From the Harvard-Thorndike Electrophysiology Institute and Arrhythmia
Service, Beth Israel Deaconess Medical Center, Boston, Mass.
Correspondence to Mark E. Josephson, MD, Director, Harvard-Thorndike Electrophysiology Institute and Arrhythmia Service, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215.
Atrial fibrillation
(AF) is the most common arrhythmia for which patients are
hospitalized.1 It imposes important morbidity and
mortality on patients' lives, engendering enormous expenditures for
its management. The frequency of AF increases with age (10% in
patients >70 years old) and with the presence of congestive heart
failure (up to 25%). Clinically, the appearance of AF may be
associated with a variety of symptoms, including palpitations, heart
failure, syncope, and chest pain, which occur primarily because of the
heart rate. In addition, AF imposes an important risk of
thromboembolism and the potential for the development of
tachycardia-mediated cardiomyopathy. It
has been estimated by some that nearly 40% of strokes in patients >70
years old may be a result of AF.2 Whereas the
financial burden imposed by AF itself is enormous, the added cost of
caring for its sequelae, particularly cerebrovascular accidents, makes
successful management of AF imperative.3 4
Heretofore, the management of AF has been empirical and not very
effective. Physicians are divided as to whether it is more important to
maintain sinus rhythm or control the heart rate. The choice of therapy
is dependent on the physician caring for the patient: internists,
cardiologists, and electrophysiologists may choose different
regimens.
Studies evaluating rate control by use of drugs singularly or in
combination have shown that 50% of patients demonstrate adequate rate
control with pharmacological therapy. Use of antiarrhythmic agents to
prevent AF and maintain sinus rhythm is fraught with lack of efficacy,
intolerance, and potentially lethal side effects. Although many studies
have demonstrated that anticoagulation with coumarin can reduce
the risk of thromboembolic phenomena, that risk is only reduced to
perhaps 1% per year, approximately the same as the risks of
coumarin.5 Thus, in my opinion, the most
desirable therapy would be the use of some therapy that maintains sinus
rhythm and eliminates the need for anticoagulation. This is supported
by a Markov model of AF management.6
Because drugs have shown limited efficacy and significant side effects,
interest in the development of nonpharmacological therapy for AF has
arisen. At the present time, ablation of the AV node with pacemaker
implantation is an accepted form of rate control that definitely works,
is associated with hemodynamic benefits, and does not
require drugs, with their attendant side
effects.7 This form of therapy, although it is
usually used for drug-refractory cases, may in fact become a procedure
of choice in patients who need pacemakers because of brady-tachy
syndrome and, in particular, those who have
cardiomyopathies and AF with rapid responses, in
whom ß-blockers and calcium blockers may be more detrimental to their
hemodynamic function. In patients with the sick sinus
syndrome, atrial pacing has been shown to be beneficial compared with
ventricular pacing for prevention of the development of
chronic AF, decreasing mortality and thromboembolic
events.8 More recent data suggest that dual-site
right atrial pacing, bicameral pacing, and coronary sinus
pacing alone may be more useful in preventing AF than high right atrial
rate pacing alone.9 10 11
The poor success of maintenance of sinus rhythm with
drugs and subsequent thromboembolic sequelae have even led to the
development of a surgical procedure (the maze operation) that
compartmentalizes the atrium so that it cannot
fibrillate.12 Although this procedure can achieve
sinus rhythm, it carries with it significant morbidity, and the actual
hemodynamic and antithrombotic benefits of sinus rhythm
with abnormal atrial contraction are not clear. Catheter techniques are
also currently being used to mimic the maze
procedure.13 These procedures have significant
morbidity and an unknown success rate of maintaining sinus rhythm. At
this time, they should be considered experimental. Recent observations
have demonstrated that focal atrial tachycardias or atrial
premature complexes can precipitate some cases of paroxysmal
AF.14 In such instances, these atrial
tachycardias and/or atrial premature complexes have been
successfully ablated and prevented AF.14 Other
investigators have demonstrated that a combination of drugs that
convert AF to atrial flutter combined with a simple flutter ablation
can restore and maintain sinus rhythm and does not result in impaired
atrial function.15
Over the past several years, evidence has accumulated that electrical
and anatomic remodeling of the atrium occurs during the initial periods
of AF.16 This has led to the concept that AF
begets AF, which in turn suggests that early restoration of sinus
rhythm might decrease the recurrence rate of AF or even, in
some cases, prevent its recurrence. About the same time, it was
demonstrated that internal cardioversion could successfully restore
sinus rhythm in patients in whom external cardioversion could
not.17 Although these initial studies required
high energies delivered between a lead in the right atrium and a patch
on the chest, Levy et al18 subsequently
demonstrated that low-energy (3-J) shocks between a right atrial and a
coronary sinus coil using biphasic waveforms could convert AF,
particularly when it was present for <1 year. These findings led
to the concept of an implantable atrial defibrillator that could
restore sinus rhythm rapidly by use of low-energy shocks, thereby
leading to maintenance of sinus rhythm for greater periods of
time, lowering the thromboembolic complications of AF, and decreasing
the negative effects of AF on cardiac function.
In this issue of Circulation, Wellens et
al19 present the first experience with an
implantable atrial defibrillator (Atrioverter) as a method of
converting AF to sinus rhythm. This multicenter, nonrandomized study
was undertaken to evaluate the efficacy, safety, and potential utility
of this device in patients with AF at low risk for
ventricular arrhythmias. This trial involved 19
sites, from which only 51 patients met inclusion criteria. In this
highly selected patient group, the Atrioverter, which was manually
activated by a physician, was able to achieve sinus rhythm for
at least a brief period of time in 96% of patients with AF. However,
early recurrence of AF within seconds to minutes was observed
in 26% of episodes (62) in 21 of the 41 patients who had AF.
This was able to be treated successfully with the device, with the
addition of intravenous or oral antiarrhythmic agents in 36
patients. The remaining 26 episodes required either external
countershock,1 subsequent intravenous
drug administration,6 or allowance for late
spontaneous conversion.19 The overall success
rate of the device for cardioversion to stable sinus rhythm with or
without additional drugs was 86%. The number of shocks required to
successfully terminate AF is difficult to ascertain. Although 670
shocks were given for 227 episodes (3 per episode), it is unclear in
how many patients the first shock was successful. Up to 8 shocks were
delivered for the acute failures or earlier recurrence of
AF.
There was a rather high complication rate in this trial: subclavian
vein thromboses (n=2), tamponade (n=1), and requirement for right
atrial lead repositioning for lead dislodgment (n=1) or increasing
defibrillation thresholds with inability to successfully convert AF
(n=3). There was 1 ventricular lead dislodgment. In all
cases, the leads could be successfully repositioned with adequate
defibrillation thresholds. In 1 patient, the system was removed because
of frequent episodes and shocks and was replaced by a standard
dual-chamber pacemaker after this bundle ablation. In another, it was
removed because of infection. Although the high incidence of
complications seems remarkable, it is somewhat reminiscent of the early
experience with ICDs. Of importance is that there were 19 sites, some
of which had only 1 patient included. If only sites with larger
experiences were included, the effect of a "learning curve" would
be seen. In 1 center that has implanted 16 systems and has a large
pacemaker and ICD experience, there were no dislodgments and no
failures (Hein Wellens, MD, oral communication, July 1998). Thus,
experience as with the implantable Atrioverter and other systems
significantly affects outcomes. Efficacy was hard to evaluate from the
data presented. Although the device can convert AF (96%
successfully), a large number of patients (52%) needed multiple shocks
and/or drugs due to early recurrence of AF, and 26 episodes
subsequently required an additional intervention or allowance of
spontaneous cardioversion. These findings stress an important
limitation of the use of the system as an automatic device. In this
study, all patients underwent initiation of therapy by a physician for
the first 3 months, after which the patient could activate the
devices themselves. This is usually done at home. It is possible,
however, that in this type of patient population (ie, low
ventricular arrhythmia risk), the device may be
initially programmed in the automatic mode. If automatically delivered
therapy fails, subsequent therapy can be initiated in a doctor's
office, emergency room, or arrhythmia clinic. In either
instance, the Atrioverter would decrease hospital admissions and
associated costs of inpatient cardioversions. Safety has been a big
concern, but in this low-risk group, 670 shocks given for 227 episodes
of AF and 3049 shocks given during testing were not associated with any
ventricular proarrhythmia. This is primarily
because therapy can be delivered only after a 500-ms RR cycle. The
sensing algorithms also were fine, with 92.3% of AF being recognized
as AF. More importantly, the system was 100% specific, ie, sinus
rhythm was recognized as sinus rhythm. The atrial defibrillator needs
to err on the side of being specific so that it does not give
inappropriate shocks for a nonlethal arrhythmia, in contrast to
ventricular defibrillators, which must err on the side of
being too sensitive so that lethal ventricular
arrhythmias are not missed. Another issue that needed to be
addressed was patient tolerance. In this study, patient tolerance
appeared to be good, particularly for the first shock. It has been
shown that patients tolerate the first shock quite well; tolerance
diminishes and sedation is required only with increasing numbers of
shocks.20 Subsequent unpublished data from
Wellens' laboratory (oral communication, July 1998) and others are all
consistent with this initial experience.
Several issues need to be addressed regarding the potential role of the
Atrioverter. The present study demonstrates that it can
successfully convert AF to sinus rhythm, that in this low-risk patient
population there was no ventricular proarrhythmia,
and that it is generally well tolerated. However, it is unclear which
patients are appropriate candidates for such a device. Only 51 patients
were selected in 19 centers, suggesting a large bias in patient
selection. One needs to know how these patients were selected and what
the clinical presentation of AF was: paroxysmal AF,
persistent versus chronic AF. It is stated that the 51 patients came
from 119 patients who were screened. This suggests that successful
cardioversion at 260 V can be achieved in only 43% of patients in whom
it is tested. The question that was not addressed is to define the
population in which the screening process would be initiated. This
would help define the population in whom the Atrioverter might be a
valuable therapy. People with paroxysmal AF are probably poor
candidates because of their very frequent nonsustained, short-lived
episodes of AF, which would require too many shocks from the device.
People with chronic AF of >1 year's duration are probably also not
ideal candidates.
What is the future role of an atrial defibrillator? Recent advances
have suggested that atrial pacing may prevent AF and that either
dual-site, bicameral, or coronary sinus pacing alone may be
beneficial.9 10 11 A natural evolution of the
current Atrioverter would be to have pacing capability in addition to
defibrillation capability. The combination of a device capable of
dual-chamber pacing and atrial defibrillation, with or without
pharmacological agents, will increase the patient population in whom
the Atrioverter could be used and ensure a higher incidence of
prevention of AF. The concept of atrial defibrillation is also
applicable to patients with primary ventricular
arrhythmias who also have AF. Perhaps 5% to 20% of patients
requiring ventricular ICDs have coexistent AF.
A combined atrial and ventricular defibrillator system with
dual-chamber pacing might be very useful for this group of patients.
Such a device, the Jewel AF, is available in Europe as an
investigational system. It is unclear what type of device should be
used in patients who have a substrate for ventricular
arrhythmias but have never experienced an episode. The
Atrioverter has a high safety record in patients without a known
ventricular arrhythmia substrate, but it is not
known how safe it will be in patients with organic heart disease. The
manufacturer is now doing a similar study of the Atrioverter in
patients with organic heart disease but without prior
ventricular arrhythmias to assess its safety in
such patients. Whether or not this device alone will be safe or whether
such patients will require ventricular defibrillation
backup is unknown.
In summary, it is clearly established that low-energy internal
cardioversion can successfully convert AF to sinus rhythm. Time will
tell whether early conversion of sinus rhythm will actually decrease
the frequency of AF, and we are awaiting data about this important
outcome. Concerns will always exist related to costs, efficacy, and
safety in all patient populations, as well as tolerability,
particularly in patients who have high defibrillation thresholds and
require multiple shocks. Present indications for the device include
recurrent symptomatic, drug-refractory AF in the absence of
a substrate of ventricular arrhythmia in patients
in whom the episodes require cardioversion every 1 to 2 months.
Expansion of these indications is on the horizon. This will be
especially true when the system is combined with dual-chamber pacing
and drugs. If proven safe in patients with organic heart disease, such
a device, particularly with dual-chamber pacing, may be a primary
potential therapeutic option or a component of hybrid therapy in
patients with recurrent symptomatic AF and mild to moderate
heart failure aggravated by AF, those with AF and hypertrophic
cardiomyopathy, those with recurrent AF who have a
high embolic risk who are poor candidates for anticoagulation, and
those with AF-induced syncope or angina, perhaps in combination with
linear RF ablations, which reduce the frequency of episodes and lower
defibrillation thresholds.
Footnotes
The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
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© 1998 American Heart Association, Inc.
Editorial
New Approaches to the Management of Atrial Fibrillation
The Role of the Atrial Defibrillator
Key Words: Editorials • fibrillation • defibrillation
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