title: Identification of Concealed and Manifest Long QT Syndrome Using a Novel T Wave Analysis Program.
abstract: Congenital long QT syndrome (LQTS) is characterized by QT prolongation. However, the QT interval itself is insufficient for diagnosis, unless the corrected QT interval is repeatedly ≥500 ms without an acquired explanation. Further, the majority of LQTS patients have a corrected QT interval below this threshold, and a significant minority has normal resting corrected QT interval values. Here, we aimed to develop and validate a novel, quantitative T wave morphological analysis program to differentiate LQTS patients from healthy controls.
  
  
  
  We analyzed a genotyped cohort of 420 patients (22±16 years, 43% male) with either LQT1 (61%) or LQT2 (39%). ECG analysis was conducted using a novel, proprietary T wave analysis program that quantitates subtle changes in T wave morphology. The top 3 discriminating features in each ECG lead were determined and the lead with the best discrimination selected. Classification was performed using a linear discriminant classifier and validated on an untouched cohort. The top 3 features were Tpeak-Tend interval, T wave left slope, and T wave center of gravity x axis (last 25% of the T wave). Lead V6 had the best discrimination. It could distinguish 86.8% of LQTS patients from healthy controls. Moreover, it distinguished 83.33% of patients with concealed LQTS from controls, despite having essentially identical resting corrected QT interval values.
  
  
  
  T wave quantitative analysis on the 12-lead surface ECG provides an effective, novel tool to distinguish patients with either LQT1/LQT2 from healthy matched controls. It can provide guidance while mutation-specific genetic testing is in motion for family members.
authors.affiliation: From the Division of Internal Medicine (A.S.), Division of Cardiovascular Diseases (P.A.N., V.K., B.Q., R.K.R., Z.I.A., P.B., S.J.A., P.A.F., M.J.A.), Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology (J.M.B., S.J.A., M.J.A.), Mayo Clinic, Rochester, MN; Czech Institute of Informatics, Robotics, and Cybernetics, Czech Technical University in Prague, Czech Republic (V.K.); Electrical and Computer Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel (Y.S., Z.I.A.); Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN (J.M.B., M.J.A.). ackerman.michael@mayo.edu.
authors.forename: Alan
authors.initials: A
authors.lastname: Sugrue
authors.affiliation: From the Division of Internal Medicine (A.S.), Division of Cardiovascular Diseases (P.A.N., V.K., B.Q., R.K.R., Z.I.A., P.B., S.J.A., P.A.F., M.J.A.), Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology (J.M.B., S.J.A., M.J.A.), Mayo Clinic, Rochester, MN; Czech Institute of Informatics, Robotics, and Cybernetics, Czech Technical University in Prague, Czech Republic (V.K.); Electrical and Computer Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel (Y.S., Z.I.A.); Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN (J.M.B., M.J.A.).
authors.forename: Peter A
authors.initials: PA
authors.lastname: Noseworthy
authors.affiliation: From the Division of Internal Medicine (A.S.), Division of Cardiovascular Diseases (P.A.N., V.K., B.Q., R.K.R., Z.I.A., P.B., S.J.A., P.A.F., M.J.A.), Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology (J.M.B., S.J.A., M.J.A.), Mayo Clinic, Rochester, MN; Czech Institute of Informatics, Robotics, and Cybernetics, Czech Technical University in Prague, Czech Republic (V.K.); Electrical and Computer Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel (Y.S., Z.I.A.); Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN (J.M.B., M.J.A.).
authors.forename: Vaclav
authors.initials: V
authors.lastname: Kremen
authors.affiliation: From the Division of Internal Medicine (A.S.), Division of Cardiovascular Diseases (P.A.N., V.K., B.Q., R.K.R., Z.I.A., P.B., S.J.A., P.A.F., M.J.A.), Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology (J.M.B., S.J.A., M.J.A.), Mayo Clinic, Rochester, MN; Czech Institute of Informatics, Robotics, and Cybernetics, Czech Technical University in Prague, Czech Republic (V.K.); Electrical and Computer Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel (Y.S., Z.I.A.); Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN (J.M.B., M.J.A.).
authors.forename: J Martijn
authors.initials: JM
authors.lastname: Bos
authors.affiliation: From the Division of Internal Medicine (A.S.), Division of Cardiovascular Diseases (P.A.N., V.K., B.Q., R.K.R., Z.I.A., P.B., S.J.A., P.A.F., M.J.A.), Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology (J.M.B., S.J.A., M.J.A.), Mayo Clinic, Rochester, MN; Czech Institute of Informatics, Robotics, and Cybernetics, Czech Technical University in Prague, Czech Republic (V.K.); Electrical and Computer Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel (Y.S., Z.I.A.); Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN (J.M.B., M.J.A.).
authors.forename: Bo
authors.initials: B
authors.lastname: Qiang
authors.affiliation: From the Division of Internal Medicine (A.S.), Division of Cardiovascular Diseases (P.A.N., V.K., B.Q., R.K.R., Z.I.A., P.B., S.J.A., P.A.F., M.J.A.), Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology (J.M.B., S.J.A., M.J.A.), Mayo Clinic, Rochester, MN; Czech Institute of Informatics, Robotics, and Cybernetics, Czech Technical University in Prague, Czech Republic (V.K.); Electrical and Computer Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel (Y.S., Z.I.A.); Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN (J.M.B., M.J.A.).
authors.forename: Ram K
authors.initials: RK
authors.lastname: Rohatgi
authors.affiliation: From the Division of Internal Medicine (A.S.), Division of Cardiovascular Diseases (P.A.N., V.K., B.Q., R.K.R., Z.I.A., P.B., S.J.A., P.A.F., M.J.A.), Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology (J.M.B., S.J.A., M.J.A.), Mayo Clinic, Rochester, MN; Czech Institute of Informatics, Robotics, and Cybernetics, Czech Technical University in Prague, Czech Republic (V.K.); Electrical and Computer Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel (Y.S., Z.I.A.); Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN (J.M.B., M.J.A.).
authors.forename: Yehu
authors.initials: Y
authors.lastname: Sapir
authors.affiliation: From the Division of Internal Medicine (A.S.), Division of Cardiovascular Diseases (P.A.N., V.K., B.Q., R.K.R., Z.I.A., P.B., S.J.A., P.A.F., M.J.A.), Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology (J.M.B., S.J.A., M.J.A.), Mayo Clinic, Rochester, MN; Czech Institute of Informatics, Robotics, and Cybernetics, Czech Technical University in Prague, Czech Republic (V.K.); Electrical and Computer Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel (Y.S., Z.I.A.); Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN (J.M.B., M.J.A.).
authors.forename: Zachi I
authors.initials: ZI
authors.lastname: Attia
authors.affiliation: From the Division of Internal Medicine (A.S.), Division of Cardiovascular Diseases (P.A.N., V.K., B.Q., R.K.R., Z.I.A., P.B., S.J.A., P.A.F., M.J.A.), Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology (J.M.B., S.J.A., M.J.A.), Mayo Clinic, Rochester, MN; Czech Institute of Informatics, Robotics, and Cybernetics, Czech Technical University in Prague, Czech Republic (V.K.); Electrical and Computer Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel (Y.S., Z.I.A.); Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN (J.M.B., M.J.A.).
authors.forename: Peter
authors.initials: P
authors.lastname: Brady
authors.affiliation: From the Division of Internal Medicine (A.S.), Division of Cardiovascular Diseases (P.A.N., V.K., B.Q., R.K.R., Z.I.A., P.B., S.J.A., P.A.F., M.J.A.), Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology (J.M.B., S.J.A., M.J.A.), Mayo Clinic, Rochester, MN; Czech Institute of Informatics, Robotics, and Cybernetics, Czech Technical University in Prague, Czech Republic (V.K.); Electrical and Computer Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel (Y.S., Z.I.A.); Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN (J.M.B., M.J.A.).
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Asirvatham
authors.affiliation: From the Division of Internal Medicine (A.S.), Division of Cardiovascular Diseases (P.A.N., V.K., B.Q., R.K.R., Z.I.A., P.B., S.J.A., P.A.F., M.J.A.), Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology (J.M.B., S.J.A., M.J.A.), Mayo Clinic, Rochester, MN; Czech Institute of Informatics, Robotics, and Cybernetics, Czech Technical University in Prague, Czech Republic (V.K.); Electrical and Computer Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel (Y.S., Z.I.A.); Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN (J.M.B., M.J.A.).
authors.forename: Paul A
authors.initials: PA
authors.lastname: Friedman
authors.affiliation: From the Division of Internal Medicine (A.S.), Division of Cardiovascular Diseases (P.A.N., V.K., B.Q., R.K.R., Z.I.A., P.B., S.J.A., P.A.F., M.J.A.), Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology (J.M.B., S.J.A., M.J.A.), Mayo Clinic, Rochester, MN; Czech Institute of Informatics, Robotics, and Cybernetics, Czech Technical University in Prague, Czech Republic (V.K.); Electrical and Computer Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel (Y.S., Z.I.A.); Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN (J.M.B., M.J.A.). ackerman.michael@mayo.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ackerman
mesh_terms: D004562:Electrocardiography / Q000379:methods*; D005260:Female; D005838:Genotype; D006801:Humans; D008133:Long QT Syndrome / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D012680:Sensitivity and Specificity; D012815:Signal Processing, Computer-Assisted; D055815:Young Adult
keywords: T wave analysis; diagnosis; electrocardiography; long QT syndrome; sudden cardiac death; ventricular repolarization