title: Electrocardiographic Predictors of Torsadogenic Risk During Dofetilide or Sotalol Initiation: Utility of a Novel T Wave Analysis Program.
abstract: BACKGROUND
  Initiation of class III anti-arrhythmic medications requires telemetric monitoring for ventricular arrhythmias and QT prolongation to reduce the risk of torsades de pointes (TdP). Heart rate-corrected QT interval (QTc) is an indicator of risk, however it is imperfect, and subtle abnormalities of repolarization have been linked with arrhythmogenesis.
  
  
  OBJECTIVE
  Identification of electrocardiographic predictors of torsadogenic risk through the application of a novel T wave analysis tool.
  
  
  METHODS
  Among all patients admitted to Mayo Clinic for initiation of dofetilide or sotalol, we identified 13 cases who developed drug-induced TdP and 26 age and sex matched controls that did not develop TdP. The immediate pre-TdP ECG of those with TdP was compared to the last ECG performed prior to hospital discharge in controls using a novel T wave program that quantified subtle changes in T wave morphology.
  
  
  RESULTS
  The QTc and 12 T wave parameters successfully distinguished TdP cases from controls. The top performing parameters were the QTc in lead V3 (mean case vs control 480 vs 420 msec, p < 0.001, r = 0.72) and T wave right slope in lead I (mean case vs control -840.29 vs -1668.71 mV/s, p = 0.002, r = 0.45). The addition of T wave right slope to QTc improved prediction accuracy from 79 to 88 %.
  
  
  CONCLUSIONS
  Our data demonstrate that, in addition to QTc, the T wave right slope is correlated strongly with TdP risk. This suggests that a computer-based repolarization measurement tool that integrates additional data beyond the QTc may identify patients with the greatest torsadogenic potential.
authors.affiliation: Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Alan
authors.identifier: http://orcid.org/0000-0001-9921-6968
authors.initials: A
authors.lastname: Sugrue
authors.affiliation: Czech Institute of Informatics, Robotics, and Cybernetics, Czech Technical University in Prague, Prague, Czech Republic.|Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA.
authors.forename: Vaclav
authors.initials: V
authors.lastname: Kremen
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Qiang
authors.affiliation: Department of Cardiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Seth H
authors.initials: SH
authors.lastname: Sheldon
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA.
authors.forename: Christopher V
authors.initials: CV
authors.lastname: DeSimone
authors.affiliation: Ben Gurion University of the Negev, Beersheba, Israel.
authors.forename: Yehu
authors.initials: Y
authors.lastname: Sapir
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA.
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Striemer
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Brady
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA.|Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Asirvatham
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA.|Division of Pediatric Cardiology, Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.|Windland Smith Rice Sudden Death Genomics Laboratory, Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ackerman
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Friedman
authors.affiliation: Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, USA. noseworthy.peter@mayo.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Noseworthy
mesh_terms: D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects; D016022:Case-Control Studies; D004562:Electrocardiography / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010627:Phenethylamines / Q000009:adverse effects*; D011237:Predictive Value of Tests; D012984:Software; D013015:Sotalol / Q000009:adverse effects*; D013449:Sulfonamides / Q000009:adverse effects*; D016171:Torsades de Pointes / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D013449:Sulfonamides; D013015:Sotalol; C063533:dofetilide
keywords: Class III antiarrhythmics; Electrocardiography; Risk stratification; T wave analysis; Torsade de pointes