Objectives: The purpose of the study was to look for the predictor factors of atrial proarrhythmic effects of class I antiarrhythmic drugs. Background: Class I anti arrhythmic drugs may induce or exacerbate cardiac arrhythmias. The predictors of ventricular proarrhythmia are known. The predictors of atrial flutter with 1:1 conduction are unknown. Methods: Clinical history, EGG, signal-averaged EGG (SAECG) and electrophysiologic study were analysed in 24 cases of 1:1 atrial flutter with class I AA drugs and in 100 control patients without history of 1:1 atrial flutter with class I AA drugs. Results: The ages of patients varied from 46 to 78 years. Underlying heart disease was present in nine patients. The surface EGG revealed the presence of a short PR interval (PR <0.13 ms), visible in leads V5, V6 in eight (35%) patients with normal P wave duration; in other patients with prolonged P wave duration, PR seemed normaL On SAECG recording, there was a pseudofusion between P wave and QRS complex. The electrophysiologic study revealed some signs indicating a rapid AV nodal conduction (short AH interval or rate of 2nd degree AV block at atrial pacing > 200 beats/mm) in 19 of the 23 studied patients. All patients, except one, had at least one sign indicating a rapid AV nodal conduction (short PR and/or P wave-QRS complex continuity on SAECG). In the control group, seven patients (7%) had a short PR interval (P <0.01) and 11 (11%) had a pseudofusion between P wave and QRS complex on SAECG (P <0.001). The P wave-QRS complex pseudofusion on SAECG had a sensitivity of 100% and a specificity of 89% for the prediction of an atrial proarrhythmic effect with class I antiarrhythmic drug. Conclusion: We recommend avoiding class I AA drugs in patients with a short PR interval on surface EGG and to record SAECG in those with apparently normal PR interval to detect a continuity between P wave and QRS complex, which could indicate a rapid AV nodal conduction, predisposing to 1: 1 atrial flutter with the drug. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.