New analysis of the actions of antiarrhythmic drugs based on the heart rate dependency of ventricular premature contractions

Abstract

Key Words. Antiarrhythmie drugs, ventricular premature contractions, heart rate dependencyDear Sir,There have been numerous studies to assess the efficacy of antiarrhythmic drugs on ventricular premature contractions (VPCs) using a 24-hour ambulatory electrocardiogram (ECG) monitoring system. Most of the studies, however, focused simply on the reduction of either the frequency of VPCs or the severity of the arrhythmias, and the mechanisms underlying the arrhythmias or the modes of drug action have scarcely been concerned.It has been known that there is a distinct relation between the frequency of VPCs and the underlying heart rate. We previously analyzed the relation between VPC frequency and underlying heart rate and grouped this into four patterns [1]. These are (1) VPC frequency increases with increasing heart rates (positive correlation), (2) VPC frequency increases up to certain heart rate and decreases at much higher heart rates (bidirectional correlation), (3) VPC frequency stays constant over the entire range of heart rates (flat correlation), and (4) VPC frequency decreases as the heart rate increases (negative correlation).We analyzed the effects of class I, II, and IV antiarrhythmic drugs of Vaughan Williams classification on VPCs by Holter ECG recording [1][2][3]. Interestingly, diltiazem (a calcium antagonist) suppressed VPCs only when there was a positive correlation with heart rate, while atenolol (a beta blocker) was similar to diltiazem [2]. The detailed analysis of these results has lead us to hypothesize that the VPCs with positive VPC-HR correlation might derive from triggered activity following delayed afterdepolarization [1,2].In contrast, disopyramide and mexiletine (class I drugs) suppressed VPCs irrespective of their VPC-HR relation. Therefore, the analysis based on this VPC-HR correlation may be useful for the understanding and elucidation of ventricular arrhythmias.