title: Evaluation of Index of Cardio-Electrophysiological Balance (iCEB) as a New Biomarker for the Identification of Patients at Increased Arrhythmic Risk.
abstract: BACKGROUND
  Recently a new risk marker for drug-induced arrhythmias called index of cardio-electrophysiological balance (iCEB), measured as QT interval divided by QRS duration, was evaluated in an animal model. It was hypothesized that iCEB is equivalent to the cardiac wavelength λ (λ = effective refractory period (ERP) x conduction velocity) and that an increased or decreased value of iCEB would potentially predict an increased susceptibility to TdP or non-TdP mediated VT/VF, respectively.
  
  
  METHODS
  First, the correlation between QT interval and ERP was evaluated by invasively measuring ERP during a ventricular stimulation protocol in humans (N = 40). Then the effect of administration of sotalol and flecainide on iCEB was measured in 40 patients with supraventricular tachycardias. Finally iCEB was assessed in carriers of a long QT syndrome (LQTS, N = 70) or Brugada syndrome (BrS, N = 57) mutation and compared them with genotype negative family members (N = 65).
  
  
  RESULTS
  The correlation between QT interval and ERP was established (Pearson R(2) = 0.25) which suggests that iCEB≈ERPxCV≈QT/QRS. Sotalol administration increased iCEB (+ 0.23; P = 0.01), while it decreased with the administration of flecainide (-0.21, P = 0.03). In the LQTS group iCEB was increased (5.22 ± 0.93, P < 0.0001) compared to genotype negative family members (4.24 ± 0.5), while it was decreased in the BrS group (3.52 ± 0.43, P < 0.0001).
  
  
  CONCLUSIONS
  Our data suggest that iCEB (QT/QRS) is a simple but effective ECG surrogate of cardiac wavelength. iCEB is increased in situations that predispose to TdP and is decreased in situations that predispose to non-TdP mediated VT/VF. Therefore, iCEB might serve as a noninvasive and readily measurable marker to detect increased arrhythmic risk.
authors: Department of Cardiovascular Diseases, University Hospitals, Leuven, Belgium.|Department of Cardiovascular Sciences, University of Leuven, Belgium.
authors: Tomas
authors: T
authors: Robyns
authors: Global Safety Pharmacology, Discovery Sciences, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, Beerse, Belgium.
authors: Hua Rong
authors: HR
authors: Lu
authors: Global Safety Pharmacology, Discovery Sciences, Janssen Research and Development, a Division of Janssen Pharmaceutica NV, Beerse, Belgium.
authors: David J
authors: DJ
authors: Gallacher
authors: Department of Cardiovascular Diseases, University Hospitals, Leuven, Belgium.|Department of Cardiovascular Sciences, University of Leuven, Belgium.
authors: Christophe
authors: C
authors: Garweg
authors: Department of Cardiovascular Diseases, University Hospitals, Leuven, Belgium.|Department of Cardiovascular Sciences, University of Leuven, Belgium.
authors: Joris
authors: J
authors: Ector
authors: Department of Cardiovascular Diseases, University Hospitals, Leuven, Belgium.|Department of Cardiovascular Sciences, University of Leuven, Belgium.
authors: Rik
authors: R
authors: Willems
authors: Department of Cardiovascular Diseases, University Hospitals, Leuven, Belgium.|Department of Cardiovascular Sciences, University of Leuven, Belgium.
authors: Stefan
authors: S
authors: Janssens
authors: Department of Cardiovascular Diseases, University Hospitals, Leuven, Belgium.|Department of Cardiovascular Sciences, University of Leuven, Belgium.
authors: Dieter
authors: D
authors: Nuyens
mesh_terms: D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D054316:Biomarkers, Pharmacological; D053840:Brugada Syndrome / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D005424:Flecainide / Q000008:administration & dosage; D006801:Humans; D008133:Long QT Syndrome / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D008297:Male; D012189:Retrospective Studies; D018570:Risk Assessment; D013015:Sotalol / Q000008:administration & dosage
chemical_list: D000889:Anti-Arrhythmia Agents; D054316:Biomarkers, Pharmacological; D013015:Sotalol; D005424:Flecainide
keywords: cardiac wavelength; iCEB, risk stratification; index of cardio-electrophysiological balance; sudden cardiac death