Electrocardiographic Digital Biomarkers in Asymptomatic Schoolchildren with Rheumatic Heart Disease

Subclinical rheumatic valvular disease is a significant yet underdiagnosed contributor to the global rheumatic heart disease (RHD) burden. Early detection through population screening is essential to prevent its progression to severe RHD. Rhythm changes and prolongations of PR and QTc intervals in the ECG are described in the advanced RHD cases. However, these parameters were not yet studied in asymptomatic RHD. We aimed to investigate the potential of ECG biomarkers for screening RHD in asymptomatic schoolchildren. ECG tracings of 611 schoolchildren aged 10 to 20 years who were screened for RHD in four schools in RHD-endemic region were analyzed. Confirmatory diagnoses were based on echocardiographic findings, where 564 (F = 326, M = 238) were healthy, and 47 (F = 28, M = 19) were positive for RHD (24 borderline RHD and 23 definite RHD). Independent, blinded reviewers manually annotated the ECGs and PR interval (PR), P-wave dispersion (PWd), and the ratio between the P-wave duration and PR interval (Pw/PR) were analyzed. The mean age of the study cohort at diagnosis was 16.1 ± 2.5 years, and 58% of the participants were females. Atrial fibrillation was seen in 2% (n = 1), and prolonged PR in 2% (n = 1) of RHD-positive cases. The mean ± std for normals vs. RHD is (PR, 138 ± 19 vs. 150 ± 19), (Pw/PR, 0.75 ± 0.06 vs. 0.71 ± 0.07), and (PWd, 49 ± 14 vs. 56 ± 17). The PR (p < 0.001), Pw/PR (p < 0.001), and PWd (p = 0.008) showed a significant difference between healthy and RHD-positive subjects. The PR was increased consistently with severity across age groups above and below 16 years. Multivariate logistic regression on PR, QTc, PWd, and Pw/PR evaluated on five-folds cross-validation yielded a sensitivity, specificity, and an AUC of 49.1 ± 9.3%, 81.2 ± 2.3%, and 69.2 ± 5.2%, respectively. The PR, PWd, and Pw/PR can serve as non-invasive biomarkers for the screening of RHD in at-risk schoolchildren. Monitoring alterations in these markers at an early stage of RHD is crucial for enabling prompt management and follow-up. It is thus evident that ECG can support an intermittent ambulatory RHD screening in resource-limited settings.