FUSTER
ET AL., ACC/AHA/ESC GUIDELINES FOR THE MANAGEMENT OF
PATIENTS WITH ATRIAL FIBRILLATION
J Am Coll Cardiol 2001;38:1266i-1xx
ACC/AHA/ESC
Guidelines for the Management of Patients with Atrial
Fibrillation
VIII.
Management
The
major issues in management of patients with AF are related
to the arrhythmia itself and to prevention of thromboembolism.
In patients with persistent AF, there are fundamentally
2 ways to manage the dysrhythmia: to restore and maintain
sinus rhythm or to allow AF to continue and ensure that
the ventricular rate is controlled. Although this decision
must be faced often by clinicians because AF is common,
remarkably little research has been conducted in the
form of controlled trials of antiarrhythmic drugs that
take into account the various mechanisms and patterns
of AF. Management strategies and therapeutic algorithms
must be based on the scant evidence available. Information
on prevention of thromboembolism is more substantial,
however, enabling recommendations to be based on a higher
level of evidence.
A.
Rhythm Control vs. Heart Rate Control
Reasons
for restoration and maintenance of sinus rhythm in patients
with AF include relief of symptoms, prevention of embolism,
and avoidance of cardiomyopathy (Table
5). The decision to convert AF (as opposed to controlling
the rate and allowing AF to continue) is commonly intended
to alleviate all these problems, but evidence documenting
the extent to which restoration and maintenance of sinus
rhythm achieves these goals is sparse. Conversion to
and maintenance of sinus rhythm offers the theoretical
advantages of reducing the risk of thromboembolism and
consequently the need for chronic anticoagulation, but
drugs used to control heart rate are generally considered
safer than those with an antiarrhythmic effect. The
relative merit of these 2 approaches—rhythm control
vs. rate control—is the subject of ongoing clinical
trials (178,179).
Limited available data suggest no clear advantage of
one approach over the other (179),
but a more complete answer awaits the results of studies
in progress.
B.
Cardioversion
1.
Basis for Cardioversion of AF
Cardioversion
is often performed electively to restore sinus rhythm
in patients with persistent AF. The need for cardioversion
may be immediate, however, when the arrhythmia is the
main factor responsible for acute HF, hypotension, or
worsening of angina pectoris in a patient with CAD.
Nevertheless, cardioversion carries a risk of thromboembolism
unless anticoagulation prophylaxis is initiated before
the procedure, and this risk appears greatest when the
arrhythmia has been present more than 48 hours.
2.
Methods of Cardioversion
Cardioversion
may be achieved by means of drugs or electrical shocks.
Drugs were commonly used before electrical cardioversion
became a standard procedure. The development of new
drugs has increased the popularity of pharmacological
cardioversion, although some disadvantages persist,
including the risk of drug-induced torsade de pointes
ventricular tachycardia or other serious arrhythmias.
Pharmacological cardioversion is still less effective
than electrical cardioversion, but the latter requires
conscious sedation or anesthesia, whereas the former
does not. (See Table 5)
There
is no evidence that the risk of thromboembolism or stroke
differs between pharmacological and electrical methods
of cardioversion. The recommendations for anticoagulation
at the time of cardioversion are the same for both methods,
as outlined in Section VIII-G, Preventing Thromboembolism.
C.
Pharmacological Cardioversion
Pharmacological
cardioversion has been the subject of intense research
for over a decade. Although pharmacological and electrical
cardioversion have not been compared directly, pharmacological
approaches appear to be simpler but less efficacious
than electrical cardioversion. In selected cases, pharmacological
cardioversion may even be attempted at home. The major
risk is the toxicity of antiarrhythmic drugs. In this
section, emphasis is given to studies in which drugs
were administered over short periods of time specifically
to restore sinus rhythm. The quality of available evidence
is limited by small samples, lack of standard inclusion
criteria, variable intervals from drug administration
to assessment of outcome, and arbitrary dose selection.
In developing these guidelines, placebo-controlled trials
of pharmacological cardioversion have been emphasized,
but trials in which the control group was given another
antiarrhythmic drug have also been considered.
Pharmacological
cardioversion appears to be most effective when initiated
within 7 days after the onset of AF (206,
207, 208,
and 209).
Most such patients have a first documented episode of
AF or an unknown pattern of AF at the time of treatment.
(See Section III, Classification.)
A large proportion of patients with recent-onset AF
experience spontaneous cardioversion within 24 to 48
hours (210,
211, and 212).
Spontaneous conversion is less frequent in patients
with AF of longer duration (greater than 7 days) before
treatment was begun, and the efficacy of pharmacological
cardioversion is also markedly reduced in patients with
persistent AF.
Some
drugs have a delayed onset of action, and conversion
may not occur for several days (213).
In some studies, drug treatment abbreviated the interval
to cardioversion compared with placebo without affecting
the proportion of patients who remained in sinus rhythm
after 24 hours (211).
Pharmacological cardioversion may accelerate the restoration
of sinus rhythm in patients with recent-onset AF, but
the advantage over placebo is quite modest after 24
to 48 hours, and it is much less effective (and with
some drugs ineffective) in patients with persistent
AF.
The
relative efficacy of various drugs differs for pharmacological
cardioversion of AF and atrial flutter, yet many studies
of drug therapy for AF have included patients with atrial
flutter. The dose, route, and rapidity of administration
influence efficacy, and this has been considered as
much as possible in developing these guidelines. The
designs of randomized trials have seldom fully accounted
for concomitant medications, on the assumption that
such treatment would be equally distributed among groups.
Several investigators have generated multiple reports,
and it is not always clear when these involve distinct
or overlapping patient cohorts. Diligence in reporting
adverse effects varies between trials, but toxicity
has been considered in the recommendations that follow.
Special populations, such as those with AF after recent
heart surgery or MI, are addressed later (Section
VIII-H, Special Considerations).
The
potential interactions of antiarrhythmic drugs with
oral anticoagulants (either increasing or decreasing
the anticoagulant effect) are always an issue when these
drugs are added or withdrawn from the treatment regimen.
The problem is amplified when anticoagulation is initiated
in preparation for elective cardioversion. Addition
of an antiarrhythmic drug to enhance the likelihood
that sinus rhythm will be restored and maintained may
perturb the intensity of anticoagulation beyond the
intended therapeutic range, raising the risk of bleeding
or thromboembolic complications.
A
summary of recommendations concerning the use of pharmacological
agents for cardioversion of AF is presented in Tables
6, 7
and 8. Algorithms for pharmacological
management of AF are given in Figures 9,
10, 11,
and 12. Considerations specific
to individual agents are summarized below. The antiarrhythmic
drugs listed have been approved by federal regulatory
agencies in the United States and Europe for clinical
use, but their use for the treatment of AF has not been
approved in all cases. Furthermore, not all agents are
approved for use in each country. Within each category,
drugs are listed alphabetically. The recommendations
given in this document are based on published data and
do not necessarily adhere to the regulations and labeling
requirements of governmental agencies.
1.
Agents With Proven Efficacy
a.
Amiodarone
Data on amiodarone are confusing because the drug may
be given intravenously, orally, or by both routes concurrently.
The drug is modestly effective for pharmacological cardioversion
of recent-onset AF (214)
but acts less rapidly and probably less effectively
than other agents. The conversion rate in patients with
AF for longer than 7 days is limited, however, and restoration
of sinus rhythm may not occur for days or weeks. Amiodarone
is effective for controlling the rate of ventricular
response to AF. Both amiodarone and dofetilide (administered
separately) have been proven effective for conversion
of persistent AF in placebo-controlled trials (214-216).
Limited information suggests that amiodarone is equally
effective for conversion of AF and atrial flutter. Adverse
effects include bradycardia, hypotension, visual disturbances,
nausea, and constipation after oral administration and
phlebitis after peripheral intravenous administration.
Serious toxicity has been reported, including 1 death
due to bradycardia ending in cardiac arrest (210,213,214,217-225).
b.
Dofetilide
Dofetilide, given orally, is more effective than placebo
for pharmacological cardioversion of AF that has persisted
longer than 1 week, but available studies have not further
stratified patients on the basis of the duration of
the dysrhythmia. Dofetilide appears to be more effective
for cardioversion of atrial flutter than of AF. A response
may take days or weeks when the drug is given orally,
and the intravenous form is investigational (215,216,226-228).
c.
Flecainide
Flecainide administered orally or intravenously was
effective for pharmacological cardioversion of recent-onset
AF in placebo-controlled trials. It has not been evaluated
extensively in patients with persistent AF, but available
information suggests lower efficacy in this setting.
Limited data suggest that flecainide may be more effective
for conversion of AF than of atrial flutter. A response
usually occurs within 3 hours after oral administration
and 1 hour after intravenous administration. Arrhythmias,
including atrial flutter with rapid ventricular rates
and bradycardia after conversion, are relatively frequent
adverse effects. Transient hypotension and mild neurological
side effects may also occur. Overall, adverse reactions
have been reported slightly more frequently with flecainide
than with propafenone, and these drugs should be given
cautiously or avoided entirely in patients with underlying
organic heart disease involving abnormal ventricular
function (206-208,210,220,229-233).
d.
Ibutilide
In placebo-controlled trials, intravenous ibutilide
has proved effective for pharmacological cardioversion
within a few weeks after onset of AF. Available data
are insufficient to establish its efficacy for conversion
of persistent AF of longer duration. Ibutilide is more
effective for conversion of atrial flutter than of AF.
An effect may be expected within 1 hour after administration.
There is a small but definite risk of torsade de pointes
ventricular tachycardia, so serum concentrations of
potassium and magnesium should be measured before administration
of ibutilide, and patients should be monitored for at
least 4 hours afterward. Hypotension is an infrequent
adverse response (234-239).
e.
Propafenone
Placebo-controlled trials have verified that propafenone,
given orally or intravenously, is effective for pharmacological
cardioversion of recent-onset AF. Limited data suggest
that efficacy is reduced in patients with persistent
AF, for conversion of atrial flutter, and in patients
with structural heart disease. The effect occurs between
2 and 6 hours after oral administration and earlier
after intravenous injection. Adverse effects are uncommon
but include rapid atrial flutter, ventricular tachycardia,
intraventricular conduction disturbances, hypotension,
and bradycardia at conversion. Available data on the
use of various regimens of propafenone loading in patients
with organic heart disease are scant. This agent should
be used cautiously or not at all for conversion of AF
in such cases and should be avoided in patients with
congestive HF or obstructive lung disease (208,211,212,221,229-233,240-249).
f.
Quinidine
Quinidine is usually administered after digoxin or verapamil
has been given to control the ventricular response rate.
It is probably as effective as most other drugs for
pharmacological cardioversion of recent-onset AF and
is sometimes effective for correction of persistent
AF. No distinction can be made between its efficacy
for AF and atrial flutter. Potential adverse effects
of quinidine include QT-interval prolongation that may
precede torsade de pointes ventricular tachycardia,
nausea, diarrhea, fever, hepatic dysfunction, thrombocytopenia,
and hemolytic anemia. During the initiation of quinidine
therapy, hypotension and acceleration of the ventricular
response to AF may occur on a vagolytic basis. A clinical
response may be expected 2 to 6 hours after administration
(206,208,211,218,219,247,250-252).
2.
Less Effective or Incompletely Studied Agents
a.
Beta-Blockers
When given intravenously, the short-acting beta-blocker
esmolol may have modest efficacy for pharmacological
cardioversion of recent-onset AF, but this has not been
established by comparison with placebo. Esmolol acts
rapidly, however, to control the rate of ventricular
response to AF. It is not useful in patients with persistent
AF, and there are no data comparing its relative efficacy
for atrial flutter and AF. A response may be expected
within 1 hour. Hypotension and bronchospasm are the
major adverse effects of esmolol and other beta-blockers
(209,253).
b.
Calcium Channel Antagonists (Verapamil and Diltiazem)
The calcium channel antagonist verapamil has not been
shown to be effective for pharmacological cardioversion
of recent-onset or persistent AF, but it acts rapidly
to control the rate of ventricular response (208,209,224,232,246).
Negative inotropic effects contribute to toxicity, which
includes hypotension.
The
calcium channel antagonist diltiazem has not been shown
to be effective for pharmacological cardioversion of
recent-onset or long-standing AF, but like verapamil,
it is effective for control of heart rate (254).
c.
Digoxin
Digitalis glycosides are generally no more effective
than placebo for conversion of recent-onset AF to sinus
rhythm. Digoxin may prolong the duration of episodes
of paroxysmal AF in some patients (255),
and it has not been evaluated adequately in patients
with persistent AF except to achieve rate control. Digoxin
has few adverse effects after acute administration in
therapeutic doses, aside from AV block and acceleration
of ventricular ectopy (211,222,229,249,255-258).
d.
Disopyramide
Disopyramide has not been tested adequately but may
be effective when administered intravenously (254).
Adverse effects include dryness of mucosal membranes,
especially of the mouth; constipation; urinary retention;
and depression of LV contractility. The latter reaction
makes it a relatively unattractive option for pharmacological
conversion of AF.
e. Procainamide
Intravenous procainamide has been used extensively for
conversion of AF within 24 hours of onset, and several
studies suggest that it may be superior to placebo (234,236,259).
Procainamide appears to be less useful than some other
drugs and has not been tested adequately in patients
with persistent AF. Hypotension is the major adverse
effect after intravenous administration of procainamide.
f.
Sotalol
Contrary to its relative efficacy for maintenance of
sinus rhythm, sotalol has no proven efficacy for pharmacological
cardioversion of recent-onset or persistent AF when
given either orally or intravenously. It does, however,
control the heart rate (237,250,251,256,260).
An
issue related to pharmacological cardioversion that
arises frequently is whether the antiarrhythmic drug
should be started in the hospital or on an outpatient
basis. The major concern is the potential for serious
adverse effects, including torsade de pointes ventricular
tachycardia. With the exception of those involving low-dose
oral amiodarone (225),
virtually all studies of pharmacological cardioversion
have been limited to hospitalized patients. (For a more
extensive discussion of out-of-hospital initiation of
antiarrhythmic agents, see Section VIII-E-4,
Out-of-Hospital Initiation of Antiarrhythmic Drugs in
Patients With AF.) (See Tables 6,
7, and 8)
D.
Electrical Cardioversion
1.
Terminology
Direct-current
cardioversion involves delivery of an electrical shock
synchronized with the intrinsic activity of the heart,
usually by sensing the R wave of the ECG. This technique
ensures that electrical stimulation does not occur during
the vulnerable phase of the cardiac cycle, from 60 to
80 ms before to 20 to 30 ms after the apex of the T
wave (263).
Electrical cardioversion is used to normalize all abnormal
cardiac rhythms except ventricular fibrillation. The
term defibrillation implies an asynchronous discharge,
which is appropriate for correction of ventricular fibrillation
but not for AF.
2.
Technical Aspects
Successful
cardioversion of AF depends on the nature of the underlying
heart disease and the current density delivered to the
atrial myocardium. The latter, in turn, depends on the
voltage of the defibrillator capacitor, the output waveform,
the size and position of the electrode paddles, and
transthoracic impedance. The current density delivered
decreases as the impedance increases for a given paddle
surface area. The impedance (264)
is related to the size and composition of the electrode
paddles, the contact medium between the electrodes and
the skin, the distance between the paddles, body size,
phase of the respiratory cycle, number of shocks delivered,
and interval between shocks. Proper attention to each
of these variables is important for successful cardioversion.
The
electrical resistance between the electrode paddles
and the skin should be minimized by the use of electrolyte-impregnated
pads. Pulmonary tissue between the paddles and the heart
inhibits conduction of current, so shocks delivered
during expiration and with chest compression deliver
higher levels of energy to the heart. Large electrode
paddles result in lower impedance than smaller ones,
but when the paddles are too large, current density
through cardiac tissue is insufficient to achieve cardioversion,
whereas undersized paddles may produce too much current
density and cause injury. Animal experiments have shown
that the optimum diameter is one that approximates the
cross-sectional area of the heart. No definite information
has been developed regarding the best paddle size for
the specific cardioversion of AF, but a diameter of
8 to 12 cm (264)
is generally recommended.
Because
the combination of high impedance and low energy reduces
the likelihood of successful cardioversion, it has been
suggested that impedance be measured to shorten the
duration of the procedure, reduce adverse responses,
and improve outcome (265,266).
Kerber et al. (267)
described a technique for automatic impedance-adjusted
energy delivery in which energy is automatically increased
when the impedance exceeds 70 ohms and claimed improved
efficacy in patients with high transthoracic impedances.
The
output waveform also influences the amount of energy
delivered to the heart during electrical cardioversion.
Most equipment used for external cardioversion has a
monophasic waveform. In a randomized trial that compared
cardioversion with a standard damped sine-wave monophasic
waveform with cardioversion applying a rectilinear biphasic
waveform, the 77 patients treated with monophasic shocks
had a cumulative success rate of 79%, whereas 94% of
88 subjects cardioverted with biphasic shocks were successfully
converted to sinus rhythm. Patients in the latter group
required less energy for cardioversion. Independent
correlates of successful conversion were rectilinear
biphasic shocks, thoracic impedance, and the duration
of AF (268).
In their original description of cardioversion, Lown
et al. (269,270)
indicated that an anterior-posterior electrode configuration
was superior to anterior-anterior positioning, but others
disagree (264,271,272).
Anterior-posterior positioning allows enough current
to reach a sufficient mass of atrial myocardium to effect
defibrillation when the pathology associated with AF
involves both the RA and the LA (as in patients with
atrial septal defect or cardiomyopathy), because the
resulting force field encompasses part of the RA wall.
A drawback of this configuration is the comparatively
wide electrode separation and the amount of pulmonary
tissue between the anterior paddle and the heart, particularly
in patients with emphysema. Placing the anterior electrode
to the left of the sternum reduces electrode separation
and the amount of interposed pulmonary tissue. The superiority
of one electrode position over another has not been
firmly established, but the paddles should be placed
directly against the chest wall, under rather than over
breast tissue.
Other
paddle positions result in less effective current flow
through crucial parts of the heart, and their use is
discouraged (264).
In a randomized controlled study of 301 subjects undergoing
elective external cardioversion, patients were allocated
to anterior-lateral (ventricular apex and right infraclavicular)
or anterior-posterior (sternum and left scapular) paddle
positions (273).
The overall success (adding the outcome of low-energy
shocks to that of high-energy shocks) was greater with
the anterior-posterior configuration (87%) than with
the anterior-lateral alignment (76%), and the energy
requirement was lower with the anterior-posterior paddle
configuration. Because the optimum paddle configuration
for a given patient is not known before cardioversion,
the clinician should consider an alternative arrangement
if the initial position proves unsuccessful.
3.
Clinical Aspects
Cardioversion
is performed with the patient having fasted and under
adequate general anesthesia to avoid pain related to
delivery of the electrical shock. Short-acting anesthetic
drugs or agents that produce conscious sedation are
preferred, because cardioversion patients should recover
rapidly after the procedure and usually do not require
overnight hospitalization (274).
The
electric shock should be properly synchronized with
the QRS complex, which calls for triggering by monitoring
the R wave with an appropriately selected lead. In addition
to R-wave amplitude, it is important that the monitored
lead give a good view of P waves, which facilitates
assessment of the outcome of the procedure. The initial
energy delivered with a monophasic waveform may be low
(50 J) for cardioversion of atrial flutter. Higher energy
is required for AF cardioversion, starting with at least
200 J. The energy output is increased successively in
increments of 100 J until a maximum of 400 J is reached.
Some physicians begin with higher energies to reduce
the number of shocks (and thus the total energy) delivered.
Lower energies are required with a biphasic waveform.
To avoid myocardial damage, the interval between 2 consecutive
shocks should not be less than 1 minute (275).
In
a recent study (276),
64 patients were randomly assigned to initial monophasic
waveform energies of 100, 200, or 360 J. Higher initial
energy was significantly more effective than lower levels
(immediate success rates were 14% with 100, 39% with
200, and 95% with 360 J, respectively), resulting in
fewer shocks and less cumulative energy when 360 J was
delivered initially. These data indicate that an initial
shock of 100 J is often too low, and an initial energy
of 200 J or greater is recommended for electrical cardioversion
of AF. Devices that deliver current with a biphasic
waveform are available, and these appear to achieve
cardioversion at lower energy levels than those using
a monophasic waveform.
Rates
of electrical cardioversion of AF vary from 70% to 90%
(277,
278 and 279).
This variability is explained in part by differences
in patient characteristics and in part by the definition
of success. The interval at which the result is evaluated
ranges in the literature from immediately after cardioversion
to several days afterward. Restoration and maintenance
of sinus rhythm are less likely to occur through cardioversion
when AF has been present for longer than a year than
in patients with AF of shorter duration.
Over
time, the proportion of AF caused by rheumatic heart
disease has declined and the average age of the population
has increased (277,279,280),
whereas the incidence of lone AF has remained constant.
These factors make it difficult to compare recent and
older data on the outcome of cardioversion. In a large
consecutive series of patients undergoing cardioversion
of AF, 24% were classified as having ischemic heart
disease, 24% rheumatic valvular disease, 15% lone AF,
11% hypertension, 10% cardiomyopathy, 8% nonrheumatic
valvular disease, 6% congenital heart disease, and 2%
treated hyperthyroidism (277).
Seventy percent of the patients were in sinus rhythm
24 hours after cardioversion. Multivariate analysis
revealed that short duration of AF, presence of atrial
flutter, and younger age were independent predictors
of success, whereas LA enlargement, underlying heart
disease, and cardiomegaly predicted failure. These authors
developed a scheme expressing the likelihood of success
to facilitate clinical decision making and improve cost-effectiveness
by avoiding cardioversion in patients unlikely to sustain
sinus rhythm.
The
primary success rate as measured 3 days after cardioversion
in 100 consecutive subjects (279)
was 86%; this increased to 94% when the procedure was
repeated during treatment with quinidine or disopyramide
after an initial failure to convert the rhythm. Only
23% of the patients remained in sinus rhythm after 1
year and 16% after 2 years; in those who relapsed, repeated
cardioversion with antiarrhythmic medication resulted
in sinus rhythm in 40% and 33% after 1 and 2 years,
respectively. For patients who relapsed again, a third
cardioversion resulted in sinus rhythm in 54% at 1 year
and 41% at 2 years. Thus, sinus rhythm can be restored
in a substantial proportion of patients by direct-current
cardioversion, but the rate of relapse is high unless
concomitant antiarrhythmic drug therapy is given (Figure
13). For patients for whom initial attempts at cardioversion
fail, available adjunctive strategies include alternative
electrode positions, concomitant administration of intravenous
ibutilide, and delivery of higher energy with the use
of 2 defibrillators. It is anticipated that external
cardioversion with a biphasic shock waveform will reduce
the need for these adjunctive maneuvers.
4.
Transvenous Electrical Cardioversion
A
technique for delivering high-energy (200 to 300 J)
direct current internally for cardioversion of AF was
introduced by Lévy et al. in 1988 (281,282),
using an RA catheter and a backplate. In a randomized
trial, internal cardioversion was superior to external
countershock, particularly in obese patients and patients
with chronic obstructive lung disease, but the frequency
of recurrence of AF over the long term did not differ
between the 2 methods. A monophasic shock waveform was
used for external cardioversion in the study; use of
a biphasic waveform would likely necessitate internal
cardioversion considerably less frequently. Other techniques
for internal cardioversion apply low-energy (less than
20 J) shocks via a large-surface cathodal electrode
in the RA and an anode in the coronary sinus or left
pulmonary artery (283-286).
These techniques have been successful for restoration
of sinus rhythm in 70% to 90% of mixed cohorts, including
those who did not respond to external cardioversion
(285-287).
Low-energy internal cardioversion does not require general
anesthesia but is performed under sedation. Indications
might include implanted pacemakers, defibrillators,
or drug infusion pumps, but these are presently under
investigation.
5.
Electrical Cardioversion in Patients With Implanted
Pacemakers and Defibrillators
Cardioversion of patients with implanted pacemaker and
defibrillator devices is feasible and safe when appropriate
precautions are taken to prevent damage. Pacemaker generators
and defibrillators are designed with circuits protected
against sudden external electrical discharges, but programmed
data may nevertheless be altered by sudden current surges.
Electricity conducted along an implanted electrode lead
to the endocardium may cause myocardial injury associated
with a temporary or permanent increase in stimulation
threshold. When pronounced, this may cause exit block
that results in failure of ventricular capture. The
implanted device should be interrogated immediately
before and after cardioversion to verify appropriate
pacemaker function and should be reprogrammed if necessary
to increase generator output. Devices are typically
implanted anteriorly, and the paddles used for external
cardioversion should be positioned as distant as possible
from them, preferably in the anterior-posterior configuration.
The risk of exit block is greatest when one paddle is
positioned near the impulse generator and the other
over the cardiac apex, or lower with the anterior-posterior
electrode configuration and in pacemakers with bipolar
lead systems (288,289).
Low-energy internal cardioversion in patients with implanted
pacemakers and electrodes positioned in the RA and coronary
sinus or left pulmonary artery does not interfere with
pacemaker function (290).
6.
Risks and Complications
The
risks of electrical cardioversion are mainly related
to embolic events and cardiac arrhythmias.
a.
Embolism
Thromboembolic events have been reported in between
1% and 7% of patients who did not receive prophylactic
anticoagulation before cardioversion of AF (291,292).
Prophylactic antithrombotic therapy is discussed below.
b.
Arrhythmias
Various benign arrhythmias may arise after cardioversion
that commonly subside spontaneously, especially ventricular
and supraventricular premature beats, bradycardia, and
short periods of sinus arrest (293).
More dangerous arrhythmias, such as ventricular tachycardia
and fibrillation, may be precipitated in patients with
hypokalemia or digitalis intoxication (294,295).
Serum potassium levels should be in the normal range
for safe, effective cardioversion. Cardioversion is
contraindicated in cases of digitalis toxicity because
the ventricular tachyarrhythmias that are provoked may
be difficult to terminate. A serum digitalis level in
the therapeutic range does not exclude clinical toxicity
but is not generally associated with malignant ventricular
arrhythmias during cardioversion (296),
so it is not routinely necessary to interrupt digoxin
use before elective cardioversion of AF. It is important
to exclude clinical and ECG signs of digitalis excess
and to delay cardioversion until the toxic state has
been eliminated, which usually requires more than 24
hours.
In
patients with long-standing AF, cardioversion commonly
unmasks underlying sinus node dysfunction. A slow ventricular
response to AF in the absence of drugs that slow conduction
across the AV node may indicate an intrinsic conduction
defect. The patient should be evaluated before cardioversion
with these issues in mind to avoid symptomatic bradycardia
(297).
When this risk is anticipated, a transvenous or transcutaneous
pacemaker can be used prophylactically.
c.
Myocardial Injury
Animal experiments show a wide margin of safety between
the energy required for cardioversion of AF and that
associated with clinically relevant myocardial depression
(298,299).
Even without apparent myocardial damage, however, transient
ST-segment elevation may appear on the ECG after cardioversion
(300,301),
and blood levels of creatine kinase may rise. In a study
of 72 elective cardioversion attempts involving an average
energy greater than 400 J (range 50 to 1280 J), serum
troponin-T and -I levels did not rise significantly.
There was a small increase in creatinine kinase-MB mass
levels above the proportion attributable to skeletal
muscle trauma in 10% of patients, and this was related
to the energy delivered (302).
Myocardial damage, even on a microscopic level, related
to direct-current cardioversion has not been confirmed
and is probably not clinically significant.
Before
electrical cardioversion, prophylactic drug therapy
to prevent early recurrence of AF should be considered
individually for each patient. For example, a patient
with lone AF of relatively short duration is less likely
to develop early recurrence than a patient with heart
disease and a longer duration of AF. The latter patient
stands to gain more potential benefit from prophylactic
antiarrhythmic drug therapy before cardioversion. Should
relapse (particularly early relapse) occur, antiarrhythmic
therapy is recommended in conjunction with the second
attempt. Further cardioversion is of limited value,
and patients should be selected carefully. In patients
who are highly symptomatic, for example, infrequently
repeated cardioversion may be an acceptable approach.
Recommendations
for Pharmacological or Electrical Cardioversion of AF
Class
I
1.
Immediate electrical cardioversion in patients with
paroxysmal AF and a rapid ventricular response who
have ECG evidence of acute MI or symptomatic hypotension,
angina, or HF that does not respond promptly to pharmacological
measures. (Level of Evidence: C)
2.
Cardioversion in patients without hemodynamic instability
when symptoms of AF are unacceptable. (Level of
Evidence: C)
Class
IIa
1.
Pharmacological or electrical cardioversion to accelerate
restoration of sinus rhythm in patients with a first-detected
episode of AF. (Level of Evidence: C) (See
Tables 6, 7,
and 8 for recommended drugs.)
2.
Electrical cardioversion in patients with persistent
AF when early recurrence is unlikely. (Level of
Evidence: C)
3.
Repeated cardioversion followed by prophylactic drug
therapy in patients who relapse to AF without antiarrhythmic
medication after successful cardioversion. (Level
of Evidence: C)
Class
IIb
1.
Pharmacological agents for cardioversion to sinus
rhythm in patients with persistent AF. (Level of
Evidence: C)
(See Tables 6, 7,
and 8 for recommended drugs.)
2.
Out-of-hospital administration of pharmacological
agents for cardioversion of first-detected, paroxysmal,
or persistent AF in patients without heart disease
or when the safety of the drug in the particular patient
has been verified. (Level of Evidence: C) (See
Table 8.)
Class III
1.
Electrical cardioversion in patients who display spontaneous
alternation between AF and sinus rhythm over short
periods of time. (Level of Evidence: C)
2.
Additional cardioversion in patients with short periods
of sinus rhythm who relapse to AF despite multiple
cardioversion procedures and prophylactic antiarrhythmic
drug treatment. (Level of Evidence: C)
E.
Maintenance of Sinus Rhythm
1.
Pharmacological Therapy to Prevent Recurrence of AF
a.
Goals of Treatment
Maintenance of sinus rhythm is relevant in patients
with paroxysmal AF (in whom episodes terminate spontaneously)
and persistent AF (in whom electrical or pharmacological
cardioversion is necessary to restore sinus rhythm).
Whether paroxysmal or persistent, AF is a chronic disorder,
and recurrence is likely at some point in most patients
(Figures 13 and 14)
(303,304,
388).
Most patients with AF will therefore need prophylactic
treatment with antiarrhythmic drugs if sinus rhythm
must be maintained.
The
goal of maintenance therapy is suppression of symptoms
and sometimes prevention of tachycardia-induced cardiomyopathy
due to AF. It is not yet known whether maintenance of
sinus rhythm prevents thromboembolism, HF, or death
(178,305).
Because the clinical factors that predispose a patient
to recurrent AF (advanced age, history of HF, hypertension,
LA enlargement, and LV dysfunction) are also risk factors
for thromboembolism, the risk of stroke may not be reduced
by correction of the rhythm. Pharmacological maintenance
of sinus rhythm may reduce morbidity in patients with
HF (227,306),
but one observational study demonstrated that the strategy
of serial cardioversion of persistent AF did not prevent
complications (307).
Pharmacological therapy to maintain sinus rhythm is
indicated in patients who have troublesome symptoms
related to paroxysmal AF or recurrence after cardioversion
and who can tolerate antiarrhythmic drugs.
Throughout
this document, reference is made to the Vaughan Williams
classification of antiarrhythmic drugs (308),
which has been modified to include drugs that became
available after the original classification was developed
(Table 9).
b. End Points in Antiarrhythmic Drug Studies
Over the past decades, various antiarrhythmic drugs
have been investigated for maintenance of sinus rhythm
in patients with AF. The number and quality of studies
with each drug are limited (few meet current standards
of good clinical practice), and end points vary. In
studies of paroxysmal AF, the proportion of patients
without recurrence at the end of follow-up, the time
to first recurrence, the number of recurrences over
a specified interval (an example of arrhythmia burden),
or combinations of these data have been reported. The
arrhythmia burden and quality-of-life assessments from
the patient's viewpoint have not been quantified consistently
in studies of maintenance antiarrhythmic therapy.
In
studies of persistent AF, the proportion of patients
in sinus rhythm at the end of follow-up is a useful
end point, but this is a less useful measure in studies
of paroxysmal AF. Most studies involving patients with
persistent AF used electrical cardioversion to restore
sinus rhythm, with antiarrhythmic drug prophylaxis started
before or after electrical cardioversion. Because transtelephonic
monitoring reveals clustering of the majority of recurrences
in the first few weeks after cardioversion (309,310),
the median time to first recurrence may not differ between
drug and placebo. Because recurrent AF tends to persist,
neither the interval between recurrences nor the number
of episodes in a given period of time (arrhythmia burden)
represents a suitable end point unless a serial cardioversion
strategy is used.
Given
these differences, the appropriate end points for evaluation
of treatment efficacy in patients with paroxysmal and
persistent AF have little in common. This hampers evaluation
of treatment strategies aimed at maintenance of sinus
rhythm in cohorts containing both paroxysmal and persistent
AF patients. Studies of mixed cohorts have not contributed
heavily to the development of these guidelines.
Recurrence
of AF is not equivalent to treatment failure. In several
studies (311,312),
patients with recurrent AF often chose to continue treatment
with a drug, perhaps because episodes of AF were less
frequent, shorter, or associated with milder symptoms.
A reduction in arrhythmia burden may constitute therapeutic
success for some patients, whereas any recurrence of
AF may seem intolerable to others. Assessment based
on time to recurrence in paroxysmal AF or the number
of patients in sinus rhythm after cardioversion in persistent
AF may overlook potentially valuable treatment strategies.
The duration of follow-up varied considerably among
studies and was generally insufficient to permit meaningful
extrapolation to years of treatment in this often lifelong
cardiac rhythm disorder.
Available studies are far from uniform in many other
respects as well. Underlying heart disease or extracardiac
disease is present in 80% of patients with persistent
AF, but this is not always described in sufficient detail.
It is also not always clear when patients had a first
episode of AF and whether it was recent or persistent
AF, and the frequency of previous episodes and previous
electrical cardioversions are not uniformly described.
The efficacy of treatment for atrial flutter and AF
is usually not reported separately. Controlled trials
of antiarrhythmic drugs usually contain few high-risk
patients (those at risk of drug-induced HF, proarrhythmia,
or conduction disturbances), and this should be kept
in mind in applying the recommendations below.
c.
Predictors of Recurrent AF After Restoration of Sinus
Rhythm
Most patients with AF, except those with postoperative
AF, eventually experience recurrence. Risk factors for
frequent recurrence of paroxysmal AF (more than 1 episode
per month) include female gender and underlying heart
disease (313).
In one study of patients with persistent AF, the 4-year
arrhythmia-free survival rate was less than 10% after
single-shock electrical cardioversion without prophylactic
drug therapy (304).
Predictors of recurrences within that interval included
hypertension, age greater than 55 years, and AF duration
greater than 3 months. Even serial cardioversions and
prophylactic drug therapy resulted in freedom from recurrent
AF in only approximately 30% of patients in the same
study (304).
With this serial approach, predictors of recurrence
included age greater than 70 years, AF duration greater
than 3 months, and HF (304).
Other risk factors for recurrent AF include atrial enlargement
and rheumatic heart disease; some of the above parameters
are interrelated (e.g., duration of AF and atrial size).
2.
General Approach to Antiarrhythmic Drug Therapy
Before
any antiarrhythmic agent is administered, reversible
cardiovascular and noncardiovascular precipitants of
AF should be addressed. Most of these relate to CAD,
valvular heart disease, hypertension, and HF. Those
who develop AF in association with alcohol intake should
practice abstinence. Prophylactic drug treatment is
not usually indicated in case of a first-detected episode
of AF. Antiarrhythmic drugs may also be avoided in patients
with infrequent and well-tolerated paroxysmal AF. Similarly,
when recurrences are infrequent and tolerated, patients
experiencing breakthrough arrhythmias may not require
a change in antiarrhythmic drug therapy. In patients
who develop AF only during exercise, administration
of a beta-blocker may be effective, but a single specific
inciting cause accounts for all episodes of AF in relatively
few patients, and a majority will not sustain sinus
rhythm without antiarrhythmic drug treatment. Selection
of an appropriate agent is based first on safety and
is tailored to any underlying heart disease that may
be present, as well as the number and pattern of previous
episodes of AF (314).
In
patients with lone AF, a beta-blocker may be tried first,
but flecainide, propafenone, and sotalol are particularly
effective. Amiodarone and dofetilide are recommended
as alternative therapies. Quinidine, procainamide, and
disopyramide are not favored unless amiodarone fails
or is contraindicated. For patients with vagally induced
AF, however, the anticholinergic activity of long-acting
disopyramide makes it a relatively attractive choice.
Flecainide and amiodarone represent secondary and tertiary
treatment options, respectively, in this situation,
whereas propafenone is not recommended because its (weak)
intrinsic beta-blocking activity may aggravate vagally
mediated paroxysmal AF. In patients with adrenergically
mediated AF, beta-blockers represent first-line treatment,
followed by sotalol and amiodarone. In patients with
adrenergically mediated lone AF, amiodarone should be
chosen later in the sequence of drug therapy (Figure
11).
When
treatment with a single drug fails, combinations of
antiarrhythmic drugs may be tried. Useful combinations
include a beta-blocker, sotalol or amiodarone, plus
a type IC agent. A drug that is initially safe may become
proarrhythmic when the patient develops CAD or HF or
starts other medication that in combination may be arrhythmogenic.
Thus, the patient should be alerted to the potential
significance of such symptoms as syncope, angina pectoris,
or dyspnea and warned about the use of noncardiac drugs
that can prolong the QT interval. A useful source of
information is the Internet site http://www.torsades.org.
Monitoring of antiarrhythmic drug treatment varies with
the agent involved and with patient factors. Prospective
trial data on upper limits of drug-induced increases
in QRS duration or QT prolongation are not available.
The following recomendations are the consensus of the
writing committee. With type IC drugs, QRS widening
should not be permitted to exceed 150% of the pretreatment
QRS duration. Exercise testing may be helpful to detect
QRS widening that occurs only at rapid heart rates (use-dependent
conduction slowing). For type IA or type III drugs,
with the possible exception of amiodarone, the corrected
QT interval in sinus rhythm should remain below 520
ms. During follow-up, plasma potassium and magnesium
levels and renal function should be checked periodically,
because renal insufficiency leads to drug accumulation
and predisposes to proarrhythmia. In individual patients,
serial noninvasive tests may be appropriate to reevaluate
LV function, especially if clinical HF develops during
treatment of AF.
3.
Pharmacological Agents to Maintain Sinus Rhythm
Fourteen
controlled trials of drug prophylaxis involving patients
with paroxysmal AF have been published, and there have
been 22 published trials of drug prophylaxis for maintenance
of sinus rhythm in patients with persistent AF. Comparative
data are not sufficient to permit subclassification
by drug or etiology. Individual drugs, listed alphabetically,
are described below, and dosages for maintenance of
sinus rhythm are given in Table
10.
a.
Amiodarone
Available evidence suggests that amiodarone is effective
for maintenance of sinus rhythm in patients with AF
but is associated with a relatively high incidence of
side effects compared with placebo (315).
Amiodarone is usually used as a second-line or last-resort
agent. Of the 403 patients in the CTAF study (316),
most had first-time paroxysmal (46%) or persistent (54%,
duration less than 6 months) AF. AF was considered persistent
when more than half the previous episodes had required
pharmacological or electrical intervention. This definition
implies that many of the patients designated as having
persistent AF actually had spontaneously terminating
paroxysmal AF. Amiodarone prevented further attacks
beyond the first month in 69% of patients, significantly
more than did propafenone or sotalol (each of which
achieved complete suppression in 39% of 101 patients).
Nevertheless, 11% of the patients assigned to sotalol
or propafenone stopped treatment because of side effects
after a mean of 468 days, compared with 18% of patients
given amiodarone. A placebo-controlled study of amiodarone
and sotalol that predominantly involved patients with
paroxysmal AF (317)
produced results similar to those in the CTAF study.
Other uncontrolled, observational studies in patients
with paroxysmal AF refractory to 1 or more type I agents
support the antiarrhythmic efficacy of amiodarone (318-320).
The
selection of a pharmacological agent should be based
on the arrhythmia burden, type of underlying heart disease,
severity of symptoms, risk of side effects, and patient
preferences. Considering the paucity of adequate data
from randomized trials, as well as its side effect profile,
amiodarone should only be used cautiously as a first-line
agent in paroxysmal AF. An exception is its use in patients
with HF, for whom amiodarone appears to offer distinct
advantages over other agents in terms of relative risks
and benefits.
There
are scant prospective comparative data available on
the use of amiodarone to maintain sinus rhythm in patients
with persistent AF, but a favorable outcome has been
reported when amiodarone was given as a last-resort
agent in uncontrolled studies. Amiodarone is particularly
useful in AF complicated by HF, but its use is limited
by potentially severe extracardiac side effects. The
use of low-dose amiodarone (200 mg daily or less) may
be effective and may be associated with fewer side effects
(218,316,322).
To
date, only a few randomized studies have been performed
with amiodarone after cardioversion in patients with
persistent AF. Amiodarone was tested as a first-line
agent in a study confined to postcardioversion patients
(322).
After electrical cardioversion, but before randomization,
patients were stratified according to age, duration
of AF, mitral valve disease, and cardiac surgery. After
6 months, amiodarone was more effective than quinidine;
83% of patients remained in sinus rhythm with amiodarone
vs. 43% who were given quinidine. Amiodarone therapy
was associated with fewer side effects than quinidine
over this interval, but side effects tend to occur after
more prolonged treatment with amiodarone. In a single-crossover
study of 32 patients randomized to amiodarone or quinidine
(218)
in which patients with persistent AF for more than 3
weeks were treated with amiodarone when pharmacological
conversion did not occur with quinidine (electrical
cardioversion was not used), amiodarone was better tolerated,
and considering the patients whose treatment crossed
over, it was far more effective in achieving conversion
of AF and long-term maintenance of sinus rhythm. After
9 months, 18 (67%) of 27 amiodarone-treated patients
were in sinus rhythm vs. 2 (12%) of 17 patients taking
quinidine.
Among
uncontrolled studies (223,318,319,323-326),
one involved 89 patients with persistent AF for whom
previous treatments had failed; actuarially, 53% of
these patients were in sinus rhythm after 3 years of
amiodarone therapy (323).
In another study (318)
of 110 patients with refractory AF or atrial flutter
for whom a median of 2 type I agents had failed (57
with paroxysmal AF) and who were followed up for 5 years,
amiodarone (268 plus or minus 100 mg daily) was associated
with recurrence in 9% of patients with persistent AF
and 40% of those with paroxysmal AF. Several other uncontrolled
studies support the use of amiodarone as a last-resort
agent (319,324-326).
In one, a dose of 200 mg per day appeared to be effective
in patients for whom cardioversion had failed; 52% underwent
repeated cardioversion with success for 12 months (223).
b.
Beta-Blockers
One randomized, open-label, crossover study showed that
atenolol 50 mg once daily was as effective as sotalol
80 mg twice daily and better than placebo at suppressing
ECG-documented episodes of AF, reducing their duration
and associated symptoms (327).
The study involved stable, nonpostoperative patients.
The dose of sotalol was lower than that generally used
for suppression of recurrent AF, and both drugs were
well tolerated. Beta-blockers have the advantage of
controlling the ventricular rate in the event AF recurs
during treatment, and they thereby reduce or abolish
associated symptoms, but the patient's unawareness of
recurrent AF may be a disadvantage in certain cases.
These agents may benefit postoperative patients but
may aggravate vagally mediated AF. One placebo-controlled
study (328)
of 394 patients found metoprolol to be moderately effective
in preventing postshock recurrences of AF (reduced to
49% vs. 60%, respectively).
c.
Digoxin
The evidence available does not support a role for digitalis
in suppressing recurrent AF in most patients. The lack
of an AV blocking effect during sympathetic stimulation
results in poor rate control with digoxin, and hence
its use does not usually reduce symptoms associated
with recurrent paroxysmal AF (22).
d.
Disopyramide
Several small randomized studies support the efficacy
of disopyramide to prevent recurrent AF after electrical
cardioversion. One study comparing propafenone and disopyramide
showed equal efficacy, but propafenone was better tolerated
(329).
Treatment with disopyramide for more than 3 months after
cardioversion was associated with an excellent long-term
outcome in an uncontrolled study (98 of 106 patients
were free of recurrent AF; of these, 67% remained in
sinus rhythm after a mean of 6.7 years). Although the
duration of AF was more than 12 months in most of these
patients, few had significant underlying cardiac disease
other than previously treated thyrotoxicosis. It is
not clear, therefore, whether disopyramide was the critical
factor in suppressing AF (330).
Disopyramide has negative inotropic and negative dromotropic
effects that respectively may cause HF or precipitate
AV block (329-333).
e.
Dofetilide
Several large-scale, double-blind, randomized studies
support the efficacy of dofetilide for prevention of
AF or atrial flutter (261,334).
To reduce the risks of proarrhythmia, dofetilide should
be initiated in the hospital at a dose titrated to renal
function and the QT interval. This provides a measure
of safety in the event of early proarrhythmic toxicity.
Combined results from 966 patients in the SAFIRE-D (Symptomatic
Atrial Fibrillation Investigative Research on Dofetilide)
and EMERALD studies found dofetilide treatment to be
associated with conversion to sinus rhythm, and this
effect was dose related: 6%, 10%, and 30% of patients
responded within 72 hours to 125, 250, and 500 mcg twice
a day, respectively (261,334).
Most (87%) conversions occurred within 30 hours after
treatment was initiated. The incidence of torsade de
pointes was 0.8%. Four of 5 of these incidents occurred
in the first 3 days. In SAFIRE-D, dofetilide was associated
with 40%, 52%, and 66% of patients in sinus rhythm at
6 months in the 125-, 250-, and 500-mcg-daily dosage
groups, respectively, compared with 21% with placebo
(261).
In EMERALD, suppression of recurrence of AF by dofetilide
was also dose dependent: 51%, 57%, and 71% of patients
were in sinus rhythm with 125, 250, and 500 mg daily,
respectively, compared with approximately 25% with placebo
and 60% with sotalol (334).
f.
Flecainide
Two placebo-controlled studies (311,335)
found flecainide to be effective in postponing the first
recurrence of AF and the overall time spent in AF; and
other randomized studies (336,337)
found its efficacy to be comparable to that of quinidine,
with fewer side effects. Efficacy is further supported
by uncontrolled studies (312,338).
Van
Gelder et al. (339)
showed that time to recurrence of AF was significantly
longer with flecainide than without treatment, and severe
ventricular proarrhythmia or sudden death was not observed
with a mean dose of 199 mg daily. Side effects occurred
in 5 patients (9%) and were predominantly related to
negative dromotropism, with or without syncope. Compared
with long-acting quinidine (1,100 mg daily), flecainide
(200 mg daily) was superior in preventing recurrent
AF after cardioversion and was associated with fewer
side effects, but 1 patient died suddenly a month after
entry, presumably due to proarrhythmia (339).
g. Morizicine
Although few data are presently available regarding
the efficacy of moricizine (340),
further studies may define a role for its use in patients
with AF.
h. Procainamide
No adequate studies are available. Long-term treatment
with procainamide is frequently associated with development
of antinuclear antibodies and is occasionally associated
with arthralgias or agranulocytosis.
i.
Propafenone
The UK PSVT (paroxysmal supraventricular tachycardia)
study was a large, randomized, placebo-controlled trial
of propafenone in which transtelephonic monitoring was
used to detect and document relapses of AF (341).
The primary end point was time to first recurrence or
adverse event. A dose of 300 mg twice daily was effective;
300 mg 3 times a day was even more effective but caused
more frequent side effects. In one small, placebo-controlled
study (342),
only those patients who tolerated an initial average
propafenone dose of 688 mg per day were randomized to
the drug group. Compared with placebo, propafenone reduced
the percentage of days in AF from 51% to 27%. Propafenone
was more effective than quinidine in another randomized
comparison (343).
In an open-label randomized study involving 100 AF patients
(approximately half with paroxysmal and half with persistent
AF), propafenone and sotalol were equally effective
in maintaining sinus rhythm (30% vs. 37% of patients
in sinus rhythm at 12 months, respectively) (344).
The pattern of AF (paroxysmal or persistent), LA size,
and previously unsuccessful drug therapy did not predict
the response, but statistical power was quite limited.
Other uncontrolled studies, usually involving selected
patients previously refractory to other antiarrhythmic
drugs, also support the efficacy of propafenone (345-349).
Like
other highly effective type IC drugs, propafenone should
not be used in patients with ischemic heart disease
or LV dysfunction. Close follow-up is necessary to avoid
adverse effects due to changes in cardiac condition
(e.g., development of ischemia or HF).
In
a randomized study, propafenone and disopyramide appeared
to be equally effective in preventing postcardioversion
AF, but propafenone was better tolerated. As mentioned
previously, in the study by Reimold et al. (344),
propafenone was as effective as sotalol. The effect
of propafenone in the CTAF study (316)
is discussed above. A few observational studies involving
mixed cohorts of patients with paroxysmal and persistent
AF have shown propafenone to be effective in terms of
maintenance of sinus rhythm and reduction of arrhythmia-related
complaints (348).
j. Quinidine
Quinidine has not been evaluated extensively in patients
with paroxysmal AF but appears to be approximately as
effective as type IC drugs (336,337,350).
In one study (343),
quinidine was less effective than propafenone (22% of
patients were attack free with quinidine vs. 50% with
propafenone). Side effects are more prominent than with
other antiarrhythmic drugs, and proarrhythmia is a particular
concern. A meta-analysis involving patients treated
with quinidine to maintain sinus rhythm after cardioversion
of AF showed an increase in mortality compared with
placebo, but this was based on a total of 12 deaths
(351).
A
meta-analysis of 6 trials found quinidine to be superior
to no treatment (50% vs. 25% of patients, respectively,
remained in sinus rhythm over a 1-year period). Total
mortality was significantly higher among patients given
quinidine (12 of 413 patients; 2.9%) than among those
not given quinidine (3 of 387 patients; 0.8%) (351).
In a registry analysis (352),
6 of 570 patients less than 65 years old died suddenly
shortly after restoration of sinus rhythm while taking
quinidine. Up to 30% of patients taking quinidine experience
intolerable side effects, most commonly diarrhea. Other
investigators (353)
found sotalol and quinidine to be equally effective
for maintaining sinus rhythm after electrical cardioversion
of AF. Sotalol but not quinidine reduced heart rate
significantly in patients with recurrent AF, contributing
to fewer symptoms with sotalol therapy (278,333,351,353-361).
k.
Sotalol
Sotalol is not effective for conversion of AF to sinus
rhythm, but it may be used to prevent AF. To date, 2
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