Prognostic Significance and Associations of Neural Network-Derived Electrocardiographic Features.
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Sau Arunashis, Ribeiro Antônio H, McGurk Kathryn A, Pastika Libor, Bajaj Nikesh, Gurnani Mehak, Sieliwonczyk Ewa, Patlatzoglou Konstantinos, Ardissino Maddalena, Chen Jun Yu, Wu Huiyi, Shi Xili, Hnatkova Katerina, Zheng Sean L, Britton Annie, Shipley Martin, Andršová Irena, Novotný Tomáš, Sabino Ester C, Giatti Luana, Barreto Sandhi M, Waks Jonathan W, Kramer Daniel B, Mandic Danilo, Peters Nicholas S, O'Regan Declan P, Malik Marek, Ware James S, Ribeiro Antonio Luiz P, Ng Fu Siong
Аннотация
METHODS: We extracted 5120 neural network-derived ECG features from an artificial intelligence-enabled ECG model trained for 6 simple diagnoses and applied unsupervised machine learning to identify 3 phenogroups. Using the identified phenogroups, we externally validated our findings in 5 diverse cohorts from the United States, Brazil, and the United Kingdom. Data were collected between 2000 and 2023.
RESULTS: In total, 1 808 584 patients were included in this study. In the derivation cohort, the 3 phenogroups had significantly different mortality profiles. After adjusting for known covariates, phenogroup B had a 20% increase in long-term mortality compared with phenogroup A (hazard ratio, 1.20 [95% CI, 1.17-1.23]; P<0.0001; phenogroup A mortality, 2.2%; phenogroup B mortality, 6.1%). In univariate analyses, we found phenogroup B had a significantly greater risk of mortality in all cohorts (log-rank P<0.01 in all 5 cohorts). Phenome-wide association study showed phenogroup B had a higher rate of future atrial fibrillation (odds ratio, 2.89; P<0.00001), ventricular tachycardia (odds ratio, 2.00; P<0.00001), ischemic heart disease (odds ratio, 1.44; P<0.00001), and cardiomyopathy (odds ratio, 2.04; P<0.00001). A single-trait genome-wide association study yielded 4 loci. SCN10A, SCN5A, and CAV1 have roles in cardiac conduction and arrhythmia. ARHGAP24 does not have a clear cardiac role and may be a novel target.
CONCLUSIONS: Neural network-derived ECG features can be used to predict all-cause mortality and future cardiovascular diseases. We have identified biologically plausible and novel phenotypic and genotypic associations that describe mechanisms for the increased risk identified.