The Impact of Non-Cardiac Drugs on the Cardiac Repolarization Phase

Certain kinds of non-cardiac drugs have been demonstrated to induce heart rhythm disorders.Although most of them are not clinically significant, lethal events have been reported.QT prolongation, a repolarization abnormality that is also referred to as secondary long QT syndrome, is a well-known disorder that is caused by non-cardiac drugs.It mainly arises due to reduced potassium channel activity. 1)This syndrome is associated with an increased risk of polymorphic ventricular tachycardia, also known as torsades de pointes (TdP). 2)By contrast, eicosapentaenoic acid (EPA), an omega-3 (n-3) fatty acid, has been reported to have favorable effects on the potassium channels. 3,4) reduction in ischemic cardiovascular events in healthy adults and patients with established coronary artery disease was demonstrated following the use of n-3 polyunsaturated fatty acids (n-3 PUFAs) (i.e., EPA and docosahexaenoic acid) in randomized controlled trials.5,6) A significant improvement was also established in left ventricular end-systolic volume and myocardial fibrosis after acute myocardial infarction (MI) by Omega-3 Acid Ethyl Esters.7) A reduction of platelet aggregation by blocking platelet-derived thromboxane A2 by EPA is reported to be a major mechanism to reduce ischemia cardiovascular risk.8) The consumption of n-3 PUFAs has been also associated with a reduction in arrhythmic risk.EPA directly affects atrial and ventricular myocyte electrophysiology via modulating cardiac potassium channel function.4) This causes a reduction in sudden cardiac death and ventricular fibrillation.9) Such results, however, have been obtained in preclinical or in vitro studies, and evidence of a direct antiarrhythmic effect of n-3 PUFAs on humans was limited.Recently, the positive impact of n-3 PUFAs (i.e., a reduction in atrial fibrillation) has been reported in a few observational studies in human. 10,11)In addition, Endo, et al. reported that J-waves were found more frequently on acute phase of MI in patients with low levels of serum EPA. 3) Low-serum EPA levels were associated with an increased incidence of ventricular arrhythmia after MI, sug-gestive that EPA is efficacious in reducing ventricular arrhythmia. 3)However, it remained uncertain as to whether serum EPA levels influence the frequency of J-waves in healthy adults.