Acquired long QT syndrome and cardiac sudden death

Molecular and cellular mechanisms underlying the prolongation of QT intervals have been elucidated largely because of the recent understanding of the generation of the congenital long QT syndrome (LQTS). LQTS is characterized by an excessive QT prolongation (usually >500 ms) on electrocardiogram (ECG) and a peculiar "polymorphic" ventricular arrhythmia so called "torsade de pointes", which sometimes degenerates into ventricular fibrillation. LQTS is therefore one of most remarkable delegates of sudden arrhythmia death syndromes. To date, at least 7 different genes encoding ion channels or their regulatory proteins that modulate cardiac ion channels were identified to be associated with the syndrome. In daily clinics, acquired LQTS is much more frequently seen than congenital LQTS and is therefore important. In secondary long QT patients, including the drug-induced cases, who were referred to us for genetic analysis, we found several mutations as well as single nucleotide polymorphisms (SNiPs) specific to the Japanese population. These findings raised the potential that there are also predisposing risk factors at patient's side, too. Recent vigorous study on the genetic basis of LQTS played an important role as a Rosetta stone to solve the mystery of both inherited and acquired arrhythmias.