Effects of amiodarone on the P-wave triggered signal-averaged electrocardiogram in patients with paroxysmal atrial fibrillation and coronary artery disease

S lowly conducted atrial activity, widening of the fragmented activity zone in response to atrial extrastimuli, and the fragmented atrial electrocardiogram during sinus rhythm are related to the development of paroxysmal atrial fibrillation (PAF).1–3 Such electrophysiologic phenomena at the atrial site could be studied noninvasively using the recently introduced technique of signal-averaged electrocardiography (SAECG) applied to analysis of the P wave.4,5 With this method, the presence of atrial conduction delay and “atrial late potentials” was shown to be associated with an increased risk of PAF.4,5 P-wave triggered SAECG may potentially be a tool of value in assessing the effects of antiarrhythmic therapy on atrial electrophysiology, and the clinical efficacy of antiarrhythmic drugs in patients with PAF.6,7 Amiodarone, a class III antiarrhythmic agent, because of its electrophysiologic properties, characterized by prolongation of atrial repolarization and an increase of the refractory period, has been shown to be effective in maintaining sinus rhythm and preventing arrhythmia episodes in patients with PAF.8,9 The aim of the present study was to investigate whether amiodarone therapy could influence P-wave triggered SAECG and the clinical significance of any changes seen in P-wave triggered signal-averaged electrocardiographic (ECG) parameters in patients with PAF and coronary artery disease. • • • Consecutive patients with angiographically documented, stable coronary artery disease referred to our institution for the further management of PAF were considered as candidates for the study. In all patients antiarrhythmic therapy (including b blockers) was discontinued for .1 week. Two-dimensional echocardiography (Acuson 128 XP/10, Mountain View, California) and 24-hour ECG ambulatory monitoring (Excel II, Oxford Medilog Instruments, Abingdon, United Kingdom) were performed. The exclusion criteria included previous therapy with amiodarone, concomitant antiarrhythmic therapy (including b blockers), history of myocardial infarction, symptoms of heart failure, echocardiographic left ventricular ejection fraction ,45%, severe liver, renal, or pulmonary disease, thyroid dysfunction, atrioventricular conduction disturbances, preexcitation, and electrolytes abnormalities. The study group consisted of 30 patients (15 men, mean age 59 6 7 years) with a history of frequent, documented symptomatic PAF (palpitations, chest pain, dyspnea, dizziness) and presenting with at least 1 episode of PAF during baseline ambulatory ECG monitoring (median amount of PAF episodes, 2; range 1 to 7). All patients included in the study had a long history of PAF (mean 56 4 years [range 1 to 18]), and their echocardiographic results were within normal limits. Patients received amiodarone treatment with a starting dose of 200 mg three times daily for the first 10 days, followed by a dose of 200 mg once daily for the next 6 weeks. Patients were asked to record symptoms during treatment and were regularly followed at the outpatient department every 3 weeks. At the end of the study 24-hour ECG monitoring was repeated in all patients. The study protocol was approved by the local ethics committee, and informed written consent was obtained before entering the study. P-wave triggered SAECG was performed twice in all patients: at baseline (before amiodarone therapy) and subsequently after completing the study. All recordings were done in an electrically shielded room with a commercially available machine (HIPEC 200HA, Aerotel, Holon, Israel). The signal obtained was amplified within the range of 0.05 to 360 Hz and was band-pass filtered using a nonrecursive, bidirectional filter 40 to 300 Hz with coefficient (n 5 6) and noise level ,1 mV. It has been previously accepted as a reliable method for the P-wave recording, allowing avoidance of ringing and phase distortion problems.4,10 Fukunami et al4 found the 40-Hz high-pass filter to be useful in classifying patients with PAF. Usually, 150 beats (range 100 to 250) were averaged, but when the noise level exceeded 1 mV, the averaging was continued until the noise level was reduced to ,1 mV. Analysis of P-wave triggered SAECG was therefore performed using a software program stored in HIPEC-200HA. Briefly, the computer program used the PQRS segment as the trigger for the signalaveraging process. The averaging window was altered and a sinus P-wave template was selected by the operator in 3 leads. The duration of the filtered P wave was defined as the time from the beginning of the From the Department of Cardiology, Clinical Military Hospital, Wroclaw, Poland; and Cardiac Department, National Heart & Lung Institute, London, United Kingdom. Dr. Ponikowski’s address is: Cardiac Department, National Heart & Lung Institute, Dovehouse Street, London SW3 6LY, England, United Kingdom. Manuscript received March 27, 1998; revised manuscript received and accepted July 28, 1998.