Genetic basis of drug-induced arrhythmias.
Drug-induced torsade de pointes arrhythmia (TdP) is frequently seen in patients. This proarrhythmia is not restricted to anti-arrhythmics but includes a variety of drugs. A genetic predisposition is an attractive explanation for this clinical problem. In this review, we: 1) explain the arrhythmogenic mechanisms of TdP, 2) provide data for a genetic cause based upon mutations in the long QT or in cytochrome genes responsible for drug metabolism, and 3) present pathology-based electrical remodeling as an alternative explanation. It can be concluded that the current evidence for a genetic basis for drug-induced TdP is weak.
Vos
Marc A
MA
Department of Medical Physiology, University Medical Center Utrecht, The Netherlands. m.a.vos@med.uu.nl
Paulussen
Aimée D C
AD
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000378:metabolism; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D004562:Electrocardiography; D008133:Long QT Syndrome / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology; D009154:Mutation; D013449:Sulfonamides / Q000009:adverse effects / Q000378:metabolism; D016171:Torsades de Pointes / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology
D000889:Anti-Arrhythmia Agents; D013449:Sulfonamides; C067192:ibutilide; D003577:Cytochrome P-450 Enzyme System