Differentiating long QT syndrome genotypes using electrocardiographic geometric parameterization and machine learning approaches

Long QT Syndrome (LQTS) is an inherited cardiac disorder characterized by dysfunctional cardiac ion channels, which result in prolonged QT intervals on electrocardiograms (ECGs). LQTS can lead to severe clinical manifestations, including syncope, ventricular arrhythmias, and sudden cardiac death. Effective genotype-specific management strategies are essential to mitigate the risk of life-threatening arrhythmias. This study aims to achieve automatic discrimination among the LQT1, LQT2, and LQT3 genotypes to enable targeted treatment and prevention strategies. Utilizing ECG data from the Telemetric and Holter ECG Warehouse's LQTS database, our methodology involves an automated extraction process of short ECG signals, geometric parameterization techniques, and classification using a two-stage cascade of binary support vector machine classifiers. The input features for the classifiers are derived from Lead I ECG signals sampled at 200 Hz, highlighting the potential application in developing single-lead ECG monitoring devices and applications, such as widely used smartwatches, for which short recording duration, low sampling frequency, and arm-to-arm lead measurements are fundamental prerequisites for practical use. The proposed classifier achieved 71% weighted accuracy on out-of-sample data (LQT1: 65% recall, 58% precision; LQT2: 79% recall, 82% precision; and LQT3: 71% recall, 77% precision). Our findings demonstrate the feasibility of noninvasive genotype differentiation for LQTS based on the morphological analysis of ECG signals, providing an advancement in the field of personalized cardiology and the development of portable diagnostic tools.