Acute Effects on Signal‐Averaged Electrogram Parameters and Suppressing Premature Ventricular Contractions in Single or Combined Use of Class I Antiarrhythmic Drugs

Abstract Disopyramide (DP), mexiletine (MX), and flecainide (FL) are class I antiarrhythmic drugs. However, these drugs exert different effects on the electrocardiogram (ECG) based on their unique actions on cardiac myocytes. The electrocardiographic changes during combination therapy with these drugs are not well understood. The purpose of the present study was to evaluate acute morphologic changes in the ECG based on signal‐averaged high resolution ECG (SAECG) after administration of the drugs in relation to their antiarrhythmic eficacy and safety. Twenty‐one patients with frequent and stable premature ventricular contractions (PVC) were studied. Changes in the filtered QRS duration (f‐QRS) and the root mean square voltage of the last 40 msec of the QRS complex (RMS40) were evaluated. Suppression of PVCs was achieved soon after intravenous administration of the drugs (63% for DP, 43% for MX, 86% for FL and 100% for DP+MX). Although DP and FL significantly prolonged f‐QRS, MX had little effect on f‐QRS. DP+MX also prolonged f‐QRS, but the degree of prolongation was moderate. RMS40 was significantly decreased by DP and FL, but not by MX. DP+MX also decreased RMS40, but the decrease was less than for DP alone. Late potentials were observed after administration in 56% of patients with DP, 0% with MX, 67% with FL and 0% with DP+MX. No adverse events were reported during the study. In summary, the class I antiarrhythmic drugs exerted different acute effects on SAECG parameters. The combination of DP and MX increased the eficacy on suppressing PVC without excess additive changes on SAECG parameters. We conclude that combination therapy with DP and MX is eficacious and safe in patients with PVC and the analysis of SAECG during antiarrhythmic therapy is clinically important.