Purpose To evaluate whether the artificial intelligence (AI)-quantified mean thoracic skeletal muscle (TSM) attenuation from coronary artery calcium (CAC) scans predicts incident cardiovascular disease (CVD), with a focus on atrial fibrillation (AF) and heart failure (HF). Materials and Methods Data from the Multi-Ethnic Study of Atherosclerosis, including participants without baseline CVD who underwent CAC scanning, were retrospectively analyzed. Myosteatosis was defined by sex-specific, AI-quantified mean TSM attenuation cutoffs. The Cox proportional hazards model was used to compare total CVD, AF, and HF risks between the bottom and top quartiles of TSM attenuation after adjusting for CVD risk factors, inflammatory markers, insulin resistance, Agatston score, TSM volume, and social determinants of health. Results Among 5739 participants (mean age, 62.1 years ± 10.3 [SD]; 3002 [52.3%] female), 1826 CVD events occurred over 19 years, including 1139 AF and 359 HF events. Myosteatosis was independently associated with increased risks of total CVD (hazard ratio [HR], 1.48 [95% CI: 1.25, 1.75]; P = .001), AF (HR, 1.68 [95% CI: 1.37, 2.07]; P < .001), and HF (HR, 1.61 [95% CI: 1.18, 2.19]; P < .002). Participants with both myosteatosis and high Agatston scores had markedly higher cumulative incidences compared with those with high Agatston scores alone (total CVD: 84.6% vs 68.6%; AF: 52.9% vs 42.4%; HF: 22.6% vs 16.1%). Adding myosteatosis to the Agatston score significantly improved prediction (time-dependent area under the receiver operating characteristic curve, total CVD: 0.74 vs 0.80, P < .001; AF: 0.68 vs 0.76, P < .001; HF: 0.73 vs 0.78, P = .007). Conclusion AI-quantified mean TSM attenuation on CAC scans independently predicted AF and HF and enhanced the Agatston score's predictive value. Keywords: Myosteatosis, Coronary Artery Calcium Scan, Atrial Fibrillation, Heart Failure, Artificial Intelligence, Applications-CT, Cardiac, Thorax, Muscular, Heart ClinicalTrials.gov NCT00005487 Supplemental material is available for this article. © RSNA, 2026.

Background:Cardiovascular health (CVH) and genetic susceptibility to adverse left ventricular (LV) remodeling are each linked to cardiovascular diseases (CVD); however, their combined role remains unclear. Methods:Framingham Heart Study participants [n=1,255 Offspring-Exam 8 (2005-2008), n=2,835 Generation 3-Exam 1 (2002-2005)] had assessment of modifiable risk factors comprising the American Heart Association's Life's Essential 8 (LE8) score with higher scores indicating better CVH health. A Polygenic Risk Score (PRS) for LV mass index (LVMI) was also calculated based on published PRS(PGS003427). We created 9 groups combining LE8 and PRS tertiles (high LE8+low PRS served as referent group reflecting optimal risk) and related these groups to presence of LVMI, LV ejection fraction (LVEF), and the ratio of the peak early diastolic mitral inflow velocity (E wave) to the peak early diastolic mitral annular velocity (e' wave; E/e'; separate model for each outcome), and incident cardiovascular disease (CVD; a composite of coronary heart disease [CHD], heart failure, stroke, peripheral arterial disease). We applied linear mixed regression and Cox regression models to evaluate the relation of LE8-PRS groups with all outcomes mentioned above. Results:Participants (56% women, mean age 47 years) had mean LE8 score 70 (SD=13), indicating intermediate CV health and normal LVMI and systolic function (LVMI 76±13 g/m2, LVEF 65±5%, E/e' 6 ±1.8 cm/s). Over 19 years of follow-up, composite CV events and CHD occurred in n=188 and n=99, respectively, of Offspring and n=83 and n=49 respectively, of Gen 3 participants. Compared to the referent group, individuals in the low LE8-high PRS group had high LVMI, E/e', and over three-fold higher risks for CVD and CHD, with incidence rates of approximately 1.84 versus 4.06 per 1,000 person-year, respectively. Conclusion:Lower LE8 scores (indicating worse CVH) combined with high genetic risk confer higher conjoint risks for adverse LV structure, function, and CVD development.

Background Implementation of cardiovascular disease (CVD) risk reduction in transgender and gender diverse (TGD) populations requires competency in both standard prevention frameworks and TGD-specific considerations. However, cardiologists’ TGD-specific knowledge and clinical decision-making remain poorly characterized. We evaluated knowledge gaps and practice variability in TGD-specific CVD risk assessment. Methods We conducted an exploratory cross-sectional survey from August 2024 to August 2025 of cardiology specialists, including practicing cardiologists and cardiology fellows in the United States and Canada. The survey assessed prior exposure to TGD-focused education, knowledge of TGD-related cardiovascular inequities and gender-affirming hormone therapy (GAHT), attitudes toward gender-affirming care, perceived barriers, and clinical decision-making for CVD primary prevention and stroke prevention in atrial fibrillation using structured vignettes. Descriptive statistics were calculated, and exploratory χ² or Fisher exact tests were performed between practicing cardiologists and trainees. Results Among 93 respondents, 76 (81.7%%) were practicing cardiologists and 17 (18.3%) were trainees. Gaps in TGD-specific education were common in both practicing cardiologists and trainees, including health disparities (70.1% and 92.9%, respectively), communication strategies (51.4% and 71.4%), and gender-affirming medical care (25.7% vs 57.1%). Most respondents agreed that affirming a patient’s gender identity confers health benefits (n=77, 88.5%), yet 51 (58.6%) reported inadequate training to care for TGD patients. Knowledge of cardiovascular effects of GAHT was limited, with 54.7% of respondents reporting uncertainty regarding cardiovascular outcomes associated with testosterone- or estrogen-based GAHT. Clinical vignettes demonstrated variability in estimating 10-year CVD risk and atrial fibrillation stroke risk in TGD patients, including differences in the application of sex-based risk estimators and thresholds for statin initiation and anticoagulation. Conclusions Respondents generally reported supportive attitudes toward TGD patients but identified gaps in training and demonstrated variability in CVD risk assessment practices. Improved education and clearer clinical guidance may reduce practice variability and support equitable, evidence-based cardiovascular care for TGD populations.

BACKGROUND:Although cardiovascular events increase sudden cardiac arrest (SCA) risk, the impact of recurrent events on subsequent SCA risk in a contemporary population is unknown. This study assessed whether patients with a first-time acute coronary syndrome (ACS) or heart failure (HF) hospitalization who experience a recurrent cardiovascular event have increased SCA risk. METHODS:The OSCAR (Observational Study of Cardiac Arrest Risk) is a prospective cohort with adjudicated SCA outcomes. The current study followed up patients who survived a first ACS or HF hospitalization (the index ACS or HF cohorts) for recurrent cardiovascular events and SCA. Recurrent event was a time-dependent variable in Cox models predicting SCA. Findings were validated in the FHS (Framingham Heart Study). RESULTS:Among 2946 patients in the index ACS cohort, incidence of SCA was higher following a recurrent ACS event than without (3.70 versus 1.28 per 100 patient-years). A recurrent ACS event was associated with higher risk of SCA (adjusted hazard ratio [HR], 3.15 [95% CI, 2.06-4.83]; P<0.0001). Among 6711 patients in the index HF cohort, incidence of SCA was higher following a recurrent HF event than without (1.35 versus 0.97 per 100 patient-years), and SCA risk was higher with recurrent HF (HR, 1.79 [95% CI, 1.44-2.23]; P<0.0001). In the FHS cohort, risk of SCA was higher with recurrent ACS (HR, 2.85 [95% CI, 1.66-4.90]; P=0.0002); the association was not significant for recurrent HF (HR, 1.49 [95% CI, 0.73-3.03]; P=0.27). CONCLUSIONS:Recurrent events were associated with higher risk of SCA; dynamic clinical trajectories of recurrent cardiovascular events may inform prevention of SCA.

BACKGROUND:Stressor-associated atrial fibrillation (AF) refers to new-onset AF that occurs with a reversible, acute stressor. Identifying individuals at highest risk for AF recurrence is essential to guide management. Although clinical factors have shown limited value, the utility of contemporary artificial intelligence (AI)-enabled models using the 12-lead ECG to estimate recurrence risk remains unknown. METHODS:We retrospectively analyzed consecutive primary care and cardiology patients with stressor-associated AF occurring during hospitalization. We quantified the cumulative incidence of recurrence accounting for death as a competing risk. We investigated the relationship between time-varying recurrence and a composite end point of AF-related adverse events (stroke, heart failure, all-cause death) using Cox models. We then developed and validated a penalized regression model to predict recurrence using clinical factors, stressor type, and AF risk estimates from a previously validated ECG-based AI model. RESULTS:We analyzed 3371 patients with stressor-associated AF (mean age, 69±12 years; 40% women). Over a median of 3.7 years (interquartile range, 1.8-7.2), the 10-year cumulative incidence of AF recurrence was 41% (95% CI, 39-44). AF recurrence was strongly associated with AF-related adverse events (hazard ratio, 2.24 [95% CI, 1.81-2.76]). A model incorporating clinical factors, stressor type, and ECG-based AI model AF risk estimates (clinical-AI) discriminated AF recurrence (area under the receiver operating characteristic curve, 0.768 [95% CI, 0.707-0.830]) favorably compared with clinical features (area under the receiver operating characteristic curve, 0.707 [95% CI, 0.642-0.772]; P<0.05). CONCLUSIONS:AF recurrence rates following stressor-associated AF are considerable and are associated with substantially higher risk of adverse cardiovascular events. Models incorporating ECG-based AI risk estimates may prioritize individuals for intensive monitoring and preventive interventions.

BACKGROUND:Body mass index (BMI) is commonly used to assess total adiposity, yet does not provide insight into overall body composition, potentially obscuring meaningful heterogeneity in cardiovascular disease (CVD) risk. Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are commonly discordant with BMI and may provide additional prognostic information. OBJECTIVES:The purpose of this study was to quantify the reclassification and misclassification of traditional normal weight/overweight/obesity categories using central adiposity and to evaluate the prognostic implications for CVD risk using the CCC (Cross-Cohort Collaboration). METHODS:We included 259,388 participants from 15 cohorts of the CCC with harmonized data on either WC or WHR data and at least 1 of 9 outcomes: time to first fatal and nonfatal myocardial infarction, fatal and nonfatal stroke, heart failure, atrial fibrillation, total coronary heart disease, total CVD, coronary heart disease mortality, CVD mortality, and all-cause mortality. Multivariable Cox proportional hazards models were used to estimate the HR of higher WC and WHR for each outcome across BMI categories. RESULTS:Our sample included 259,351 individuals with WC data and 218,984 with WHR data, with a median follow-up of 20.0 years (95% CI: 12.7-23.5 years). Among individuals with normal weight, 5% had high WC and 18% had high WHR; among those with overweight, 39% had high WC and 40% had high WHR. Among those with obesity, 9% had low WC and 45% had low WHR. Among individuals with normal weight or overweight, clinically defined high WC or WHR was associated with 15% to 50% greater risk for most outcomes. Among those with obesity, low WC was not associated with a significantly different risk compared with normal weight and low WC, except for all-cause mortality, for which risk was significantly lower. In contrast to men, women with obesity but low WHR retained significantly higher risk for all outcomes compared with normal weight and low WHR; however, the HRs were smaller compared with those with obesity and high WHR. Among individuals with obesity, the population attributable risk associated with elevated WC or WHR ranged from 13% to 49%, with the highest estimates observed for elevated WC in heart failure and atrial fibrillation. CONCLUSIONS:WC and WHR identifies misclassification of conventional BMI categories and reclassifies CVD risk across normal weight, overweight, and obesity, adding diagnostic and prognostic value.

Each mitochondrion contains 2-10 copies of the mitochondrial genome. Multiple mitochondria in a cell allow for mitochondrial genomes carrying different variants to co-exist within a cell or tissue, termed heteroplasmy. The extent to which mitochondrial genetic variation differs across tissues of the human body and the origins of heteroplasmic variants is largely unknown. Using next-generation sequencing of 47 paired tissues from 947 donors in the Genotype-Tissue Expression dataset, we found that 39% of unique mitochondrial DNA variants identified were present in one tissue (tissue-specific) and 7% of unique variants were found in several but not all tissues of a donor. Tissue-specific variants were more likely to be transversions, nonsynonymous, deleterious, and present at lower variant allele fractions compared to variants shared across all tissues within a donor. Tissues primarily composed of proliferative cell types had the most tissue-specific variants, while highly energetic tissues had the least. The number of tissue-specific variants was associated with donor age for the tissues with the most tissue-specific variants. We determined that most of the heteroplasmic variants likely arise de novo after tissue differentiation. Our study suggests that mitochondrial DNA variants arise throughout an individual's lifetime in a tissue-dependent manner, which may have disease implications.

Abstract Mechanical twisting and untwisting of the left ventricle as well as abnormal hemodynamic aortic‐ventricular coupling are recognized as contributors to left ventricular diastolic function. However, energy associated with proximal aortic stretch during systole can be recovered as diastolic elastic recoil that may facilitate diastolic left ventricular filling. To investigate this “aortic spring” mechanism, we assessed the cross‐sectional and longitudinal associations of systolic atrioventricular plane displacement (AVPD), a surrogate measure of stretch of the mechanically coupled ascending aorta, with measures of left ventricular diastolic function. At two examinations (14 ± 1 years apart) in Framingham Heart Study participants (N = 7117; mean age 50 years, 55% women), we assessed AVPD and left ventricular diastolic function using echocardiography. In cross‐sectional analyses, higher AVPD was associated with higher e' (β per SD ± standard error = 0.49 ± 0.01; p < 0.001) and lower E/e' (β = −0.39 ± 0.01; p < 0.001). In longitudinal models, greater change in (Δ) AVPD between visits was associated with higher Δe' (β = 0.38 ± 0.01; p < 0.001) and lower ΔE/e' (β = −0.19 ± 0.01; p < 0.001). We observed effect modification (interaction p‐values: <0.001 to 0.03) for cross‐sectional and longitudinal associations by median age, sex, obesity status, hypertension treatment, and the extent of aortic stiffness (assessed via carotid‐femoral pulse wave velocity). Thus, the aortic spring function may contribute to left ventricular diastolic function.

Background:The epidemiology of permanent pacemaker [PPM] implantation in the community setting is unclear. Methods:We examined Framingham Heart Study cohort participants aged ≥45 years, without a history of PPM, who attended ≥1 exam cycle during 1972-2019. Fine-Gray subdistribution hazard models were used to calculate subdistribution hazard ratios [sHR] and 95% confidence intervals [CI] for the association between clinical characteristics (age, sex, body mass index [BMI], systolic and diastolic blood pressure [BP], smoking, hypertension treatment, diabetes, history of atrial fibrillation [AF], myocardial infarction, and heart failure) and incident PPM implantation. For continuous measures, sHRs were expressed per 1 standard deviation [SD]. Multiple imputation was used to account for missing data. Results:A total of 11,993 participants contributed 44,711 exam cycles (mean age 63 ± 11 years, 56% women) to the analysis. During follow-up (mean 4.9 ± 2.2 years), there were 382 PPM implantations and 4298 deaths. In multivariable-adjusted models, the following factors were associated with incident PPM implantation: age (sHR [per 1 SD = 11 years] =1.39), female sex (sHR = 0.49), BMI (sHR [per 1 SD = 5.1 kg/m2] =1.17), higher systolic BP (sHR [per 1 SD = 20 mmHg] =1.46), lower diastolic BP (sHR [per 1 SD = 10 mmHg] = 0.68), hypertension treatment (sHR = 1.40), smoking (sHR = 0.59), and history of AF (sHR = 2.60). Conclusions:Higher age, BMI, systolic BP, hypertension treatment, and history of AF were associated with increased rate of PPM implantation, while female sex, smoking, and diastolic BP showed an inverse association. Further study is needed to confirm these findings.

Purpose To evaluate the predictive value of myosteatosis as an opportunistic finding in coronary artery calcium (CAC) CT scans for clinically diagnosed chronic obstructive pulmonary disease (COPD) and compare it with an artificial intelligence (AI)-measured biomarker of emphysema derived from the same scans. Materials and Methods In this prospective study, baseline CAC CT scans and 20-year follow-up data were analyzed. Myosteatosis was defined as the lowest quartile of thoracic skeletal muscle mean attenuation (males < 33.5 HU, females < 27.0 HU). The emphysema-like lung biomarker was quantified as the percentage of lung voxels below -950 HU in CAC CT scans. COPD was identified using the International Classification of Diseases, Ninth Revision, Clinical Modification, and International Classification of Diseases, 10th Revision, Clinical Modification diagnostic codes from hospital discharge records. Hazard ratios (HRs) for COPD were calculated using proportional hazard regression models, comparing the bottom versus top quartiles of myosteatosis and emphysema-like lung measurements. Results Among 5535 participants in the Multi-Ethnic Study of Atherosclerosis (mean age ± SD, 62.2 years ± 10.3, 47.6% males), 396 (7.1%) were diagnosed with COPD over the 20-year follow-up period. Myosteatosis showed a stronger association with COPD than emphysema (unadjusted HRs, 5.98 [95% CI: 4.14, 8.63] and 2.12 [95% CI: 1.61, 2.78], respectively [P < .001]). After adjusting for covariates (age, sex, smoking status, body mass index, race, asthma, physical activity, inflammatory markers, and insulin resistance), the HRs were reduced to 2.74 (95% CI: 1.81, 4.16) and 1.50 (95% CI: 1.12, 2.00), respectively (P = .02). Conclusion AI-measured myosteatosis in CAC CT scans strongly predicted future diagnosed COPD independently of known risk factors. Keywords: Applications-CT, Pulmonary, Thorax, Adipose Tissue (Obesity Studies), Chronic Obstructive Pulmonary Disease, Metabolic Disorders, Myosteatosis, Coronary Artery Calcium Scan, Emphysema, AI-CVD ClinicalTrials.gov: NCT00005487 Supplemental material is available for this article. © The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license.

INTRODUCTION:Central arterial stiffness and pressure pulsatility are key measures of arterial health and cardiovascular disease (CVD). Acute physical activity (PA) improves vascular function; however, its relationship with arterial health across varying habitual PA levels remains understudied. METHODS:We analyzed Framingham Heart Study (FHS) data (Generation 2: Exam 8, 2005-2008, n = 2999 and Generation 3: Exam 1, 2002-2005, n = 4064). Habitual PA was assessed using a standardized questionnaire. Carotid-femoral pulse wave velocity (niCFPWV, inverse-transformed CFPWV), central pulse pressure (CPP), and forward wave pressure (FWP) were measured using applanation tonometry. We examined associations between PA scores (as quintiles) and arterial health using linear regression and effect modification by age and sex, as well as mediation by arterial health measures on heart failure, CVD mortality, and all-cause mortality. RESULTS:In 6451 FHS participants (mean age 50 ± 15 years, 55% women), the highest quintile of PA was associated with lower aortic stiffness (niCFPWV, β = -0.06 ± 0.02, p = 0.01). Continuous PA was associated with higher CPP (std β = 0.02 ± 0.01, p = 0.03) but not FWP. We observed an age-interaction: PA was associated with lower niCFPWV in individuals ⩾ 48 years (std β = -0.21 ± 0.07, p = 0.005) and higher CPP in those < 48 years (std β = 0.01 ± 0.004, p = 0.01). No significant effect modification by sex was noted. In stratified analyses, PA was associated with higher CPP among individuals without hypertension (β = 0.02 ± 0.01, p = 0.02), but not among those with hypertension. In mediation analyses, vascular measures did not contribute significantly to cardiovascular outcomes. CONCLUSION:Higher PA score was associated with lower arterial stiffness, particularly in older adults, and with higher pressure pulsatility in younger adults.

AIMS:Comparing temporal trends in the incidence and prevalence of major cardiovascular diseases (CVDs) provides insights into their evolving relative burden. We examined incidence and prevalence trends of atrial fibrillation (AF), heart failure (HF), myocardial infarction (MI), and stroke from 2000 to 2022 and projected these measures to 2040. METHODS AND RESULTS:In this Danish nationwide cohort study, we analysed data from national registries and Statistics Denmark for individuals aged 20-94 years. Each CVD was modelled separately using a statistical framework combining parametric survival modelling with an age-period-cohort incidence model, accounting for temporal trends and enabling future burden extrapolation. From 2000 to 2022, AF incidence increased, while HF, MI, and stroke incidences decreased. The prevalence of all four conditions increased. By 2040, AF incidence in Denmark is projected to rise by 28% from 20 683 to 26 376 new cases, and prevalence by 56% from 175 697 to 274 379 cases. HF and stroke incidences are expected to decrease by 2%, while MI incidence will decline by 30%. HF and stroke prevalence are projected to increase by 52% and 31%, respectively, whereas MI prevalence will decrease by 3%. Among individuals aged 65-94 years, new AF cases are projected to surpass the combined new cases of HF, MI, and stroke in 2040. CONCLUSION:AF has become the most frequently diagnosed and prevalent major CVD, with a growing burden surpassing HF, MI, and stroke in older adults. These findings underscore the urgent need for updated healthcare policies and integrated care strategies to address the growing burden of AF.