title: Drug-induced proarrhythmia: risk factors and electrophysiological mechanisms.
abstract: Drug-induced ventricular tachyarrhythmias can be caused by cardiovascular drugs, noncardiovascular drugs, and even nonprescription agents. They can result in arrhythmic emergencies and sudden cardiac death. If a new arrhythmia or aggravation of an existing arrhythmia develops during therapy with a drug at a concentration usually considered not to be toxic, the situation can be defined as proarrhythmia. Various cardiovascular and noncardiovascular drugs can increase the occurrence of polymorphic ventricular tachycardia of the 'torsade de pointes' type. Antiarrhythmic drugs, antimicrobial agents, and antipsychotic and antidepressant drugs are the most important groups. Age, female sex, and structural heart disease are important risk factors for the occurrence of torsade de pointes. Genetic predisposition and individual pharmacodynamic and pharmacokinetic sensitivity also have important roles in the generation of arrhythmias. An increase in spatial or temporal dispersion of repolarization and a triangular action-potential configuration have been identified as crucial predictors of proarrhythmia in experimental models. These studies emphasized that sole consideration of the QT interval is not sufficient to assess the proarrhythmic risk. In this Review, we focus on important triggers of proarrhythmia and the underlying electrophysiological mechanisms that can enhance or prevent the development of torsade de pointes.
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Albert-Schweitzer Strasse 33, D-48149 Münster, Germany.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Frommeyer
authors.affiliation: Division of Electrophysiology, Department of Cardiovascular Medicine, University of Münster, Albert-Schweitzer Strasse 33, D-48149 Münster, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Eckardt
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000009:adverse effects; D000890:Anti-Infective Agents / Q000009:adverse effects; D000928:Antidepressive Agents / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000009:adverse effects; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000235:genetics; D008297:Male; D012307:Risk Factors; D017180:Tachycardia, Ventricular / Q000139:chemically induced* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D000890:Anti-Infective Agents; D000928:Antidepressive Agents; D014150:Antipsychotic Agents