Further evidence of inherited long QT syndrome gene mutations in antiarrhythmic drug-associated torsades de pointes

Heart Rhythm. 2007 May;4(5):603-7. doi: 10.1016/j.hrthm.2007.01.019. Epub 2007 Jan 18.


Background: Pathophysiologically significant ion-channel mutations have been detected in only a minority of cases of acquired long QT syndrome (LQTS).

Objective: The aim of this study was to clarify the putative role of subclinical inherited LQTS in drug-associated torsades de pointes (TdP) and to assess the concomitant proarrhythmic factors.

Methods: We evaluated 16 consecutive cases with documented, antiarrhythmic drug-induced TdP who were referred to the Laboratory of Molecular Medicine at Helsinki University for LQTS genetic testing between September 2000 and August 2005.

Results: A prolonged QTc interval was observed in 56% of the patients before administration of the drug. TdP was associated with amiodarone in seven, sotalol in six, flecainide in two, and propafenone in one of the cases. Except for the culprit drug, one or more risk factors such as female sex, congestive heart failure, and atrial fibrillation were present in each drug-associated TdP. DNA samples were screened for the four common Finnish founder mutations (KCNQ1 G589D and IVS7-2A-->G, HERG L552S, and R176W), which are known to account for the majority of inherited LQTS in Finland. A total of three (19%) individuals carried one of these four mutations.

Conclusions: Our data show that previously unsuspected LQTS mutations may be present in patients with antiarrhythmic drug-associated TdPs. A normal QTc interval does not exclude the risk of proarrhythmia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amiodarone / adverse effects
  • Anti-Arrhythmia Agents / adverse effects*
  • DNA Mutational Analysis
  • ERG1 Potassium Channel
  • Electrocardiography
  • Ether-A-Go-Go Potassium Channels / genetics
  • Female
  • Finland / epidemiology
  • Flecainide / adverse effects
  • Founder Effect
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Heart Conduction System / physiopathology
  • Humans
  • KCNQ1 Potassium Channel / genetics
  • Long QT Syndrome / epidemiology
  • Long QT Syndrome / etiology
  • Long QT Syndrome / genetics*
  • Long QT Syndrome / physiopathology*
  • Male
  • Middle Aged
  • Mutation*
  • Propafenone / adverse effects
  • Risk Factors
  • Sotalol / adverse effects
  • Torsades de Pointes / chemically induced*
  • Torsades de Pointes / complications
  • Torsades de Pointes / epidemiology
  • Treatment Outcome


  • Anti-Arrhythmia Agents
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • KCNH2 protein, human
  • KCNQ1 Potassium Channel
  • Propafenone
  • Sotalol
  • Flecainide
  • Amiodarone