| Title: | Artificial intelligence-enabled electrocardiographic sex discordance and the risk of incident atrial fibrillation: a multi-national cohort study |
| Journal: | Heart Rhythm |
| Published: | 5 Dec 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41352445/ |
| DOI: | https://doi.org/10.1016/j.hrthm.2025.12.005 |
Publication 16736
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Abstract
BACKGROUND: Binary classification of sex fails to capture the sex-related continuum of atrial fibrillation (AF) risk.</p>
OBJECTIVE: This study aimed to develop an artificial intelligence (AI)-enabled electrocardiography (ECG) model for sex prediction and explore its association with AF risk.</p>
METHODS: An AI-ECG model for sex prediction was developed from the Severance Hospital training set and externally validated using Clinical Outcomes in Digital Electrocardiography 15% (area under the curve 0.91) and Medical Information Mart for Intensive Care IV (area under the curve 0.90) datasets. A sex discordance score-defined as 1 minus the AI-ECG-predicted probability (continuous) for self-reported sex-was estimated in AF-free individuals on 3 multinational test sets (Severance Hospital [n = 205,769], Yongin Severance Hospital [n = 112,942], and UK Biobank [n = 40,525]).</p>
RESULTS: In the Severance Hospital and Yongin Severance Hospital test sets, sex discordance score increase was associated with higher AF risk in females, with Cohorts for Heart and Aging Research in Genomic Epidemiology Atrial Fibrillation (CHARGE-AF)-adjusted hazard ratio per standard deviation of 1.28 (95% confidence interval [CI] 1.24-1.33) and 1.32 (95% CI 1.27-1.36), respectively. No significant association was observed in males. Adding sex discordance score to the CHARGE-AF model significantly improved discrimination for AF in females, with a C-index increase of 0.026 (95% CI 0.013-0.037) and 0.020 (95% CI 0.010-0.032) in the respective datasets, but not in males. In the UK Biobank test set, a similar association between sex discordance score and incident AF risk was observed in females (CHARGE-AF-adjusted hazard ratio per standard deviation 1.23 [95% CI 1.13-1.32]; C-index increase 0.024 [95% CI 0.005-0.040]). In females, sex discordance score correlated with sex hormone imbalance, pericardial and visceral adiposity, atrial remodeling, and adverse lifestyle factors.</p>
CONCLUSION: The AI-ECG sex discordance score captures females with disproportionately elevated AF risk with implications for enhanced risk factor modification and surveillance.</p>
12 Authors
- Hanjin Park
- Oh-Seok Kwon
- Dong Won Kim
- Daehoon Kim
- Je-Wook Park
- Hee Tae Yu
- Tae-Hoon Kim
- Jae-Sun Uhm
- Boyoung Joung
- Moon-Hyoung Lee
- Dukyong Yoon
- Hui-Nam Pak
Enabling scientific discoveries that improve human health