Support vector machine-based assessment of the T-wave morphology improves long QT syndrome diagnosis.

Aims Diagnosing long QT syndrome (LQTS) is challenging due to a considerable overlap of the QTc-interval between LQTS patients and healthy controls. The aim of this study was to investigate the added value of T-wave morphology markers obtained from 12-lead electrocardiograms (ECGs) in diagnosing LQTS in a large cohort of gene-positive LQTS patients and gene-negative family members using a support vector machine. Methods and results A retrospective study was performed including 688 digital 12-lead ECGs recorded from genotype-positive LQTS patients and genotype-negative relatives at their first visit. Two models were trained and tested equally: a baseline model with age, gender, RR-interval, QT-interval, and QTc-intervals as inputs and an extended model including morphology features as well. The best performing baseline model showed an area under the receiver-operating characteristic curve (AUC) of 0.821, whereas the extended model showed an AUC of 0.901. Sensitivity and specificity at the maximal Youden's indexes changed from 0.694 and 0.829 with the baseline model to 0.820 and 0.861 with the extended model. Compared with clinically used QTc-interval cut-off values (>480 ms), the extended model showed a major drop in false negative classifications of LQTS patients. Conclusion The support vector machine-based extended model with T-wave morphology markers resulted in a major rise in sensitivity and specificity at the maximal Youden's index. From this, it can be concluded that T-wave morphology assessment has an added value in the diagnosis of LQTS.

[1]  Andrew C Oehler,et al.  QRS‐T Angle: A Review , 2014, Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc.

[2]  W. Shen,et al.  Epinephrine-induced T-wave notching in congenital long QT syndrome. , 2005, Heart rhythm.

[3]  J. Healey,et al.  Derivation and Validation of a Simple Exercise-Based Algorithm for Prediction of Genetic Testing in Relatives of LQTS Probands , 2011, Circulation.

[4]  W. Shen,et al.  Epinephrine-induced QT interval prolongation: a gene-specific paradoxical response in congenital long QT syndrome. , 2002, Mayo Clinic proceedings.

[5]  P. Caraballo,et al.  Automated T‐wave analysis can differentiate acquired QT prolongation from congenital long QT syndrome , 2017, Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc.

[6]  W. Zareba,et al.  T-wave morphology can distinguish healthy controls from LQTS patients , 2016, Physiological measurement.

[7]  M. Josephson,et al.  Interlead heterogeneity of R‐ and T‐wave morphology in standard 12‐lead ECGs predicts sustained ventricular tachycardia/fibrillation and arrhythmic death in patients with cardiomyopathy , 2017, Journal of cardiovascular electrophysiology.

[8]  R. Pallàs-Areny,et al.  The QT Scale: A Weight Scale Measuring the QTc Interval , 2017, Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc.

[9]  A. Sittig,et al.  Reconstruction of the Frank vectorcardiogram from standard electrocardiographic leads: diagnostic comparison of different methods. , 1990, European heart journal.

[10]  Trevor Hastie,et al.  Regularization Paths for Generalized Linear Models via Coordinate Descent. , 2010, Journal of statistical software.

[11]  A. Wilde,et al.  Exercise extreme caution when calling rare genetic variants novel arrhythmia syndrome susceptibility mutations. , 2010, Heart rhythm.

[12]  A. Wilde,et al.  Safe drug use in long QT syndrome and Brugada syndrome: comparison of website statistics. , 2013, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[13]  H. Zou,et al.  Regularization and variable selection via the elastic net , 2005 .

[14]  Trevor Hastie,et al.  An Introduction to Statistical Learning , 2013, Springer Texts in Statistics.

[15]  M. Lehmann,et al.  T wave "humps" as a potential electrocardiographic marker of the long QT syndrome. , 1994, Journal of the American College of Cardiology.

[16]  Wataru Shimizu,et al.  HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndromes , 2013 .

[17]  A. Wilde,et al.  Diagnostic value of T-wave morphology changes during "QT stretching" in patients with long QT syndrome. , 2015, Heart rhythm.

[18]  A. Wilde,et al.  The response of the QT interval to the brief tachycardia provoked by standing: a bedside test for diagnosing long QT syndrome. , 2010, Journal of the American College of Cardiology.

[19]  Stefan Neubauer,et al.  Electrocardiographic abnormalities of hypertrophic cardiomyopathy , 2014, Computing in Cardiology 2014.

[20]  Willis J. Tompkins,et al.  A Real-Time QRS Detection Algorithm , 1985, IEEE Transactions on Biomedical Engineering.

[21]  Peter W Macfarlane,et al.  A comparison of commonly used QT correction formulae: the effect of heart rate on the QTc of normal ECGs. , 2004, Journal of electrocardiology.

[22]  M. P. Andersen,et al.  A robust method for quantification of IKr-related T-wave morphology abnormalities , 2007, 2007 Computers in Cardiology.

[23]  S. Viskin,et al.  The QT interval: too long, too short or just right. , 2009, Heart rhythm.

[24]  A. Moss,et al.  ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome. , 1995, Circulation.