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Original Investigation
February 10, 2021

Use of Artificial Intelligence and Deep Neural Networks in Evaluation of Patients With Electrocardiographically Concealed Long QT Syndrome From the Surface 12-Lead Electrocardiogram

Author Affiliations
  • 1Division of Pediatric Cardiology, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota
  • 2Department of Molecular Pharmacology & Experimental Therapeutics, Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, Minnesota
  • 3Division of Heart Rhythm Services, Department of Cardiovascular Medicine, Windland Smith Rice Genetic Heart Rhythm Clinic, Mayo Clinic, Rochester, Minnesota
  • 4AliveCor Inc, Mountain View, California
JAMA Cardiol. 2021;6(5):532-538. doi:10.1001/jamacardio.2020.7422
Key Points

Question  Can artificial intelligence and machine learning, using an artificial intelligence–enhanced, 12-lead electrocardiogram (AI-ECG), distinguish patients with long QT syndrome from those who do not have the syndrome?

Findings  In a diagnostic study using a deep neural network, the AI-ECG successfully distinguished patients with long QT syndrome (n = 967) from those who were evaluated for long QT syndrome but discharged without this diagnosis (n = 1092) presenting to a specialized arrhythmia clinic. The model performed better than the corrected QT alone, even in the setting of a normal QT interval.

Meaning  The AI-ECG model evaluated was able to distinguish patients with electrocardiographically concealed long QT syndrome from those without the syndrome and could potentially provide a simple and inexpensive method for early detection of congenital long QT syndrome.


Importance  Long QT syndrome (LQTS) is characterized by prolongation of the QT interval and is associated with an increased risk of sudden cardiac death. However, although QT interval prolongation is the hallmark feature of LQTS, approximately 40% of patients with genetically confirmed LQTS have a normal corrected QT (QTc) at rest. Distinguishing patients with LQTS from those with a normal QTc is important to correctly diagnose disease, implement simple LQTS preventive measures, and initiate prophylactic therapy if necessary.

Objective  To determine whether artificial intelligence (AI) using deep neural networks is better than the QTc alone in distinguishing patients with concealed LQTS from those with a normal QTc using a 12-lead electrocardiogram (ECG).

Design, Setting, and Participants  A diagnostic case-control study was performed using all available 12-lead ECGs from 2059 patients presenting to a specialized genetic heart rhythm clinic. Patients were included if they had a definitive clinical and/or genetic diagnosis of type 1, 2, or 3 LQTS (LQT1, 2, or 3) or were seen because of an initial suspicion for LQTS but were discharged without this diagnosis. A multilayer convolutional neural network was used to classify patients based on a 10-second, 12-lead ECG, AI-enhanced ECG (AI-ECG). The convolutional neural network was trained using 60% of the patients, validated in 10% of the patients, and tested on the remaining patients (30%). The study was conducted from January 1, 1999, to December 31, 2018.

Main Outcomes and Measures  The goal of the study was to test the ability of the convolutional neural network to distinguish patients with LQTS from those who were evaluated for LQTS but discharged without this diagnosis, especially among patients with genetically confirmed LQTS but a normal QTc value at rest (referred to as genotype positive/phenotype negative LQTS, normal QT interval LQTS, or concealed LQTS).

Results  Of the 2059 patients included, 1180 were men (57%); mean (SD) age at first ECG was 21.6 (15.6) years. All 12-lead ECGs from 967 patients with LQTS and 1092 who were evaluated for LQTS but discharged without this diagnosis were included for AI-ECG analysis. Based on the ECG-derived QTc alone, patients were classified with an area under the curve (AUC) value of 0.824 (95% CI, 0.79-0.858); using AI-ECG, the AUC was 0.900 (95% CI, 0.876-0.925). Furthermore, in the subset of patients who had a normal resting QTc (<450 milliseconds), the QTc alone distinguished those with LQTS from those without LQTS with an AUC of 0.741 (95% CI, 0.689-0.794), whereas the AI-ECG increased this discrimination to an AUC of 0.863 (95% CI, 0.824-0.903). In addition, the AI-ECG was able to distinguish the 3 main genotypic subgroups (LQT1, LQT2, and LQT3) with an AUC of 0.921 (95% CI, 0.890-0.951) for LQT1 compared with LQT2 and 3, 0.944 (95% CI, 0.918-0.970) for LQT2 compared with LQT1 and 3, and 0.863 (95% CI, 0.792-0.934) for LQT3 compared with LQT1 and 2.

Conclusions and Relevance  In this study, the AI-ECG was found to distinguish patients with electrocardiographically concealed LQTS from those discharged without a diagnosis of LQTS and provide a nearly 80% accurate pregenetic test anticipation of LQTS genotype status. This model may aid in the detection of LQTS in patients presenting to an arrhythmia clinic and, with validation, may be the stepping stone to similar tools to be developed for use in the general population.