Author + information
- Received March 19, 1999
- Revision received April 13, 2000
- Accepted June 16, 2000
- Published online November 1, 2000.
- Pablo A Chiale, MDa,* (, )
- D.Alejandro Franco, MDa,
- Horacio O Selva, MDa,
- Claudio A Militello, MDa and
- Marcelo V Elizari, MD, FACCa
- ↵*Reprint requests and correspondence: Dr. Pablo A. Chiale, Division of Cardiology, Ramos Mejı́a Hospital, Urquiza 609, Buenos Aires 1221, Argentina
The goal of this study was to report a variety of atrial tachycardia that might be caused by an unusual electrophysiologic substrate.
The mechanism of atrial tachycardias is attributed to re-entry, abnormal automaticity or triggered activity, based on their electropharmacological responses. A rate-related and lidocaine-sensitive atrial tachycardia has not been reported.
Eight patients (3 women and 5 men, aged 14 to 60 years) with repetitive, uniform atrial tachycardias were studied. In six patients the arrhythmia had been refractory to at least three antiarrhythmic agents (class 1A and C sodium channel blockers, amiodarone, beta-adrenergic blocking agents, verapamil, digoxin). Conventional electrocardiograms, Holter recordings and B mode echocardiograms were performed in each patient. Intravenous lidocaine and verapamil were tested in the eight patients. Six patients underwent an electrophysiologic study.
The baseline electrocardiogram showed nearly incessant runs of atrial tachycardia in all patients. The mean atrial ectopic cycle length ranged from 376 to 502 ms. In seven patients a progressive prolongation of the cycle length from the beginning to the end of the salvos was documented. The arrhythmia was suppressed by increments of sinus node rate and by atrial pacing at cycle lengths longer than that of the atrial tachycardia. In all patients the arrhythmia was abolished by intravenous lidocaine, whereas intravenous verapamil was ineffective. Four symptomatic patients were successfully treated with radiofrequency ablation of the ectopic focus, and two patients were treated with oral mexiletine.
The peculiar electropharmacological responses of this arrhythmia suggest an uncommon underlying mechanism that remains to be elucidated.
Lidocaine, a class 1B antiarrhythmic agent known to block the inactivated sodium channels (1) and to shorten repolarization and refractoriness in the His-Purkinje and the working ventricular fibers (2), has been used as a first line therapy for ventricular arrhythmias occurring in the setting of the acute myocardial infarction (3,4). This drug has no significant electrophysiologic effects on atrial, sinus node and atrioventricular (AV) nodal tissues (5), and there is general agreement about its inefficacy for the treatment of atrial arrhythmias (6,7). However, Cotoi and Luca (8) reported that lidocaine may terminate diverse atrial tachyarrhythmias and, recently, Markowitz and coworkers (9) described a patient with a repetitive atrial tachycardia that was responsive to lidocaine.
In this communication, a peculiar form of chronic, repetitive, uniform atrial tachycardia will be described. The arrhythmia was refractory to the most commonly used antiarrhythmic agents, but extremely sensitive to lidocaine, and was suppressed by modest increments in heart rate. These unique characteristics might indicate an unusual arrhythmogenic mechanism operating in human atrial tissue.
Eight patients (three women and five men; mean age: 30.1 years; range: 14 to 60 years) referred within the last 5 years for repetitive, self-limited, uniform atrial tachycardias (Table 1), were selected for this report due to their similar and particular electrocardiographic and electropharmacological behavior. Six of them complained about palpitations, and two were asymptomatic. The arrhythmia was diagnosed 6 months to 3 years before referral, and six patients had been unsuccessfully treated with standard doses of at least three antiarrhythmic agents—class 1A and C drugs, beta-blockers, amiodarone, verapamil and digoxin—alone and in various combinations. The following studies were performed in every patient: conventional electrocardiogram (ECG), 24-h ECG Holter recordings and B-mode echocardiograms. Six patients underwent an electrophysiologic study. The effects of lidocaine and verapamil were acutely tested in the eight patients: in six of them at the end of the electrophysiologic study and in the remaining two patients during one of the electrocardiographic controls. All the procedures were performed after discontinuance of any antiarrhythmic agent for at least five half-lives. Patients were informed about the characteristics of the evaluation procedures and signed a written consent.
Simultaneous 12-lead ECG recordings were obtained at rest as well as during maneuvers performed to modify the heart rate (slight exercising, Valsalva maneuver, carotid sinus massage). The presence and duration of the bursts of atrial tachycardia were evaluated taking into account the duration of either the sinus node cycle length or the sinus node pauses after single or repetitive atrial premature impulses, depending on the case.
24 h ECG Holter recordings
Recordings were obtained with simultaneous 3-channel ECG tape recorders (Del Mar Avionics model 423, Delmar Avionics, Irvine, California) and analyzed in a Burdick, Inc. Altair V5.08C electroscanner, in an attempt to discover a relationship between the sinus node cycle length and the initiation, duration and disappearance of the arrhythmia.
The electrophysiologic studies were performed in the fasting, nonsedated state. Three 6F quadripolar electrode catheters were introduced percutaneously through the femoral veins and positioned into the right atrial appendage (for atrial electrogram recording and pacing), across the tricuspid valve (for His bundle electrogram recording) and in the apex of the right ventricle (for ventricular pacing). In four patients who underwent a radiofrequency ablation procedure, a 6F decapolar electrode catheter was introduced through the right internal jugular vein and positioned into the coronary sinus in order to record atrial electrograms from the left AV ring. To assess the rate-dependence of the atrial tachycardia, atrial pacing was performed with a Medtronic 5328 stimulator (Medtronic Inc., Minneapolis, Minnesota) at cycle lengths 100 to 300 ms shorter (depending on the case) than that of sinus node rhythm or the post-tachycardia sinus node pauses, but always longer than the atrial tachycardia cycle length. Once abolition of the arrhythmia was obtained, the paced cycle length was gradually increased in 10 ms steps until reappearance of the arrhythmia. This protocol was repeated at least twice to test the reproducibility of the effect of atrial pacing in suppressing the arrhythmia. Programmed atrial pacing with 1, 2 and 3 extrastimuli at progressively decreasing coupling intervals, from late diastole to the atrial refractory period, was performed during the bursts of atrial tachycardia (to test whether or not the arrhythmia could be interrupted by premature atrial impulses). Programmed atrial pacing with 1, 2 and 3 extrastimuli at progressively decreasing coupling intervals was also performed after trains of eight atrial paced beats at the longest possible basic cycle length suppressing atrial ectopic activity (to assess inducibility of the arrhythmia). Tracings were stored and analyzed in a 2.57.23 software Bard Lab system (Bard Electrophysiology, New Jersey).
Intravenous lidocaine and verapamil were administered to the eight patients. A single dose of 0.5 mg/kg in 60 s of lidocaine was used in four patients, and an additional dose of 0.5 mg/kg was injected 3 min after the first one in the other four patients. The ECG was continuously monitored, and recordings were obtained right after the end of the lidocaine injections to document changes in the pattern of the arrhythmia. Once the baseline conditions returned, verapamil was given by intravenous injection at a dose of 10 mg in 60 s. The ECG was continuously monitored to assess drug-related changes in the pattern of the arrhythmia during a 30 min period. Bradycardia-inducing maneuvers were performed at different intervals after administration of both drugs.
The ECG at rest was normal (except for the atrial tachyarrhythmia) in five patients; multiform isolated premature ventricular beats were observed in one patient; a pattern of left ventricle hypertrophy was present in another patient, and an inferior myocardial fibrosis was suspected in the remaining patient. The B mode echocardiogram was normal in five patients and showed mild left ventricle dilation in two young patients and concentric left ventricle hypertrophy and mild left atrial enlargement in the oldest patient who was suffering from arterial hypertension.
In all patients, the baseline ECG showed almost incessant runs of self-limited atrial tachycardia (single or double atrial premature beats were also observed) separated by one to three sinus node beats (Fig. 1A). Duration of the bursts was variable (between three or four beats and several seconds), even in the same patient, and most of them showed 1:1 AV conduction. Rate-related changes in the PR interval (due to P-P interval variations during the runs of atrial tachycardia) and, eventually, a Mobitz I second degree AV block were observed. The mean atrial tachycardia cycle length, measured in at least 10 salvos, was also highly different from case to case (from 376 to 502 ms).
The arrhythmia showed a stereotyped pattern in seven patients, with a progressive prolongation of cycle length from the beginning to the end of the salvos (see below). In addition, shortening of the sinus node cycle length induced by mild exercising suppressed or abbreviated the repetitive atrial discharges (Fig. 1B), while prolongation of the sinus node cycle length, obtained by vagal stimulating maneuvers, tended to prolong the bursts of ectopic atrial activity.
The morphology and polarity of the ectopic P waves suggested that the arrhythmia arose from different regions of the right atrium.
The 24-h ECG Holter recordings confirmed the relationship between the sinus node rate and ectopic atrial activity. In six patients, the runs of atrial tachycardia were present when the sinus node rate was slow, or relatively slow, and disappeared (or were abbreviated) at higher heart rates. However, in two patients the arrhythmia was not only suppressed by mild increments of sinus node rate but also by sinus node slowing during sleep (Fig. 2). This indicates that in these two cases, appropriate changes in the sinus node rate, reflecting the predominance of either the sympathetic or the vagal driving of the heart, had the same suppressing effect on the arrhythmia mechanism. Finally, in no instance was the arrhythmia found to deteriorate into atrial fibrillation or flutter.
At baseline the six patients who underwent an electrophysiologic study showed the same patterns of repetitive atrial activity that was found during the electrocardiographic recordings. Two different patterns of repetitive atrial discharges were identified (Fig. 3). In five patients (as well as in the two patients who did not undergo the electrophysiologic study) the first tachycardia cycle length was relatively long; the second was almost always the shortest, and, after that, the cycle length showed a gradual prolongation until spontaneous termination of the arrhythmia (Fig. 3, A and B). In one patient the cycle length of the atrial tachycardia was erratic, thus, clearly differing from all the other cases (Fig. 3C).
The arrhythmia was not consistently altered by atrial premature impulses elicited by programmed pacing but was suppressed in every patient by asynchronous atrial pacing at cycle lengths longer than those of the atrial tachycardia (Fig. 4, A and B). A critically long atrial paced cycle length could be identified for arrhythmia reappearance (Table 2; Fig. 4B), initially as single or double atrial premature beats and under the form of progressively longer runs of atrial tachycardia as the paced cycle length was prolonged. To be noted is that in no instance could the arrhythmia be induced by atrial premature stimuli, while in the six patients (100%) it reappeared immediately after discontinuance of atrial pacing with a pattern identical to that observed at baseline.
Intravenous lidocaine caused a rapid suppression of the arrhythmia (between 30 to 60 s after the end of injection) in all patients, an effect that persisted for 8 to 25 min. In no case was the suppression of the arrhythmia by lidocaine related to sinus node acceleration. In fact, sinus node rate during the peak effect of the drug was slower than the critical heart rate that consistently caused the arrhythmia disappearance in each patient, and not a single atrial ectopic impulse was observed during sinus node slowing by bradycardia-inducing maneuvers. Figure 5 shows the gradual shortening of the salvos of atrial ectopic discharges and their disappearance after lidocaine administration. In contrast, the arrhythmia was not modified by verapamil in the eight patients, but five of them showed a Mobitz I type AV block during the bursts of atrial tachycardia.
Therapeutic approach and follow-up
Radiofrequency ablation of the arrhythmia was successfully performed in four highly symptomatic patients. The site of origin of the atrial tachycardia was located in the high posterior right atrium in two patients, in the body of the right atrial appendage in one patient and in the low septal right atrium in the remaining patient. The atrial electrograms recorded at the successful sites preceded the onset of the ectopic P waves by 25 to 40 ms. No arrhythmias were documented on repeated 24-h ECG Holter recordings during follow-up periods of 3, 6, 18 and 32 months. In the other two symptomatic patients, the arrhythmia was controlled with mexiletine (360 mg twice a day orally). Repeated 24-h ECG Holter recordings showed no atrial arrhythmias in one of these patients, whereas only isolated premature atrial beats were documented in the other patient.
In the two patients showing a mild left ventricle dilation before the ablation procedure, the B-mode echocardiogram obtained about one month after resolution of the arrhythmia revealed a clear-cut reduction of the left ventricle diastolic diameter (from 57 to 48 mm in one patient and from 56 to 50 mm in the other).
The two asymptomatic patients received no further antiarrhythmic treatments, and their clinical, electrocardiographic and echocardiographic conditions remained stable after a six-month and a two-year follow-up, respectively.
Atrial tachycardias account for 7% to 15% of all supraventricular tachycardias (10–12) and for up to 34% in referral pediatric populations (13). Classically, atrial tachycardias are classified based upon the arrhythmia response to pacing and pharmacologic interventions (14–16) as due to re-entry, abnormal automaticity or delayed afterdepolarizations.
The electrophysiologic mechanism
The atrial tachycardia described in this article did not show the electropharmacologic responses that are expected to occur whenever the mechanisms mentioned above are in operation. As stated, the arrhythmia could neither be induced nor consistently terminated by programmed premature atrial stimulation, which, although not totally exclusive, is a strong argument against a re-entrant mechanism. On the other hand, the occurrence of delayed afterdepolarizations may be reasonably ruled out, taking into account that the arrhythmia was triggered by slowing down the heart rate and was systematically suppressed by atrial pacing at relatively short cycle lengths (but always longer than those of the tachycardia). The lack of response to verapamil also stands against this mechanism.
The bursts of ectopic atrial activity were always dependent on a preceding sinus beat closing long, or relatively long, diastolic intervals. This, and the absence of “overdrive suppression” after interruption of rapid atrial pacing and of the “warming up” phenomenon during the bursts of atrial tachycardia would suggest that an automatic mechanism due to spontaneous diastolic depolarization was not the underlying mechanism. This analysis would imply the presence of a different electrophysiologic mechanism, which remains to be elucidated. It may be speculated that the long cycle length dependence of the arrhythmia and the response to lidocaine might fit with the presence of atrial re-excitation due to local differences of membrane potential or early afterdepolarizations, two mechanisms that have been demonstrated in ventricular tissue (17–19). Wang et al. (20) and Feng et al. (21) identified clear-cut disparities in the atrial action potential morphology caused by the dissimilar magnitudes of the repolarizing currents Ito, Ikr and Ica, which might set the stage for atrial re-excitation (22). The striking sensitivity of the arrhythmia to lidocaine might be the result of a more homogeneous atrial repolarization induced by this drug (2,23). It is worth mentioning that sodium channel blocking agents that prolong (quinidine, amiodarone) (24,25), or do not modify significantly repolarization (flecainide, propafenone) (26,27) thoroughly failed to suppress the arrhythmia. It was this particular finding that led us to test lidocaine, a drug that shortens repolarization.
It can also be speculated that the bursts of atrial tachycardia might well be caused by early afterdepolarizations due to a mechanism similar to that described in the M ventricular cells (18). This possiblility depends on long cycle lengths (19) and is abolished by mexiletine (23).
Markowitz et al. (10) recently reported four patients with repetitive monomorphic atrial tachycardia. Although the electrocardiographic pattern and the responses of the arrhythmia to atrial stimulation and verapamil clearly differed from our cases, in one patient the tachycardia was terminated by lidocaine. In the four patients studied, the atrial tachycardias were suppressed by adenosine and verapamil, and the mechanism of the arrhythmia was attributed to delayed afterdepolarizations.
Etiology and clinical significance
The fact that in our patients the arrhythmogenic focus was located in the right atrium, together with the uniform electropharmacological responses, would suggest a common etiology, either congenital (most likely in younger patients) or acquired. An inherited disorder is improbable because the arrhythmia was not found in any of the relatives of our patients who underwent a systematic clinical and electrocardiographic evaluation.
It should be stressed that the arrhythmia described in this article is rare, representing approximately only 0.5% of the cases of supraventricular tachycardias referred to our electrophysiology laboratory.
Whatever its electrophysiologic mechanism and etiology, the arrhythmia was seen to be clinically well-tolerated for years. Nevertheless, prolonged and frequent episodes of atrial tachycardia may induce a tachycardiomyopathy, as actually occurred in two of our patients.
The precise mechanism of the lidocaine-sensitive, rate-related atrial tachycardia could not yet be defined. Efforts made to convert the self-limited arrhythmia into a sustained and steady rhythm by a beta-adrenergic agonist in order to assess more accurately the effects of premature atrial stimulation were unfruitful. Recordings of atrial monophasic action potentials (not performed in our patients) from the area of the ectopic atrial activity and surrounding tissues could eventually provide valuable information to unveil the electrophysiologic substrate of this singular atrial tachycardia.
We are indebted to Jorge Schmidberg, MD, and Rafael Acunzo, MD, for their help in the preparation of this manuscript and to Mrs. Cecilia McKeon for her secretarial work.
☆ Supported, in part, by the Fundación de Investigaciones Cardiológicas Einthoven, Buenos Aires, Argentina.
- Received March 19, 1999.
- Revision received April 13, 2000.
- Accepted June 16, 2000.
- American College of Cardiology
- Bigger J.T.,
- Mandel W.J.
- Dhingra R.C.,
- Deedwania P.C.,
- Cumnings J.M.,
- et al.
- Campbell T.J.
- Wellens H.J.J.
- Chen S.-A.,
- Chiang C.E.,
- Yang C.J.,
- et al.
- Engelstein E.D.,
- Lippman N.,
- Stein K.M.,
- et al.
- Kuo C.-S.,
- Pratap Reddy C.,
- Munakata K.,
- et al.
- Antzelevitch C.,
- Sicouri S.
- Sicouri S.,
- Moro S.,
- Elizari M.V.
- Wang Z.,
- Fermini B.,
- et al.
- Feng J.,
- Yue L.,
- Wang Z.,
- Nattel S.
- Spach M.S.,
- Dolber P.C.,
- Anderson P.A.W.
- Morikawa Y.,
- Rosen M.R.
- Ikeda N.,
- Singh B.N.,
- Davis L.D.,
- et al.