6. Atrial Fibrillation

Atrial fibrillation is the commonest chronic arrhythmia, with an incidence and prevalence that rise with age, so that it affects nearly 10% of individuals over age 80. It occurs in rheumatic and other forms of valvular heart disease, dilated cardiomyopathy, atrial septal defect, hypertension, and coronary heart disease as well as in patients with no apparent cardiac disease; it may be the initial presenting sign in thyrotoxicosis, and this condition should be excluded with the initial episode. Atrial fibrillation often appears paroxysmally before becoming the established rhythm. Pericarditis, chest trauma, thoracic or cardiac surgery, or pulmonary disease (as well as medications such as theophylline and beta-adrenergic agonists) may cause attacks in patients with normal hearts. Acute alcohol excess and alcohol withdrawal-and, in predisposed individuals, even consumption of small amounts of alcohol-may precipitate atrial fibrillation. This latter presentation, which is often termed “holiday heart,” is usually transient and self-limited. Short-term rate control usually suffices as treatment.

Atrial fibrillation is the only common arrhythmia in which the ventricular rate is rapid and the rhythm very irregular. The atrial rate is 400-600/min, but most impulses are blocked at the atrioventricular node.

The ventricular response is completely irregular, ranging from 80 to 180/min in the untreated state. Because of the varying stroke volumes resulting from varying periods of diastolic filling, not all ventricular beats produce a palpable peripheral pulse. The difference between the apical rate and the pulse rate is the “pulse deficit”; this deficit is greater when the ventricular rate is high.

Atrial fibrillation itself is rarely life-threatening; however, it can have serious consequences if the ventricular rate is sufficiently rapid to precipitate hypotension, myocardial ischemia, or tachycardia-induced myocardial dysfunction. Although many patients-particularly older or inactive individuals-have relatively few symptoms if the rate is controlled, some patients are aware of the irregular rhythm and may experience it as very uncomfortable. Perhaps the most serious consequence of atrial fibrillation is the propensity for thrombus formation due to stasis in the atria (particularly the atrial appendages) and consequent embolization, most devastatingly to the cerebral circulation. Overall, the rate of stroke is approximately five events per 100 patient-years of follow-up. However, patients with significant obstructive valvular disease, chronic heart failure or left ventricular dysfunction, diabetes, hypertension, or age over 75 years and those with a history of prior embolic events are at substantially higher risk (up to nearly 20 events per 100 patient-years in patients with multiple risk factors). Patients with one or more of these risk factors for stroke should be treated with warfarin. Patients with none of these factors may be treated with aspirin if conditions are present that increase the risk of warfarin. Patients below the age of 60-65 years without any of these stroke risk factors (“lone atrial fibrillation”) may be treated with aspirin or no antithrombotic therapy.

Newly Diagnosed Atrial Fibrillation

A. Initial Management
The approach to the initial management of atrial fibrillation depends on the clinical presentation. If, as is often the case-particularly in older individuals-the patient presents without symptoms, hemodynamic instability, or evidence of important precipitating conditions (such as silent myocardial infarction or ischemia, decompensated heart failure, pulmonary embolus, or hemodynamically significant valvular disease), hospitalization is usually not necessary. In most such cases, atrial fibrillation is an unrecognized chronic or paroxysmal condition and should be managed accordingly (see below).

In contrast, if the patient is hemodynamically unstable-usually as a result of a rapid ventricular rate or associated cardiac or noncardiac conditions-hospitalization and immediate treatment of atrial fibrillation are required. Urgent cardioversion is usually indicated in patients with shock or severe hypotension, pulmonary edema, or ongoing myocardial infarction or ischemia. Although if atrial fibrillation has been present for more than 48 hours there is a potential risk of thromboembolism, the need for immediate rate control in these very unstable patients outweighs that risk. Electrical cardioversion is usually preferred in unstable patients. An initial shock with 100-200 J is administered in synchrony with the R wave. If sinus rhythm is not restored, an additional attempt with 360 J is indicated. If this fails, cardioversion may be successful after loading with intravenous ibutilide (1 mg over 10 minutes, repeated in 10 minutes if necessary) or intravenous procainamide (500-1000 mg administered at a rate of 20 mg/min with careful monitoring of blood pressure).

In less unstable patients or those at particularly high risk for embolism (underlying mitral stenosis, a history of prior emboli, or severe heart failure), a strategy of rate control is appropriate. A rate control strategy is appropriate both when the conditions that precipitated atrial fibrillation are likely to persist (such as following cardiac or noncardiac surgery, respiratory failure, or pericarditis) and when these conditions might resolve spontaneously over a period of hours to days (such as alcohol-induced atrial fibrillation, electrolyte or fluid imbalances, excessive exposure to theophylline or sympathomimetic agents, or some of the same previously cited conditions). The choice of agent is guided by the hemodynamic status of the patient, associated conditions, and the urgency of achieving rate control. Although both hypotension and heart failure may improve when the ventricular rate is slowed, calcium channel blockers and beta-blockers may themselves precipitate hemodynamic deterioration. Digoxin is less risky, but even when used aggressively (0.5 mg intravenously over 30 minutes, followed by increments of 0.25 mg every 1-2 hours to a total dose of 1-1.5 mg over 24 hours in patients not previously receiving this agent), rate control is rather slow and may be inadequate, particularly in patients with sympathetic activation. In the setting of myocardial infarction or ischemia, beta-blockers are the preferred agent. The most frequently used agents are either metoprolol (administered as a 5-mg intravenous bolus, repeated twice at intervals of 5 minutes and then given as needed by repeat boluses or orally at total daily doses of 50-400 mg) or, in very unstable patients, esmolol (0.5 mg/kg intravenously, repeated if necessary, followed by a titrated infusion of 0.05-0.2 mg/kg/min). If hypertension is present or beta-blockers are contraindicated, calcium channel blockers are immediately effective. Diltiazem (20-mg bolus, repeated after 15 minutes if necessary, followed by a maintenance infusion of 5-15 mg/h) is the preferred calcium blocker if hypotension or left ventricular dysfunction is present. Otherwise, verapamil (5-10 mg intravenously over 2-3 minutes, repeated after 30 minutes if necessary) may be used. Amiodarone, even when administered intravenously, has a relatively slow onset but is often a useful adjunct when rate control with the previously cited agents is incomplete or contraindicated or when cardioversion is planned in the near future.

If rate control proves unsuccessful or early cardioversion is considered necessary and the duration of atrial fibrillation exceeds 2-3 days or is unknown, a strategy of transesophageal echo-guided cardioversion should be considered. By this approach, the presence of atrial thrombus is excluded and electrical cardioversion is attempted while the patient remains under sedation. If thrombus is present, the cardioversion is delayed until after a 3- to 4-week period of therapeutic anticoagulation. In any case, because atrial contractile activity may not recover for several weeks after restoration of sinus rhythm in patients who have been in atrial fibrillation for more than several days, cardioversion is usually followed by anticoagulation for at least 1 month unless it is contraindicated.

B. Subsequent Management
Up to two-thirds of patients experiencing a first episode of atrial fibrillation will spontaneously revert to sinus rhythm within 24 hours. If atrial fibrillation persists or has been present for more than a week, spontaneous conversion is unlikely. In most such cases early cardioversion is not required, so management consists of rate control and anticoagulation whether or not the patient has been admitted to hospital. Rate control is usually relatively easy to achieve with beta-blockers, rate-slowing calcium blockers, and digoxin, used as single agents or more often in combination. Good rate control should consist of a ventricular rate between 50 and 100 beats/min with usual daily activities and a ventricular rate not exceeding 120 beats/min except with moderate to strenuous activity. In older patients, who often have diminished atrioventricular nodal function and relatively limited activity, this can often be achieved with a single agent. Most younger or more active individuals require a combination of two agents. Choice of the initial medication is best based on the presence of accompanying conditions: Hypertensive patients should be given beta-blockers or calcium blockers; coronary patients should usually receive a beta-blocker; and heart failure patients should be given digoxin or a beta-blocker. Adequacy of rate control should be evaluated by recording the apical pulse rate both at rest and with an appropriate level of activity (such as after brisk walking around the corridor or climbing stairs).

Anticoagulation with warfarin to an INR target of 2.0-3.0 should be established and maintained as long as the patient is in atrial fibrillation. The only exception is the patient with “lone atrial fibrillation” (eg, no evidence of associated heart disease, hypertension, atherosclerotic vascular disease, or diabetes) who is under age 60. Cardioversion, if planned, should be performed after at least 3 weeks of anticoagulation at a therapeutic level. Except in patients with mitral stenosis or a history of prior embolic events or those with demonstrated thrombus on transesophageal echocardiography, it is not necessary to achieve therapeutic anticoagulation levels in hospital, so the use of intravenous heparin or low-molecular-weight heparin while transitioning to oral warfarin is not necessary.

C. Rate Control or Elective Cardioversion
Two recent large randomized controlled trials (the 4060-patient Atrial Fibrillation Follow-up Investigation of Rhythm Management, or AFFIRM trial, and the Rate Control Versus Electrical Cardioversion for Persistent Atrial Fibrillation, or RACE trial) compared strategies of rate control and rhythm control. In both, a strategy of rate control and chronic anticoagulation was associated with no higher rates of death or stroke-both, if anything, favored rate control-and only a modestly increased risk of hemorrhagic events than a strategy of restoring sinus rhythm and maintaining it with antiarrhythmic drug therapy. Of note is that exercise tolerance and quality of life were not significantly better in the rhythm control group. Nonetheless, the decision as to whether to attempt to restore sinus rhythm following the initial episode remains controversial. Elective cardioversion following an appropriate period of anticoagulation is generally recommended for the initial episode in patients in whom atrial fibrillation is thought to be of recent onset and when there is an identifiable precipitating factor. Similarly, cardioversion is appropriate in patients who remain symptomatic from the rhythm despite aggressive efforts to achieve rate control. However, it should be noted that even in patients for whom this is the initial episode of atrial fibrillation, the recurrence rate is sufficiently high that longer-term anticoagulation is generally appropriate until persistence of sinus rhythm can be confirmed for at least 6 months.

In cases where elective cardioversion is required, it may be accomplished electrically (as described above) or pharmacologically. Intravenous ibutilide may also be used as described above in a setting where the patient can undergo continuous electrocardiographic monitoring for at least 3 hours following administration. In patients in whom a decision has been made to continue antiarrhythmic therapy to maintain sinus rhythm (see next paragraph), cardioversion can be attempted with an agent that is being considered for long-term use. For instance, after therapeutic anticoagulation has been established, amiodarone can be initiated on an outpatient basis (300-400 mg twice daily for 2 weeks, followed by 200 mg twice daily for at least a 2-4 weeks and then a chronic dose of 200 mg daily). Since amiodarone increases the prothrombin time in patients taking warfarin and digoxin levels, careful monitoring of anticoagulation and drug levels is required. Other agents that may be used for both cardioversion and maintenance therapy include propafenone (150-300 mg twice daily; should be avoided in patients with structural heart disease), flecainide (50-150 mg twice daily; should be avoided in patients with structural heart disease), and dofetilide (0.5 mg twice daily; downward dose adjustment is required with renal dysfunction and dosing must be initiated in hospital because of risk of torsade de pointes). Sotalol (80-160 mg twice daily; should be initiated in hospital in patients with structural heart disease because of risk of torsade de pointes) is not very effective for converting atrial fibrillation but can be used to maintain sinus rhythm following cardioversion.

Unfortunately, sinus rhythm will persist in only 25% of patients who have had a sustained (lasting more than several days) or recurrent episode of atrial fibrillation. However, if the patient is treated chronically with an antiarrhythmic agent, sinus rhythm will persist in approximately 50%. The most commonly employed medications are amiodarone, sotalol, propafenone, flecainide, and dofetilide, but the latter four agents are associated with a clear risk of proarrhythmia, and amiodarone frequently causes other adverse effects. Therefore, it may be prudent to determine whether atrial fibrillation recurs during a period of 6 months without antiarrhythmic drugs during which anticoagulation is maintained. If it does recur, the decision as to whether to restore sinus rhythm and initiate chronic antiarrhythmic therapy can be based on how well the patient tolerates atrial fibrillation. In such a patient, chronic anticoagulation is probably indicated in any case, because of the high rate of recurrence and the likely occurrence of asymptomatic paroxysmal episodes.