Clin. Cardiol. 13, 209-212 (1990)
En@Gtrophysionogy9 P8GirmgJ9amdl Arrhflhmia 771s section edired by A. John Camm, M.D . , F. R. C.P . , F. A. C.C.
Clinical Approach to Paroxysmal Atrial Fibrillation P.
COUMEL. M.D.,
HBpital Lariboisikre, Pans, France
Summary: In addition to the role of the electrophysiological substrate, paroxysmal atrial fibrillation depends on the modulation of the atrial tissues by the autonomic nervous system. Experimentally, models of atrial fibrillation can be based on either adrenergic or vagal stimulations that provoke the arrhythmia by disturbing in a different way conduction and refractory periods of the atrium. Clinically, the role of the autonomic nervous system can be suspected from the clinical history, and paroxysmal attacks can typically be observed either at daytime or at night, at exercise or at rest. Careful attention should be paid to the changes of heart rate that occur in the minutes or tens of minutes prior to the attacks, and the trend of acceleration or slowing of cardiac frequency observed in Holter tracings provides reliable indications of the state of the vago-sympathetic balance in these patients. During the attacks, the electrocardiographic aspect of atrial flutter alternating with a pattern of atrial fibrillation is typical of vagally dependent arrhythmias, whereas atrial tachycardia is more frequently observed at the onset of adrenergic atrial fibrillation. When the paroxysmal forms of arrhythmia are resistant to usual pure antiarrhythmic therapy including type IA agents and flecainide or encainide, one should take into account the role of the autonomic nervous system. Propafenone, or beta-blockers combined with type I drugs, are very effective every time an adrenergic factor is involved, but prevent the benefi-
Address for reprints: Philippe Coumel, M.D. Hdpital Lariboisitre 2, rue Arnbroise-Par6 F-75010 Pans, France Received: July 1, 1989 Accepted: July 27. 1989
cia1 role of other agents if a vagal mechanism is predominant. Amiodarone, a complex drug with multiple facets, can be active in many different situations but its use should be reserved to definitely resistant cases, in combination with other agents, in order to limit its potential long-term side effects. Digitalis and verapamil mainly address the tolerance to arrhythmias, rather than their prevention.
Key words: atrial flutter, atrial fibrillation, autonomic nervous system, antiarrhythmic therapy, electrophysiology
Introduction A substantial amount of literature has been published on atrial fibrillation (AF) since its first delineation as “pulsus imgularis perpetuus” by Hering in 1908.This arrhythmia is present in about 0.4%of the general population, 2-5% of the hospital population, and up to 25-40% of elderly people or patients with cardiac heart failure. The management of patients with attacks of paroxysmal AF is a frequent clinical problem. Curiously, it was classically considered as an incident or an accident in the setting of a known disease that formed the main clinical problem. The situation has progressively changed with the diminution of the rheumatic valvular disease, and the less than clear relationships between AF and its usually attributable causes such as hypertension or coronary disease. In practice, very often the paroxysmal AF constitutes the main clinical problem. Even though reference to “primary electrophysiological disease” is probably not adequate, at least this description has the advantage of implicating the absence of any causal disease. Experimentally, atrial vulnerability depends on several factors such as intraatrial conduction, the stimulation threshold, the duration of the refractory period, and its rate-related variations. These variables are probably not independent. The local application of aconitine, like electrical stimulation, permits mimicking of the presence of
210
Clin. Cardiol. Vol. 13, March 1990
a rapidly firing ectopic focus, and when the rate reaches 400-600/min, the atrial activation becomes disorganized. It is important to note that the fibrillating process is permanently reinduced as long as either the stimulation- or the aconitine-induced focus is present. The same situation applies to humans in the case of artificial stimulation, rapidly firing pathological ectopic focus, re-entrant atrial flutter, or even junctional re-entry. Increased sympathetic activity by itself does not trigger the fibrillating process, but it does promote it in diseased tissues by enhancing the activity of potential ectopic foci. Vagal stimulation, on the other hand, is a very classic model of experimental AF. Vagosympathetic interactions are always very complex, and at the atrial level, if both limbs of the autonomic nervous system do have the same effect of shortening the action potential, they do not modify the intra-atrial conduction in the same way. More than this gross effect, its inhomogeneity is the major factor, and it may come either from the nonuniformity of the neural distribution or from the nonuniform state of the diseased atrial cells. In this article we focus on particular forms of idiopathic paroxysmal AF. By definition, if the fibrillatory process ends spontaneously after some seconds, minutes, hours, or days, this means that the conditions for its continuation are absent. In fact, by studying systematically patients who have frequent paroxysmal attacks of AF without any apparent cause, we found that disorders of autonomic nervous balance seem to play a major role, with two opposite mechanisms related to either an increased vagal or a sympathetic drive. I
Clinical Considerations Atrial Flutter and Fibrillation of Vagal Origin Since our former studies,*our experience confirmed our initial observations. The predominance of men over women is constant, with a ratio of about 4: 1. The age when the first symptom appears is between 40 and 50 years, with extremes ranging from 25 to 60. These patients have no detectable heart disease, and they usually consult for resistance to treatment after some years, with a history ranging from 2 to 10 years and up to 15-20 years: a remarkable pattern of the syndrome is the lack of tendency toward permanent AF. The number of attacks is variable from patient to patient, depending in part on the duration of the syndrome, but it may take from 2 to 15 years for episodic attacks to develop into daily attacks. The most common feature is that of weekly episodes, lasting from a few minutes to several hours, often experienced overnight, ending in the morning. The occurrence of the attacks at night, at rest, or in the digestive periods (particularly after dinner) rather than during the day or while engaged in physical activity is common. Exercise or emotional stress do not trigger the arrhythmia. On the con-
trary, on feeling the sensation of an incoming arrhythmia (frequent atrial premature beats), many patients observed that they could prevent it by exercising. But the resting period that follows an effort, or relaxation following emotional stress, frequently coincides with the onset of symptoms. The ECG pattern of the attacks has some important characteristics. The arrhythmia itself typically consists of a mixed picture of alternating flutter and fibrillation. If the conversion of a typical atrial flutter into AF is a somewhat common feature, it is peculiar to these patients to have the reverse phenomenon; that is, an AF converting into typical flutter. When we had the opportunity to record endocavitary tracings during these changes in surface leads, they corresponded in fact to slight variations of a rapid and regular atrial activity. The phenomena that precede the arrhythmia on a short- and mean-term basis serve to characterize the syndrome. The arrhythmia typically occurs at night, precipitated by the progressive sinus bradycardia that normally accompanies sleeping, and reflects the predominance of the vagal drive. It is usually possible to define a threshold value (55-60/min) of this relative bradycardia in a given patient, and the onset of AF is often immediately preceded by a further lengthening of the sinus cycle. Probably even more important than the rate itself, the heart rate variability should be considered: our experience in this field is more recent, but very confirmative of the vagal mechanism by displaying, just before the arrhythmia onset, a dramatic increase of respiratory-related cycle length variations. This short-term, high-frequency heart rate variability is vagally mediated. Frequently, atrial trigeminy or bigeminy with a fixed and relatively long coupling interval is observed. After some hours of alternating flutter and fibrillation, the anhythmias often terminates in the early morning hours. Vagal maneuvers or injection of vagotonic drugs may confirm the mechanism during the electrophysiological procedures. At the very beginning of the attack, that is, at the maximum of the vagal stimulation, the local response of the atrium is extremely rapid, usually 450500/min, which reflects the dramatic but very transient shortening of the atrial refractory period. Pacing the atrium at a relatively rapid rate (90/min) can prevent the arrhythmia. We never found any alteration of the sinus function in these patients, even after years of evolution of the disease, and this syndrome of vagal atrial arrhythmia should be clearly distinguished from the bradycardiatachycardia or the sick sinus syndrome. Adrenergic Atrial Arrhythmias Though less frequently, patients suffering from paroxysmal attacks of AF have a different history. Different trends on Holter recordings suggest that the AF depends on the sympathetic tone rather than on the vagal drive. In most cases the arrhythmia was idiopathic. Not surprisingly, we detected in some patients a hyperthyroidism.
P. Coumel: Clinical approach to paroxysmal atrial fibrillation
If the cause and effect relationship with an underlying disease is always difficult to establish, it is clear that, in contrast with the preceding syndrome, finding a myocardial disease in these patients is not unusual. The palpitations occur exclusively in the daytime, particularly in the morning, at exercise, or during periods of emotional stress. They are frequently accompanied by a polyuria, and they completely disappear at night. The ECG pattern may be a pure AF, but frequently, at least in the early stages of the episodes, it consists of runs of atrial tachycardia alternating with sinus rhythm, with no aspect of common atrial flutter. Typically, the anhythmia onset coincides with a definite value of the sinus frequency which is progressively attained and well-evidenced by the heart rate trend analysis of the Holter recording. The opposition is striking between the increasing sinus frequency up to a value of about 90/min in these patients on the one hand, and the decreasing sinus rate “down” to 5560/min of the vagal arrhythmias on the other hand. Usually, the arrhythmia can be reproduced during the electrophysiological procedure by administering betaadrenergic agonists and, not surprisingly, the reaction to antianhythmic therapy serves to oppose these two forms of paroxysmal AF. Therapeutic Considerations Type I Antiarrhythmic Drugs
Quinidine constitutes the classical preventive treatment of paroxysmal AF, quite logically as its main electrophysiological effect is to prolong the action potential of the atrial cells. The vagolytic action certainly also plays a role when the mechanism of initiation is an increased vagal drive, but this accessory property is more marked in disopyramide and explains why this drug may be more efficacious in some patients. Among the recently developed type I antianhythmic drugs, two should be mentioned for their singular efficacy, as well as for their indications in the different forms of paroxysmal AF we have just described. Flecainide is a very powerful type I agent, and our initial experience3with resistant AF is now largely confirmed. Our limited experience with encainide is also very promising in this indication. We also used propafenone in paroxysmal AF,4 and the effect of this drug, which does not prolong the cellular action potential and has a beta-inhibitory effect, was strongly correlated with the mechanism of the arrhythmias: the vagally dependent AFs did not respond to or were aggravated by propafenone, while the adrenergic forms were very much improved or completely cured. Beta Blockers
As a preventive treatment, beta-blocker therapy has either a favorable or a deleterious effect according to the
21 1
facet of the autonomic nervous system which is implicated in the triggering of the arrhythmia. Not only does it increase the number of the attacks in the vagally induced AF, but it tends to prolong the episodes, inducing them to occur at any time within the 24-h period rather than being confined to the evening hours, or to the resting or digestive periods. On the contrary, beta blockers are indeed indicated in the adrenergic forms, if used in large dosages of powerful drugs, preferably without any betaadrenergic intrinsic activity. In this regard, our experience of nadolo15 is particularly favorable, with the limitation of a curious escape phenomenon. In patients with severe forms of adrenergic tachyanhythmia, a dramatic improvement was first obtained, but after 2 weeks to 2 months the attacks recurred in about two thirds of the cases. At that time, the combination of nadolol with the previously uneffective type I drug was the only way to control the arrhythmia. Digitalis
By its vagotonic action, digitalis favors the attacks of vagal AF. In patients who are prone to this arrhythmia, its combination with amiodarone counteracts the favorable effect of the latter. On the other hand, the vagotonic effect of digoxin may be helpful in the presence of adrenergic factors, particularly in diseased hearts. Its combination with quinidine is classically considered as dangerous: in fact, moderate dosing is indeed favorable in many cases. Verapamil
Though theoretically logical and promising, it must be recognized that verapamil is practically useless in the preventive treatment of AF. In clinical practice its effect is rather comparable to that of digitalis: it may convert typical flutter into AF, but vagal arrhythmias are usually aggravated. The improvement of some patients is in fact related to the depressive effect on the ventricular response to AF. In fact, we sometimes use it combined with digitalis to try to perpetuate AF in cases of intractable paroxysmal AF. Amiodarone
This drug is outstandingly effective regardless of the AF mechanism. This is explained by the marked lengthening of the atrial action potential, the shortening of which is a common denominator of the various forms. In addition, its beta-adrenergic inhibitory effect is helpful whenever an adrenergic factor is involved. However, this effect is somewhat deleterious in vagal arrhythmias and explains why about 50% of the cases may be resistant. In order to reduce the dosage as much as possible, we almost always use it in combination with a type I agent.
212
Clin. Cardiol. Vol. 13, March 1990
Electrical Therapy
The electrical countershock can re-establish, for a short while, a homogeneous state of the atrial cells. This does not modify in any way the problem of prophylactic treatment, which is purely drug dependent and starts immediately after the shock has been delivered. In fact, in the setting of paroxysmal AF, this technique is rarely indicated. Another method of electrical therapy has some indications in definitely resistant vagal atrial arrhythmias: implanting an atrial pacemaker at a rate of 90/min may prevent the relative bradycardia which is a determinant of the arrhythmia onset. It should be stressed that this indication differs from the pacemaker implantation in the setting of a sick sinus syndrome where the bradycardia is the therapeutic target.
References I . Coumel Ph: Atrial fibrillation. In Tachycurdius (Surawicz B, Reddy CP, Prystowsky EN, Eds). Martinus Nijhoff, Boston (1984) 231-244
2. Cournel Ph, Attuel P, Lavallee JP, Flammang D. Leclercq JF, Slarna R: Syndrome d'arythmie auriculaire d'origine vagale. Arch Ma/ Coeur 71, 645 (1978) 3. Leclercq JF, Coumel Ph: La flecainide: Un nouvel antiarythmique. Arch Ma1 Coeur 76, 1218 (1983) 4 . Coumel Ph, Leclercq JF, Assayag P: European experience with the antiarrhythrnic efficacy of propafenone for supraventricular and ventricular arrhythmias. Am J Curdiol54. 60D (1984) 5 . Cournel Ph, Leclercq JF, Escoubet B: Beta-blocking therapy in atrial and ventricular tachyarrhythmias. Experience with nadolol. Am Heart J 108, 1098 (1984)
En@Gtrophysionogy9 P8GirmgJ9amdl Arrhflhmia 771s section edired by A. John Camm, M.D . , F. R. C.P . , F. A. C.C.
Clinical Approach to Paroxysmal Atrial Fibrillation P.
COUMEL. M.D.,
HBpital Lariboisikre, Pans, France
Summary: In addition to the role of the electrophysiological substrate, paroxysmal atrial fibrillation depends on the modulation of the atrial tissues by the autonomic nervous system. Experimentally, models of atrial fibrillation can be based on either adrenergic or vagal stimulations that provoke the arrhythmia by disturbing in a different way conduction and refractory periods of the atrium. Clinically, the role of the autonomic nervous system can be suspected from the clinical history, and paroxysmal attacks can typically be observed either at daytime or at night, at exercise or at rest. Careful attention should be paid to the changes of heart rate that occur in the minutes or tens of minutes prior to the attacks, and the trend of acceleration or slowing of cardiac frequency observed in Holter tracings provides reliable indications of the state of the vago-sympathetic balance in these patients. During the attacks, the electrocardiographic aspect of atrial flutter alternating with a pattern of atrial fibrillation is typical of vagally dependent arrhythmias, whereas atrial tachycardia is more frequently observed at the onset of adrenergic atrial fibrillation. When the paroxysmal forms of arrhythmia are resistant to usual pure antiarrhythmic therapy including type IA agents and flecainide or encainide, one should take into account the role of the autonomic nervous system. Propafenone, or beta-blockers combined with type I drugs, are very effective every time an adrenergic factor is involved, but prevent the benefi-
Address for reprints: Philippe Coumel, M.D. Hdpital Lariboisitre 2, rue Arnbroise-Par6 F-75010 Pans, France Received: July 1, 1989 Accepted: July 27. 1989
cia1 role of other agents if a vagal mechanism is predominant. Amiodarone, a complex drug with multiple facets, can be active in many different situations but its use should be reserved to definitely resistant cases, in combination with other agents, in order to limit its potential long-term side effects. Digitalis and verapamil mainly address the tolerance to arrhythmias, rather than their prevention.
Key words: atrial flutter, atrial fibrillation, autonomic nervous system, antiarrhythmic therapy, electrophysiology
Introduction A substantial amount of literature has been published on atrial fibrillation (AF) since its first delineation as “pulsus imgularis perpetuus” by Hering in 1908.This arrhythmia is present in about 0.4%of the general population, 2-5% of the hospital population, and up to 25-40% of elderly people or patients with cardiac heart failure. The management of patients with attacks of paroxysmal AF is a frequent clinical problem. Curiously, it was classically considered as an incident or an accident in the setting of a known disease that formed the main clinical problem. The situation has progressively changed with the diminution of the rheumatic valvular disease, and the less than clear relationships between AF and its usually attributable causes such as hypertension or coronary disease. In practice, very often the paroxysmal AF constitutes the main clinical problem. Even though reference to “primary electrophysiological disease” is probably not adequate, at least this description has the advantage of implicating the absence of any causal disease. Experimentally, atrial vulnerability depends on several factors such as intraatrial conduction, the stimulation threshold, the duration of the refractory period, and its rate-related variations. These variables are probably not independent. The local application of aconitine, like electrical stimulation, permits mimicking of the presence of
210
Clin. Cardiol. Vol. 13, March 1990
a rapidly firing ectopic focus, and when the rate reaches 400-600/min, the atrial activation becomes disorganized. It is important to note that the fibrillating process is permanently reinduced as long as either the stimulation- or the aconitine-induced focus is present. The same situation applies to humans in the case of artificial stimulation, rapidly firing pathological ectopic focus, re-entrant atrial flutter, or even junctional re-entry. Increased sympathetic activity by itself does not trigger the fibrillating process, but it does promote it in diseased tissues by enhancing the activity of potential ectopic foci. Vagal stimulation, on the other hand, is a very classic model of experimental AF. Vagosympathetic interactions are always very complex, and at the atrial level, if both limbs of the autonomic nervous system do have the same effect of shortening the action potential, they do not modify the intra-atrial conduction in the same way. More than this gross effect, its inhomogeneity is the major factor, and it may come either from the nonuniformity of the neural distribution or from the nonuniform state of the diseased atrial cells. In this article we focus on particular forms of idiopathic paroxysmal AF. By definition, if the fibrillatory process ends spontaneously after some seconds, minutes, hours, or days, this means that the conditions for its continuation are absent. In fact, by studying systematically patients who have frequent paroxysmal attacks of AF without any apparent cause, we found that disorders of autonomic nervous balance seem to play a major role, with two opposite mechanisms related to either an increased vagal or a sympathetic drive. I
Clinical Considerations Atrial Flutter and Fibrillation of Vagal Origin Since our former studies,*our experience confirmed our initial observations. The predominance of men over women is constant, with a ratio of about 4: 1. The age when the first symptom appears is between 40 and 50 years, with extremes ranging from 25 to 60. These patients have no detectable heart disease, and they usually consult for resistance to treatment after some years, with a history ranging from 2 to 10 years and up to 15-20 years: a remarkable pattern of the syndrome is the lack of tendency toward permanent AF. The number of attacks is variable from patient to patient, depending in part on the duration of the syndrome, but it may take from 2 to 15 years for episodic attacks to develop into daily attacks. The most common feature is that of weekly episodes, lasting from a few minutes to several hours, often experienced overnight, ending in the morning. The occurrence of the attacks at night, at rest, or in the digestive periods (particularly after dinner) rather than during the day or while engaged in physical activity is common. Exercise or emotional stress do not trigger the arrhythmia. On the con-
trary, on feeling the sensation of an incoming arrhythmia (frequent atrial premature beats), many patients observed that they could prevent it by exercising. But the resting period that follows an effort, or relaxation following emotional stress, frequently coincides with the onset of symptoms. The ECG pattern of the attacks has some important characteristics. The arrhythmia itself typically consists of a mixed picture of alternating flutter and fibrillation. If the conversion of a typical atrial flutter into AF is a somewhat common feature, it is peculiar to these patients to have the reverse phenomenon; that is, an AF converting into typical flutter. When we had the opportunity to record endocavitary tracings during these changes in surface leads, they corresponded in fact to slight variations of a rapid and regular atrial activity. The phenomena that precede the arrhythmia on a short- and mean-term basis serve to characterize the syndrome. The arrhythmia typically occurs at night, precipitated by the progressive sinus bradycardia that normally accompanies sleeping, and reflects the predominance of the vagal drive. It is usually possible to define a threshold value (55-60/min) of this relative bradycardia in a given patient, and the onset of AF is often immediately preceded by a further lengthening of the sinus cycle. Probably even more important than the rate itself, the heart rate variability should be considered: our experience in this field is more recent, but very confirmative of the vagal mechanism by displaying, just before the arrhythmia onset, a dramatic increase of respiratory-related cycle length variations. This short-term, high-frequency heart rate variability is vagally mediated. Frequently, atrial trigeminy or bigeminy with a fixed and relatively long coupling interval is observed. After some hours of alternating flutter and fibrillation, the anhythmias often terminates in the early morning hours. Vagal maneuvers or injection of vagotonic drugs may confirm the mechanism during the electrophysiological procedures. At the very beginning of the attack, that is, at the maximum of the vagal stimulation, the local response of the atrium is extremely rapid, usually 450500/min, which reflects the dramatic but very transient shortening of the atrial refractory period. Pacing the atrium at a relatively rapid rate (90/min) can prevent the arrhythmia. We never found any alteration of the sinus function in these patients, even after years of evolution of the disease, and this syndrome of vagal atrial arrhythmia should be clearly distinguished from the bradycardiatachycardia or the sick sinus syndrome. Adrenergic Atrial Arrhythmias Though less frequently, patients suffering from paroxysmal attacks of AF have a different history. Different trends on Holter recordings suggest that the AF depends on the sympathetic tone rather than on the vagal drive. In most cases the arrhythmia was idiopathic. Not surprisingly, we detected in some patients a hyperthyroidism.
P. Coumel: Clinical approach to paroxysmal atrial fibrillation
If the cause and effect relationship with an underlying disease is always difficult to establish, it is clear that, in contrast with the preceding syndrome, finding a myocardial disease in these patients is not unusual. The palpitations occur exclusively in the daytime, particularly in the morning, at exercise, or during periods of emotional stress. They are frequently accompanied by a polyuria, and they completely disappear at night. The ECG pattern may be a pure AF, but frequently, at least in the early stages of the episodes, it consists of runs of atrial tachycardia alternating with sinus rhythm, with no aspect of common atrial flutter. Typically, the anhythmia onset coincides with a definite value of the sinus frequency which is progressively attained and well-evidenced by the heart rate trend analysis of the Holter recording. The opposition is striking between the increasing sinus frequency up to a value of about 90/min in these patients on the one hand, and the decreasing sinus rate “down” to 5560/min of the vagal arrhythmias on the other hand. Usually, the arrhythmia can be reproduced during the electrophysiological procedure by administering betaadrenergic agonists and, not surprisingly, the reaction to antianhythmic therapy serves to oppose these two forms of paroxysmal AF. Therapeutic Considerations Type I Antiarrhythmic Drugs
Quinidine constitutes the classical preventive treatment of paroxysmal AF, quite logically as its main electrophysiological effect is to prolong the action potential of the atrial cells. The vagolytic action certainly also plays a role when the mechanism of initiation is an increased vagal drive, but this accessory property is more marked in disopyramide and explains why this drug may be more efficacious in some patients. Among the recently developed type I antianhythmic drugs, two should be mentioned for their singular efficacy, as well as for their indications in the different forms of paroxysmal AF we have just described. Flecainide is a very powerful type I agent, and our initial experience3with resistant AF is now largely confirmed. Our limited experience with encainide is also very promising in this indication. We also used propafenone in paroxysmal AF,4 and the effect of this drug, which does not prolong the cellular action potential and has a beta-inhibitory effect, was strongly correlated with the mechanism of the arrhythmias: the vagally dependent AFs did not respond to or were aggravated by propafenone, while the adrenergic forms were very much improved or completely cured. Beta Blockers
As a preventive treatment, beta-blocker therapy has either a favorable or a deleterious effect according to the
21 1
facet of the autonomic nervous system which is implicated in the triggering of the arrhythmia. Not only does it increase the number of the attacks in the vagally induced AF, but it tends to prolong the episodes, inducing them to occur at any time within the 24-h period rather than being confined to the evening hours, or to the resting or digestive periods. On the contrary, beta blockers are indeed indicated in the adrenergic forms, if used in large dosages of powerful drugs, preferably without any betaadrenergic intrinsic activity. In this regard, our experience of nadolo15 is particularly favorable, with the limitation of a curious escape phenomenon. In patients with severe forms of adrenergic tachyanhythmia, a dramatic improvement was first obtained, but after 2 weeks to 2 months the attacks recurred in about two thirds of the cases. At that time, the combination of nadolol with the previously uneffective type I drug was the only way to control the arrhythmia. Digitalis
By its vagotonic action, digitalis favors the attacks of vagal AF. In patients who are prone to this arrhythmia, its combination with amiodarone counteracts the favorable effect of the latter. On the other hand, the vagotonic effect of digoxin may be helpful in the presence of adrenergic factors, particularly in diseased hearts. Its combination with quinidine is classically considered as dangerous: in fact, moderate dosing is indeed favorable in many cases. Verapamil
Though theoretically logical and promising, it must be recognized that verapamil is practically useless in the preventive treatment of AF. In clinical practice its effect is rather comparable to that of digitalis: it may convert typical flutter into AF, but vagal arrhythmias are usually aggravated. The improvement of some patients is in fact related to the depressive effect on the ventricular response to AF. In fact, we sometimes use it combined with digitalis to try to perpetuate AF in cases of intractable paroxysmal AF. Amiodarone
This drug is outstandingly effective regardless of the AF mechanism. This is explained by the marked lengthening of the atrial action potential, the shortening of which is a common denominator of the various forms. In addition, its beta-adrenergic inhibitory effect is helpful whenever an adrenergic factor is involved. However, this effect is somewhat deleterious in vagal arrhythmias and explains why about 50% of the cases may be resistant. In order to reduce the dosage as much as possible, we almost always use it in combination with a type I agent.
212
Clin. Cardiol. Vol. 13, March 1990
Electrical Therapy
The electrical countershock can re-establish, for a short while, a homogeneous state of the atrial cells. This does not modify in any way the problem of prophylactic treatment, which is purely drug dependent and starts immediately after the shock has been delivered. In fact, in the setting of paroxysmal AF, this technique is rarely indicated. Another method of electrical therapy has some indications in definitely resistant vagal atrial arrhythmias: implanting an atrial pacemaker at a rate of 90/min may prevent the relative bradycardia which is a determinant of the arrhythmia onset. It should be stressed that this indication differs from the pacemaker implantation in the setting of a sick sinus syndrome where the bradycardia is the therapeutic target.
References I . Coumel Ph: Atrial fibrillation. In Tachycurdius (Surawicz B, Reddy CP, Prystowsky EN, Eds). Martinus Nijhoff, Boston (1984) 231-244
2. Cournel Ph, Attuel P, Lavallee JP, Flammang D. Leclercq JF, Slarna R: Syndrome d'arythmie auriculaire d'origine vagale. Arch Ma/ Coeur 71, 645 (1978) 3. Leclercq JF, Coumel Ph: La flecainide: Un nouvel antiarythmique. Arch Ma1 Coeur 76, 1218 (1983) 4 . Coumel Ph, Leclercq JF, Assayag P: European experience with the antiarrhythrnic efficacy of propafenone for supraventricular and ventricular arrhythmias. Am J Curdiol54. 60D (1984) 5 . Cournel Ph, Leclercq JF, Escoubet B: Beta-blocking therapy in atrial and ventricular tachyarrhythmias. Experience with nadolol. Am Heart J 108, 1098 (1984)
