by Morton F Arnsdorf, MD
GENERAL PRINCIPLES – DC shock and antiarrhythmic drugs are usually effective in converting atrial fibrillation (AF) to a sinus mechanism, thereby improving symptoms, lessening the liability for the development of a tachycardia-induced cardiomyopathy involving the ventricles and atria, and minimizing the long-term risk of peripheral and cerebral emboli. (See "Restoration of sinus rhythm in atrial fibrillation: Recommendations").
However, maintenance of normal sinus rhythm (NSR) is often problematic. Only 20 to 30 percent of patients who are successfully cardioverted will maintain NSR for more than one year without chronic antiarrhythmic therapy [1-7]. The risk of recurrence is highest in the patient who has hypertension, an enlarged LA, AF for more than one year, or heart failure [8]. On the other hand, patients who are most likely to maintain NSR usually have one or more of the following characteristics:
• LA size less than 4.5 or 5 cm
• AF of recent onset
• Little or no heart failure
• A reversible underlying disorder such as hyperthyroidism, myocardial infarction, or pulmonary embolism
• No hypertension or hypertensive heart disease
Prophylactic antiarrhythmic drug therapy should be effective and have a low incidence of toxicity and proarrhythmic effects are low. These are rather strict requirements and a number of unsettled issues remain. As an example, the expectation that maintenance of NSR with antiarrhythmic drugs will reduce the long-term risks of stroke or death remains unproven [9]. Thus, a sensible goal of AF treatment is the reduction of symptoms by decreasing the frequency of recurrences and prolonging the time between them.
Recommendations concerning the use of pharmacologic therapy in the prevention of recurrent AF will be reviewed here. The clinical trials describing the efficacy and toxicity (including proarrhythmia) of the different drugs and the role of alternative methods to maintain NSR in selected patients who are refractory to conventional therapy, including surgical and radiofrequency ablative procedures and insertion of an implantable atrial defibrillator, are discussed separately. (See "Antiarrhythmic drugs to maintain sinus rhythm after cardioversion in atrial fibrillation: Clinical trials-I" and see "Nonpharmacologic strategies to prevent recurrent atrial fibrillation").
RECOMMENDATIONS – The recommendations that follow should be considered general guidelines that need to be evaluated in light of clinical features of an individual patient (show algorithm 1A-1B). As examples:
• Patients at low risk for recurrence (LA <4.5 or 5 cm, good LA function, AF of recent onset, little or no heart failure, no hypertensive heart disease, or an underlying reversible disorder such as hyperthyroidism, myocardial infarction, or pulmonary embolism) may not require antiarrhythmic therapy after initial cardioversion. (See "Restoration of sinus rhythm in atrial fibrillation: Recommendations").
• Patients who have recurrent AF or who are at high risk for recurrence are generally treated with long-term antiarrhythmic drugs. Since there are as yet no data that prevention of AF will reduce the long-term risks of stroke or death, a sensible goal of therapy is to reduce symptoms by decreasing the frequency of recurrences and prolonging the time between them [9].
Our personal choice for the medical treatment of AF in patients with normal hepatic and renal function is quinidine (given as quinidine sulfate 200 to 400 mg QID or quinidine gluconate 324 to 648 mg every 8 to 12 hours). We believe that the long-term benefits of maintaining NSR outweigh the potential risks from the proarrhythmic activity and possible small increase in mortality from quinidine. Quinidine acts both to suppress initiating premature beats and to increase the refractoriness of the atrium to reentry.
An AV nodal blocker is usually added in patients who have demonstrated a moderate to rapid ventricular response to AF. The major goal of combination therapy is to protect against a rapid ventricular response should AF recur and to prevent a 1:1 response should atrial flutter occur. A class I antiarrhythmic drug such as quinidine may suppress most, but not all, reentrant circuits. Although the atrial myocardium is not capable of sustaining AF in this setting, it may be able to generate and sustain atrial flutter.
A beta blocker or calcium channel blocker is used if there are no contraindications, since the withdrawal of vagal tone and increase in sympathetic tone with exercise often renders digoxin relatively ineffective for controlling the heart rate. On the other hand, digoxin is often used in patients with AF associated with heart failure because of its positive inotropic activity. The negative inotropic activity of beta blockers and calcium channel blockers makes them less desirable in this setting. (See "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy").
The vagotonic activity of digoxin may counteract the vagolytic effect of quinidine. However, the digoxin-quinidine interaction must be appreciated in this setting, with the digoxin dose initially being halved to 0.125 mg daily in the patient with normal renal function. Plasma digoxin and quinidine levels should then be followed. (See "Digoxin drug interactions").
Low-dose amiodarone may replace quinidine as the drug of choice in the treatment of chronic AF because of its efficacy and relatively low toxicity [4,10,11]. Furthermore, since amiodarone has beta blocking and calcium channel blocking activity, the ventricular rate is usually slow and well tolerated if AF does recur.
Unfortunately, fewer than one-third of patients are able to tolerate chronic quinidine therapy without recurrent AF or side effects. The following alternatives can be considered:
• Disopyramide (100 to 200 mg every 8 hours in the presence of normal renal and hepatic function) may be used if the patient is not in heart failure and prostatism has not been a problem. An AV nodal blocking drug (beta blocker, calcium channel blocker, or digoxin) is again given in the presence of normal AV nodal function to decrease conduction through the AV node should AF recur. However, beta blockers and calcium channel blockers must be used cautiously with disopyramide because of the additive negative inotropic effects.
• Amiodarone and sotalol, the so-called class III agents, are widely used in patients with significant organic heart disease who have ventricular arrhythmias. Because of the proarrhythmic effects of the class IA and IC drugs, many cardiologists are initiating therapy with one of these class III agents which seem to be less proarrhythmic. However, torsade de pointes (possibly associated with an increase in mortality) has been reported with sotalol although it appears to be rare with amiodarone.
Amiodarone is preferred in patients with an ejection fraction of less than 40 percent. Amiodarone has a long list of toxicities that can be minimized, but not eliminated, using low dose therapy. Guidelines for the use of amiodarone were published by the North American Society of Pacing and Electrophysiology in 2000 [12]. (See "Major side effects of amiodarone"). Sotalol has a negative inotropic effect.
• Propafenone and flecainide can effectively maintain NSR in some patients. The potential for fatal proarrhythmic effects with flecainide in patients with underlying structural heart disease has limited its use [13]. However, flecainide should be considered for the prevention of recurrent paroxysmal AF in individuals without organic heart disease as demonstrated by echocardiography and by exercise testing with nuclear scintigraphy.
Propafenone does not appear to have the same potential for proarrhythmia as flecainide but more experience with this agent is necessary [14].
• For patients who are refractory to individual antiarrhythmic agents or who develop side effects on doses of drugs necessary for arrhythmia prevention, the use of combination drug therapy (often with lower doses) may be an alternative. In most cases, drugs with different electrophysiologic properties are combined, for example, a class I or III antiarrhythmic drug with a beta blocker or a class IC agent with a class IA or III drug [15-17].
• The use of surgery (such as the maze operation), radiofrequency ablation, and the implantable atrial defibrillator remain experimental and should be considered only in centers with experience in these procedures. (See "Nonpharmacologic strategies to prevent recurrent atrial fibrillation").
References
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14. Podrid, PJ, Lampert, S, Graboys, TB, et al. Aggravation of arrhythmia by antiarrhythmic drugs-incidence and predictors. Am J Cardiol 1987; 59:38E.
15. Lau, C, Chow, MS, Tse, H, et al. Control of paroxysmal atrial fibrillation recurrence using combined administration of propafenone and quinidine. Am J Cardiol 2000; 86:1327.
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17. Kerin, NZ, Ansari-Leesar, M, Faitel, K, et al. The effectiveness and safety of the simultaneous administration of quinidine and amiodarone in the conversion of chronic atrial fibrillation. Am Heart J 1993; 125:1017.
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