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.

Non‐invasive recording of the late potential (LP) by signal‐averaging technique is useful in predicting ventricular tachycardia (VT), especially in patients with myocardial infarction (MI). However, the rate of positive LP is much lower in anterior or anteroseptal MI than inferior MI since the LP is sometimes masked by QRS complex. The purpose of the present study is firstly, to detect local conduction delay in initial portion of QRS complex and secondarily, to evaluate the clinical significance of the initial delay in patients with MI. Eighty patients with MI were analyzed in 4 groups as follows: AS: anteroseptal, n = 18, including 6 VT; A: anterior, n = 22, 7 VT; I: inferior, n = 28, 9 VT; and P: posterior, n = 12, noVT. Twenty non‐MI patients were used as normal controls (N). A signal processor (NEC 7T 18) was used to record signal‐averaged electrocardiograms and each 10 msec integral value of filtered QRS complex from the initial upstroke to the 60 msec point was automatically measured. The integral values of groups AS and A were lower than those of groups I, P, and N. AS patients with VT showed a lower integral value than AS patients without VT, but no differences were observed between A patients with VT and A patients without VT. We conclude that there is a much more sluggish upstroke in the signal‐averaged initial QRS complex in anteroseptal MI patients with VT, suggesting that the local conduction delay at the ventricular septum plays an important role in the mechanism of VT in these patients.

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 efficacy 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 efficacy on suppressing PVC without excess additive changes on SAECG parameters. We conclude that combination therapy with DP and MX is efficacious and safe in patients with PVC and the analysis of SAECG during antiarrhythmic therapy is clinically important. (J Arrhythmia 2006; 22: 155-160)

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