Dataset Information

Genetic Susceptibility to Atrial Fibrillation Identified via Deep Learning of 12-Lead Electrocardiograms.

ABSTRACT:

Background

Artificial intelligence (AI) models applied to 12-lead ECG waveforms can predict atrial fibrillation (AF), a heritable and morbid arrhythmia. However, the factors forming the basis of risk predictions from AI models are usually not well understood. We hypothesized that there might be a genetic basis for an AI algorithm for predicting the 5-year risk of new-onset AF using 12-lead ECGs (ECG-AI)-based risk estimates.

Methods

We applied a validated ECG-AI model for predicting incident AF to ECGs from 39 986 UK Biobank participants without AF. We then performed a genome-wide association study (GWAS) of the predicted AF risk and compared it with an AF GWAS and a GWAS of risk estimates from a clinical variable model.

Results

In the ECG-AI GWAS, we identified 3 signals (P<5×10^-8) at established AF susceptibility loci marked by the sarcomeric gene TTN and sodium channel genes SCN5A and SCN10A. We also identified 2 novel loci near the genes VGLL2 and EXT1. In contrast, the clinical variable model prediction GWAS indicated a different genetic profile. In genetic correlation analysis, the prediction from the ECG-AI model was estimated to have a higher correlation with AF than that from the clinical variable model.

Conclusions

Predicted AF risk from an ECG-AI model is influenced by genetic variation implicating sarcomeric, ion channel and body height pathways. ECG-AI models may identify individuals at risk for disease via specific biological pathways.

SUBMITTER: Wang X

PROVIDER: S-EPMC10524395 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Genetic Susceptibility to Atrial Fibrillation Identified via Deep Learning of 12-Lead Electrocardiograms.

Wang Xin X Khurshid Shaan S Choi Seung Hoan SH Friedman Samuel S Weng Lu-Chen LC Reeder Christopher C Pirruccello James P JP Singh Pulkit P Lau Emily S ES Venn Rachael R Diamant Nate N Di Achille Paolo P Philippakis Anthony A Anderson Christopher D CD Ho Jennifer E JE Ellinor Patrick T PT Batra Puneet P Lubitz Steven A SA

Circulation. Genomic and precision medicine 20230606 4

<h4>Background</h4>Artificial intelligence (AI) models applied to 12-lead ECG waveforms can predict atrial fibrillation (AF), a heritable and morbid arrhythmia. However, the factors forming the basis of risk predictions from AI models are usually not well understood. We hypothesized that there might be a genetic basis for an AI algorithm for predicting the 5-year risk of new-onset AF using 12-lead ECGs (ECG-AI)-based risk estimates.<h4>Methods</h4>We applied a validated ECG-AI model for predicti ...[more]

PMID: 37278238

Similar Datasets

Project description:ImportanceEarly detection of atrial fibrillation (AF) may help prevent adverse cardiovascular events such as stroke. Deep learning applied to electrocardiograms (ECGs) has been successfully used for early identification of several cardiovascular diseases.ObjectiveTo determine whether deep learning models applied to outpatient ECGs in sinus rhythm can predict AF in a large and diverse patient population.Design, setting, and participantsThis prognostic study was performed on ECGs acquired from January 1, 1987, to December 31, 2022, at 6 US Veterans Affairs (VA) hospital networks and 1 large non-VA academic medical center. Participants included all outpatients with 12-lead ECGs in sinus rhythm.Main outcomes and measuresA convolutional neural network using 12-lead ECGs from 2 US VA hospital networks was trained to predict the presence of AF within 31 days of sinus rhythm ECGs. The model was tested on ECGs held out from training at the 2 VA networks as well as 4 additional VA networks and 1 large non-VA academic medical center.ResultsA total of 907 858 ECGs from patients across 6 VA sites were included in the analysis. These patients had a mean (SD) age of 62.4 (13.5) years, 6.4% were female, and 93.6% were male, with a mean (SD) CHA2DS2-VASc (congestive heart failure, hypertension, age, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age, sex category) score of 1.9 (1.6). A total of 0.2% were American Indian or Alaska Native, 2.7% were Asian, 10.7% were Black, 4.6% were Latinx, 0.7% were Native Hawaiian or Other Pacific Islander, 62.4% were White, 0.4% were of other race or ethnicity (which is not broken down into subcategories in the VA data set), and 18.4% were of unknown race or ethnicity. At the non-VA academic medical center (72 483 ECGs), the mean (SD) age was 59.5 (15.4) years and 52.5% were female, with a mean (SD) CHA2DS2-VASc score of 1.6 (1.4). A total of 0.1% were American Indian or Alaska Native, 7.9% were Asian, 9.4% were Black, 2.9% were Latinx, 0.03% were Native Hawaiian or Other Pacific Islander, 74.8% were White, 0.1% were of other race or ethnicity, and 4.7% were of unknown race or ethnicity. A deep learning model predicted the presence of AF within 31 days of a sinus rhythm ECG on held-out test ECGs at VA sites with an area under the receiver operating characteristic curve (AUROC) of 0.86 (95% CI, 0.85-0.86), accuracy of 0.78 (95% CI, 0.77-0.78), and F1 score of 0.30 (95% CI, 0.30-0.31). At the non-VA site, AUROC was 0.93 (95% CI, 0.93-0.94); accuracy, 0.87 (95% CI, 0.86-0.88); and F1 score, 0.46 (95% CI, 0.44-0.48). The model was well calibrated, with a Brier score of 0.02 across all sites. Among individuals deemed high risk by deep learning, the number needed to screen to detect a positive case of AF was 2.47 individuals for a testing sensitivity of 25% and 11.48 for 75%. Model performance was similar in patients who were Black, female, or younger than 65 years or who had CHA2DS2-VASc scores of 2 or greater.Conclusions and relevanceDeep learning of outpatient sinus rhythm ECGs predicted AF within 31 days in populations with diverse demographics and comorbidities. Similar models could be used in future AF screening efforts to reduce adverse complications associated with this disease.

Project description:IntroductionThe diagnostic performance of automated analysis of electrocardiograms for screening children with pediatric heart diseases at risk of sudden cardiac death is unknown. In this study, we aimed to develop and validate a deep learning-based model for automated analysis of ECGs in children.MethodsWave data of 12-lead electrocardiograms were transformed into a tensor sizing 2 × 12 × 400 using signal processing methods. A deep learning-based model to classify abnormal electrocardiograms based on age, sex, and the transformed wave data was developed using electrocardiograms performed in patients at the age of 6-18 years during 2003-2006 at a tertiary referral hospital in Japan. Eighty-three percent of the patients were assigned to a training group, and 17% to a test group. The diagnostic performance of the model and a conventional algorithm (ECAPS12C, Nihon Kohden, Japan) for classifying abnormal electrocardiograms were evaluated using the cross-tabulation, McNemar's test, and decision curve analysis.ResultsWe included 1,842 ECGs performed in 1,062 patients in this study, and 310 electrocardiograms performed in 177 patients were included in the test group. The specificity of the deep learning-based model for detecting abnormal electrocardiograms was not significantly different from that of the conventional algorithm. For detecting electrocardiograms with ST-T abnormality, complete right bundle branch block, QRS axis abnormality, left ventricular hypertrophy, incomplete right bundle branch block, WPW syndrome, supraventricular tachyarrhythmia, and Brugada-type electrocardiograms, the specificity of the deep learning-based model was higher than that of the conventional algorithm at the same sensitivity.ConclusionsThe present new deep learning-based method of screening for abnormal electrocardiograms in children showed at least a similar diagnostic performance compared to that of a conventional algorithm. Further studies are warranted to develop an automated analysis of electrocardiograms in school-age children.

Project description:BackgroundAblation is a widely used therapy for atrial fibrillation (AF); however, arrhythmia recurrence and repeat procedures are common. Studies examining surrogate markers of genetic susceptibility to AF, such as family history and individual AF susceptibility alleles, suggest these may be associated with recurrence outcomes. Accordingly, the aim of this study was to test the association between AF genetic susceptibility and recurrence after ablation using a comprehensive polygenic risk score for AF.MethodsTen centers from the AF Genetics Consortium identified patients who had undergone de novo AF ablation. AF genetic susceptibility was measured using a previously described polygenic risk score (N=929 single-nucleotide polymorphisms) and tested for an association with clinical characteristics and time-to-recurrence with a 3 month blanking period. Recurrence was defined as >30 seconds of AF, atrial flutter, or atrial tachycardia. Multivariable analysis adjusted for age, sex, height, body mass index, persistent AF, hypertension, coronary disease, left atrial size, left ventricular ejection fraction, and year of ablation.ResultsFour thousand two hundred seventy-six patients were eligible for analysis of baseline characteristics and 3259 for recurrence outcomes. The overall arrhythmia recurrence rate between 3 and 12 months was 44% (1443/3259). Patients with higher AF genetic susceptibility were younger (P<0.001) and had fewer clinical risk factors for AF (P=0.001). Persistent AF (hazard ratio [HR], 1.39 [95% CI, 1.22-1.58]; P<0.001), left atrial size (per cm: HR, 1.32 [95% CI, 1.19-1.46]; P<0.001), and left ventricular ejection fraction (per 10%: HR, 0.88 [95% CI, 0.80-0.97]; P=0.008) were associated with increased risk of recurrence. In univariate analysis, higher AF genetic susceptibility trended towards a higher risk of recurrence (HR, 1.08 [95% CI, 0.99-1.18]; P=0.07), which became less significant in multivariable analysis (HR, 1.06 [95% CI, 0.98-1.15]; P=0.13).ConclusionsHigher AF genetic susceptibility was associated with younger age and fewer clinical risk factors but not recurrence. Arrhythmia recurrence after AF ablation may represent a genetically different phenotype compared to AF susceptibility.

Dataset Information

Genetic Susceptibility to Atrial Fibrillation Identified via Deep Learning of 12-Lead Electrocardiograms.

Background

Methods

Results

Conclusions

Publications

Genetic Susceptibility to Atrial Fibrillation Identified via Deep Learning of 12-Lead Electrocardiograms.

Similar Datasets

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