Medina‐Inojosa, Betsy J.

Abstract Introduction Atrial fibrillation (AF) is a major contributor to stroke risk, yet many cases remain undiagnosed due to its silent and paroxysmal nature. To address this, multiple risk scores have been developed to predict incident AF. This study aimed to evaluate the predictive accuracy of five widely used clinical AF prediction tools (i.e., CHARGE-AF, CHA2DS2-VASc, mC2HEST, HATCH, and HAVOC) among patients undergoing long-term continuous monitoring with implantable loop recorders (ILRs). Methods We conducted a retrospective cohort study across three major US academic medical centers, including patients with ILRs and no prior diagnosis or ECG evidence of AF. Clinical variables used to calculate each risk score were extracted from electronic health records. Discrimination was assessed using the area under the receiver operating characteristic curve (AUC). Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate the association between each score’s risk categories and incident AF (defined as any episode lasting ≥6 minutes). Calibration was assessed using calibration plots and Brier scores. Results A total of 3,895 patients were included (mean age 61 ± 17 yrs.; 51% male). Incident AF was detected in 879 patients (22%) over a median follow up of 17 months (IQR 8-35). Table 1 presents baseline characteristics and device detected AF event data during follow up. CHARGE-AF had the highest AUC (0.68) but also the highest Brier score (Fig. 1). Failure curves showed clear risk stratification across all tools (Fig. 2). Calibration plots (Fig. 3) demonstrated modest agreement between predicted and observed risk across all models. Using CHARGE-AF as the reference, pairwise comparisons of Brier scores via the Wilcoxon signed-rank test showed lower calibration accuracy than CHA2DS2-VASc (p = 0.03), mC2HEST (p = 0.001), and HAVOC (p = 0.001), with no significant difference compared to HATCH (p = 0.15). Conclusions In patients undergoing continuous rhythm monitoring with ILRs, commonly used AF prediction scores demonstrated modest discriminatory ability and similar calibration performance. These findings suggest that existing risk models, which were largely developed in cohorts with clinically diagnosed AF, may not optimally translate to continuously monitored populations. Future work is needed to develop and validate AF prediction models specifically in cohorts undergoing long-term continuous cardiac monitoring.Figure 1Figure 2-3

Background Inadequate preventive dental care may contribute to inflammatory conditions such as periodontitis, increasing cardiovascular disease risk. Artificial intelligence–enabled electrocardiography (AI‐ECG) algorithms accurately estimate cardiovascular disease risk. We investigated the association between inadequate preventive dental care and the AI‐ECG–estimated risk of atrial fibrillation, aortic stenosis, low ejection fraction, cardiac amyloid, cardiovascular aging, and all‐cause mortality. Methods We retrospectively analyzed 266 637 Mayo Clinic patients (2018–2024) who completed a Social Determinants of Health Survey and had an ECG performed within 1 year of survey completion. AI‐ECG algorithms generated continuous risk scores (0 or 1) for atrial fibrillation, aortic stenosis, low ejection fraction, and amyloid. Cardiac aging was assessed by delta age, calculated as AI‐ECG–estimated physiological age minus the chronological age. Associations with preventive dental care were analyzed using logistic regression. Cox regression evaluated dental care predictiveness on all‐cause mortality. Results Among 266 637 individuals (mean age, 59.5±16.4 years; 51.1% women), 49 918 (18.7%) reported inadequate preventive dental care. These individuals had higher delta age and increased AI‐ECG–predicted risks of atrial fibrillation, aortic stenosis, amyloid, and reduced ejection fraction (all P <0.001). In multivariable logistic regression models including all AI‐ECG scores, inadequate preventive dental care was associated with higher probabilities of low ejection fraction (odds ratio [OR], 1.80 [95% CI, 1.69–1.91]), atrial fibrillation (OR, 1.10 [95% CI, 1.04–1.17]), aortic stenosis (OR, 1.90 [95% CI, 1.64–2.20]), amyloid (OR, 1.18 [95% CI, 1.12–1.25]), and higher delta age (OR, 1.03 [95% CI, 1.02–1.03]) (all P <0.001). Inadequate preventive dental care predicted all‐cause mortality after adjusting for demographics, risk factors, and AI‐ECG algorithms (HR, 1.45 [95% CI, 1.38–1.53], P <0.001). Conclusions Inadequate preventive dental care is associated with subclinical cardiovascular disease. AI‐ECG algorithms may facilitate cardiovascular risk stratification among individuals with limited preventive dental care access.

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 Atherosclerotic cardiovascular disease (ASCVD) develops over a prolonged latent period, progressing from subclinical ASCVD to major cardiovascular events due to plaque accumulation. Subclinical ASCVD is a valid subrogate to assess potential risk factors or ASCVD. Dietary patterns are known to contribute to or prevent ASCVD. Dairy consumption has been associated with lower rates of obesity, hypertension, and diabetes, while saturated fats, present in most dairy products, have been associated with ASCVD. Studies assessing the association between subclinical ASCVD and dairy consumption have shown mixed results but have not been systematically analyzed Purpose This study aimed to systematically review and synthesize the existing evidence on the association between dairy product consumption and subclinical ASCVD Methods The study protocol was registered in the International Prospective Register of Systematic Reviews and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. We conducted a comprehensive search of PubMed, EMBASE, Scopus, Cochrane Central Register, Google Scholar, and Web of Science to identify experimental and observational studies that examined the association of dairy product consumption with measures of subclinical ASCVD assessed through coronary artery calcium (CAC) scanning, intima-media thickness (IMT), pulse pressure (PP) or pulse wave velocity (PWV), from inception to July 9, 2024. Titles and abstracts were screened in duplicate, followed by a full-text review and data abstraction from articles that met the study criteria. Dairy products were classified as: a) Dairy, according to the United States Department of Agriculture, encompassing milk, yogurt, cheese, lactose-free milk, and fortified soy milk/yogurt; and b) Dairy+, which further included higher fat content products such as cream cheese, sour cream, cream, and butter Results A total of 973 articles were identified; 22 met inclusion criteria representing 20 studies; being predominantly cross-sectional (55%) conducted in North America (50%); food frequency questionnaires were the most implemented tool for dietary assessment (86%), and 41% used PWV for subclinical ASCVD assessment; Fig. 1. Total Dairy and Dairy+ exhibited predominantly neutral effects with a trend toward a beneficial effect, similar to yogurt intake. Milk and cheese demonstrated contrasting effects, with studies reporting protective, neutral, and harmful associations, particularly for PWV and IMT. Limited data on CAC suggested no strong relationship with dairy consumption; Table 1 Conclusion Available evidence on the association between dairy consumption and subclinical ASCVD is complex with mixed effects across dairy products. No consistent evidence of harm or benefit was found; future research is needed to clarify the role of different dairy components in the development of subclinical ASCVD and incidence of cardiovascular eventsFig1.Summary of studies characteristics Table 1.Summary of effects

Background: The gap between artificial intelligence-derived age (ECG-Age) and chronological age has been validated as a strong predictor of increased cardiovascular morbidity and mortality, independent of age, and is a potential biomarker of biological aging. Acute stress may cause real-time, transient changes in autonomic function via electrophysiological signals that, when repeated over time, may contribute to biological aging and represent mechanisms linking stress and Major Adverse Cardiovascular Events (MACE). We hypothesized that acute mental stress induced in a laboratory is associated with increased ECG and that this increase is associated with a higher risk of MACE among individuals with stable coronary heart disease (CHD). Methods: We pooled two prospective cohorts of participants with stable CHD from a university-based hospital network in Atlanta. Stress was induced using a standardized mental stress test (public speaking task) and measured 12-lead ECGs during rest, mental stress, and recovery periods. To measure ECG-age, we utilized a published algorithm using a neural network on >500,000 independent patients. The study endpoint was MACE including nonfatal myocardial infarction, hospitalization for heart failure, or cardiovascular death. The difference in ECG-Age between resting and acute mental stress was used to define the stress Age-Gap. Cox proportional hazard regression modeled the association of stress Age-Gap operationalized as tertiles adjusting for chronological age, sex, race, cardiovascular risk factors, and baseline Cohen perceived stress scale. Results: 442 participants in the total sample pool (38% women). Over a 5-year median follow-up, 95 participants (21%) experienced MACE. At rest, the mean chronologic age was 55.7±9.9 years, and ECG-Age was 57.1 ±10.7 years, with rest Age-Gap of 0. 9±9.6 (p=0.16). During stress, the stress Age-Gap of 1.95±9.8 (p<0.0001), while recovery Age-Gap was 1.1±10.3 (p=0.13). Those that demonstrated the largest ECG-Age positive change between rest and stress by ECG (top tertile) had a higher risk for MACE when compared to those with the lowest or negative ECG age change (bottom tertile), see Figure. Conclusion: Among patients with stable CHD, acute mental stress caused changes in biological age as measured by AI-ECG consistent with accelerated biological aging. Such changes were associated with MACE. These results uncover accelerated biological aging as a mechanism linking acute stress to CVD outcomes.

Methods: From a sample cohort of 274,539 consecutive adults who sought care at Mayo Clinic between 2018-2022, we ascertained demographic and clinical information, including clinically indicated TTE within 15 days and up to a year after the index clinical visit. The Area Deprivation Index (ADI), a tool that captures neighborhood-level disadvantages that are linked to cardiovascular morbidity and outcomes, was extracted from the Neighborhood Atlas and ranked accordingly as state percentiles stratified in quintiles, with the highest values representing “most disadvantaged” areas. We performed non-parametric multivariate regression models that adjusted for cardiovascular risk factors expressed in odds ratio (OR) and 95% confidence interval (CI). Results: A total of 45,823 (16.9%) subjects had a TTE performed, with a mean age of 63±16 years, 48% were women, and 86% were non-Hispanic white. According to the TTE, 4% of subjects had LVSD, while 11% had a high probability of LVSD by AI-ECG. Median state ADI was 4 IQR (2-7). In the whole cohort, subjects residing in the most disadvantaged areas were less likely to have a TTE [OR 0.94 CI (0.91- 0.97)] see Fig. 1-A ; conversely, they were more likely to have LVSD by TTE [OR 1.80 CI (1.52-2.13)] see Fig. 1-B , and higher probability of LVSD by AI-ECG [OR 1.43 CI (1.36-1.51)] when compared to those with the least disadvantage see Fig. 1-C , independent of age, sex, and cardiovascular risk factors, p for trend<0.001. Conclusion: Individuals living in socially disadvantaged areas were slightly less likely to have an echocardiogram despite a significantly higher likelihood of having an LVSD (suspected by AI-ECG and confirmed by TTE), independent of cardiovascular risk factors. Highlighting an important disparity in the diagnosis of LVSD.

Background: We previously developed deep-learning algorithms that identify coronary artery disease (CAD) risk based on (i) coronary artery calcium (CAC), (ii) obstructive CAD by angiography, and (iii) left ventricular akinesis in ≥1 segment by echocardiogram, using a 12-lead electrocardiogram (CAD ECG-AI). We tested the hypothesis that those with increased probability of CAD by CAD ECG-AI algorithms will have an increased risk of atherosclerotic cardiovascular disease (ASCVD) events and would refine the AHA Predicting Risk of Cardiovascular Disease Events (PREVENT TM ) equations’ predictive capabilities. Methods: We assessed a group of consecutive patients who sought primary care in Olmsted County, MN, between 1997 and 2003. Passive follow-up was conducted using the Rochester Epidemiology Project's record linkage system. Patients included met the same criteria of the original PREVENT TM equations. The probability output of each CAD ECG-AI algorithm was used to predict ASCVD (fatal and non-fatal myocardial infarction and ischemic stroke) and ASCVD-Plus [further including percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and all-cause mortality]. Events were validated in duplicate. Cox proportional hazard models adjusted for age, sex, and risk factors while modeling each CAD ECG-AI algorithm as an individual and additive predictor (see footnote). PREVENT TM risk categories stratified analysis to evaluate the effect of the CAD ECG-AI models on predicted ASCVD risk. Results: We included 21,193 patients, with mean ± SD age 51.6 ± 12.0, 54% women and 95% white. After 14.2±12.4 years follow-up, 1,351 (6.4%) developed ASCVD, and 2,808 (13.2%) had ASCVD-Plus. The risk of ASCVD and ASCVD-Plus increased with positivity for the CAD ECG-AI algorithms after adjustments for age, sex, and PREVENT TM equations factors, all p for trend <0.001 (data not shown). In additive analyses, the risk of ASCVD and ASCVD-Plus increased with increased CAD ECG-AI factors, all p for trend <0.001 ( Fig. A-B ). Furthermore, the CAD ECG-AI algorithm enhanced the predictive capabilities of PREVENT TM equations across most risk subgroups ( Fig. C-E ). Conclusions: The deep-learning CAD ECG-AI algorithms displayed an independent and additive association with long-term ASCVD and ASCVD-Plus events in the community and improved the PREVENT TM predicted ASCVD risk. The CAD ECG-AI algorithms could help identify individuals at risk in primary prevention of cardiovascular events.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have known cardiovascular benefits. We aimed to assess the efficacy of GLP1-RA or SGLT2i initiation in reducing mortality or cardiovascular events in a community-based cohort of adults with ischemic stroke. Methods: Patients ≥18 years old admitted for acute ischemic stroke between Jan 2000 and June 2022 were identified using the Rochester Epidemiology Project. Subjects were considered exposed to SGLT-2i or GLP1-RA if they were treated with either medication after the index stroke and before the primary (all-cause mortality) or secondary outcomes (MI, recurrent ischemic stroke or composite). Kaplan-Meier curves and Cox models are shown in the Figures . Results: We included 7044 subjects, mean age 72±14 yr, 52% male, 94% white, over a median follow-up of 3 [1-7] years, 416 subjects (6%) had a second stroke, 426 (6%) had an incident MI and 3738 (53%) died. Those on SGLT2i/GLP1-RA had a decreased risk for mortality, incident MI, and composite in the univariate analysis. These associations remained significant after multivariable adjustment and were not affected by minimum time of exposure Figure 1&2 . SGLT2i/GLP1-RA use was associated with recurrent ischemic stroke in the multivariate analysis Figure 2C . All associations remained significant in most sub-analyses of individual medications except for the association between GLP1-RA and recurrent stroke Figure 3 Conclusions: SGLT2i or GLP-1 RA use was associated with decreased mortality and risk of myocardial infarction and recurrent stroke in patients with ischemic stroke.

Background: Our team recently developed an Artificial Intelligence model that enables the identification of increased left ventricular filling pressures using a single-lead electrocardiogram (AI-ECG) with excellent performance (AUC 0.91). However, its ability to predict incident heart failure (HF) in the community is yet to be evaluated. Hypothesis: We tested the hypothesis that the output from the AI-ECG will predict the long-term incidence of heart failure (HF) and HF with preserved ejection fraction (HFpEF), and would refine the HF predictive capabilities of the AHA Predicting Risk of Cardiovascular Disease EVENTs (PREVENT TM ) Equations. Methods: Leveraging the resources of the Rochester Epidemiology Project (REP) we analyzed data from patients who sought primary care in Olmsted County, MN, between 1997-2003 with passive follow-up until April 2024. We included those with a digital ECG at baseline and excluded those who were part of the original algorithm development or history of heart failure. The diagnosis of heart failure was ascertained by using ICD codes (ICD9-428,ICD10-I.50) and a word search for the terms related to heart failure. HFpEF was ascertained using the Ejection Fraction (EF) data closest to the heart failure diagnosis date, using EF more than 40% as the criterion. We tested the association between AI-ECG predicted probabilities and new-onset HF and HFpEF using Cox proportional hazard models. These models were also adjusted for cardiovascular risk factors and were stratified to evaluate the effect of the AI-ECG output on PREVENT TM -predicted HF at 10 years. Results: We included 20,276 subjects, mean age 55±14.03, 52% women, 92% non-Hispanic white. After 18.2±8.5 years of follow-up, 4,008 (19.76%) were diagnosed with HF and 3,812 (18.8%) HFpEF. Risks of HF and HFpEF significantly increased in patients with increased left ventricular filling pressures by AI-ECG, independent of risk factors, all p for trend <0.001, see Fig A-B , respectively. AI-ECG enhanced the prediction capabilities of the PREVENT TM score across all risk groups, see Fig-C. Conclusions: AI-ECG-Derived increased left ventricular filling pressure is associated with new-onset HF and HFpEF in the community and was associated with incidental heart failure at any PREVENT TM risk category. Those results suggest a potential role of AI ECG in predicting heart failure.