title: Postpacing abnormal repolarization in catecholaminergic polymorphic ventricular tachycardia associated with a mutation in the cardiac ryanodine receptor gene.
abstract: BACKGROUND
  Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an arrhythmogenic disease for which electrophysiological studies (EPS) have shown to be of limited value.
  
  
  OBJECTIVE
  This study presents a CPVT family in which marked postpacing repolarization abnormalities during EPS were the only consistent phenotypic manifestation of ryanodine receptor (RyR2) mutation carriers.
  
  
  METHODS
  The study was prompted by the observation of transient marked QT prolongation preceding initiation of ventricular fibrillation during atrial fibrillation in a boy with a family history of sudden cardiac death (SCD). Family members underwent exercise and pharmacologic electrocardiographic testing with epinephrine, adenosine, and flecainide. Noninvasive clinical test results were normal in 10 patients evaluated, except for both epinephrine- and exercise-induced ventricular arrhythmias in 1. EPS included bursts of ventricular pacing and programmed ventricular extrastimulation reproducing short-long sequences. Genetic screening involved direct sequencing of genes involved in long QT syndrome as well as RyR2.
  
  
  RESULTS
  Six patients demonstrated a marked increase in QT interval only in the first beat after cessation of ventricular pacing and/or extrastimulation. All 6 patients were found to have a heterozygous missense mutation (M4109R) in RyR2. Two of them, presenting with aborted SCD, also had a second missense mutation (I406T- RyR2). Four family members without RyR2 mutations did not display prominent postpacing QT changes.
  
  
  CONCLUSIONS
  M4109R- RyR2 is associated with a high incidence of SCD. The contribution of I406T to the clinical phenotype is unclear. In contrast to exercise testing, marked postpacing repolarization changes in a single beat accurately predicted carriers of M4109R- RyR2 in this family.
authors.affiliation: Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Israel. eyalnof.dr@gmail.com
authors.forename: Eyal
authors.initials: E
authors.lastname: Nof
authors.forename: Bernard
authors.initials: B
authors.lastname: Belhassen
authors.forename: Michael
authors.initials: M
authors.lastname: Arad
authors.forename: Zahurul A
authors.initials: ZA
authors.lastname: Bhuiyan
authors.forename: Charles
authors.initials: C
authors.lastname: Antzelevitch
authors.forename: Raphael
authors.initials: R
authors.lastname: Rosso
authors.forename: Rami
authors.initials: R
authors.lastname: Fogelman
authors.forename: David
authors.initials: D
authors.lastname: Luria
authors.forename: Dalia
authors.initials: D
authors.lastname: El-Ani
authors.forename: Marcel M A M
authors.initials: MM
authors.lastname: Mannens
authors.forename: Sami
authors.initials: S
authors.lastname: Viskin
authors.forename: Michael
authors.initials: M
authors.lastname: Eldar
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
authors.forename: Michael
authors.initials: M
authors.lastname: Glikson
mesh_terms: D000293:Adolescent; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D002304:Cardiac Pacing, Artificial; D017115:Catheter Ablation; D002648:Child; D016757:Death, Sudden, Cardiac; D017147:Defibrillators, Implantable; D004562:Electrocardiography; D005260:Female; D005424:Flecainide / Q000627:therapeutic use; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D017180:Tachycardia, Ventricular / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D000098850:Polymorphic Catecholaminergic Ventricular Tachycardia
chemical_list: D000889:Anti-Arrhythmia Agents; D019837:Ryanodine Receptor Calcium Release Channel; D005424:Flecainide