The objectives of therapy include (1) achieving rate control, (2) restoring sinus rhythm (where feasible), and (3) decreasing
the risk of CVA. The principles of treatment discussed in this chapter
largely follow those promulgated in the recent ACC/AHA/ESC
If the patient has atrial fibrillation and a rapid rate associated with severe heart failure or cardiogenic shock, emergency direct-current
cardioversion is indicated. For patients with atrial fibrillation
associated with rapid rate but with stable hemodynamics, attempts
to achieve acute rate control are indicated. Drugs to slow the ventricular
rate in patients with atrial fibrillation (Table
21–1) include digitalis preparations, calcium channel
blockers (verapamil or diltiazem), and β-blockers.
If rapid rate control is desired, then calcium channel blockers
and β-blockers are far more effective than digitalis,
which may require many hours before rate control is achieved. In
addition, a common misconception is that digitalis therapy is associated
with acute conversion to sinus rhythm, but carefully controlled
studies have shown that conversion to sinus rhythm is no more likely with
digoxin than with placebo. As emphasized later, digitalis and intravenous
calcium channel blocker therapy are contraindicated in patients
with Wolff-Parkinson-White syndrome and atrial fibrillation. Intravenous
diltiazem has been shown to be safe and effective for patients with
atrial fibrillation and a modest degree of heart failure.
Table 21–1. Intravenous Pharmacologic Agents for Heart Rate Control in Atrial Fibrillation.
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Table 21–1. Intravenous Pharmacologic Agents for Heart Rate Control in Atrial Fibrillation.
|Drug||Loading Dose||Onset||Maintenance Dose||Major Side Effects|
|Diltiazem||0.25 mg/kg IV over 2 min||2–7 min||5–15 mg/h infusion||Hypotension, heart block, HF|
|Esmolol||0.5 mg/kg over 1 min||5 min||0.05–0.2 mg kg–1 min–1||Hypotension, heart block, bradycardia, asthma, HF|
|Metoprolol||2.5–5 mg IV bolus over 2 min; up to 3 doses||5 min||NA||Hypotension, heart block, bradycardia, asthma, HF|
|Propranolol||0.15 mg/kg IV||5 min||NA||Hypotension, heart block, bradycardia, asthma, HF|
|Verapamil||0.075–0.15 mg/kg IV over 2 min||3–5 min||NA||Hypotension, heart block, HF|
|Digoxin||0.25 mg IV each 2 h, up to 1.5 mg||2 h||0.125–0.25 mg daily||Digitalis toxicity, heart block, bradycardia|
In patients with a known history of congestive heart failure, use of intravenous β-blockers or calcium channel blockers may aggravate the cardiac failure. In this subset, digitalis
or intravenous amiodarone would be the preferred agents for rate control.
Antiarrhythmic Therapy and Elective Cardioversion
For patients who have had a single, initial episode of atrial
fibrillation with no significant hemodynamic problems, no specific
therapy is required because repeat episodes may not occur for many years.
In contrast, patients who manifest frequent recurrences may be candidates for
long-term antiarrhythmic therapy with class IA (quinidine, procainamide,
and disopyramide), class IC (propafenone and flecainide), or class
III (sotalol, amiodarone, and dofetilide) agents, all of which are
more effective than placebo in maintaining sinus rhythm (Table 21–2).
Table 21–2. Typical Doses of Drugs Used to Maintain Sinus Rhythm in Atrial Fibrillation, Listed Alphabetically.
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Table 21–2. Typical Doses of Drugs Used to Maintain Sinus Rhythm in Atrial Fibrillation, Listed Alphabetically.
|Drug||Daily Dosage||Potential Adverse Effects|
|Amiodarone||100–400 mg||Photosensitivity, pulmonary toxicity, polyneuropathy, GI upset, bradycardia, torsades de pointes (rare), hepatic toxicity, thyroid dysfunction|
|Disopyramide||400–750 mg||Torsades de pointes, HF, glaucoma, urinary retention, dry mouth|
|Dofetilide||500–1000 mcg||Torsades de pointes|
|Flecainide||200–300 mg||Ventricular tachycardia, congestive HF, enhanced AV nodal
conduction (conversion to atrial flutter)|
|Procainamide||1000–4000 mg||Torsades de pointes, lupus-like syndrome, GI symptoms|
|Propafenone||450–900 mg||Ventricular tachycardia, congestive HF, enhanced AV nodal conduction (conversion to atrial flutter)|
|Quinidine||600–1500 mg||Torsades de pointes, GI upset, enhanced AV nodal conduction|
|Sotalol||240–320 mg||Torsades de pointes, congestive HF, bradycardia, exacerbation of chronic obstructive or bronchospastic lung disease|
Drug Therapy for Atrial Fibrillation
For patients with lone atrial fibrillation, use of any of the
antiarrhythmic drugs listed is appropriate. In general, the class
IC agents (flecainide or propafenone) are the first choice in terms
of efficacy and lowest incidence of side effects. It would be wise,
for example, to withhold amiodarone as a first-line drug in view
of the potential for adverse effects. Only two drugs have been proved
safe for patients with severe congestive heart failure: dofetilide
For patients with atrial fibrillation associated with coronary
artery disease, consider use of sotalol as initial drug therapy.
This agent has class III antiarrhythmic effects and is a potent β-blocker.
Class IC drugs should not be used in patients with significant structural
cardiac disease or in those with ischemic heart disease. They have,
however, been found to be safe and effective for patients with hypertension
and atrial fibrillation.
In addition, extra cardiac factors are very important in the
choice of antiarrhythmic drugs. For example, dose adjustments are
mandatory for patients with renal insufficiency. This is especially
true for procainamide, sotalol, and dofetilide. Dofetilide, for
example, requires hospital admission, calculation of the creatinine
clearance, and drug titration according to the QT corrected for
heart rate as well as renal function. An algorithm for antiarrhythmic
drug usage is summarized in Figure 21–2.
Antiarrhythmic drug therapy to maintain sinus rhythm in patients with recurrent paroxysmal or persistent atrial fibrillation.
Drugs in boxes are listed alphabetically and not in order of suggested
use. CAD, coronary artery disease; HF, heart failure; LVH, left
Even with drug therapy, recurrence rates for atrial fibrillation approach 50% per year (as opposed to recurrences with placebo therapy of 75% per year). In addition,
these agents may be associated with significant side effects. For
class IA drugs, these include induction of torsades de pointes, especially
for those with congestive heart failure. For example, a meta-analysis
compared quinidine with placebo for patients with atrial fibrillation and
found that death from all causes was higher in the groups treated
with quinidine. In addition, in the Stroke Prevention in Atrial
Fibrillation (SPAF) trials, substantial numbers of patients were
treated with antiarrhythmic agents; in patients with heart failure,
those treated with class I drugs had significantly increased mortality
rates compared with those not treated with antiarrhythmic drugs.
Great care must be exercised in the use of these agents, balancing
the benefits against the potential for adverse effects. General
rules include avoidance of all class IA drugs or sotalol for patients
with congestive heart failure and avoidance of class IC agents for
patients with structural heart disease. In addition, sotalol is contraindicated
for patients with severe depression of the left ventricular ejection fraction
and severe left ventricular hypertrophy. Patients with significant
sinus node or atrioventricular (AV) conduction disease may require
pacemaker therapy before use of antiarrhythmic drugs because these
drugs may further depress sinus node or AV conduction. The only
drugs that appear to be both effective and safe for patients with
heart failure and atrial fibrillation are amiodarone and dofetilide.
Amiodarone is associated with a host of both cardiac (eg, severe
sinus bradycardia or arrest or AV block) and noncardiac (eg, thyroid abnormalities,
pulmonary fibrosis) adverse effects, but low-dose amiodarone (ie,
200 mg/day) appears to be effective and very well tolerated.
Dofetilide has a narrow therapeutic window and can cause life-threatening
arrhythmias; it can be used in patients with atrial fibrillation
and congestive heart failure but requires a 2–3 day in-hospital
stay for monitoring of the agent.
Recent studies have emphasized the use of drugs for acute conversion
of atrial fibrillation. It has been shown that intravenous ibutilide
or intravenous dofetilide (not available in the United States) are effective
for conversion of approximately 35% of patients with atrial
fibrillation. It should be emphasized that this drug should be used
only in a monitored environment. The usual dose is 1 mg over 10
minutes, followed by a 10-minute interlude, followed by an additional
1 mg over 10 minutes if necessary. Facilities with intravenous management,
and a defibrillator should be readily available because the incidence of
sustained torsades de pointes is 1–2%. Ibutilide
should be avoided for patients with severe heart failure or bradycardia.
Other Drugs for Chemical
Other drug combinations have also been found effective. For example,
it has been found that use of large oral doses of either flecainide
(300 mg) or propafenone (600 mg) may terminate up to 80% of
episodes of atrial fibrillation within 2 hours (pill-in-the-pocket).
This approach should be used only in patients who are pretreated
with β-blocking drugs and in the absence of significant
cardiac disease or heart failure.
The risk of CVA in patients with nonrheumatic atrial fibrillation
is 4–7% per year. Patients at particularly high
risk include those over age 70 years or with hypertension, a history
of heart failure, increased left atrial size, diabetes, or prior
CVA. The risks of CVA are similar in patients with paroxysmal versus
chronic atrial fibrillation. Numerous studies have documented the remarkable
efficacy of warfarin in decreasing the risk of emboli by 45–85% in
patients with nonrheumatic atrial fibrillation with a low risk of
significant hemorrhage, provided the international normalized ratio
(INR) is in the range of 2.0 to 2.5. Still controversial is the
need for anticoagulant therapy in younger patients with lone atrial
fibrillation because the risk of emboli is very low in this group.
The role of aspirin therapy for patients with atrial fibrillation
remains controversial. In one study, 75 mg of aspirin failed to
decrease the stroke risk compared with placebo (5.5%/year).
In contrast, the SPAF I trials showed that a higher dose of aspirin,
325 mg, appeared to be of benefit in patients under 75 years of
age. In a follow-up study (SPAF II), the incidence of stroke was
higher with aspirin (4.8%) compared with warfarin (3.6%).
The SPAF III trials demonstrated that aspirin (325 mg/day)
and fixed low-dose warfarin (1, 2, or 3 mg) were ineffective for
stroke prevention. Therefore, the weight of current data favors
use of warfarin with an INR of 2.0–3.0 as the best strategy
to prevent systemic embolization. A number of studies involving
use of newer antithrombin agents, are in clinical trials. Initial
trials with ximelagatran in patients with atrial fibrillation showed non-inferiority
compared with warfarin but it failed FDA clearance because of hepatotoxicity.
The advantage of these agents will be to obviate the need for blood
testing of INR levels. Trials of aspirin and clopidogrel proved
inferior to warfarin.
Direct-current cardioversion is a very effective technique for restoration of sinus rhythm. Because of the benefits of sinus rhythm in
terms of improved cardiac output and decreased risk of embolic phenomena,
in general, at least one attempt should be made to restore sinus
rhythm. Several precautions are in order. If the patient has a history
of recurrent episodes of atrial fibrillation then he or she should
be pretreated with an antiarrhythmic agent because reversion to
atrial fibrillation after shock therapy is very high. Use of antiarrhythmic
drugs before direct-current shock, however, is inappropriate for the
patient with an initial episode of well-tolerated atrial fibrillation.
Unless urgent cardioversion is required because of hemodynamic decompensation,
severe ischemia, or congestive heart failure, it is imperative to
follow one of several options for reducing the risk of systemic embolization:
a. For patients with atrial fibrillation of less than
48 hours duration it would appear to be safe to proceed with application
of direct-current shock.
b. If atrial fibrillation persists for more than 48 h, then the risk of embolization increases and anticoagulants are required prior to ablation. One recommended option for patients with atrial fibrillation of more than 48 hours duration is to perform transesophageal echocardiography (TEE), which is excellent for detecting clots in the left atrium or the left atrial appendage. Evidence from several studies indicates that the finding of either a clot or spontaneous echocardiographic contrast in the left atrium is associated with higher risks of systemic embolization. In the absence of such findings on TEE, systemic emboli are rare. Therefore, patients with recent-onset atrial fibrillation with no evidence of atrial clots or spontaneous contrast by TEE may undergo direct-current cardioversion after initiation of heparin therapy. A recent report from the ACUTE trial showed that treatment of patients with atrial fibrillation treated on the basis of TEE-guided therapy versus a group treated with a 3-week course of anticoagulant therapy had similar rates of thromboembolism (< 1%). It must be appreciated that atrial function is depressed (atrial stunning) after cardioversion and that anticoagulant therapy is recommended for at least 1 month after cardioversion. This is true whether the duration of atrial fibrillation was either less than or greater than 48 hours. For those patients with clot or dense spontaneous echocardiographic
contrast with TEE, full anticoagulant therapy with an INR of 2.0–3.0 is recommended for at least 2–3 weeks before cardioversion.
c. An alternative approach is that patients with atrial fibrillation of greater than 48 hours be fully anticoagulated for at least 3 consecutive weeks before attempting direct-current cardioversion and for about 4 weeks afterward to decrease the risk of an embolism after successful reversion to sinus rhythm. This approach tends to be less efficient than the TEE-guided approach for recent-onset atrial fibrillation but is an acceptable alternative treatment for atrial fibrillation.
Direct-current external shock is usually performed in a monitored area under supervision of an anesthesiologist. Pads are placed in
an anterior-posterior orientation in order to maximize current delivered
to the atrium. It is wise to check the arterial oxygen saturation,
serum potassium level, digoxin, or antiarrhythmic blood drug levels
before cardioversion. Direct-current shocks beginning with at least
200 J are used in an attempt to achieve sinus rhythm. Multiple shocks
of lesser energy are to be avoided. If the patient fails to revert
after maximal external shocks (360 J monophasic or 200 J biphasic), then
successful cardioversion can almost always be achieved either by
the use of a biphasic waveform defibrillator or supplemental doses
of ibutilide. Ibutilide has been shown to lower the atrial defibrillation
threshold. An attempt at internal cardioversion using small energy
shocks delivered between the coronary sinus and the right atrium
is seldom necessary because the above-described treatments are almost
Clinicians should be especially careful to identify patients whose atrial fibrillation might be cured. Examples include patients
with hyperthyroidism as well as those in whom other cardiac arrhythmias appear
to trigger atrial fibrillation. For example, patients with atrial
flutter or paroxysmal supraventricular tachycardia may experience
atrial premature impulses during tachycardia that trigger atrial
fibrillation. In selected patients, it is possible to apply catheter
ablation to cure the underlying supraventricular arrhythmia and,
hence, prevent the trigger for atrial fibrillation. Therefore, in
the evaluation of patients with atrial fibrillation, initial testing
should include obtaining a thyroid-stimulating hormone assay, an
echocardiogram, and a 48-hour ambulatory electrocardiogram recording for
those with paroxysmal atrial fibrillation. In analyses of these
recordings, the clinician seeks evidence for triggering arrhythmias.
In addition, the clinician looks for vagal triggers of atrial fibrillation,
such as sinus bradycardia associated with sleep or heavy meals,
that initially may be treated with vagolytic antiarrhythmic agents
such as disopyramide. Alternatively, if atrial fibrillation appears
only with enhanced sympathetic tone, such as with exercise, a trial
of β-blocker therapy is appropriate.
One important special circumstance is that of atrial fibrillation in the patient with Wolff-Parkinson-White syndrome. These patients
may have a very rapid irregular rate and wide complex tachycardia owing
to conduction over the accessory pathway (Figure 21–3). After recognition of this entity, appropriate immediate therapy includes use of intravenous ibutilide or procainamide or direct-current cardioversion. It is important to remember that intravenous digoxin and calcium channel blockers are contraindicated. In addition, use of lidocaine, β-blockers, or adenosine is not effective and is contraindicated because they delay appropriate therapy. After the rhythm is stabilized, these patients should undergo catheter ablation of the accessory pathway.
The 12-lead electrocardiogram shows a rapid irregular rhythm with broad QRS complex. This is pathognomonic of atrial fibrillation
in a patient with Wolff-Parkinson-White syndrome. This arrhythmia requires
urgent treatment. Acceptable therapy includes use of intravenous ibutilide or procainamide or direct-current shock.
The natural history of atrial fibrillation associated with structural cardiac disease or in patients with lone atrial fibrillation is
for spontaneous recurrence of the arrhythmia. Unfortunately, no
drug is universally effective, and the decision of how many drugs
to try before a judgment is made to terminate antiarrhythmic drugs
and focus on rate control depends on how symptomatic the patient
is during atrial fibrillation. If the episodes are poorly tolerated,
then multiple drug trials or even various ablative procedures may be
required (see section on Nonpharmacologic Treatment of Atrial Fibrillation). On the other hand, if rate control can be readily achieved with drugs,
such as digoxin, β-blockers, or calcium antagonists
that block AV nodal conduction and the patient has a good symptomatic
outcome, then an acceptable alternative is to use drugs that control
rate combined with long-term anticoagulant treatment. A large, randomized trial (AFFIRM) compared the strategy of rate control and anticoagulation
versus maintaining sinus rhythm with antiarrhythmic drugs. The AFFIRM
trial randomized over 4000 patients with atrial fibrillation to
either rate or rhythm control. The patient cohort consisted in large
measure of older (mean age 69 years) patients who were not very
symptomatic. They found no difference in mortality or quality of
life between groups. The rhythm control group had a higher incidence
of hospitalizations and episodes of torsades de pointes. In addition,
stroke risk was related to presence of no or inadequate anticoagulant
treatment. This study showed that for most patients with atrial fibrillation,
rate control was equally effective as rhythm control and that long-term anticoagulation
therapy is required for both groups.
Nonpharmacologic Treatment of Atrial Fibrillation
Because pharmacologic therapy for atrial fibrillation is not ideal, a number of nonpharmacologic treatment modalities have been
introduced. For atrial fibrillation that proves refractory to drug
management, one time-tested approach is catheter ablation of the
AV junction and permanent pacemaker insertion.
Patients with persistent tachycardia may suffer from a tachycardia-induced cardiomyopathy with left ventricular failure superimposed on their
native cardiac disease. Hence, in the management of chronic atrial fibrillation, rate control is an important objective that must be achieved either via AV nodal blocking drugs or, failing these, with catheter ablative procedures. Catheter ablation of the AV junction involves insertion of an electrode catheter in the region of the His bundle with application of radiofrequency energy in order to destroy AV
conduction. The chief benefit of this technique is achievement of perfect rate control without need for drugs. The drawbacks include the need for permanent pacing and a continued need for anticoagulant therapy.
For most of these patients, especially for those with left ventricular ejection fraction greater than 40%, single chamber pacing
appears to be sufficient. In some patients, left ventricular function
may deteriorate and biventricular pacing may be helpful (PAVE trial).
It has been shown that atrial-based pacing systems will decrease the incidence of atrial fibrillation in patients with the tachycardia-bradycardia
syndrome. In addition, pacing may allow for safe use of antiarrhythmic
drugs. In patients with vagally mediated atrial fibrillation, atrial pacing
may be effective in decreasing episodes of atrial fibrillation. Experimental studies have shown that either dual-site atrial pacing (ie, from coronary sinus and right atrium) or from the atrial septum
in conjunction with antiarrhythmic therapy, may suppress atrial fibrillation, but this technique has not been shown to be clinically useful.
An innovative approach to the management of atrial fibrillation involves use of an internal atrial defibrillator. This device has
been shown to be safe and effective in conversion of atrial fibrillation
in 85% of instances. The chief drawback is that although
the energy required for internal defibrillation is quite low, nevertheless, internal
shocks are painful and not well tolerated. Currently, atrial defibrillators are
combined with ventricular defibrillators and may prove to be very
helpful for patients with infrequent episodes of atrial fibrillation. “Stand
alone” atrial internal defibrillation has been abandoned.
A number of surgical centers are currently using the maze procedure to try to cure atrial fibrillation. This procedure involves placing
transmural lesions over both atria in such a manner that the fibrillatory
impulses cannot complete a reentrant circuit. The maze procedure involves
all of the risks of major open-heart surgery. This procedure should
be considered for patients with atrial fibrillation who require
cardiac surgery for correction of valvular diseases, coronary artery
disease, or congenital heart disease.
In some patients with paroxysmal atrial fibrillation, a rapidly firing ectopic focus, often near the pulmonary veins, may cause
atrial fibrillation. The current experience using catheter ablative
procedures to cure atrial fibrillation has been validated by a number
of studies. It was found that attempts to ablate a specific focus
within the pulmonary vein resulted in a long-term success rate of
50–60% but was associated with an unacceptably
high incidence of pulmonary vein stenosis (2–8%).
Currently most groups have advocated use of pulmonary vein isolation,
which involves placement of a number of lesions around the ostium
of the pulmonary vein in order to isolate discharges from pulmonary
venous focus. Isolation procedures for at least three of the four
pulmonary veins are associated with short-term success rates of
70–90% and are associated with a zero incidence
of pulmonary vein stenosis. Pulmonary vein isolation is currently
reserved for highly symptomatic patients with atrial fibrillation
that is resistant to multiple drug trials.
More recent trials have emphasized the use of wide area ablative lesions around the pulmonary veins as well as use of lesions connecting
the left atrial roof and isthmus. In addition, a number of groups have designed lesions to ablate areas of fractionated potentials. These potentials are thought to be derived from the pivot points of random
reentrant circuits or from activation of vagal ganglion, or both. The ablative procedures have matured, and in the current ACC/AHA/ESC guidelines, these procedures may be used after failure of a single
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