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Background Multimorbidity is common in patients with atrial fibrillation (AF); however, the impact of the number and type of comorbid conditions on outcomes remains uncertain. Methods This cohort study included patients with new‐onset AF from a Midwest region between 2013 and 2017. Eighteen chronic conditions at the time of AF were classified into groups: cardiometabolic, other somatic, and mental health. Cox regression determined associations between the number of each condition type with death, ischemic stroke/transient ischemic attack, and congestive heart failure, stratified by age. Results Among 16 509 patients with AF (mean age, 74 years; 43% women), the mean number of cardiometabolic, other somatic, and mental health conditions was 2.7, 1.4, and 0.5, respectively. The number and type of conditions had a varying impact on outcomes and differed by age. A higher number of cardiometabolic conditions were associated with increased risk of death within 90 days only in people aged ≥85 years (≥4 conditions versus 0: hazard ratio [HR], 1.74 [95% CI, 1.05–2.87]), whereas for death after 90 days, associations were strongest in the youngest age group (<65 years: HR, 1.83 [95% CI, 1.35–2.46]; 65–74 years: HR, 1.34 [95% CI, 1.04–1.73]; 75–84 years: HR, 1.32 [95% CI, 1.09–1.60]; ≥85 years: HR, 1.14 [95% CI, 0.96–1.35]). Associations with outcomes were generally strongest in the youngest age group and attenuated with older age for higher number of other somatic conditions, whereas the pattern was less consistent for mental health conditions. Conclusions Along with cardiometabolic‐related conditions, other somatic and mental health conditions are important predictors of outcomes in AF, with effects differing by age, and should be considered when caring for these patients.

Abstract Objective To investigate the ability of artificial intelligence‐enabled electrocardiogram (AI‐ECG) atrial fibrillation (AF) prediction model output and delta age, defined as AI‐estimated age minus chronological age, to predict adverse vascular outcomes in patients with migraine. Background Migraine, especially migraine with aura, is associated with an increased risk of cardiovascular events. Using normal sinus rhythm ECG, our institution has developed AI‐ECG models that predict the probability of AF and estimate patients' age, and from that, delta age (estimated age minus actual age) has been shown to reflect cardiovascular health and physiologic aging. Methods We conducted a retrospective cohort study that included adult patients with migraine who had at least one digital, standard 12‐lead ECG from 2000 to 2020 at any Mayo Clinic site. The first normal sinus rhythm ECG was defined as the index ECG, and those with adverse vascular events or AF prior to, or within 3 days after, index ECG were excluded. AI‐ECG AF prediction model output and delta age were obtained from the index ECG. The primary outcome was a composite endpoint of adverse vascular events that included acute myocardial infarction, acute ischemic stroke, venous thromboembolism, and death. New‐onset AF was also recorded as a secondary outcome. Results A total of 29,928 patients were included. The mean age was 44.3 ± 14.5 years, and the median follow‐up time was 54 months. During the study period, 4662 (15.6%) patients had adverse vascular events, and 1384 (4.6%) patients developed new‐onset AF. A higher AF prediction model output was associated with a higher risk of adverse vascular outcomes (adjusted hazard ratio [aHR]:1.15 [95% confidence interval: 1.12 to 1.18] for every 10% increase in prediction model output), as was a larger delta age (aHR:1.16 [1.12 to 1.21] for every 10‐year increase in delta age). Moreover, AI‐ECG AF prediction model outputs of ≥1% (aHR: 1.45 [1.36 to 1.54]) and delta age ≥−1 years (aHR: 1.09 [1.02 to 1.16]) were found to be the optimal cutoffs to dichotomize patients into high‐risk and low‐risk groups for adverse vascular events. Higher AI‐ECG AF prediction model output at baseline also predicted a higher likelihood of having new‐onset AF during the study period (aHR: 1.31 [1.26 to 1.37]), and the development of new‐onset AF was associated with a higher risk of adverse vascular events (aHR: 2.43 [2.17 to 2.73]). Conclusions For patients with migraine, a higher AI‐ECG AF prediction model output and delta age are predictive of adverse vascular outcomes. A higher AF prediction model output is also predictive of future AF development. Furthermore, we identified the cutoffs for both AI‐ECG models that can distinguish patients between high‐ and low‐risk groups. Our results showed that AI‐ECG models could inform clinical practice and identify patients with migraine at risk for future adverse vascular events.

Abstract Aims Artificial intelligence electrocardiography (AI-ECG) algorithms are emerging tools for identifying individuals at risk of atrial fibrillation (AF). We evaluated the predictive performance of a validated AI-ECG algorithm for incident AF in UK Biobank participants with AF risk factors, irrespective of prevalent cardiovascular disease, and its incremental value when added to clinical predictors. Methods and results The AI-ECG tool was applied to sinus rhythm ECGs from UK-Biobank participants with risk factors for AF but no AF. Model performance was evaluated using time-dependent ROC-AUC and Harrell’s C-index. Multivariable Cox regression was used to identify clinical risk factors associated with incident AF and to quantify the contribution of AI-ECG. A total of 21 842 participants (56% male) were included. The median follow-up time was 3.7 years (IQR 0.5–5.4) The ECG-AI tool achieved a ROC-AUC of 0.73 (95% CI 0.68–0.78) at 1 and 0.69 (95% CI 0.66–0.72) at 3 years. A multivariable Cox regression model using clinical parameters achieved a ROC-AUC of 0.71 (95% CI 0.66–0.75) at 1 and 0.71 (95% CI 0.68–0.74) at 3 years. By adding ECG-AI to the clinical Cox regression model, the ROC-AUC increased to 0.75 (95%CI 0.71–0.80) at 1 and 0.74 (95% CI 0.71–0.77) at 3 years. AI-ECG showed a hazard ratio of 1.23 per decile increase (95% CI 1.18–1.27). Conclusion An AI-ECG algorithm improved the prediction of incident AF when added to a clinical parameter-based model over a median follow-up time of 3.7 years among individuals with comorbidities predisposing to AF who may benefit from targeted screening and preventive strategies.

Abstract Introduction Atrial fibrillation (AF) is a major contributor to stroke risk, yet many cases remain undiagnosed due to its silent nature. Deep learning-based electrocardiogram (DL-ECG) analysis can streamline AF risk stratification, providing a more reliable and accessible method to stratify risk using only a standard resting ECG. However, this tool has been validated only on AF detected clinically or with short ECG event monitors. Purpose This study aimed to validate the predictive accuracy of a DL-ECG model for identifying AF in normal sinus rhythm (NSR) ECGs among patients undergoing continuous cardiac monitoring with implantable loop recorders (ILRs). Methods We conducted a historical cohort study across three major U.S. academic medical centers, enrolling patients with an ILR and no prior diagnosis or documented ECG evidence of AF. Pre-implantation 10-second, 12-lead ECGs in NSR were analyzed using the DL-ECG model. Performance was evaluated using the area under the receiver operating characteristic curve (AUC) and compared with the CHARGE-AF score. Kaplan-Meier survival analysis and Cox proportional hazards models assessed the association between DL-ECG risk categories and incident AF, defined as any episode lasting ≥6 minutes. Results We included 2,523 patients (mean age 66 ± 17 years, 52% male). AF was detected in 658 (26%) over a median follow-up of 19 months (IQR 8-37), Table 1. The DL-ECG model classified 1,634 patients (65%) as at low-risk and 889 (35%) as at high-risk. AF developed in 242 (14.8%) of the low-risk group and 416 (46.8%) of the high-risk group, yielding an AUC of 0.73 (95% CI 0.70-0.75), surpassing the CHARGE-AF AUC of 0.69 (95% CI 0.66-0.71). A combined DL-ECG and CHARGE-AF model yielded an AUC of 0.74 (95% CI 0.72-0.76), Figure 1 presents the AUC, Net Reclassification Index, and DeLong test comparisons among the three models. High-risk patients had a significantly higher incidence of AF, which remained significant after adjusting for CHARGE-AF variables, Figure 2. AF incidence increased as DL-ECG quartiles increased, with 61% of patients at the top quartile developing AF during follow-up, Figure 3. False negatives (patients initially classified as low-risk but in whom later AF was detected) had a longer median time to AF detection (127 days [IQR 28-425] vs. 101 days [IQR 20-318] for true positives, p = 0.01), and where found to have at least one positive ECG during follow-up in 36%, compared to 32% of true negatives, indicating eventual risk reclassification. Conclusions Among patients undergoing ILR monitoring, the DL-ECG model demonstrated superior predictive performance compared to CHARGE-AF, offering a promising and accessible alternative for early detection of silent AF. This approach could aid early AF detection, particularly in resource-limited settings where access to specialized rhythm monitoring services is limited.Table 1 and Figure 1 Figure 2 and 3

Abstract Background Left ventricular diastolic function (LVDF) and left bundle branch block (LBBB) are both linked with increased risk of LV systolic dysfunction, heart failure, and mortality. Assessing LVDF, which is typically done through echocardiography, becomes challenging in the presence of LBBB due to the intraventricular conduction delay that disrupts the reliability of tissue Doppler imaging. Recently, we validated an artificial intelligence-enabled electrocardiogram (AI-ECG) model to assess LVDF and filling pressures. Methods We performed a retrospective study among patients with ECG-confirmed LBBB who also underwent comprehensive echocardiography within 14 days of the index ECG between September 2001 and June 2022. Using multivariable survival models, we assessed the risk of all-cause mortality across AI-ECG-derived LVDF grades. Results Of 2,554 patients with LBBB (mean age 72.0+12.6, 54.6% women), 252 (9.8%), 656 (25.7%), and 1,436 (56.2%), and 210 (8.2%) had normal LVDF, G1 LVDF, G2 LVDF, and G3 LVDF, respectively. The median LV ejection fraction (LVEF) was 54% and 49.3% of the patients had heart failure. Worse LVDF was associated with older age, lower LVEF, and higher rates of diabetes, hypertension, chronic pulmonary disease, renal failure, cardiovascular disease, and heart failure (p-of-trend&lt;0.001 for all). During a median follow-up of 2.6 years (interquartile range 0.5-4.0 years), 847 (33.2%) patients died. In multivariable survival analysis, adjusted to multiple risk factors including baseline LVEF and heart failure, worse LVDF was independently associated with a higher risk of death [G1 LVDF: adjusted hazard ratio (aHR) 2.15 (95% confidence interval (95%CI) 0.75-1.77), G2 LVDF: aHR 2.25 (95%CI 1.50-3.38) G3 LVDF: aHR 2.96 (95%CI 1.88-4.65); p&lt;0.001 for both)]. These findings were consistent also in a subgroup of patients with baseline LVEF &gt; 50%. Conclusion Among patients with LBBB, worse LVDF, as derived by a dedicated AI-ECG algorithm is independently associated with all-cause mortality beyond baseline LVEF and clinical heart failure.survival across AI-ECG LVDF grades

Abstract Background Artificial intelligence (AI) models trained on 12-lead ECGs effectively detect left ventricular systolic dysfunction (LVSD; left ventricular ejection fraction [LVEF] &lt;=40%). Continuous ECG monitoring via Holter recordings provides an opportunity for opportunistic screening for structural heart disease beyond rhythm disorders. We hypothesized that a lead-invariant version of the 12-lead AI model would enable a Holter monitor to screen for both arrhythmias and ventricular dysfunction. Methods We retrospectively analyzed continuous Holter ECGs from 17,665 patients who underwent a Holter and transthoracic echocardiogram (TTE) within 30 days of each other at Mayo Clinic. From each Holter, a random 20-minute of valid (non-flatline/lead disconnect) ECG segment was extracted and analyzed for LVSD detection using the adapted lead-invariant AI model. To evaluate stability, we examined model performance across different time points of the day, presenting results as area under the receiver operating characteristic curve (AUC) over time. Moreover, we illustrated the model’s robustness to noisy data by comparing its performance on raw ECG signals with that on bandpass-filtered inputs. Results Among 17,665 patients (mean age 59 years, 48.57% female), 4.96% had an LVEF &lt;=40%. The AI model demonstrated strong predictive performance (20-minute segment AUC 0.90, mean prediction of 24-hour AUC 0.92). Analysis of results over time (Figure) revealed temporal patterns in predictive accuracy, with specific time periods showing greater stability. Despite modest variability, model performance remained consistently high throughout the day, confirming robustness across different physiological states. The predictions remained robust with noisy input. We did not observe performance improvement when the baseline wander and high frequency noise are removed by the bandpass filter. Conclusion Applying a 12-lead AI ECG model with a lead-invariant framework to a continuous Holter ECG enables effective screening for left ventricular dysfunction. This suggests that AI-based analysis of Holter-monitors can facilitate opportunistic screening of ventricular dysfunction and may enable assessment of an arrhythmia’s impact on LVEF, as well as the relationship between arrhythmia burden and LVEF.Figure 1.Mean prediction AUC of the day Figure 2.AUC for different time point

Abstract Background Elevated left ventricular filling pressure (LVFP) is associated with an increased risk of heart failure and mortality. Pulmonary artery wedge pressure (PAWP) is considered the gold standard for assessing LVFP. Recently, we validated an artificial intelligence-enabled electrocardiogram (AI-ECG) to assess LV diastolic function (LVDF) and LVFP. Herein, we compare AI-ECG with PAWP in predicting long-term mortality. Methods We included adults who had comprehensive echocardiography with available ECG within 14-days and right-heart-catheterization (RHC) within 30-days of echocardiography. Elevated-LVFP was defined as PAWP&gt;15 mmHg by RHC, grades 2-3 LVDF by echocardiography, or as adjudicated by the AI-ECG algorithm. Prognosis by AI-ECG was compared to that by echocardiography and PAWP. Results Among 4,168 patients (median age 64 years, 47.7% female), 1,841 had normal-LVFP, and 2,327 had elevated-LVFP by RHC. Echocardiography classified 1,502 patients as normal-LVFP, 1,643 as elevated-LVFP, and 1,023 as indeterminate-LVFP. AI-ECG demonstrated an area-under-the-curve of 0.879 (95%-confidence-interval 0.867-0.891) for predicting elevated-LVFP as determined by echocardiography and 0.742 (95%-confidence-interval 0.724-0.759) for predicting elevated-LVFP as determined by RHC. Over a median follow-up of 7.7 years, 2,735 (34.4%) patients died. In multivariable models, elevated-LVFP by any modality was associated with an increased risk of death (AI-ECG: adjusted-hazard-ratio 1.80, 95% confidence-interval 1.55-2.09; echocardiography: adjusted-hazard-ratio 1.74, 95% confidence-interval 1.51-2.02; PAWP: adjusted-hazard-ratio 1.26, 95% confidence-interval 1.11-1.43). AI-ECG-derived LVFP provided incremental prognostic discrimination compared to echocardiography- or RHC-derived LVFP. Conclusions AI-ECG-derived LVFP offers an accessible, affordable, and noninvasive alternative for detecting elevated LVFP, with potential independent prognostic value beyond traditional echocardiographic and invasive assessments.Survival across LVFP concordance

Background: Etripamil nasal spray is a fast-acting, calcium channel blocker in development for the conversion of paroxysmal supraventricular tachycardia (PSVT) outside of a health-care setting. Studies have demonstrated the favorable safety and efficacy of self-administered etripamil in restoring sinus rhythm (SR) and reducing emergency department visits. Purpose: This report analyzes the efficacy, safety, and test-dose tolerability of etripamil across PSVT clinical studies. Methods: We systemically examined randomized, controlled and open-label trials evaluating etripamil in patients with PSVT. Efficacy measures included the proportion of patients converting from PSVT to SR within 30 minutes and the median times to conversion across all Phase 3 studies. Safety data for treatment-emergent adverse events (TEAEs), serious AEs, and test dose tolerability from Phase 2/3 studies were summarized descriptively. Results: NODE-1, NODE-301 Part 1, NODE-301 Part 2 (RAPID, including RAPID Extension, RAPID Open Label, RAPID Open Label Extension periods), NODE-302, and NODE-303 studies were analyzed (Table 1). The Kaplan-Meier estimate of etripamil exposed patients converting to SR within 30 minutes (n= 622) was 59.6% (range, 53.6% to 64.3%) with a median time to conversion of 18.5 minutes (95% CI, 15.7 to 21.0). The proportions of RCT placebo group patients converting from SVT to SR by 30 minutes ranged from 26.7% to 34.7%. Estimates of conversion of SVT to SR with etripamil at 60 minutes for individual studies ranged from 63.2% to 73.5% (Figure). Combined analysis showed mainly the occurrence of mild, transient TEAEs, primarily nasal discomfort, nasal congestion, rhinorrhea, throat irritation, and epistaxis (Table 2). 1,107 patients took at least one etripamil test dose while in SR; no significant change in average baseline heart rate or blood pressure was observed within 45 minutes of administration, and test dose failure occurred in only 16 patients (1.4%). Conclusions: Across multiple clinical studies of acute PSVT management, self-administered etripamil consistently demonstrated robust efficacy and a favorable safety profile for acute PSVT management. Safety data and the low rate of test dose failures indicate favorable tolerability, suggesting no need for a pretreatment test dose. These findings support the potential of etripamil as a patient-administered therapy for PSVT, which may reduce reliance on emergency care.

Background: Atrial arrhythmia recurrence after surgical ablation remains challenging to predict and integrating novel biomarkers may improve risk stratification. Objective: To evaluate whether combining preoperative transthoracic echocardiography (TTE) with artificial intelligence-enabled ECG (AI-ECG) scores enhances prediction of atrial fibrillation/flutter (AF/AFl) recurrence post surgical ablation. Methods: We retrospectively analyzed 1,696 patients undergoing Surgical AF/AFl Ablation between 2006 and 2025 with preoperative TTE and post-blanking ECGs. Clinical variables, TTE indices, and AI-ECG scores (AF probability, ECG-estimated age, HFpEF, LV dysfunction, and aortic stenosis scores) were assessed. The primary outcome was time to AF/AFl recurrence. Univariate/multivariable Cox models and a Random Survival Forest (RSF) model (80:20, training: testing) were developed to identify predictors. Results: Of 1,696 patients (mean age 67.3±10.2 years; 61.7% male) undergoing surgical AF/AFl ablation, 949 (56%) experienced AF/AFl recurrence during a median follow-up of 3.14 years. Patients with recurrence had larger left atria (mean LA area 30.4 vs 24.5 cm 2 , p < 0.001), more diastolic dysfunction (mitral inflow E-wave velocity 1.015 m/s vs 0.896 m/s , p < 0.001), and adverse AI-ECG biomarkers. In multivariable analysis, independent predictors of recurrence included a higher ECG-AF score (p < 1 x 10 -300 ), an older AI-ECG age (p = 0.0002), LA area (p = 0.046), body mass index (p = 0.036), and elevated diastolic blood pressure (HR 1.008 per mmHg, 95% CI 1.002 – 1.014; p = 0.010). The final Cox model achieved a C-index of ~0.67 and stratified patients into risk quartiles with 3-year freedom-from-arrhythmia rates of ~85% (lowest-risk) vs ~43% (highest-risk). An RSF model yielded a slightly higher test C-index (≈0.69), suggesting modest improvement with non-linear modeling. Conclusions: Preoperative AI-ECG biomarkers (AF probability, age discordance) and TTE markers of atrial remodeling independently predicted AF/AFl recurrence after surgical AF/AFl ablation and integration of these metrics improved risk stratification.

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia with prevalence increasing over the last decade. However, data on recent temporal trends in incidence of AF have been inconsistent, with some reports of increasing trends over time and others indicating no change in incidence over time. Therefore, we aimed to determine how the incidence of AF has changed over the last decade in a community in the Midwest USA. Methods: Between 2013 and 2023, adults (aged 18 and older) with incident AF were identified in a 27-county region in the Midwest. AF was identified using diagnostic codes by employing an electronic algorithm requiring 1 inpatient code or 2 outpatient codes separated by >7 days but within 1 year. For total rates, age - and sex-adjusted incidence rates were standardized to the 2010 US total population. Poisson regression was used to calculate the incidence rate ratio of AF for 2023 vs 2013. Results: We identified 44,930 individuals with incident AF from 2013 to 2023. Of these, 56.4% were male, the mean (SD) age was 72.8 (13.5) years, and 95.8% were non-Hispanic white. The age-and sex-adjusted incidence rates (per 1,000) and 95% confidence intervals standardized to the 2010 US total population were 5.24 (5.07-5.41) in 2013, 5.73 (5.56-5.91) in 2018, and 5.44 (5.28-5.61) in 2023. Although a drop in incidence was observed corresponding to the COVID-19 pandemic, a small increase in the overall incidence of AF was observed over time. The overall incidence rate ratio (95% CI) for 2023 vs 2013 was 1.07 (1.02-1.11), P=0.003. The incidence rates were higher in men compared to women and increased with older age ( Figure 1 ). However, differences in AF incidence by sex were greatest in the youngest age group and attenuated with older age (incidence rate ratio (95% CI): 2.18 (2.10-2.28) for ages 18-64 years, 1.76 (1.70-1.83) for ages 65-74 years, 1.38 (1.33-1.42) for ages 75-84 years, and 1.23 (1.18-1.28) for ages 85 years and older). Conclusion: In this 27-county region in the Midwest, although small in magnitude, a statistically significant increase in AF incidence was observed over time from 2013 to 2023. Furthermore, the incidence of AF was higher in men compared with women, especially in younger age groups.