Risk Of Atrial Fibrillation Research Articles

Construction and validation of a nomogram prediction model for the risk of new-onset atrial fibrillation following percutaneous coronary intervention in acute myocardial infarction patients

Construction and validation of a nomogram prediction model for the risk of new-onset atrial fibrillation following percutaneous coronary intervention in acute myocardial infarction patients

Abstract 4138564: Fitbit-Measured Physical Activity Is Inversely Associated With Incident Atrial Fibrillation Among All Of Us Participants

Background: Studies show that moderate to vigorous physical activity (MVPA) reduces atrial fibrillation (AF) risk. However, these studies used subjective questionnaires or short-term (<1 week) accelerometry assessments. Objective: This study investigated the link between MVPA levels and AF incidence using long-term (1-year) accelerometry data from the NIH All of Us Fitbit database. Methods: The study included All of Us participants who agreed to share electronic health record (EHR) and Fitbit data between January 1, 2016 to July 1, 2022. Among participants without an existing diagnosis of AF, the average weekly minutes of MVPA over the first year of Fitbit use was computed. Incident AF events were identified using validated ICD-10 codes in a five-year follow-up period. The risk of incident AF was evaluated using Cox proportional hazards regression models, for both MVPA as a continuous and a categorical variable (<30, 30-150,151-300, and >300 minutes MVPA per week; aligned with WHO guidelines). Covariates included age, sex, race/ethnicity, BMI, smoking status, and diagnoses of hypertension and diabetes. In a subset of participants with whole genome data, we evaluated if the association between MVPA and AF incidence varied by a participant’s AF genetic risk score (GRS) Results: 6086 participants (mean age 50 years, 71% female, 83% White) had EHR and at least 1 year of Fitbit data. Over the 1-year MVPA assessment period, participants had 41±12 weeks of complete data and a median 202 [241] minutes of MVPA per week. 55 participants (0.9%) experienced incident AF in the five-year follow-up period. In adjusted analysis, every additional hour of MVPA was associated with an 11% reduced risk of AF (HR = 0.89 [0.81,0.98], p = 0.02). There was a step-wise reduction in risk of AF by MVPA category with <30 min/week as the reference: 30-150 (HR = 0.62 [0.24,1.6], p = 0.31), 151-300 (HR = 0.40 [0.15,1.07], p = 0.07), and >300 (HR = 0.35 [0.13,0.95], p = 0.04) ( Figure 1 ). These associations also held after adjusting for GRS. Conclusion: Higher amounts of objectively measured MVPA were inversely associated with risk of incident AF, independent of clinical and genetic risk factors.

Abstract 4135754: Prediction of Incident Atrial Fibrillation Using Handheld Single-Lead Electrocardiograms from the VITAL-AF Trial

Background: Deep learning of 12-lead electrocardiograms (ECGs) can estimate future atrial fibrillation (AF) risk. Whether these models can be applied to single-lead ECGs (1L ECGs) from wearable or handheld devices is unknown. Aim: To apply a previously published deep learning model to estimate 2-year incident AF risk using handheld 1L ECGs obtained prospectively in a large AF screening trial. Methods: In the VITAL-AF trial (NCT03515057), over 16,000 primary care patients aged ≥65 years underwent AF screening with handheld 1L ECG. We applied our published deep learning model (ECG-AI) derived using single leads of over 450,000 standard 12-lead ECGs external to the VITAL-AF study (1L ECG-AI). We compared the performance of 1L ECG-AI to the validated CHARGE-AF clinical risk score and calculated net reclassification indices. Results: Among 15,694 individuals enrolled in VITAL-AF and without prevalent AF (age 74±7 years, 9,104 [58%] women), 1L ECG-AI discriminated 2-year incident AF (area under receiver operating characteristic curve [AUROC] 0.666 [95% CI 0.603-0.721]). With addition of age and sex (1L ECG-AI AS), 2-year AF discrimination (0.695 [0.637-0.742]) was comparable to the 11-component CHARGE-AF clinical risk score (0.679 [0.625-0.729]). Two-year AF incidence was markedly higher with 1L ECG-AI AS in the top 5% (8.0% [5.7-10.2]) vs bottom 5% (0.89% [0.23-0.55]). At a threshold of ≥3% estimated 2-year AF risk, AF incidence was progressively higher among patients at high risk according to neither model (1.5% [1.2-1.8]), one model (1L ECG-AI: 3.3% [2.3-4.2]; CHARGE-AF 3.4% [2.2-4.6]), and both models (5.8% [5.0-6.5]), implying that clinical risk and ECG-AI signals are complementary ( Figure ). Compared to screening all individuals at the guideline-based threshold of ≥65 years, 1L ECG-AI AS resulted in favorable net reclassification improvement (0.27 [0.22-0.32]). Conclusion: An ECG-AI algorithm developed using single leads of a 12-lead ECG combined with age and sex can discriminate AF risk using real-world handheld 1L ECGs with comparable performance to the CHARGE-AF score. 1L ECG-AI signals complement clinical risk factors. ECG-AI applied to 1L ECG may increase the reach and efficiency of AF screening.

Abstract 4115541: Association of Glucagon-like Peptide 1 Receptor Agonist Use with Incident Atrial Fibrillation

Background: Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have shown efficacy for reducing cardiovascular morbidity and mortality in patients with diabetes mellitus (DM), but conflicting evidence exists regarding their impact on cardiac arrhythmias. Whereas some studies suggested a possible association between GLP-1RA use and arrhythmogenesis, other studies suggested decreased association with atrial fibrillation (AF). Overall, large-scale real-world data evaluating risk of AF in association with GLP-1RAs are lacking. Objective: To compare risk of incident AF after initiation of GLP1-RA vs Dipeptidyl peptidase-4 inhibitors (DPP4i), as active comparators, in patients with DM. Methods: This retrospective propensity score-matched cohort study was conducted within the Veterans Health Administration from fiscal years 2006 to 2021. The study included U.S. veterans aged 35 years or older who initiated either GLP1-RA or DPP4i prescriptions. The primary outcome assessed was a composite outcome of atrial fibrillation (AF), defined as a diagnosis of AF/flutter based on administrative codes or undergoing an AF procedure. Results: Out of 116,235 GLP1-RA users and 217,668 DPP4i users, we propensity score-matched 80,948 pairs, on 88 characteristics, including demographics, comorbidities, vital signs, cardiovascular risk score, healthcare utilization, DM control, laboratory investigation, and medications. Composite outcome of AF was similar in GLP-1RA group (4.1%) and DPP4i group (4.3%); odds ratio (OR) 0.96, 95% confidence interval (CI) 0.92-1.01. Secondary analyses stratified by medication use duration showed no significant differences in composite AF risk (P>0.05). Notably, individuals achieving weight loss of 2%, 5%, or 10% of baseline body weight had significantly lower AF incidence, whereas no significant differences were observed in those with no weight loss or weight gain (OR 0.99, 95% CI 0.91-1.07). Conclusions: Use of GLP1-RA in patients with DM was not associated with a decreased risk of AF when compared with the use of DPP4i. In the subgroup analysis, significantly lower AF risk was seen in the GLP-1 RA group who achieved weight loss vs. DPP4i and this highlights weight loss as a potential modifier of cardiovascular outcomes in DM.

Abstract 4113188: Increased Physical Activity Intensity Associated with Reduced Risk of Atrial Fibrillation among Older Adults in South Korea: A Retrospective Cohort Study

Introduction: Physical activity (PA) may be associated with a lower risk of atrial fibrillation (AF), but this relationship remains controversial. In particular, further research is needed on the association between changes in PA intensity and AF risk among older adults. Hypothesis: We hypothesized that an increase in PA intensity would be associated with a reduced risk of AF among older adults aged 65 years and older in South Korea. Aim: This cohort study aimed to evaluate the association between changes in metabolic equivalent tasks (METs)-min/week and the risk of AF in the elderly using a nationally representative database. Methods: We conducted a retrospective cohort study using the Korea National Health Insurance Service (KNHIS) database. This cohort included 1,726,697 individuals aged 65 years and older without a history of cardiovascular disease diagnosis who underwent two consecutive health screening examinations from 2009 to 2012. PA was defined as MET-min/week derived from two consecutive health examinations during 2009-2010 (1st period) and 2011-2012 (2nd period), respectively. The primary outcome was an AF diagnosis during the follow-up period from 2013 to 2021. We estimated the sub-distribution hazard ratio (sHR) and 95% confidence interval (CI) for the association of changes in PA intensity with AF using Fine-Gray sub-distribution hazard models after adjustment for covariates. Results: This study included 1,726,697 participants (mean age 71.08; 46.78% male). An increase in PA intensity was associated with a reduced risk of AF (P for trend<0.001). Compared to persisting in physical inactivity, a change in PA intensity from physically inactive to ≥1000 MET–min/week was associated with a lower risk of AF (sHR, 0.83, 95% CI, 0.81-0.85). In contrast, a change in PA intensity from ≥1000 MET–min/week to being physically inactive was associated with a higher risk of AF (sHR, 1.30, 95% CI, 1.27-1.33) as compared to persistence in ≥1000 MET–min/week of PA intensity. Conclusions: An increase in MET-min/week may be associated with a reduced risk of AF among adults aged 65 years and older. Therefore, interventions encouraging PA should be recommended to maximize the health benefits of AF prevention in the elderly.

Abstract 4136900: Left-to-right ventricular volume ratio as a predictor of cardiovascular events: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background: The left ventricle (LV) and right ventricle (RV) are closely connected anatomically and functionally. Therefore, relative volume alterations signify pathologic disequilibrium even when within the normal range for chamber volumes. We aimed to define the prognostic value of volumetric imbalance between the LV and RV in the general population. Methods: The study sample consisted of 4073 asymptomatic participants from the Multi-Ethnic Study of Atherosclerosis who had a cardiac MRI at baseline. The left to right ventricular volume ratio (LRVR) was defined as LV volume/RV volume at end diastole. LRVR was categorized into balanced reference category 0.8-1.3, low (RV predominance) <0.8, and high (LV predominance) >1.3. Multivariable cox regression models were used to study the association between LRVR and heart failure (HF), atrial fibrillation (AF), and death. Results: The mean age of participants was 61.3±10 years, with 52% females. Participants were followed for a median of 17.8 years for HF, 16.7 years for AF, and 17.1 years for death. During follow up, 239 (5.9%) participants developed HF, 772 (19%) developed AF, and 906 (22.2%) died. When compared with the reference balanced LRVR group, those with high LRVR had increased risk of HF (HR 2.55; 95% CI 1.7-3.8; p <0.01), AF (HR 1.57; 95% CI: 1.2-2.06; p<0.01), and death (HR 1.63; 95% CI: 1.29-2.07; p<0.01) after adjusting for demographics and traditional cardiovascular risk factors. Participants with low LRVR had increased risk of HF (HR 1.88; 95% CI 1.1-3.2; p=0.02) and death (HR 1.51; 95% CI 1.12-2.04; p<0.01) in crude models. Adjusting for risk factors maintained increased risk of HF and death, but statistical significance was lost. Low LRVR was not associated with increased risk of AF. In a subgroup of participants with both absolute RV and LV volumes within normal ranges, high LRVR was still associated with increased risk of HF, AF, and death after adjusting for risk factors. Conclusion: In healthy asymptomatic participants at baseline, LV volume exceeding RV volume by at least 30% is associated with increased risk of HF, AF, and death. This relationship is independent of cardiovascular risk factors and absolute dilatation of either ventricle.

Abstract 4137717: Atrial Fibrillation in Valvular Heart Disease: Assessing the Impact of Genetics in the UK Biobank

Background: Atrial fibrillation (AF) in valvular heart disease (VHD) is typically linked to pressure or volume overload resulting in atrial remodeling. However, the independent contribution of genetics to AF in VHD beyond abnormal hemodynamics and other risk factors remains unclear. Objective: To study the role of a previously developed Polygenic Risk Score (PRS) for AF in predicting AF across different VHDs in the UK Biobank cohort. Methods: We analyzed UK Biobank data between 2000 and 2022. ICD codes were used to define incident AF and VHD status, including mitral valve (MV) disease [prolapse (MVP), regurgitation (MR) and stenosis (MS)] and aortic (AV) disease [stenosis (AS) and regurgitation (AR)]. Prior AF was excluded. Participants were divided into quintiles based on the PRS: the top quintile was defined as high genetic AF risk, second through fourth as intermediate genetic risk, and bottom quintile as low genetic risk. Results: Among 452841 participants with available PRS, 2238 had at least one VHD (385 MVP, 1058 MR, 81 MS, 421 AR, and 509 AS). AF incidence was 9.9%, 13.6%, and 19% in the low, intermediate and high genetic risk groups respectively, compared to 1.4%, 2.8%, and 5.7% in the general population (all p<0.05) - Figure 1A . Cox regression models adjusted for cardiovascular risk factors showed different genetic effects on AF across VHD types. Censoring patients at death, including valve intervention as a time-dependent variable, and excluding AF within 30 days post-intervention, PRS independently predicted AF in MV disease (hazard ratio [HR] 1.7, p=0.03 for the intermediate risk/mid PRS; HR 2.3, p=0.002 for the high risk PRS), particularly in those with MVP (HR 3.1, p=0.03 for the high PRS). However, in those with AV disease, PRS was not significantly associated with AF (p=0.93 and p=0.07) - Figure 1B. Conclusion: In patients with VHD, AF PRS is significantly associated with an increased risk of developing AF. However, the genetic impact varies across different VHD. In AV disease, there is a minimal genetic contribution, and the elevated AF risk may be predominantly due to pressure or volume overload. In contrast, in MV disease, particularly in MVP, there is a substantial genetic influence on AF risk.

Abstract 4123653: Association of Inflammatory Bowel Disease with the Risk of Atrial Fibrillation: A Meta-Analysis

Background: Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a prevalent condition associated with chronic noninfectious inflammation of the gastrointestinal tract. It has been hypothesized that chronic inflammation can predispose patients to atrial fibrillation (AF), with proposed mechanisms being structural remodeling of atrial tissue, autonomic dysfunction, and oxidative stress; however, no clear evidence exists to support this. Aims: Our meta-analysis aims to pool all existing data to determine if there is an increased risk of AF in patients with IBD, providing more robust evidence on the matter. Methods: A systematic literature search was conducted using major databases (PubMed, EMBASE, and SCOPUS) aimed at studies focusing on AF development in patients with IBD. Further subgroup analyses were performed for ulcerative colitis (UC) and crohn’s disease (CD). Risk ratios (RR) with their corresponding 95% confidence intervals (CI) were pooled using a random-effects model in the Review Manager Software. Statistical significance was set at p < 0.05. Results: Seven studies with 88,893,407 patients were included (1,002,719 and 87, 890, 688 patients in the IBD and non-IBD groups, respectively). IBD patients were at an increased risk of developing AF [RR: 1.52; 95% CI: 1.19-1.95; p=0.0009] compared to the non-IBD group. In subgroup analyses, patients with UC were at an increased risk of developing AF [RR: 1.29; 95% CI: 1.08-1.53; p=0.004], as were CD patients [RR: 1.30; 95% CI: 1.07-1.58; p=0.008] compared to the non-UC and non-CD groups, respectively (Figure 1). Conclusion: Patients with IBD are at nearly 1.5 times the risk of developing AF compared to the non-IBD population. Our meta-analysis was limited by heterogeneity among the studies, highlighting the importance of further large-scale prospective studies to establish more robust evidence and determine the real-world clinical significance of our findings. Furthermore, future research should explore the impact of confounding variables such as disease severity, medication usage, and lifestyle factors on the observed association between IBD and AF.

Abstract 4113263: Serum Metabolomics Adds Predictive Value to Clinical and Polygenic Risk Scores for Atrial Fibrillation: A UK Biobank study of >240,000 Patients

Background: Atrial fibrillation (AF) poses substantial morbidity and mortality burdens globally. It is critical to identify individuals at high-risk for AF to implement both lifestyle modifications and close monitoring for initiation of oral anticoagulants. Currently, risk prediction in AF relies on clinical scores such as CHARGE-AF. Small molecule metabolites are thought to play a role in AF pathogenesis, but the additional predictive value of metabolomics over clinical and genetic risk factors is unknown. Using the UK Biobank (UKBB), we sought to perform this evaluation. Methods: We included all UKBB participants with complete 1 H-NMR metabolite measurements. We excluded participants with prior history of AF or with incomplete AF Polygenic Risk Score (AF-PRS) or CHARGE-AF components. The final cohort included 240,628 patients. In-patient records, primary care notes, and death registries were queried to identify patients who had developed incident AF within 5 years of enrollment. The cohort was divided into a 80/20:Train/Test split. We compared the performance of an Elastic-Net regularized Cox Proportional Hazards (EN-CPH) model trained on CHARGE-AF, AF-PRS, and the full 170 metabolite panel to a CPH model trained only on CHARGE-AF and AF-PRS. Results: Within 5 years, 4,174 (1.7%) patients developed AF. Compared to the control population, the incident AF cases were more likely to be older (62 vs. 56, p<0.001), male (65% vs 45%, p<0.001), and have higher CHARGE-AF and AF-PRS scores (p<0.001). After training the EN-CPH model on CHARGE-AF, AF-PRS, and 170 metabolites, the final model included 8 metabolites on top of CHARGE-AF (HR: 1.28) and AF-PRS (HR: 1.11). After adjusting for CHARGE-AF and AF-PRS, creatinine level was associated with increased risk of AF (HR: 1.01) while linoleic acid level (HR: 0.985) was associated with decreased risk. Furthermore, total cholesterol, esterified cholesterol, free cholesterol, cholesteryl esters in IDL, omega-6 fatty acids, and cholesterol in large LDL were associated with HR 0.993-0.999. The EN-CPH model out-performed the CPH model without metabolomics on the test set (AUC 0.786 vs 0.753, p < 0.001). Conclusions: The addition of metabolomics to clinical and genomic risk scores improves prediction of 5-year incident AF within a general population. This study highlights the significance of the metabolome as an independent prognosticator of AF risk. Further study of the mechanisms by which selected metabolites alter AF risk is needed.

Abstract 4135617: Large Scale Proteomics Identifies Circulating Biomarkers Relating Atrial Fibrillation to Heart Failure: the Atherosclerosis Risk in Communities Study

Introduction: There is a bidirectional relationship between atrial fibrillation (AF) and heart failure (HF) risk. Data regarding shared and unique pathways underlying each are limited. Aims: Identify plasma proteins associated with both incident AF and HF and determine the extent to which associations with one outcome are conditional on interval occurrence of the other outcome. Methods: Among participants in the community-based Atherosclerosis Risk in Communities study free of HF and AF at study visit 5 (2011-2013), we measured 4,955 plasma proteins (SomaScan aptamer-affinity assay). We performed parallel analyses of individual protein associations with incident HF and AF using multivariable Cox regression adjusted for demographic and clinical covariates at Bonferroni significance. We then repeated the analysis for each outcome in models censoring participants with interval occurrence of the other outcome (i.e. incident AF censoring for interval HF, and vice versa). We tested associations of AF-related proteins with echocardiographic and Zio patch measures at Visit 5. Results: Among 4,118 participants included, mean age was 75±5 years, 60% were female, and 18% reported Black race. We identified 83 proteins associated with incident HF (n=355 incident events at 7 [IQR 6-8] year follow-up) and 24 with incident AF (n=517 incident events at 8 [7-9] years), of which 10 were associated with both. In models of incident HF censoring for interval AF, 63 (76%) proteins remained significantly associated with HF. In contrast, in the analysis of incident AF censoring for interval HF, only 4 (17%) proteins remained associated with AF, of which 3 were also associated with HF risk (Figure). These 4 AF-related proteins were associated with measures of LV diastolic function (LA volume, E/e’. average), LV mass index, LA function (LA reservoir, LA contraction), and supraventricular ectopy density (all p<0.05). Conclusion: Nearly half of proteins reflecting AF risk also associate with HF, greater than 80% of AF-associated proteins are HF-dependent, and even those that are not correlate with measures of LV remodeling and dysfunction. These findings suggest that AF-related mechanisms among older adults are part of a wider HF syndrome.

Abstract 4137272: The Impact of Genotype in Dilated and Arrhythmogenic Cardiomyopathy: Insights from the SHaRE Registry

Background: The impact of genotype on the risk of arrhythmia and heart failure in dilated and arrhythmogenic cardiomyopathy (DCM/ACM) is not well defined. Better understanding of genetic risk factors is needed to improve patient risk stratification, management, and outcomes. Methods: In this observational study, we leveraged the international Sarcomeric Human Cardiomyopathy Registry (SHaRe) to analyze the effect of arrhythmic gene variants on clinical events in patients with DCM/ACM (excluding arrhythmogenic right ventricular cardiomyopathy). Patients were stratified by the presence of pathogenic variants in 8 genes most commonly associated with ACM (AR(+): LMNA , DSP , FLNC , RBM20 , PLN , SCN5A , DES , and TMEM43 ). We assessed for risk of clinical events including ventricular arrhythmia (VA), atrial fibrillation (AF), heart failure (HF), death, and the overall composite of any of these events. Analyses were adjusted for age at diagnosis, sex, and baseline left ventricular ejection fraction (EF). Patients were also stratified by EF ≥50% in subgroup analyses. Results: A total of 1373 genotyped adults with DCM/ACM from 6 centers were included with median follow-up of 5.5 (IQR 2.4-10.4) years. Mean diagnosis age was 48 (± 15) years, and 39.5% were female. The cohort included 185 (13.5%) AR(+) patients. AR(+) compared to genotype-negative patients (N=486, 35.4%) had increased risk of VA (HR 5.02, 95% CI 3.46-7.29) and AF (HR 3.02, 95% CI 2.20-4.10). Risk of HF (HR 2.32, 95% CI 1.55-3.49) and the overall composite (HR 2.12, 95% CI 1.68-2.67) were also increased ( Figure ). Risk of each event remained significant after adjusting for age, sex, and baseline EF ( Table ). AR(+) patients with EF ≥50% also had increased risk of VA (HR 4.56, 95% CI 2.16-9.63), AF (HR 2.94, 95% CI 1.72-5.03), and the overall composite (HR 2.15, 95% CI 1.41-3.28). Conclusions: Genetic testing enables powerful risk stratification for both arrhythmias and heart failure in DCM/ACM independent of age, sex, or EF.

Abstract 4124709: Accelerometer-Measured Sedentary Behavior and Future Cardiovascular Disease

Background: Current consensus guidelines emphasize the importance of achieving 150 minutes or more of moderate to vigorous physical activity (MVPA) per week to promote cardiovascular health but give little guidance about sedentary behavior. Research Question: Is sedentary behavior associated with cardiovascular (CV) disease in a manner distinct from insufficient physical activity? Aims: Examine associations between accelerometer-measured sedentary behavior with risk of specific CV outcomes, including potential interactions with MVPA. Methods: Using 89,530 individuals providing one week of accelerometer-based physical activity data from the UK Biobank, we fit Cox models adjusted for demographic and lifestyle factors to assess associations between sedentary time (as a spline term) and incident atrial fibrillation (AF), myocardial infarction (MI), heart failure (HF), and CV mortality. We assessed the potential effect of MVPA on these associations by including MVPA as an adjustment variable, as well as performing subgroup analyses stratified at the guideline-recommended MVPA threshold. Results: Among 89,530 individuals (age 62±8 years, 56.4% women) undergoing accelerometry, median sedentary time was 9.4 hours/day (quartile-1: 8.2, quartile-3: 10.6). In multivariable models, using the second quartile (8.2-9.4 hours/day) as a referent, sedentary time in the top quartile (>10.6 hours/day) was associated with greater risk of HF (hazard ratio [HR] 1.45, 95% CI 1.28-1.65), and CV mortality (HR 1.62, 95% CI 1.34-1.96), with evidence of a threshold effect at 10.6 hours/day. Higher sedentary time was also associated with greater risk of incident AF (HR 1.11, 95% CI 1.01-1.21) and MI (HR 1.15, 95% CI 1.00-1.32), with an approximately linear relation. Associations with HF and CV mortality persisted after adjustment for MVPA, as well as among individuals both above and below the guideline-based activity threshold of ≥150 minutes MVPA/week. Conclusions and Relevance: Sedentary behavior is broadly associated with future adverse CV outcomes. For HF and CV mortality, associations appear distinct from insufficient MVPA, and sedentary time in excess of 10.6 hours/day conferred an increased risk.

Abstract 4138611: Impact of SGLT-2 Inhibitor Use on Atrial Fibrillation Incidence Following Heart Failure Hospitalization

Introduction: The development of atrial fibrillation (AF) in patients with heart failure (HF) is associated with increased morbidity and mortality. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have demonstrated cardiovascular benefit in patients with both preserved and reduced ejection fractions. Meta analysis of prospective trials suggest reduced incidence and burden of atrial fibrillation in patients taking SGLT-2 inhibitors, though this has not been specifically addressed in prospective trials. Hypothesis: SGLT-2 inhibitors reduce the incidence of atrial fibrillation in patients with heart failure. Aim: The goal of the study is to assess the impact of SGLT-2 inhibitor on the incidence of atrial fibrillation following heart failure hospitalization. Methods: The study included consecutive patients who were admitted to an academic tertiary care center over a 3 year time period with a primary diagnosis of heart failure exacerbation and no prior diagnosis of AF. The primary outcome was development of AF within 12 months after hospitalization. Demographic, comorbidity, echocardiographic data, and medications were obtained. Cox-regression analysis was performed to identify the predictors of new-onset AF after HF hospitalization. Results: Among the 3,953 patients included in our study, 704 (17.8%) patients were prescribed SGLT-2 inhibitors. Of those taking SGLT-2 inhibitors, 559 (79.4%) patients had diabetes. SGLT-2 inhibitor use is associated with significant reduction of AF at one year ( p<0.001; RR 0.65; 95% CI: 0.51-.81 ). This finding was consistent across patients with reduced ejection fractions (EF<50%) ( p=0.001; RR 0.56; 95% CI: 0.40-.80 ) and preserved ejection fraction (EF>50%)( p=0.001; RR 0.58; 95% CI: 0.42-0.80 ). Conclusion: In patients with reduced ejection fraction and preserved ejection fraction heart failure, use of an SGLT-2 inhibitor is associated with a statistically significant lower risk of new-onset atrial fibrillation at one year following HF hospitalization.

Abstract 4136932: Impact of Different Socioeconomic Metrics on Heart Failure-Related Admission and Short-Term Outcomes in Maryland

Introduction: Annually, over 500,000 Americans are hospitalized due to heart failure (HF), marking it as a major contributor to morbidity and mortality. It also poses a significant financial burden and leads to considerable losses in productivity. Objective: This study investigates the predictive accuracy of different socioeconomic metrics on the risk and outcomes of HF in Maryland. Methodology: A retrospective analysis of the Maryland State Inpatient Database (2016-2020) was conducted to assess the predictive accuracy of race/ethnicity, insurance status, household median income, and neighborhood poverty level (measured by the Distressed Communities Index) on the risk of heart failure-related hospital admissions and outcomes. Multivariate logistic regression models were also used to adjust for confounders. Result: During the study period, a total of 389,220 cases of HF were reported in the Maryland SID. The majority of these patients were white (56.8%) and female (51.1%), with a median age of 73 years (interquartile range [IQR] 62-82 years). The in-hospital mortality rate was 5.1%, while rates of atrial fibrillation, cardiac arrest and prolonged hospital stay were 34.4%, 0.3%, and 48.4%, respectively. Multivariate analysis revealed a substantial area under the ROC curve (AUC) indicating good model performance: 0.88 for predicting HF, 0.64 for atrial fibrillation, 0.64 for cardiac arrest 0.57 for prolonged hospital stays, 0.63 for mortality. Subgroup analyses showed variable predictiveness by race (AUC = 0.4378), payment method (AUC = 0.5754), income quartile (AUC = 0.5202), and deprivation composite score (AUC = 0.4751). Patients with private insurance had the highest risk of stress cardiomyopathy (odds ratio [OR] = 1.98; 95% confidence interval [CI] 1.70-2.29). Socioeconomic metrics, including neighborhood distress, showed varying predictive accuracy for the HF-related admissions and selected short-term outcomes, with the highest predictive accuracy for neighborhood distress on the risk of HF (AUC = 0.50, std: 0.006), atrial fibrillation (AUC = 0.48, std: 0.0007), cardiac arrest (AUC = 0.51, std: 0.007), and prolonged hospital stays (AUC = 0.53, std: 0.0005) and mortality (AUC = 0.50, std: 0.0015). Conclusion: Neighborhood poverty level demonstrates significant predictive power for assessing the risk of HF-related hospital admissions and the short-term outcomes among Maryland residents, exceeding factors like insurance and race/ethnicity.

Abstract 4141454: Atrial Fibrillation in American Indians: Comparative Analysis of Characteristics and Anticoagulation Use for Stroke Prevention of Atrial Fibrillation

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United States, affecting individuals of all races. Anticoagulation (AC) therapy is recommended by the guidelines to reduce the risk of stroke in AF patients. Previous reports indicate that American Indians (AI) have a higher risk of AF and an increased risk of stroke from AF. Aim: To describe the demographic and clinical characteristics of the AI population with AF and compare their AC status with other racial groups. Methods: We retrospectively analyzed AF patients age >18 years hospitalized between January 2022 and October 2023 in two hospitals serving a large Navajo Nation AI population in rural Northern Arizona. We compared baseline characteristics, AC status and direct oral anticoagulant (DOAC) use between AI and other races. Between group statistical analysis was completed using a chi-square for categorical variables and a Mann-whiney U test for continuous variables, with statistical significance defined as a p-value ≤ 0.05. Results: In total, 9255 patients were admitted with AF: 871 (9.4%) were AI, with 696 (79.9%) being Navajo Nation AI and 8284 (89.5%) from other non-AI races. AI patients with AF were younger (average age 65±15.9 vs 75±11.2; p <0.0001), had fewer female patients (30.5% vs 39.3%; p <0.0001), and were less likely to be treated with oral anticoagulation (40.5% vs 50.9%; p <0.0001; OR 0.66; 95% CI: 0.57 to 0.76) compared to non-AI races (table 1). Among those anticoagulated, AI patients were less likely to receive a DOAC (38.0% vs 44.7%; p = 0.0002; OR 0.76; 95% CI: 0.66 to 0.88) compared to non-AI races (table 2). Conclusions: Our analysis, with a significant number of AI pts, reveal that AI patients develop AF at a younger age and despite an increased risk of stroke, have significantly lower rates of anticoagulation use, particularly with DOACs. Our findings underscore the need for guideline-adherent AC use in this AI population.

Abstract 4138212: Efficacy of Left Atrial Appendage Occlusion in Reducing Mortality and Major Bleeding Events in Cancer Patients with Atrial Fibrillation

Introduction: Atrial fibrillation (AF) is a common comorbidity in cancer patients, increasing their risk of stroke and mortality. Cancer patients are often excluded from anticoagulation and AF intervention trials due to the nature of their disease, and risk scores such as HAS-BLED, CHADS2/CHADS2-VASc often underpredict the high risk of AF and related complications for these patients. Research Question: Does left atrial appendage occlusion (LAAO) reduce mortality, major bleeding events (MBE), and stroke in cancer patients with AF? Methods: Using TriNetX, an international health research network with data from over 100 million patients, cancer patients with AF, with and without LAAO were identified between 2015 and 2022. Equal cohorts of 147 patients were created after propensity score matching for demographics, diabetes, hypertension, and heart failure. Measures of Association and Survival Analysis were conducted between 3-months and 5-years. The primary outcome was mortality. The secondary outcomes were MBE and stroke. Results: The study included 294 cancer patients with AF, with 147 having received LAAO. The risk of mortality at 3 months was 6.8% in the LAAO+ group compared to 15% in the LAAO- group (p-value= 0.025). At 6 months, the mortality risk was 8.8% in the LAAO+ group and 18.4% in the LAAO- group (p-value= 0.017). At 1 year, the mortality risk was 12.2% in the LAAO+ group and 23.8% in the LAAO- group (p-value=0.010). At 5 years, the mortality risk was 28.6% in the LAAO+ group and 49.7% in the LAAO- group (p-value<0.0001). The MBE risk was 20.4% for the LAAO+ group and 32% for the LAAO- group at 3 months (p-value= 0.024). At 6 months, the MBE risk was 25.9% in the LAAO+ group and 40.1% in the LAAO- group (p-value=0.009). Although there was no significant difference in risk of MBE at 1 year and 5 years, survival was higher among the LAAO+ group than the LAAO- group (64.92% vs 52.76%; p-value= 0.038 at 1 year and 52.67% vs 39.23%; p-value=0.029 at 5 years). However, there was no difference between stroke risk or survival probability across all measured time points. Conclusion: LAAO in cancer patients with AF was associated with significantly reduced mortality and major bleeding events over a 5-year period compared to those without LAAO. These findings suggest that LAAO may be a beneficial intervention for improving survival and reducing bleeding complications in cancer patients with AF.

Abstract 4134896: Clinical and Echocardiographic Markers for the Prediction of Incident Atrial Arrhythmias in Hypertrophic Cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM), in addition to increasing the risk for heart failure and sudden cardiac death, augments the risk for atrial fibrillation (AF) and atrial flutter (AFL). We aimed to identify clinical and echocardiographic risk factors that are predictive of incident AF/AFL in HCM patients. Methods: This retrospective study included 99 HCM patients from University of Chicago without prior AF/AFL, followed for a median of 3.2 years (IQR: 11.5 months-6.9 years). Clinical data were obtained via chart review; echocardiographic findings were obtained using AI software (Us2.ai) with measurements audited by a level III echocardiography reader. Statistical testing included Chi-square/Fisher’s exact (categorical variables) and T-test/Wilcoxon rank sum (continuous variables). Univariate and multivariate Cox regressions assessed predictive value of risk factors for AF/AFL. Results: 18 HCM patients (18%) developed AF/AFL ( Table 1 ). On univariate analysis, older age (HR 1.06, 95%CI 1.02-1.11, p=0.002), hypertension (HR 8.32, 95%CI 1.10-63.20, p=0.04), diabetes (HR 3.90, 95%CI 1.51-10.03, p=0.005), prior stroke (CVA, HR 3.81, 95%CI 1.34-10.86, p=0.012), and NYHA class II-IV (HR 8.48, 95%CI 2.97-24.21, p<0.001) predicted AF/AFL. E/A (p=0.04), E/e’ (p=0.028), MV-A (p=0.022), and LVEF (p=0.02) were also significant predictors ( Figure 1 ). LVEF (HR 0.92, 95%CI 0.87-0.98, p=0.013) remained a significant predictor of AF/AFL on multivariate analysis controlling for age, hypertension, diabetes, CAD, CVA, and NYHA class. Conclusions: Traditional risk factors including age, hypertension, diabetes, CVA, and NYHA class are significant predictors of incident AF/AFL in HCM patients, highlighting the need for comprehensive risk factor evaluation. Even after adjustment for these clinical markers, LVEF independently predicts new AF/AFL in HCM patients, underscoring the importance of routine echocardiographic assessment for risk stratification in this patient population.

Abstract 4145826: Atrial Fibrillation Screening During Sinus Rhythm Periods by Interrelated Systems Dynamics Analysis

Background: Previous studies have shown that AF screening in at-risk populations can reduce stroke incidence. However, non-targeted screening approaches often result in high false positive rates, placing an unnecessary burden on the healthcare system. In contrast, artificial intelligence-guided screening has been demonstrated to increase diagnostic yield in large prospective clinical trials. This approach, however, requires recording an ECG and a large-scale dataset for model training. Heart rate variability (HRV) analysis has proven effective in deciphering key heart dynamics. By analyzing HRV as interrelated dynamic systems, it may be possible to facilitate targeted AF screening using wearable devices that measure heart rate. The Koopman operator, used for data-driven modeling of interrelated dynamic systems, has been shown to accurately predict complex phenomena in chaotic systems such as climate forecasting and drug adverse reaction prediction. This is achieved by utilizing common characteristics of the systems for most model parameters, with only a small fraction of the parameters being specific to a certain system. Methods: Long (>10 hour) records from 361 individuals (AFDB, LTAFDB) and healthy individuals' datasets from PhysioNet and THEW were analyzed for inter-beat intervals. The unified dataset was then split into 94 training, 17 validation, and 250 test set patients. Recordings from the training set were used to train both the common and specific parts of the interrelated dynamic systems model for each patient, along with a shared small neural network classifying patients into low and high risk for AF based on the unique (not shared between patients) singular values of the dynamic system model. Patient-specific dynamic system models were then fitted for the validation and test sets to calculate the patient dynamic singular values, which were used to classify patients into low and high risk for AF groups. Results: Atrial fibrillation occurred in 48 of 202 (23%) patients classified as low risk and 35 of 48 (72.9%) patients classified as high risk (odds ratio 8.63, 95% CI 4.23-17.64), yielding 72.9% sensitivity with 76.2% specificity. Conclusion: In this retrospective analysis, classification of the dynamic system model singular values identified patients at high risk for atrial fibrillation from sinus rhythm period.

Abstract 4143227: Incidence of Hemorrhagic Stroke in Hypertrophic Cardiomyopathy

Background: Individuals with hypertrophic cardiomyopathy (HCM) have an elevated risk of ischemic stroke, primarily driven by the increased risk of atrial fibrillation (AF) development in this patient population. This risk remains elevated regardless of CHADS2VASC score; thus, anticoagulation is recommended for all HCM patients with AF. Given the known association between anticoagulant medications and hemorrhagic events, there is likely an assumed risk of hemorrhagic stroke in these individuals. Currently, the incidence of hemorrhagic stroke in HCM and its relationship to AF and anticoagulation has not been well-established in the literature. The goal of this study was to establish the presence of and risk factors for hemorrhagic stroke in individuals with HCM. Methods: A retrospective review of all HCM patients ages 18 and older in our institution’s health system was performed from 2019-2023. ICD 10 codes were used to identify individuals with hemorrhagic stroke. Patient charts were reviewed for additional data including demographics, comorbid conditions, anticoagulant prescription, and other inciting factors prior to the hemorrhagic event. Results: The study cohort comprised 343 HCM patients, of which 47.1% were female and 72.7% were Caucasian. Concurrently, 30% (n=103) had a diagnosis of AF. The overall incidence of hemorrhagic stroke was 2.9% (5.8%, n=6 in those with AF vs 1.7%, n=4 in those without AF); furthermore, AF was associated with a non-statistically significant increased risk of hemorrhagic stroke (RR = 3.36, 95% CI 0.97-11.7). Anticoagulant use at the time of hemorrhagic event was observed in 4 individuals (67%) with AF and 1 individual (25%) without AF. Head trauma and falls were frequently observed as precipitating events prior to hospital admission for hemorrhagic stroke, occurring in 83% (n = 5) of patients with AF and 50% (n = 2) of those without AF. Conclusions: While ischemic stroke and anticoagulant use are commonly studied in those with HCM, the incidence of hemorrhagic stroke in this population is not negligible. Risk of hemorrhagic events in HCM appears largely influenced by anticoagulant use, particularly in those with concurrent AF, and by head trauma. Given the known benefits of anticoagulation on ischemic stroke risk in the HCM population, appropriate counseling and careful attention to individual patient factors may be warranted in the administration of anticoagulants.

Abstract 4137249: Left atrial functional reserve predicts recurrence of atrial arrhythmia following catheter ablation in patients with persistent atrial fibrillation

Background: Left atrial (LA) functional remodeling plays an essential role in the pathophysiological mechanisms of atrial fibrillation (AF). LA reservoir strain (LARS) measured by speckle-tracking echocardiography (STE) exhibits acceptable predictive value for recurrent atrial arrhythmia in patients with paroxysmal AF, while its performance in persistent AF remains inconclusive. Recently, LA functional reserve, a novel concept of LA mechanics in response to acute-volume overload, is drawing attention. Research Questions: Are LARS and LA functional reserve associated with recurrent atrial arrhythmia after catheter ablation in patients with persistent AF? Methods: Ninety-two patients who underwent first catheter ablation for persistent AF were included in the study. LARS at rest and LA functional reserve were assessed by STE 1-4 days before catheter ablation. LA functional reserve was calculated as change in LARS after passive leg lifting. Recurrence of arrhythmia was defined as atrial arrhythmia of ≥ 30 seconds duration after a 2-month blanking period. Results: The median values of LARS and LA functional reserve were 14.4 % (interquartile range [IQR] 10.9 to 18.2) and 1.0% (IQR -1.2 to 3.6), respectively. During a mean follow-up of 13.2 ± 9.9 months, 29 (31.5%) patients experienced recurrent AF. When we stratified patients into 2 groups according to LARS and LA functional reserve (below vs. above median values), patients with impaired LA functional reserve (< 1.0%) were at higher risk of AF recurrence (log-rank test p value=0.026), but this was not observed for LARS (Figure). In multivariable Cox proportional hazard analysis, impaired LA functional reserve was associated with recurrent atrial arrhythmia independent of AF risk factors, left ventricular ejection fraction and LARS at rest (adjusted hazard ratio 3.99, p=0.004). Conclusions: Evaluation of LA functional reserve may provide valuable information for optimal patient selection as well as follow-up strategy after catheter ablation in patients with persistent AF.