Polymorphic ventricular tachycardia and KCNJ2 mutations

Terrence U H Chun, Michael R. Epstein, Macdonald Dick, Gregor Andelfinger, Leomar Ballester, Carlos G. Vanoye, Alfred L. George, D. Woodrow Benson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

We sought to identify the electrophysiologic basis of life-threatening events associated with polymorphic ventricular tachycardia (PVT) in young patients with heterozygous KCNJ2 mutations. PVT describes a beat-to-beat alternating QRS axis and morphology during ventricular tachycardia. PVT may be well tolerated and even asymptomatic in young patients without other heart disease, but an association with syncope, cardiac arrest, or sudden death has long been known. Little is known of the basis of life-threatening events associated with PVT in this setting. We identified heterozygous KCNJ2 mutations (R67W and C101R respectively) in 2 adolescents with PVT (cycle length > 375 ms, < 160 beats/minute). Biophysical properties of wild-type and mutant KCNJ2 channels were characterized during heterologous expression in Xenopus oocytes. Despite a large tachycardia burden, neither patient experienced symptoms during electrocardiographic documentation of PVT. One patient had a history of cardiac arrest, but neither had other evidence of heart disease. Both patients were treated with an implantable cardioverter-defibrillator (ICD). In one patient, ICD interrogation identified rapid ventricular tachycardia (cycle length of 190 to 270 ms), terminated with a single 29-J asynchronous shock, as the cause of 2 syncopal episodes occurring 19 months apart. Biophysical characterization of KCNJ2-C101R demonstrated a loss-of-function and a dominant-negative effect on Kir2.1. Similar effects were previously observed for KCNJ2-R67W. Heterozygous mutations in KCNJ2 can cause life-threatening ventricular arrhythmias. Arrhythmia documented during cardiac arrest is rapid ventricular tachycardia; ICD is effective therapy for cardiac arrest in patients with PVT due to KCNJ2 mutation.

Original languageEnglish (US)
Pages (from-to)235-241
Number of pages7
JournalHeart rhythm
Volume1
Issue number2
DOIs
StatePublished - Jul 2004

Keywords

  • Bidirectional VT
  • Cardiac arrest
  • Sudden death
  • Syncope
  • Torsades de pointes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Polymorphic ventricular tachycardia and KCNJ2 mutations'. Together they form a unique fingerprint.

Cite this