Pathophysiology Of Atrial Fibrillation Research Articles

Effects of Sex on the Susceptibility for Atrial Fibrillation in Pigs with Ischemic Heart Failure.

Atrial fibrillation (AF) is the most prevalent arrhythmia, often caused by myocardial ischemia/infarction (MI). Men have a 1.5× higher prevalence of AF, whereas women show a higher risk for new onset AF after MI. However, the underlying mechanisms of how sex affects AF pathophysiology are largely unknown. In 72 pigs with/without ischemic heart failure (IHF) we investigated the impact of sex on ischemia-induced proarrhythmic atrial remodeling and the susceptibility for AF. Electrocardiogram (ECG) and electrophysiological studies were conducted to assess electrical remodeling; histological analyses were performed to assess atrial fibrosis in male and female pigs. IHF pigs of both sexes showed a significantly increased vulnerability for AF, but in male pigs more and longer episodes were observed. Unchanged conduction properties but enhanced left atrial fibrosis indicated structural rather than electrical remodeling underlying AF susceptibility. Sex differences were only observed in controls with female pigs showing an increased intrinsic heart rate, a prolonged QRS interval and a prolonged sinus node recovery time. In sum, susceptibility for AF is significantly increased both in male and female pigs with ischemic heart failure. Differences between males and females are moderate, including more and longer AF episodes in male pigs and sinus node dysfunction in female pigs.

MicroRNAs as Biomarkers of Endothelial Dysfunction and Therapeutic Target in the Pathogenesis of Atrial Fibrillation.

The pathophysiology of atrial fibrillation (AF) may involve atrial fibrosis/remodeling and dysfunctional endothelial activities. Despite the currently available treatment approaches, the progression of AF, its recurrence rate, and the high mortality risk of related complications underlay the need for more advanced prognostic and therapeutic strategies. There is increasing attention on the molecular mechanisms controlling AF onset and progression points to the complex cell to cell interplay that triggers fibroblasts, immune cells and myofibroblasts, enhancing atrial fibrosis. In this scenario, endothelial cell dysfunction (ED) might play an unexpected but significant role. microRNAs (miRNAs) regulate gene expression at the post-transcriptional level. In the cardiovascular compartment, both free circulating and exosomal miRNAs entail the control of plaque formation, lipid metabolism, inflammation and angiogenesis, cardiomyocyte growth and contractility, and even the maintenance of cardiac rhythm. Abnormal miRNAs levels may indicate the activation state of circulating cells, and thus represent a specific read-out of cardiac tissue changes. Although several unresolved questions still limit their clinical use, the ease of accessibility in biofluids and their prognostic and diagnostic properties make them novel and attractive biomarker candidates in AF. This article summarizes the most recent features of AF associated with miRNAs and relates them to potentially underlying mechanisms.

Iron and atrial fibrillation: A review.

Atrial fibrillation (AF), one of the most common arrhythmias in clinical practice, is classified into paroxysmal, persistent, and permanent AF according to its duration. The development of AF is associated with increased cardiovascular morbidity and mortality. However, the exact etiology of this disease remains poorly understood. Recent studies found disorders of iron metabolism might be involved in the progression of AF. Abnormal iron metabolism in cardiomyocytes provides arrhythmogenic substrates through a variety of mechanisms, including calcium mishandling, ion channel remodeling, and oxidative stress overaction. Interestingly, in AF patients with iron overload, interventions on iron metabolism, such as iron chelators and ferroptosis inhibitors, has been shown to prevent AF via reducing ferroptosis. Herein, we review the possible mechanisms, consequences, and therapeutic implications of altered atrial iron handling for AF pathophysiology.

Abstract P101: Effect of an Intensive Lifestyle Intervention on Biomarkers of Atrial Fibrillation-Related Pathways Among Overweight Adults: The PREDIMED-PLUS Trial

Background: Lifestyles influence atrial fibrillation (AF) risk. Blood biomarkers can characterize the atrial substrate that facilitates the development of AF. Therefore, determining the effect of lifestyle interventions on blood concentrations of biomarkers of AF-related pathways could help understand AF pathophysiology and contribute to AF prevention. Methods: The PREDIMED-PLUS study is a Spanish multicenter randomized trial in adults (55-75 years) with metabolic syndrome and body mass index between 27-40 kg/m 2 . Participants were randomized 1:1 to an intensive lifestyle intervention (ILI) program, emphasizing physical activity, weight loss, and adherence to the Mediterranean diet, or a control intervention. In a sub-sample, serum biomarkers including carboxy-terminal propeptide of procollagen type I (PICP), high-sensitivity troponin T (hsTnT), high-sensitivity C reactive protein (hsCRP), N-terminal propeptide of B-type natriuretic peptide (NT-proBNP), and 3-nitrotyrosine (3-NT) were measured at baseline and years 3 and 5 after randomization. Mixed models were used to evaluate the effect of ILI on changes in biomarkers through years 3 and 5. Follow-up time was modeled as a categorical and continuous variable. Results: Of 481 participants (65 mean age, 40% female, 49% assigned to ILI), 453 (94%) and 442 (92%) had available samples at years 3 and 5. After 5 years, mean changes in log-transformed biomarkers were -0.01 (PICP), 0.20 (hsTnT), -0.17 (hsCRP), 0.12 (3-NT), and 0.25 (NT-proBNP). Participants in the ILI group experienced greater decreases in hsCRP or smaller increases in 3-NT, NT-proBNP, and in hsTnT to a lesser extent, as compared to the control group (Table). The ILI did not affect PICP concentrations. Results were consistent when modeling follow-up time as a continuous variable. Conclusion: Over five years, an ILI favorably affected concentrations of hsCRP, 3-NT, and NT-proBNP, and of hs-TnT to a lesser degree, pointing to specific mechanisms in the pathways linking lifestyles and AF.

Prognostic impact of plasma xanthine oxidoreductase activity in patients with heart failure with atrial fibrillation

BackgroundXanthine oxidoreductase (XOR) is a rate-limiting enzyme for uric acid (UA) production and plays an important role in generating reactive oxygen species (ROS). Overproduction of ROS is reported to contribute to the pathophysiology of atrial fibrillation (AF), however, the prognostic impact of plasma XOR activity in patients with heart failure (HF) with AF is undetermined. MethodsWe measured plasma XOR activity in 475 HF patients, including those with sinus rhythm (HF-SR, n = 211), and those with AF (HF-AF, n = 264). The type of AF included paroxysmal (n = 128) and persistent (n = 136) AF. All patients were prospectively followed up for a median period of 804 days. ResultsHF-AF patients had significantly higher plasma XOR activity and serum UA levels compared with HF-SR patients. Both plasma XOR activity and serum UA levels were higher in patients with persistent AF than in those with SR and with paroxysmal AF. Multivariate linear regression analysis showed that persistent AF was independently associated with increased XOR activity. During the follow-up period, there were 79 major adverse cardiovascular events (MACEs). HF-AF patients with MACEs had higher plasma XOR activity compared with those without MACEs, while there were no significant differences in serum UA levels. Multivariate Cox proportional analysis showed that high XOR activity was an independent risk factor for MACEs after adjustment for confounding factors. Kaplan-Meier analysis revealed that the high XOR activity group had a higher risk of MACEs than the low XOR activity group. The prediction model was significantly improved by the addition of XOR activity to the basic predictors. ConclusionsHF-AF patients had significantly higher plasma XOR activity compared with HF-SR patients. Plasma XOR activity proved to be a reliable indicator for MACEs in HF-AF patients.

Serum Catestatin Concentrations Are Increased in Patients with Atrial Fibrillation

The autonomic nervous system is crucial in initiating and maintaining atrial fibrillation (AF). Catestatin is a multipurpose peptide that regulates cardiovascular systems and reduces harmful, excessive activity of the sympathetic nervous system by blocking the release of catecholamines. We aimed to determine whether serum catestatin concentrations are associated with AF severity, duration indices, and various clinical and laboratory indicators in these individuals to better define the clinical value of catestatin in patients with AF. The present single center study enrolled 73 participants with AF and 72 healthy age-matched controls. Serum catestatin concentrations were markedly higher in AF patients than controls (14.11 (10.21-26.02) ng/mL vs. 10.93 (5.70-20.01) ng/mL, p = 0.013). Furthermore, patients with a more severe form of AF had significantly higher serum catestatin (17.56 (12.80-40.35) vs. 10.98 (8.38-20.91) ng/mL, p = 0.001). Patients with higher CHA2DS2-VASc scores (17.58 (11.89-37.87) vs. 13.02 (8.47-22.75) ng/mL, p = 0.034) and higher NT-proBNP levels (17.58 (IQR 13.91-34.62) vs. 13.23 (IQR 9.04-22.61), p = 0.036) had significantly higher serum catestatin concentrations. Finally, AF duration correlated negatively with serum catestatin levels (r = -0.348, p = 0.003). The results of the present study implicate the promising role of catestatin in the intricate pathophysiology of AF, which should be explored in future research.

Sex differences in electrophysiology of the intact atria.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with electrophysiological and calcium (Ca) handling remodeling. Though AF affects both sexes, there is disparity in the onset, presentation, treatment efficacy and outcomes of the disease: males develop AF earlier, but females experience abnormal symptoms, treatment side effects, and increased risk of mortality. Treatment success likely depends on the underlying arrhythmogenic substrate. However, sex-related differences in AF pathophysiology are currently unclear, complicated by sparse knowledge about how even the healthy atria differs between males and females. As such, this study aims to investigate sex differences in electrophysiology, Ca handling and arrhythmia susceptibility in the intact atria. Hearts were extracted from young (3-4 month) rabbits and optically mapped using voltage (RH237) and Ca-sensitive (Rhod-2 AM) indicators. Signals from the atria were isolated with minimal ventricular interference by covering all tissue beneath the coronary sulcus. Electrical stimulation was performed via a pacing electrode on the right atrium. Rapid pacing and premature stimuli protocols were performed to examine baseline electrophysiology and arrhythmia susceptibility that was further tested with pharmacological intervention with carbachol (0.5 µM). Females had longer action potential duration at 25% repolarization (APD25) but no difference in APD50, APD80 or Ca transient duration (CaTD50 or CaTD80) vs. males. There was similarly no difference in the pacing thresholds for emergence of alternans between sexes; however, females had steeper APD and CaTD restitution. Despite this, arrhythmia vulnerability was greater in males, with sustained reentry observed following application of carbachol and rapid pacing in 66% of animals. Our data suggests that males are more susceptible to reentrant arrhythmias due to innate differences in electrophysiology that may include autonomic modulation. Future work will focus on potential sex differences in the age-associated remodeling that predisposes to AF.

The higher recurrence rate after catheter ablation in younger patients with atrial fibrillation suggesting different pathophysiology.

Young atrial fibrillation (AF) patients have been underrepresented in studies of radiofrequency catheter ablation (RFCA) and the outcome of RFCA has not been widely addressed. We investigated age-related differences in clinical features, the recurrence of atrial tachyarrhythmia, and its predictors of patients who underwent RFCA for AF. This is a multicenter prospective study of 2799 patients who underwent RFCA for AF in 2017-2020. The patients were divided into two groups - group A (age < 60years, n = 1269) and group B (age ≥ 60years, n = 1530) - and a recurrence of any atrial tachyarrhythmia 1year after RFCA following a 90-day blanking period was compared. The mean age was 51.6 ± 6.7 and 66.8 ± 5.2years for groups A and B, respectively. Higher body mass index, smaller left atrium, and more prevalent cardiomyopathy and obstructive sleep apnea were observed in group A. Overall, 1-year atrial tachyarrhythmia-free survival was 85.6% and lower in young patients (83.1% in group A vs. 87.7% in group B, log-rank p < 0.01): adjusted hazard ratio (aHR) of recurrence (95% confidence interval (CI)), 1.45 (1.13-1.86) for group A compared to group B (p < 0.01). The association between younger age and higher recurrence was continuously observed in patients under 60years. Any non-PV ablation was associated with a lower recurrence of atrial tachyarrhythmia in group B (aHR 0.68 (0.47-0.96), p < 0.05), but not in group A. AF patients younger than 60years had a higher 1-year AF recurrence after RFCA. Young AF patients might have distinctive pathophysiology of AF requiring more integrated management.

Long non-coding RNA and circular RNA: new perspectives for molecular pathophysiology of atrial fibrillation.

Many studies have demonstrated the association of atrial fibrillation (AF) with endogenous genetic regulatory mechanisms. These interactions could advance the understanding of the AF pathophysiological process, supporting the search for early biomarkers to improve diagnosis and disease monitoring. Among the endogenous genetic regulatory mechanisms, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) have gained special attention, and studies have demonstrated their involvement in AF development and other AF-related diseases such as coronary artery disease and cardiomyopathy. This review describes the main experimental results reported by studies that analyzed the expression of lncRNAs and circRNAs in AF associated with miRNA or mRNA. The search was conducted in PubMed public database using the terms "lncRNA and atrial fibrillation" or "long ncRNA and atrial fibrillation" or "long non-coding RNA and atrial fibrillation" or "circular RNA and atrial fibrillation" or "circRNA and atrial fibrillation". There was no overlapping of lncRNA or circRNA among the studies, attributed to the different sample types, methods, species, and patient classification evaluated in these studies. Although the regulatory mechanisms in which these molecules are involved are not yet well understood, the studies analyzed show their importance in the pathophysiological process of AF, supporting the idea that lncRNAs and circRNAs are involved in miRNA or mRNA regulation in the molecular mechanism of this disease.

Development of Complementary Encounter and Patient Decision Aids for Shared Decision Making about Stroke Prevention in Atrial Fibrillation.

Decision aids (DAs) are helpful instruments used to support shared decision making (SDM). Patients with atrial fibrillation (AF) face complex decisions regarding stroke prevention strategies. While a few DAs have been made for AF stroke prevention, an encounter DA (EDA) and patient DA (PDA) have not been created to be used in conjunction with each other before. Using iterative user-centered design, we developed 2 DAs for anticoagulation choice and stroke prevention in AF. Prototypes were created, and we elicited feedback from patients and experts via observations of encounters, usability testing, and semistructured interviews. User testing was done with 33 experts (in AF and SDM) and 51 patients from 6 institutions. The EDA and PDA underwent 1 and 4 major iterations, respectively. Major differences between the DAs included AF pathophysiology and a preparation to meet with the clinician in the PDA as well as different language throughout. Content areas included personalized stroke risk, differences between anticoagulants, and risks of bleeding. Based on user feedback, developers 1) addressed feelings of isolation with AF, 2) improved navigation options, 3) modified content and flow for users new to AF and those experienced with AF, 4) updated stroke risk pictographs, and 5) added structure to the preparation for decision making in the PDA. These DAs focus only on anticoagulation for stroke prevention and are online, which may limit participation for those less comfortable with technology. Designing complementary DAs for use in tandem or separately is a new method to support SDM between patients and clinicians. Extensive user testing is essential to creating high-quality tools that best meet the needs of those using them. First-time complementary encounter and patient decision aids have been designed to work together or separately.User feedback led to greater structure and different experiences for patients naïve or experienced with anticoagulants in patient decision aids.Online tools allow for easier dissemination, use in telehealth visits, and updating as new evidence comes out.

Review article: diagnosis, pathophysiology and management of atrial fibrillation in cirrhosis and portal hypertension.

Atrial fibrillation (AF) is the most common arrhythmia and its management in cirrhosis can be challenging due to the altered hepatic metabolism of medications and increased risk of bleeding. To provide a comprehensive overview of the diagnosis, pathophysiology and management of AF in patients with cirrhosis from both a cardiology and a hepatology perspective. An extensive literature search was performed using the terms 'atrial fibrillation' and 'cirrhosis'. Guideline documents and consensus statements were explored. The prevalence of AF in patients with cirrhosis ranges between 6.6% and 14.2%, while the incidence of new-onset AF in the post-operative period after liver transplant ranged between 6.8% and 10.2%. AF in patients with cirrhosis is associated with adverse outcomes in both pre-transplant and post-transplant settings, including an increased risk of stroke when compared to the general population. We review the pathogenesis of AF in general and in cirrhosis. This review also provides guidance on the management of AF, including the use of anticoagulation and rate versus rhythm control. In the absence of strict contraindications, all patients with cirrhosis and AF should be anticoagulated. The use of DOACs is preferred over vitamin K antagonists. In patients with a high bleeding risk, a DOAC with an approved antidote may be preferred. Atrial fibrillation is increased in patients with cirrhosis. AF management requires careful consideration of treatment options. Since patients with cirrhosis were excluded from all major randomised clinical trials, dedicated research on the pathophysiology and management of AF in cirrhosis is needed.

Alarmins as a Possible Target of Future Therapies for Atrial Fibrillation.

To date, worldwide, atrial fibrillation is the most common cardiovascular disease in adults, with a prevalence of 2% to 4%. The trigger of the pathophysiological mechanism of arrhythmia includes several factors that sustain and exacerbate the disease. Ectopic electrical conductivity, associated with the resulting atrial mechanical dysfunction, atrial remodeling, and fibrosis, promotes hypo-contractility and blood stasis, involving micro endothelial damage. This causes a significant local inflammatory reaction that feeds and sustains the arrhythmia. In our literature review, we evaluate the role of HMGB1 proteins, heat shock proteins, and S100 in the pathophysiology of atrial fibrillation, offering suggestions for possible new therapeutic strategies. We selected scientific publications on the specific topics "alarmins" and "atrial fibrillation" from PubMed. The nonsystematic review confirms the pivotal role of molecules such as S100 proteins, high-mobility group box-1, and heat shock proteins in the molecular pattern of atrial fibrillation. These results could be considered for new therapeutic opportunities, including inhibition of oxidative stress, evaluation of new anticoagulant drugs with novel therapeutic targets, molecular and genetic studies, and consideration of these alarmins as predictive or prognostic biomarkers of disease onset and severity.

Mechanisms and Management of Thyroid Disease and Atrial Fibrillation: Impact of Atrial Electrical Remodeling and Cardiac Fibrosis.

Atrial fibrillation (AF) is the most common cardiac arrhythmia associated with increased cardiovascular morbidity and mortality. The pathophysiology of AF is characterized by electrical and structural remodeling occurring in the atrial myocardium. As a source of production of various hormones such as angiotensin-2, calcitonin, and atrial natriuretic peptide, the atria are a target for endocrine regulation. Studies have shown that disorders associated with endocrine dysregulation are potential underlying causes of AF. The thyroid gland is an endocrine organ that secretes three hormones: triiodothyronine (T3), thyroxine (T4) and calcitonin. Thyroid dysregulation affects the cardiovascular system. Although there is a well-established relationship between thyroid disease (especially hyperthyroidism) and AF, the underlying biochemical mechanisms leading to atrial fibrosis and atrial arrhythmias are poorly understood in thyrotoxicosis. Various animal models and cellular studies demonstrated that thyroid hormones are involved in promoting AF substrate. This review explores the recent clinical and experimental evidence of the association between thyroid disease and AF. We highlight the current knowledge on the potential mechanisms underlying the pathophysiological impact of thyroid hormones T3 and T4 dysregulation, in the development of the atrial arrhythmogenic substrate. Finally, we review the available therapeutic strategies to treat AF in the context of thyroid disease.

Conventional and Two-dimensional Strain Echocardiography in Predicting Postoperative Atrial Fibrillation after Coronary Artery Bypass Grafting Surgery in Shahid Madani Hospital of Tabriz, Iran

Objectives: Atrial fibrillation (AF) is a common complication of heart surgery with favorable short- and long-term outcomes. Preoperative left atrial (LA) dysfunction may be a significant component in identifying patients at risk for postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG (surgery. Advances in imaging technologies and an understanding of AF pathophysiology can lead to more definitive potential therapeutic approaches. The paper has the aim to present the role of conventional echocardiography and LA two-dimensional (2D) strain. 2D Strain echocardio graphies in assessing LA function in predict POAF after CABG surgery.&#x0D; Materials and Methods: In this study, all patients with sinus rhythm who underwent CABG surgery were selected. All the patients had undergone conventional echocardiography and LA 2D-strain echocardiography 24 hours before surgery. In addition to demographic, clinical, and intraoperative features, other assessments, including electrocardiogram (ECG) and Holter monitoring, were recorded. The obtained information was recorded, and the study results were reported using descriptive statistics (mean, standard deviation, and percentage frequency). A Chi-square test was used to evaluate the qualitative variables, and a t-test was used to compare the quantitative variables. Given the multi-factorial nature of AF, univariate and multivariate methods were used to analyze the data and the effect of STRAIN. In this study, P &lt; 0.05 was considered significant.&#x0D; Results: According to the findings, 85 patients (81%) were male with a mean age of 60.26 ± 10.61 years. 50% of the patients underwent off-pump CABG surgery, and 50% underwent on-pump surgery with a mean time of 98.52 ± 22.44 minutes. POAF was seen in 22.9% of patients during hospitalization, and AF's duration was 13.85 ± 14.41 hours. AF patients had higher LA volume index (LAVI) than non-AF patients (p = 0.018). There was no significant difference between the two groups in terms of left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), E/e, E/A,and deceleration time(DT) . Non-AF patients had higher rates of LA reservoir (26.97 ± 6.87 VS. 20.46 ± 4.27, p &lt;0.001), LA contractile (14.98 ± 3.68 VS. 12.76 ± 3.72, p =0.012) and LA global (24.28 ± 6.57 VS. 17.71 ± 4.11, p &lt;0.001) than AF patients. The results of the multivariate logistic regression showed that LAVI (p= 0.014) and LA global (p = 0.027) were significant predictors of AF detection. Thus with increasing LAVI, the probability of developing AF increases, and with decreasing LA global, this probability decreases.&#x0D; Conclusions: Compared to conventional echocardiography, 2D-strain echocardiography is a more effective diagnostic tool in predicting the possibility of post-CABG AF.

Association of Increased Fructose Consumption with Atrial Fibrillation Symptoms

Atrial fibrillation (AF) is the most common and increasingly common rhythm disorder . There is the AF classification model accepted by the European Society of Cardiology (ESC) and the European Heart Rhythm Society (EHRA) and the EHRA score (mEHRA score) for the evaluation of AF symptoms. Apart from its carbohydrate role, dietary fructose (as sucrose or high fructose corn syrup) has come to the fore in nutrition and dietetic studies whether it can be considered harmful or even a toxin by nature. High fructose consumption induces oxidative stress and thus causes mitochondrial damage in cells. In the light of this information, it is thought that high fructose consumption triggers mitochondrial dysfunction, which causes skeletal specific cells to enter the apoptosis pathway, by oxidative stress. Chronic fructose intake is thought to cause metabolic diseases and heart inflammation. Fructose consumption is the main dietary sugar that causes the progression of cardiovascular diseases and cardiac arrhythmias. AF patients admitted to the outpatient clinic were retrospectively scanned from the archive. Four groups of 40 patients were formed randomly according to EHRA scoring. Participants used a dietary record to provide details of nutrient consumption and all of the data from the 2 groups were compared. This study revealed statistically that a relationship between fructose consumption level and increased AF symptoms and mEHRA score (p<0,001), left atrium diameter and mEHRA score (p<0,001). Increased fructose consumption has been associated with increased AF symptoms. Excessive fructose consumption may play a role in AF pathophysiology.

Adenosine and Adenosine Receptors: Advances in Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia in the world. Because the key to developing innovative therapies that limit the onset and the progression of AF is to fully understand the underlying molecular mechanisms of AF, the aim of the present narrative review is to report the most recent advances in the potential role of the adenosinergic system in the pathophysiology of AF. After a comprehensive approach describing adenosinergic system signaling and the mechanisms of the initiation and maintenance of AF, we address the interactions of the adenosinergic system's signaling with AF. Indeed, adenosine release can activate four G-coupled membrane receptors, named A1, A2A, A2B and A3. Activation of the A2A receptors can promote the occurrence of delayed depolarization, while activation of the A1 receptors can shorten the action potential's duration and induce the resting membrane's potential hyperpolarization, which promote pulmonary vein firing, stabilize the AF rotors and allow for functional reentry. Moreover, the A2B receptors have been associated with atrial fibrosis homeostasis. Finally, the adenosinergic system can modulate the autonomous nervous system and is associated with AF risk factors. A question remains regarding adenosine release and the adenosine receptors' activation and whether this would be a cause or consequence of AF.

Bone morphogenetic protein 10: a novel risk marker of ischaemic stroke in patients with atrial fibrillation.

Biomarkers specifically related to atrial tissue may increase the understanding of the pathophysiology of atrial fibrillation (AF) and further improve risk prediction in this setting. Bone morphogenetic protein 10 (BMP10) is a protein expressed in the atrial myocardium. We evaluated the association between BMP10 and the risk of ischaemic stroke and other cardiovascular events in large cohorts of patients with AF, treated with and without oral anticoagulation (OAC). BMP10 was measured in plasma samples collected at randomisation in patients with AF without OAC in the ACTIVE A and AVERROES trials (n = 2974), and with OAC in the ARISTOTLE trial (n = 13 079). BMP10 was analysed with a prototype Elecsys immunoassay. Associations with outcomes were evaluated by Cox-regression models adjusted for clinical characteristics, kidney function, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Median concentrations of BMP10 were 2.47 and 2.44 ng/mL, in the non-OAC and OAC cohort, respectively. Increasing BMP10 was associated with lower body mass index, older age, female sex, kidney dysfunction, and AF rhythm. BMP10 was consistently associated with ischaemic stroke. In the non-OAC cohort, BMP10 increased the concordance index of the multivariable model from 0.713 to 0.733 (P = 0.004) and in the OAC cohort from 0.673 to 0.694 (P < 0.001). Additionally, BMP10 maintained a significant prognostic value after additionally adjusting for NT-proBNP. BMP10 was not independently associated with bleeding or with death. The novel atrial biomarker BMP10 was independently associated with ischaemic stroke in patients with AF irrespective of OAC treatment. BMP10 seems to be more specifically related to the risk of ischaemic stroke in AF. In this study, BMP10 may be a novel specific biomarker of ischaemic stroke in patients with atrial fibrillation, irrespective of oral anticoagulation.

Abstract 14554: Novel Upstream Targets for Atrial Fibrillation

Introduction: Atrial fibrillation (AF) represents one of the most common arrhythmias seen clinically and is associated with a significant increase in morbidity and mortality, yet, current treatment paradigms have proven largely inadequate. One of the main contributors to the pathophysiology of AF is inflammation. Hence, reduction of inflammation associated atrial remodeling represents a novel therapeutic strategy for the treatment of AF. One of the most biologically important groups of oxylipins (oxygenated lipids) is the eicosanoids that are potent modulators of immune responses and are derived from arachidonic acid, linoleic acid among others, which are metabolized through three pathways including the cytochrome P450 (CYP) pathway. The CYP products are major anti-inflammatory metabolites with several cardioprotective effects. Hypothesis: We hypothesize that lipid metabolites may represent a new therapeutic target for AF Methods: In the cross-sectional study, human atrial appendage specimens and blood from informed and consented patients were obtained in accordance with the approved UC Davis IRB protocol. Metabolomic profiling for over 100 metabolites was assessed from the plasma of patients using LC-MS/MS. We used Functional Connectome, an extension of the singular value decomposition for matrices, to determine how the metabolites were functionally related to each other. The underlying mechanisms of AF were determined using an integrated approach with molecular biology, flow cytometry, and electrophysiology. Results: Metabolomic profiling shows a significant difference in several metabolites from the arachidonic and linoleic acid pathways in the cohort with AF compared to patients in NSR. There was a significant increase in oxidative stress, endoplasmic reticulum stress, inflammatory cytokines, nuclear translocation of NF-κB, and the activation of MAPK and TGF-b pathways from patients with AF compared to NSR cohort. Conclusions: The study provides important insights into the functional relatedness of the metabolites from the CYP pathway in patients with AF and reveals the prospect of arachidonic and linoleic acid metabolites being novel therapeutic targets in the treatment of AF.

Atrial fibrillation: Insights from animal models, computational modeling, and clinical studies.

Atrial fibrillation (AF) is the most common human arrhythmia, affecting millions of patients worldwide. A combination of risk factors and comorbidities results in complex atrial remodeling, which increases AF vulnerability and persistence. Insights from animal models, clinical studies, and computational modeling have advanced the understanding of the mechanisms and pathophysiology of AF. Areas of heterogeneous pathological remodeling, as well as altered electrophysiological properties, serve as a substrate for AF drivers and spontaneous activations. The complex and individualized presentation of this arrhythmia suggests that mechanisms-based personalized approaches will likely be needed to overcome current challenges in AF management. In this paper, we review the insights on the mechanisms of AF obtained from animal models and clinical studies and how computational models integrate this knowledge to advance AF clinical management. We also assess the challenges that need to be overcome to implement these mechanistic models in clinical practice.

Atrial Fibrillation Detected After Acute Ischemic Stroke

Atrial fibrillation (AF) increases 4-5 times incidence of cardiac embolic stroke. In contrast, as many as 70% of AF cases can be detected in stroke within three days of onset, and this can affect the patient's prognosis. This case report describes the causal pathophysiology of AF and acute stroke and identifies the associated risk factors. Case 1 is a 44-year-old woman, acute stroke with acute decrease level of consciousness. The patient came with status epilepticus and a hypertensive emergency. Obtained a history of stroke, uncontrolled hypertension, and myocardial infarction. Initial Score National Institutes of Health Stroke Scale (NIHSS) was 33 and CHA2DS2-VASc was 5. Investigation non-contrast head Computed Tomography (CT) scan showed no bleeding and echocardiography (ECG) showed AF with rapid ventricular response. The patient died after 3 days of treatment. Case 2 is an 83-year-old woman, acute stroke with acute decrease level of consciousness and right motor lateralization. There was a history of hypertension and stroke with left hemiparesis. The initial NIHSS was 28 and CHA2DS2-VASc was 6. Investigations non-contrast head CT scan showed no bleeding and ECG showed AF with normal ventricular response. The patient was discharged from the hospital after being treated for 22 days with NIHSS of 20. Several risk factors for post-stroke AF are elderly, hypertension, subtype of ischemic stroke, prior stroke, and comorbidities such as DM and hypertension. Post-stroke AF can occur because of changes in heart rhythm through autonomic disorders, increased plasma catecholamine levels, and inflammatory reactions. Early Recognition of risk factors, focusing on patients at higher risk of AF detected after stroke becomes important for comprehensive management of stroke with AF.&#x0D; Keywords: acute ischemic stroke, atrial fibrillation, CHA2DS2-VASc score, risk factors.