title: Load-induced changes in repolarization: evidence from experimental and clinical data.
abstract: The high incidence of arrhythmias in patients with heart failure, hypertension, valvular heart disease, or mitral walve prolapse suggests a strong link between wall motion abnormalities and arrhythmias. A potential common mechanism underlying these observations may be that overload leads to electrophysiologic changes and facilitates arrhythmias. This article summarizes the interaction between changes in atrial and ventricular loading conditions and repolarization. Most experimental and clinical studies demonstrated 1) a reduction of action potential duration and refractoriness, 2) development of early afterdepolarizations, and 3) ectopic beats originating from these afterdepolarizations. Discrepancies between studies are related to different study designs, i.e., varying magnitude, velocity, and timing of increased load, the level of repolarization at which action potential duration is measured as well as different animal species. Direct effects of increased load on repolarization are most likely caused by activation of stretch-activated nonselective cation ion channels and changes in calcium handling. Current antiarrhythmic drug therapy is aimed at electrical disorders as the primary cause of arrhythmias. If mechanical disorders play a central role in the genesis of cardiac arrhythmias, future treatment should be directed at restoring a more normal mechanical function of the heart. Additional studies will further clarify the nature and clinical significance of load-related changes in repolarization and arrhythmogenesis.
authors.affiliation: Westfälische Wilhelms-Universität Innere Medizin C, Münster, Germany. l.eckardt@uni-muenster.de
authors.forename: L
authors.initials: L
authors.lastname: Eckardt
authors.forename: P
authors.initials: P
authors.lastname: Kirchhof
authors.forename: G
authors.initials: G
authors.lastname: Breithardt
authors.forename: W
authors.initials: W
authors.lastname: Haverkamp
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D001794:Blood Pressure; D001810:Blood Volume; D004594:Electrophysiology; D005246:Feedback; D006321:Heart / Q000503:physiopathology*; D006801:Humans