the effects of resolvin-D1 on atrial arrhythmogenic remodelling resulting from left ventricular (LV) dysfunction induced by myocardial infarction (MI) in rats.

MI was produced by left anterior descending coronary artery ligation. Intervention groups received daily intraperitoneal resolvin-D1, beginning before MI surgery (early-RvD1) or Day 7 post-MI (late-RvD1) and continued until Day 21 post-MI. AF vulnerability was evaluated by performing an electrophysiological study. Atrial conduction was analysed by using optical mapping. Fibrosis was quantified by Masson's trichrome staining and gene expression by quantitative polymerase chain reaction and RNA sequencing. Investigators were blinded to group identity. Early-RvD1 significantly reduced MI size (17 ± 6%, vs. 39 ± 6% in vehicle-MI) and preserved LV ejection fraction; these were unaffected by late-RvD1. Transoesophageal pacing induced atrial tachyarrhythmia in 2/18 (11%) sham-operated rats, vs. 18/18 (100%) MI-only rats, in 5/18 (28%, P < 0.001 vs. MI) early-RvD1 MI rats, and in 7/12 (58%, P < 0.01) late-RvD1 MI rats. Atrial conduction velocity significantly decreased post-MI, an effect suppressed by RvD1 treatment. Both early-RvD1 and late-RvD1 limited MI-induced atrial fibrosis and prevented MI-induced increases in the atrial expression of inflammation-related and fibrosis-related biomarkers and pathways.

RvD1 suppressed MI-related atrial arrhythmogenic remodelling. Early-RvD1 had MI sparing and atrial remodelling suppressant effects, whereas late-RvD1 attenuated atrial remodelling and AF promotion without ventricular protection, revealing atrial-protective actions unrelated to ventricular function changes. These results point to inflammation resolution-promoting compounds as novel cardio-protective interventions with a particular interest in attenuating AF substrate development.

Sleep-disordered breathing (SDB) and atrial fibrillation (AF) are highly prevalent in patients with stroke and are recognized as independent risk factors for stroke. Little is known about the impact of comorbid SDB and AF on long-term outcomes after stroke.

In this prospective cohort study, 353 patients with acute ischemic stroke or transient ischemic attacks were analyzed. Patients were screened for SDB by respiratory polygraphy during acute hospitalization. Screening for AF was performed using a 7-day ECG up to 3× in the first 6 months. Follow-up visits were scheduled at 1, 3, 12, 24, and 36 months poststroke. Cox regression models adjusted for various factors (age, sex, body mass index, hypertension, diabetes, dyslipidemia, and heart failure) were used to assess the impact of comorbid SDB and AF on subsequent death or cerebro-cardiovascular events.

Among 353 patients (299 ischemic stroke and 54 transient ischemic attacks), median age, 67 (interquartile range, 57-74) years with 63% males. Moderate-to-severe SDB (apnea-hypopnea index score, ≥15/h) was present in 118 (33.4%) patients. Among the 56 (15.9%) patients with AF, 28 had comorbid moderate-to-severe SDB and AF. Over 36 months, there were 12 deaths and 67 recurrent cerebro-cardiovascular events. Patients with comorbid moderate-to-severe SDB and AF had a higher risk of subsequent death or cerebro-cardiovascular events compared with those with only moderate-to-severe SDB without AF (hazard ratio, 2.49 [95% CI, 1.18-5.24]) and to those without moderate-to-severe SDB or AF (hazard ratio, 2.25 [95% CI, 1.12-4.50]). However, no significant difference was found between the comorbid moderate-to-severe SDB and AF group and the group with only AF without moderate-to-severe SDB (hazard ratio, 1.64 [95% CI, 0.62-4.36]).

Comorbid moderate-to-severe SDB and AF significantly increase the risk of long-term mortality or recurrent cerebro-cardiovascular events after acute ischemic stroke. Considering both conditions as cumulative and modifiable cerebro-cardiovascular risk factors is of interest for the management of acute stroke.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT02559739.

Previous observational studies indicated that atrial fibrillation may increase the risk of breast cancer. Following a breast cancer diagnosis, the chance of developing atrial fibrillation may increase as well. However, it is uncertain whether the link is causal or just due to confounding factors.

Using bidirectional Mendelian randomization (MR) analysis, we sought to assess the bidirectional causal relationship between atrial fibrillation and breast cancer from a genetic level.

Large genome-wide association studies yielded summary-level data for atrial fibrillation and breast cancer. The preliminary estimate was inverse variance weighted (IVW) under a random model. MR-Egger, weighted median, simple mode, weighted mode, and multivariable MR (adjusting body mass index, smoking, and alcohol drinking) were performed as sensitivity analyses.

Genetically predicted atrial fibrillation presented no statistically significant association with overall breast cancer (odds ratio [OR] = 1.00; 95% confidence interval [CI]: 0.97-1.04; p = 0.79), estrogen receptor (ER) + (OR = 1.00; 95% CI: 0.96-1.03; p = 0.89) or ER- subtypes (OR = 1.00; 95% CI: 0.97-1.04; p = 0.89). Similarly, genetically predicted overall breast cancer (OR = 1.01; 95% CI: 0.98-1.04; p = 0.37), ER+ (OR = 1.02; 95% CI: 0.99-1.05; p = 0.16) or ER- (OR = 0.98; 95% CI: 0.93-1.02; p = 0.32) subtypes had no causal effect on atrial fibrillation. Sensitivity analyses yielded similar results. Individual single nucleotide polymorphism had little effect on the total estimate. We did not observe any evidence of horizontal pleiotropy.

Our bidirectional MR studies revealed that there may be no causal links between atrial fibrillation and breast cancer.