Increased Risk Of Atrial Fibrillation Research Articles

Sodium Intake and Incident Atrial Fibrillation in Individuals With Vascular Disease

Numerous prospective cohort studies have reported a J-shaped association of urinary sodium excretion with cardiovascular events and mortality. To study the association between sodium intake and incident atrial fibrillation (AF). This cohort study included participants in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan Randomised Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND) multicenter, randomized clinical trials comparing the effect of ramipril 10 mg daily with telmisartan 80 mg daily, or their combination (ONTARGET) or 80 mg telmisartan daily with placebo (TRANSCEND) for the outcome of death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure. ONTARGET and TRANSCEND included 31 546 participants with vascular disease or high-risk diabetes, and this study excluded participants without a urine sample for sodium measurement, missing data for key covariates, a history of AF, or AF detected in the first year after enrollment. Analyses were performed in July 2023 to May 2024. Estimated sodium intake from a morning fasting urine sample (Kawasaki formula). The main outcome was incident AF. The association between estimated sodium intake and incident AF was modeled using multivariable adjusted Cox regression and cubic splines. A total of 27 391 participants (mean [SD] age, 66.3 [7.2] years; 19 310 [70.5%] male) were included. Mean (SD) estimated sodium intake was 4.8 (1.6) g/d. During a mean (SD) follow-up of 4.6 (1.0) years, 1562 participants (5.7%) had incident AF. After multivariable adjustment, a J-shaped association between sodium intake and AF risk was observed (P for nonlinearity = .03). Sodium intake of 8 g/d or greater (3% of participants) was associated with incident AF (hazard ratio, 1.32; 95% CI, 1.01-1.74) compared with sodium intake of 4 to 5.99 g/d. Cubic splines showed that sodium intake greater than 6 g/d (19% of participants) was associated with a 10% increased AF risk per additional 1-g/d sodium intake (hazard ratio, 1.10; 95% CI, 1.03-1.18), but with no further lowering of AF risk at lower levels of sodium intake. In this cohort study of sodium intake and AF risk, there was a J-shaped association between sodium intakes and AF risk in patients with cardiovascular disease or diabetes. Lowering sodium intake for AF prevention is best targeted at individuals who consume high sodium diets.

β-blockades and the risk of atrial fibrillation in patients with cardiovascular diseases.

β-blockers have been widely used in patients with extensive cardiovascular disease (CVD) and have provided benefits. However, they are more likely to cause symptomatic bradycardia, hypotension, or glucose metabolism disorders, which may lead to an increased risk of atrial fibrillation (AF), but evidence is lacking. This study was to analyze the association between the use of β-blockers and the risk of developing AF. This nationwide, prospective cohort study utilized data from the 2013-2020 National Health and Nutrition Examination Survey (NHANES). The patients were stratified into a β-blocker treatment group (n = 2585) and a non-β-blocker treatment group (n = 8525). Univariate and multivariate logistic regression analyses were performed to identify the relationship between β-blockades and the risk of AF. Propensity matching analysis was used to balance patient baseline characteristics and to control for confounders. A total of 11,110 subjects were included in this study (mean [SD] age, 59.89 [15.07] years; 5657 [49.7%] males). A total of 111/2585 subjects developed AF in the β-blocker treatment group, and 75/8525 developed AF in the non-β-blocker treatment group (incidence rate, 4.2% vs. 0.8%). Compared with the non-β-blocker group, the β-blocker group had an increased risk of incident AF (aOR, 2.339; 95% CI, 1.614-3.410). Some sensitivity analyses also revealed consistent findings of increased AF risk associated with β-blocker treatment. The findings from this study suggest that β-blocker treatment is associated with an increased risk of incident AF and may help physicians select a modest medication for patients while also assessing the risk of AF.

Association of Serum Thyroxine and Atrial Fibrillation in Patients on Levothyroxine.

Excess thyroid hormone is a well-documented risk factor for the development of atrial fibrillation (AF). The purpose of the study is to assess incidence of AF in patients taking levothyroxine for hypothyroidism and correlate it with biochemical thyroid function. This was a retrospective cohort study of patients aged 18 years and older who were treated with levothyroxine. Exclusion criteria were pre-existing diagnosis of AF and use of amiodarone in the prior year. Patients were followed 2012 through 2019 and stratified into 4 groups based on mean thyroid-stimulating hormone (TSH) value or mean fT4 value in 2012. Primary outcome was incidence of AF. Rates of AF between groups were assessed via Poisson regression with control of underlying confounders. Of 21,035 patients, 1091 (5.2%) developed AF during follow-up. Thyroid-stimulating hormone at baseline was not significantly associated with incident AF. Higher fT4 levels at baseline were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio 1.22; 95% CI, 1.03-1.44) for the highest quartile versus the lowest quartile of fT4. In hypothyroid patients treated with levothyroxine, higher circulating fT4 levels are associated with increased risk of incident AF. There is no association of serum TSH with risk of AF. In patients at risk for AF, consideration should be given to avoiding fT4 levels in the highest quartile.

Associations of lipids and lipid-modifying drug target genes with atrial fibrillation risk based on genomic data

BackgroundThe causal associations of lipids and the drug target genes with atrial fibrillation (AF) risk remain obscure. We aimed to investigate the causal associations using genetic evidence.MethodsMendelian randomization (MR) analyses were conducted using summary-level genome-wide association studies (GWASs) in European and East Asian populations. Lipid profiles (low-density lipoprotein cholesterol, triglyceride, and lipoprotein[a]) and lipid-modifying drug target genes (3-hydroxy-3-methylglutaryl-CoA reductase, proprotein convertase subtilisin/kexin type 9, NPC1-like intracellular cholesterol transporter 1, apolipoprotein C3, angiopoietin-like 3, and lipoprotein[a]) were used as exposures. AF was used as an outcome. The inverse variance weighted method was applied as the primary method. Summary-data-based Mendelian randomization analyses were performed for further validation using expression quantitative trait loci data. Mediation analyses were conducted to explore the indirect effect of coronary heart disease.ResultsIn the European population, MR analyses demonstrated that elevated levels of lipoprotein(a) increased AF risk. Moreover, analyses focusing on drug targets revealed that the genetically proxied target gene LPA, which simulates the effects of drug intervention by reducing lipoprotein(a), exhibited an association with AF risk. This association was validated in independent datasets. There were no consistent and significant associations observed for other traits when analyzed in different datasets. This finding was also corroborated by Summary-data-based Mendelian randomization analyses between LPA and AF. Mediation analyses revealed that coronary heart disease plays a mediating role in this association. However, in the East Asian population, no statistically significant evidence was observed to support these associations.ConclusionsThis study provided genetic evidence that Lp(a) may be a causal factor for AF and that LPA may represent a promising pharmacological target for preventing AF in the European population.

Associations of fat and muscle mass indices with incident atrial fibrillation: data of PREVEND

Abstract Background Whether the association between body mass and atrial fibrillation (AF) risk is driven by fat mass or muscle mass remains unclear. Objective To examine the association of relative fat mass (RFM, a novel marker of whole-body fat percentage) and 24-hour urinary creatinine excretion (a marker of total muscle mass) with incident AF. Participants: We included 8120 community-dwelling adults from the PREVEND cohort without prevalent AF. Results The mean age of the population was 49.8±12.6 years and 50.0% (n=4060) were women. The mean RFM was 30.2±7.4 % and the mean creatinine excretion was 12.3±3.5 mmol/24h. During a mean follow-up period of 9.7±2.4 years, 261 AF events (3.2%) occurred. We included RFM, creatinine excretion, age, sex, height, heart rate, hypertension and cardiovascular disease history in a multivariable Cox regression model. The association between RFM and AF risk was linear, and the hazard ratio per 1 SD increase in RFM was 1.40; 95%CI: 1.17-1.66 (P<0.001). The association between creatinine excretion and AF risk was non-linear (P-value quadratic trend=0.006): compared with individuals in tertile 2 of creatinine excretion, those in tertile 1 had a HR of 1.70; 95%CI: 1.21-2.29 (P=0.002) and those in tertile 3 also had a HR of 1.74; 95%CI: 1.22-2.47 (P=0.002). Conclusion In the general population, both fat mass and muscle mass are associated with incident AF. While obesity should be considered as a major risk factor for AF, increased AF risk in individuals with low and high muscle mass warrants further investigation.

Primary prevention of atrial fibrillation with pharmacological therapy

Abstract Background Primary prevention of atrial fibrillation (AF) is important given its rising incidence, associated disease burden, and cost (1-3). The effect of pharmacological therapies on incidence of new-onset AF is uncertain, (1) leading to an absence of clear guideline recommendations for prevention of AF (3). Purpose To perform a meta-analysis of the effect of pharmacological therapies on new-onset AF as reported in published randomised clinical trials (RCTs), and investigate for changes by individual agents and clinically relevant subgroups. Methods We performed a systematic review of RCTs that evaluated the relationship between a pharmacological therapy and the development of new-onset AF in a non-hospitalised patient cohort, using Medline, Embase and Cochrane-controlled Trials Register from inception through 19 July 2023. Results of the AF outcome are expressed as relative ratio (RR) with 95% confidence interval (CI) between the intervention and control group for each study. A fixed-effect model was used to combine results from studies when I2<50% and random-effect model when I2>50%. Risk of bias was assessed using the Cochrane RoB2 tool. Meta-regression was performed by mean age of study participants, percentage of men, follow-up duration, indication (e.g. heart failure) and each agent. Results From 11872 unique records we included 101 RCTs with 794775 patients. Overall, risk of bias was considerable (48% high, 35% medium); driven by outcome measurement (67% high/medium) as AF was not the primary outcome of studies. Of pharmacological therapies, patients treated with angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) demonstrated a lower risk of AF compared with controls (RR 0.87, 95% CI 0.78-0.98), and patients treated with omega-3 fatty acids demonstrated a higher risk of AF (RR 1.26, 95% CI 1.11-1.42) (Figure 1). Analysis by indication demonstrated that the reduction in AF risk with treatment with ACEIs/ARBs was only for patients with heart failure with reduced ejection fraction (HFrEF) (RR 0.57, 95% CI 0.34-0.94). Amongst individual ACEIs/ARBs, only treatment with valsartan (RR 0.79, 95% CI 0.66-0.95) and olmesartan (RR 0.87, 95% CI 0.45-0.99) led to a lower risk of AF. On meta-regression each year of increased age increased AF risk when treated with ACE-I/ARB therapy (RR 1.08, 95% CI 1.04-1.13). Whilst no reduction in AF was observed for other pharmacological classes overall, treatment with Semaglutide demonstrated a 40% lower risk of AF compared with controls (RR 0.60, 95% CI 0.45-0.80) (Figure 2). Conclusions ACEIs and ARBs appear to be effective in the primary prevention of AF, but this benefit may be limited to patients with HFrEF, especially younger patients. Effect on AF occurrence varies within pharmacological classes, and Semaglutide specifically may be an effective in preventing new-onset AF. Appropriately powered RCTs with new-onset AF as the primary outcome are required.Figure 1:Forest plot by pharmacotherapyFigure 2:Forest plot by GLP-1RA agent

N-3 fatty acids and the risk of atrial fibrillation, review.

Atrial fibrillation (AF) is the most frequent type of cardiac arrhythmia that affects over six million individuals in Europe. The incidence and prevalence of AF rises with age, and often occurs after cardiac surgery. Other risk factors correlated with AF comprise high blood pressure, diabetes mellitus, left atrial enlargement, ischemic heart disease, and congestive heart failure. Considering the high prevalence of AF in aging societies, strategies to prevent serious complications, such as stroke or heart failure, are important because they are correlated with high morbidity and mortality. The supplementation of sea-derived n-3 polyunsaturated fatty acids (PUFA) is widely discussed in this context, but the results of experimental and observational studies are in contrast to randomized placebo-controlled intervention trials (RCTs). Specifically, larger placebo-controlled n-3 PUFA supplementation studies with long follow-up showed a dose-dependent rise in incident AF. Daily n-3 PUFA doses of≥1 g/d are correlated with a 50 % increase in AF risk, whereas a daily intake of <1 g/d causes AF in only 12 %. Individuals with a high cardiovascular risk (CVD) risk and high plasma-triglycerides seem particularly prone to develop AF upon n-3 PUFA supplementation. Therefore, we should exercise caution with n-3 PUFA supplementation especially in patients with higher age, CVD, hypertriglyceridemia or diabetes. In summary, existing data argue against the additive intake of n-3 PUFA for preventative purposes because of an incremental AF risk and lacking CVD benefits. However, more clinical studies are required to disentangle the discrepancy between n-3 PUFA RCTs and observational studies showing a lower CVD risk in individuals who regularly consume n-3 PUFA-rich fish.

Genetically predicted systemic inflammation and the risk of atrial fibrillation: A bidirectional two-sample Mendelian randomization study

BackgroundSystemic inflammation has been proposed to be associated with the incidence of atrial fibrillation (AF), but whether it is a cause or a consequence of AF remains uncertain. We sought to explore the causal associations between systemic inflammation and AF using bidirectional Mendelian randomization (MR) analysis. MethodsIndependent genetic variants strongly associated with AF were selected as instrumental variables from the largest genome-wide association study (GWAS) with up to 1,030,836 individuals. Regarding inflammation traits, genetic associations with 41 inflammatory cytokines and 5 inflammatory biomarkers were obtained from their corresponding GWASs databases. Effect estimates were primarily evaluated using the inverse-variance weighted (IVW) method, supplemented by sensitivity analyses using MR-Egger, weighted median, and MR-PRESSO methods. ResultsIn our initial MR analyses, we observed suggestive associations of genetically predicted interleukin-17 (IL-17), interleukin-2 receptor subunit alpha (IL-2rα), and procalcitonin (PCT) with AF. One standard deviation (SD) increase in IL-17, IL-2rα, and PCT caused an increase in AF risk by 6.3 % (OR 1.063, 95 %CI 1.011–––1.118, p = 0.018), 4.9 % (OR 1.049, 95 %CI 1.007–––1.094, p = 0.023) and 3.4 % (OR 1.034, 95 %CI 1.005–––1.064, p = 0.022), respectively. Furthermore, our reverse MR analyses indicated that genetically predicted AF contributed to a suggestive increase in the levels of macrophage inflammatory protein-1β (MIP1β) (β 0.055, 95 %CI 0.006 to 0.103, p = 0.028), while a decrease in the levels of fibrinogen (Fbg) (β −0.091, 95 %CI −0.140 to −0.041, p < 0.001), which remained significant after multiple test correction. ConclusionsOur MR study identified several inflammatory biomarkers with suggestive causal associations regarding the upstream and downstream regulation of AF occurrence, offering new insights for therapeutic exploitation of AF. Further research is required to validate the underlying link between systemic inflammation and AF in larger cohorts.

Thyroid function effect on cardiac structure, cardiac function, and disease risk: Evidence of causal associations in European ancestry

BackgroundThyroid hormones play a crucial role in cardiovascular physiology. Subclinical thyroid dysfunction has been associated with adverse cardiovascular outcomes, but evidence is mixed regarding causality. ObjectiveThe purpose of this study was to investigate the potential causal relationships of thyroid-stimulating hormone (TSH), free thyroxine, hypothyroidism, and hyperthyroidism with cardiovascular outcomes, including atrial fibrillation (AF), coronary artery disease, myocardial infarction, heart failure, and ischemic stroke, as well as their effect on cardiac structure and function assessed by cardiac magnetic resonance imaging. MethodsA comprehensive 2-sample Mendelian randomization analysis was performed using summary data from large-scale meta-analyses of European ancestry individuals. ResultsGenetically determined lower TSH levels (odds ratio 0.928; 95% confidence interval 0.884–0.974; P = .003) and genetic risk of hyperthyroidism (odds ratio 1.049; 95% confidence interval 1.016–1.083; P = .003) were associated with increased AF risk. These associations remained significant even after adjusting for cardiovascular risk factors. Colocalization and multivariable Mendelian randomization revealed height as a key mediator between TSH/hyperthyroidism and AF. These findings were further corroborated in the independent FinnGen cohort. However, no clear evidence was found for relationships between thyroid function and other cardiovascular outcomes and cardiac structure and function. ConclusionOur study shows that reduced TSH levels and hyperthyroidism heighten AF risk, with height serving as an important mediator in these associations. The primary focus of thyroid management in cardiovascular health should be on preventing and treating arrhythmias, particularly AF. Our research highlights the importance of routine screening and timely treatment of thyroid dysfunction to optimize the prevention and management of arrhythmias.

Artificial-intelligence-based risk prediction and mechanism discovery for atrial fibrillation using heart beat-to-beat intervals

Early diagnosis of atrial fibrillation (AF) is important for preventing stroke and other complications. Predicting AF risk in advance can improve early diagnostic efficiency. Deep learning hasbeen used for disease risk prediction; however, it lacks adherenceto evidence-based medicine standards. Identifying the underlyingmechanisms behind disease risk prediction is important and required. We developed an explainable deep learning model called HBBI-AI to predict AF risk using only heart beat-to-beat intervals (HBBIs) during sinus rhythm. We proposed a possible AF mechanism based on the model's explainability and verified this conjecture using confirmed AF risk factors while also examining new AF risk factors. Finally, we investigated the changes in clinicians' ability to predict AF risk using only HBBIs before and after learning the model's explainability. HBBI-AI consistently performed well across large in-house and external public datasets. HBBIs with large changes or extreme stability were critical predictors for increased AF risk, and the underlying cause was autonomic imbalance. We verified various AF risk factors and discovered that autonomic imbalance was associated with all these factors. Finally, cardiologists effectively understood and learned from these findings to improve their abilities in AF risk prediction. HBBI-AI effectively predicted AF risk using only HBBI information through evaluating autonomic imbalance. Autonomic imbalance may play an important role in many risk factors of AF rather than in a limited number of risk factors. This study was supported in part by the National Key R&D Program and the National Natural Science Foundation of China.

Vigorous physical activity and atrial fibrillation in healthy individuals: What is the correct approach?

Sport activity compared to sedentary life is associated with improved wellbeing and risk reduction in many different health conditions including atrial fibrillation (AF). Vigorous physical activity is associated with increased AF risk. We describe four individuals, who regularly perform endurance sport activity and developed AF. We discuss the changes occurring in the heart of endurance athletes and the possible etiology for AF, as well as currently available treatment options in this seemingly healthy population. Although the etiology of AF in the general population differs from the one in the usually younger endurance sport activity population, the treatment options are similar. There are several factors unique to those involved in vigorous physical activity that can influence their management. Despite a lack of evidence, endurance athletes with AF have traditionally been advised to "de-training,"to reduce both the amount and intensity of exercise. Some of the current offered treatment options (beta-blockers, class III antiarrhythmic) have a varied range of adverse effect, hindering them unattractive for these individuals. Depending on risk stratification tools, anticoagulation may be indicated. Some suggest an intermittent dosing therapy, while others recommend following current guidelines. AF ablation is recommended in exercising individuals with recurrent, symptomatic AF and/or in those who do not want drug therapy, given its impact on athletic performance, AF treatment decisions should be individualized for those engaging vigorous physical activity, while considering the potential risks, the urgency of returning to training, and the will and expectations of the patient.

Coexistent HCN4 and GATA5 Rare Variants and Atrial Fibrillation in a Large Spanish Family

BackgroundFamilial association of atrial fibrillation (AF) can involve single gene variants related to known arrhythmogenic mechanisms; however, genome-wide association studies often disclose complex genetic variants in familial and nonfamilial AF, making it difficult to relate to known pathogenetic mechanisms. MethodsThe finding of 4 siblings with AF led to studying 47 members of a family. Long-term Holter monitoring (average 298 hours) ruled out silent AF. Whole-exome sequencing was performed, and variants shared by the index cases were filtered and prioritised according to current recommendations. HCN4 currents (IHCN4) were recorded in Chinese hamster ovary cells expressing human p.P1163H or native HCN4 channels with the use of the patch-clamp technique, and topologically associating domain analyses of GATA5 variant were performed. ResultsThe clinical study diagnosed 2 more AF cases. Five family members carried the heterozygous p.P1163H HCN4 variant, 14 carried the intronic 20,61040536,G,A GATA5 rare variant, and 9 carried both variants (HCN4+GATA5). Five of the 6 AF cases (onset age ranging from 33 to 70 years) carried both variants and 1 carried the GATA5 variant alone. Multivariate analysis showed that the presence of HCN4+GATA5 variants significantly increased AF risk (odds ratio 32.7, 95% confidence interval 1.8-591.4) independently from age, hypertension, and overweight. Functional testing showed that IHCN4 generated by heterozygous p.P1163H were normal. Topologically associating domain analysis suggested that GATA5 could affect the expression of many genes, including those encoding microRNA-1. ConclusionThe coincidence of 2 rare gene variants was independently associated with AF, but functional studies do not allow the postulation of the arrhythmogenic mechanisms involved.

Mid- and long-term risk of atrial fibrillation among breast cancer surgery survivors

BackgroundThe risk of incident atrial fibrillation (AF) among breast cancer survivors, especially for younger women, and cancer treatment effects on the association remain unclear. This study aimed to investigate the risk of AF among breast cancer survivors and evaluate the association by age group, length of follow-up, and cancer treatment.MethodsUsing data from the Korean Health Insurance Service database (2010–2017), 113,232 women newly diagnosed with breast cancer (aged ≥ 18 years) without prior AF history who underwent breast cancer surgery were individually matched 1:5 by birth year to a sample female population without cancer (n = 566,160) (mean[SD] follow-up, 5.1[2.1] years). Sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) considering death as a competing risk were estimated, adjusting for sociodemographic factors and cardiovascular/non-cardiovascular comorbidities.ResultsBCS had a slightly increased AF risk compared to their cancer-free counterparts (sHR 1.06; 95% CI 1.00–1.13), but the association disappeared over time. Younger BCS (age < 40 years) had more than a 2-fold increase in AF risk (sHR 2.79; 95% CI 1.98–3.94), with the association remaining similar over 5 years of follow-up. The increased risk was not observed among older BCS, especially those aged > 65 years. Use of anthracyclines was associated with increased AF risk among BCS (sHR 1.57; 95% CI 1.28–1.92), which was more robust in younger BCS (sHR 1.94; 95% CI 1.40–2.69 in those aged ≤ 50 years).ConclusionsOur findings suggest that younger BCS had an elevated risk of incident AF, regardless of the length of follow-up. Use of anthracyclines may be associated with increased mid-to-long-term AF risk among BCS.Graphical

Impact of Obesity on Atrial Fibrillation Pathogenesis and Treatment Options.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF increases the risk of stroke, heart failure, dementia, and hospitalization. Obesity significantly increases AF risk, both directly and indirectly, through related conditions, like hypertension, diabetes, and heart failure. Obesity-driven structural and electrical remodeling contribute to AF via several reported mechanisms, including adiposity, inflammation, fibrosis, oxidative stress, ion channel alterations, and autonomic dysfunction. In particular, expanding epicardial adipose tissue during obesity has been suggested as a key driver of AF via paracrine signaling and direct infiltration. Weight loss has been shown to reverse these changes and reduce AF risk and recurrence after ablation. However, studies on how obesity affects pharmacologic or interventional AF treatments are limited. In this review, we discuss mechanisms by which obesity mediates AF and treatment outcomes, aiming to provide insight into obesity-drug interactions and guide personalized treatment for this patient subgroup.

Risk of newly developed atrial fibrillation by alcohol consumption differs according to genetic predisposition to alcohol metabolism: a large-scale cohort study with UK Biobank

BackgroundThe predictive relationship between mild-to-moderate alcohol consumption and the risk of incident atrial fibrillation (AF) remains controversial.ObjectiveWe investigated whether the relationship between alcohol consumption and the risk of incident AF could be associated with the genetic predisposition to alcohol metabolism.MethodsA total of 399,329 subjects with genetic data from the UK Biobank database, enrolled between 2006 and 2010, were identified and followed for incident AF until 2021. Genetic predisposition to alcohol metabolism was stratified according to the polygenic risk score (PRS) tertiles. Alcohol consumption was categorized as non-drinkers, mild-to-moderate drinkers (< 30 g/day), and heavy drinkers (≥ 30 g/day).ResultsDuring the follow-up (median 12.2 years), 19,237 cases of AF occurred. When stratified by PRS tertiles, there was a significant relationship between genetic predisposition to alcohol metabolism and actual alcohol consumption habits (P < 0.001). Mild-to-moderate drinkers showed a decreased risk of AF (HR 0.96, 95% CI 0.92–0.99), and heavy drinkers showed an increased risk of AF (HR 1.06, 95% CI 1.02–1.10) compared to non-drinkers. When stratified according to PRS tertiles for genetic predisposition to alcohol metabolism, mild-to-moderate drinkers had equivalent AF risks, and heavy drinkers showed increased AF risk in the low PRS tertile group. However, mild-to-moderate drinkers had decreased AF risks and heavy drinkers showed similar risks of AF in the middle/high PRS tertile groups.ConclusionsDifferential associations between alcohol consumption habits and incident AF across genetic predisposition to alcohol metabolism were observed; individuals with genetic predisposition to low alcohol metabolism were more susceptible to AF.

Abstract 12930: Atrial Myopathy and the Risk of Incident Atrial Fibrillation in People With Newly Diagnosed Cavotricuspid Isthmus-Dependent Atrial Flutter

Background New cavotricuspid isthmus-dependent atrial flutter (AFL) is associated with increased risk of incident atrial fibrillation (AF). It is unclear which patients with AFL will develop AF. Hypothesis: Patients with new AFL who have co-existing atrial myopathy, detected by measuring left atrial emptying fraction (LAEF) and left atrial reservoir strain (LARS), may be at increased risk for developing AF. Methods: There were 210 patients who received an ablation or cardioversion for AFL at a tertiary care medical center between 2015-2022. Patients were excluded for prior AF (118), congenital heart disease (16), valve surgery and heart transplant (9), no echocardiogram available (9), and less than 6 months of follow up (9). Data was obtained by retrospective chart review. Covariates included coronary heart disease, heart failure, diabetes, age, sex, vascular disease, and stroke. Exposure variables included LAEF and LARS. We used Cox proportional hazards models to estimate the risk of AF for LAEF and LARS. Results: 49 patients (mean age 62.3 years, 18.3% female) met criteria for inclusion, and 18 developed atrial fibrillation over a mean follow up period of 29.9 months (19.7 months). Those who developed AF had lower LAEF and LARS compared to those who did not. For every 5% decrease in LAEF and LARS, there was a 1.79 (1.33, 2.38) and 5.26 (1.75, 16.67)-fold increase in risk of AF after adjustment for covariates. Conclusion: Co-existing atrial myopathy, measured by decreased LAEF and LARS, is associated with increased risk of AF in people with new AFL.

Abstract 14968: Clonal Hematopoiesis and Cardiotoxic Risk After Hematopoietic Stem Cell Transplantation

Background: Clonal hematopoiesis (CH) occurs as part of normal hematopoietic stem cell senescence and prior chemotherapy administration. As such, CH is frequent for patients undergoing allogeneic stem cell transplants (ASCT). CH has been identified as a driver of inflammation. In animals, inflammation plays a role in atrial fibrillation (AF) development, the most common cardiotoxicity after ASCT treatment. Yet, whether the presence of post-ASCT CH associates with AF risk is unknown. Methods: We analyzed bone marrow derived mononuclear cells from 201 cancer patients treated with ASCT by deep targeted amplicon sequencing (next generation sequencing) to detect the presence of select CH (defined as DNMT3A, TET2, ASXL1, IDH1, FLT3, JAK2 at VAF of ≥ 2%), irrespective of relapse status; at median 4 months post ASCT. Observed incident AF rates were compared to Framingham heart predicted rates. Cox regression and survival analysis were used to define factors associated with incident AF and MACE, as well as the relationship between the presence of post-transplant CH mutations and MACE risk. Further, we also assessed the effect of CH on post-ASCT survival outcomes. The presence of mutations was analyzed for an association with post-ASCT incident AF and overall survival. Results: Overall, the prevalence of CH in post-ASCT patients was 42.3% (85), including 29.5% with ≥2 mutations. Over a median follow-up of 33 months, 11.5% of patients developed incident AF and 29.9% experienced MACE. In those without prior AF, the weighted average incidence was 407/10,000 person-years compared to the Framingham-predicted 63/10,000 person-years (RR 6.4, P &lt;0.001; AER 344). In follow-up, increased CH burden associated with increased risk of incident AF (HR 3.6, P =0.04), cancer-progression (HR 2.6, P =0.006), and mortality (HR 2.09, P =0.047); Figure . There was no difference in non-AF MACE. Conclusions: The presence of CH in ASCT treated cancer patients appears to associate with increased AF risk.

Insomnia and Cardiovascular Health: Exploring the Link Between Sleep Disorders and Cardiac Arrhythmias.

Cardiovascular diseases (CVDs), driven by modern lifestyles, have increased, with atrial fibrillation (AF) being a major concern linked to heart failure and stroke. Insomnia affects a large population, especially younger individuals, males, and menopausal women, decreasing the quality of life and potentially causing autonomic disturbances and cardiac arrhythmias. PURPOSE OF REVIEW: This review explores the link between insomnia and cardiac arrhythmias, particularly AF, and its impact on cardiovascular health and emphasizes the need to address insomnia in individuals with cardiac arrhythmias by tailored strategies for sleep management to improve their overall well-being. RECENT FINDINGS: Recent findings emphasize maintaining a regular sleep schedule to lower AF and bradyarrhythmia risks. Better sleep scores correlate with reduced AF and bradyarrhythmia risks, while insomnia increases AF risk, particularly in those under 40years of age. Studies underscore the potential impact of sleep management in reducing cardiovascular risks and highlight the importance of addressing sleep issues to improve cardiovascular health outcomes. Our review presents compelling evidence connecting insomnia and AF. Improving sleep patterns and addressing sleep issues can reduce AF risk, benefiting cardiovascular health. A comprehensive approach for managing at-risk individuals with cardiac arrhythmias, considering co-existing conditions, can decrease long-term disease burden and expenses. Incorporating sleep assessments and interventions into cardiovascular risk management, especially for those with insomnia, is recommended. Further research is needed to fully comprehend the complex relationship between insomnia and cardiac arrhythmias.

Association of hypertension severity and control with risk of incident atrial fibrillation: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

The association of hypertension (HTN) severity and control with the risk of incident atrial fibrillation (AF) is unclear. Increased HTN severity and poorer blood pressure control would be associated with an increased risk of incident AF. This analysis included 9485 participants (mean age 63 ± 8 years; 56% women; 35% Black). Participants were stratified into six mutually exclusive groups at baseline-normotension (n = 1629), prehypertension (n = 704), controlled HTN (n = 2224), uncontrolled HTN (n = 4123), controlled apparent treatment-resistant hypertension (aTRH) (n = 88), and uncontrolled aTRH (n = 717). Incident AF was ascertained at the follow-up visit, defined by either electrocardiogram or self-reported medical history of a physician diagnosis. Multivariable logistic regression analyses adjusted for demographic and clinical variables. Over an average of 9.3 years later, 868 incident AF cases were detected. Compared to those with normotension, incident AF risk was highest for those with aTRH (controlled aTRH: odds ratio (OR) 2.95; 95% confidence interval (CI) 1.60, 5.43, & uncontrolled aTRH: OR 2.47; 95% CI 1.76, 3.48). The increase in AF risk was smaller for those on no more than three antihypertensive agents regardless of their blood pressure control (controlled OR 1.72; 95% CI 1.30, 2.29 and uncontrolled OR 1.56; 95% CI 1.14, 2.13). The risk of developing AF is increased in all individuals with HTN. Risk is highest in those aTRH regardless of blood pressure control. A more aggressive approach that focuses on lifestyle and pharmacologic measures to either prevent HTN or better control HTN during earlier stages may be particularly beneficial in reducing related AF risk.

Incident Atrial Fibrillation and Survival Outcomes in Esophageal Cancer following Radiotherapy

Radiation therapy (RT) associates with long-term cardiotoxicity. In preclinical models, RT exposure induces early cardiotoxic arrhythmias including atrial fibrillation (AF). Yet, whether this occurs in patients is unknown. Leveraging a large cohort of consecutive patients with esophageal cancer treated with thoracic RT from 2007 to 2019, we assessed incidence and outcomes of incident AF. Secondary outcomes included major adverse cardiovascular events (MACE), defined as AF, heart failure, ventricular arrhythmias, and sudden death, by cardiac RT dose. We also assessed the relationship between AF development and progression-free and overall survival. Observed incident AF rates were compared with Framingham predicted rates, and absolute excess risks were estimated. Multivariate regression was used to define the relationship between clinical and RT measures, and outcomes. Differences in outcomes, by AF status, were also evaluated via 30-day landmark analysis. Furthermore, we assessed the effect of cardiac substructure RT dose (eg, left atrium, LA) on the risk of post RT-related outcomes. Overall, from 238 RT treated patients with esophageal cancer, 21.4% developed incident AF, and 33% developed MACE with the majority (84%) of events occurring ≤2 years of RT initiation (median time to AF, 4.1 months). Cumulative incidence of AF and MACE at 1 year was 19.5%, and 25.7%, respectively; translating into an observed incident AF rate of 824 per 10,000 person-years, compared with the Framingham predicted rate of 92 (relative risk, 8.96; P < .001, absolute excess risk 732). Increasing LA dose strongly associated with incident AF (P=.001); and those with AF saw worse disease progression (hazard ratio, 1.54; P=.03). In multivariate models, outside of traditional cancer-related factors, increasing RT dose to the LA remained associated with worse overall survival. Among patients with esophageal cancer, radiation therapy increases AF risk, and associates with worse long-term outcomes.