1. health and fitness
2. disease

UPDATE ARTICLE
JIACM 2003; 4(3): 213-27
Atrial Fibrillation :
Present Treatment Protocols by Drugs and Interventions
Indranill Basu Ray*
Abstract
Atrial fibrillation is the commonest arrhythmia encountered in clinical practice. Whereas in western nations it is the elderly
population who are at risk, in countries like India, where rheumatic heart disease is rampant, it is a common cause of mortality and
morbidity in the young. The last decade has witnessed the emergence of a number of therapeutic protocols, both invasive and noninvasive, to treat this rhythm disorder. This article intends to provide a comprehensive profile of the latest treatment modalities
for this arrhythmia.
Atrial fibrillation (AF) is the most common sustained
arrhythmia encountered in clinical practice.
Approximately 0.4 percent of persons in the general
population have permanent or intermittent atrial
fibrillation, and the prevalence of the arrhythmia increases
to 6 percent in persons older than 80 years 1. Atrial
fibrillation can result in serious complications, including
congestive heart failure, myocardial infarction, and
thromboembolism. Considerable evidence has
accumulated that points to the fact; atrial fibrillation
occurring in a background of Rheumatic Heart Disease,
as is rampant in India, is decidedly associated with
increased risk of stroke than that without. In the
Framingham Heart Study, patients with rheumatic heart
disease and AF had a 17-fold increased risk of stroke
compared with age matched controls, and the attributable
risk was 5 times greater than in those with non-rheumatic
AF2. In recent years, management strategies for atrial
fibrillation have expanded significantly, and new drugs for
ventricular rate control and rhythm conversion have been
introduced 3. Despite this, its medical control is still
unsatisfactory. Recurrence of arrhythmia is common and
upto 50 % of patients may experience a relapse of atrial
fibrillation during a given anti-arrhythmic drug therapy
within one year4. On the other hand, almost 20% of
patients do not tolerate effective drugs, and proarrhythmic
events may occur, specially in the patients with left
ventricular dysfunction5. In permanent atrial fibrillation,
the lack of success of drugs is usually demonstrated as an
inadequate ventricular rate control during exercise and
the daily activity of the patients 6. The limitations of
pharmacological therapy have led to novel nonpharmacological, interventional approaches for treatment
of atrial fibrillation. They can be used to prevent atrial
fibrillation, to control ventricular rhythm during
arrhythmia, to eliminate arrhythmogenic substrate
responsible for maintenance of atrial fibrillation, or to
convert atrial fibrillation to sinus rhythm. Thus, the
appropriate treatment in a case of atrial fibrillation must
be tailored to the particular patient’s needs; with the
choice available from drug therapy to interventional
procedures, or a combination of both. Physicians handling
such cases, whether in office practice, or in emergencies,
have the challenge of keeping current with
recommendations on heart rate control, antiarrhythmic
drug therapy, cardioversion, antithrombotic therapy, and
which cases need to be referred for interventional therapy.
This article intends to provide a panoramic view of the
present management strategies for atrial fibrillation.
Diagnosis
The diagnosis of atrial fibrillation should be considered in
patients who present with complaints of shortness of
breath, dizziness, or palpitations. The arrhythmia should
also be suspected in patients with acute fatigue or
exacerbation of congestive heart failure7. In some patients,
atrial fibrillation may be identified on the basis of an
irregularly irregular pulse or an electrocardiogram (ECG)
obtained for the evaluation of another condition. Cardiac
* Cardiologist, Interventional Electrophysiology and Device Therapy, Cardiac Arrhythmia Service,Terrence Donnelly
Heart Centre, Department of Cardiology, Faculty of Medicine, St Michael’s Hospital,
University of Toronto, Ontario, Canada. M5Y W1B.
conditions commonly associated with the development
of atrial fibrillation include rheumatic mitral valve disease,
coronary artery disease, congestive heart failure, and
hypertension. Non-cardiac conditions that can predispose
patients to develop atrial fibrillation include
hyperthyroidism, hypoxia, alcohol intoxication, and
surgery7.
The ECG is the mainstay for diagnosis of atrial
fibrillation (Figure 1). An irregularly irregular rhythm,
inconsistent R-R interval, and absence of P waves are
usually noted on the cardiac monitor or ECG. Atrial
fibrillation waves (f waves), which are small, irregular
waves seen as a rapid-cycle baseline fluctuation,
indicate rapid atrial activity (usually between 150 and
300 beats per minute) and are the hallmark of the
arrhythmia. Atrial fibrillation should also be
distinguished from atrial tachycardia with variable
atrioventricular block, which usually presents with an
atrial rate of approximately 150 beats per minute. In
this condition, the atrial rate is regular (unlike the
irregular disorganised f waves of atrial fibrillation), but
conduction to the ventricles is not regular. The
resultant irregularly irregular rhythm may be difficult
to differentiate from atrial fibrillation. It is also
important to comprehend that variation exists, though
rare, where AF can present with regular RR interval.
Situations such as the presence of AV block or
interference by ventricular or junctional tachycardia
can induce such a possibility.
Emergency management protocol
Recent advances in treatment and the introduction of
new drugs have not changed initial management goals
in patients with atrial fibrillation. These goals are
essentially three: haemodynamic stabilisation,
ventricular rate control, and prevention of embolic
complications 8-10 . When atrial fibrillation does not
terminate spontaneously, the ventricular rate should
be treated to slow ventricular response and, if
appropriate, efforts should be made to terminate atrial
fibrillation and restore sinus rhythm8. The algorithm to
follow is depicted in figure 2.
Beta blockers and calcium channel blockers are the
drugs of choice because they provide rapid rate
control8,11. These drugs are effective in reducing the
heart rate at rest and during exercise in patients with
atrial fibrillation 8,11. Factors that should guide drug
selection include the patient’s medical condition, the
presence of concomitant heart failure, the
characteristics of the medication, and the physician’s
experience with specific drugs. An illustrative example
would be: unless contraindicated it would be pertinent
to add a beta blocker to a patient with known coronary
artery disease. Whereas in the patient with similar
disease profile but having additionally bronchial
asthma, a calcium channel blocker would be an
appropriate prescription. Compared with beta blockers
and calcium channel blockers, digoxin is less effective
for ventricular rate control, particularly during exercise.
Digoxin is most often used as adjunctive therapy
because of its slower onset of action (usually 60
minutes or more), and its weak potenc y as an
atrioventricular node- blocking agent12. It can be used
when rate control during exercise is of less concern11.
Digoxin being a positive inotrope is a suitable
alternative in patients with systolic heart failure.
Fig. 1 : ECG showing atrial fibrillation. Note varying RR intervals. No discrete P waves are seen. Undulating baseline is due to fibrillatory f waves.
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Vol. 4, No. 3
July-September 2003
Fig. 2 : Algorithm for acute AF management. Key:TEE = transoesophageal echocardiography.
The calcium channel blockers diltiazem and verapamil are
effective for initial ventricular rate control in patients with
atrial fibrillation. These agents are given intravenously in
bolus doses until the ventricular rate becomes slower11.
Other calcium channel blockers do not show antiarrythmic effect and are thus not used. A common
emergency protocol is to first give; 15 mg of diltiazen
Journal, Indian Academy of Clinical Medicine
intravenously over two minutes, repeat the dose in 15
minutes if necessary, and then start an intravenous
infusion of 15 mg per hour; titrate the dose to control the
ventricular rate (5 to 15 mg per hour). Verapamil, in a dose
of 5 to 10 mg administered intravenously over two
minutes and repeated in 30 minutes if needed, can also
be used for initial rate control. Although all calcium
Vol. 4, No. 3
July-September 2003
215
channel blockers can cause hypotension, verapamil
should be used with particular caution because of the
possibility of prolonged hypotension as a result of the
drug’s relatively long duration of action.
Beta blockers such as propranolol and esmolol may be
preferable to calcium channel blockers in patients with
myocardial infarction or angina, but they should not be
used in patients with asthma as stated before. As initial
treatment, 1 mg of propranolol is given intravenously over
two minutes; this dose can be repeated every five minutes
upto a maximum of 5 mg. Maintenance dosing of
propranolol is 1 to 3 mg given intravenously every four
hours. Esmolol has an extremely short half-life and may
be given as a continuous intravenous infusion to maintain
rate control.
An issue for concern about calcium channel blockers
and beta blockers when used for initial ventricular rate
control is their cardio-depressive effects, particularly
in patients with heart failure. However, as a common
practice – though not appropriately supported by data,
one should feel comfortable in using these agents with
an echocardiographic or MUGA determined ejection
fraction of over 20%. It is evident that oxygen delivery
to the heart is usually much improved once the
ventricular rate is controlled (less than 100 beats per
minute). A slower ventricular response rate, it may be
recalled, also allows more filling time for the heart and,
thus, improved cardiac output. There is evidence that
combination regimens provide better rate control than
any agent alone1. Table I shows the drugs used for rate
control.
Rate or rhythm control
Haemodynamically unstable AF requires electrical
cardioversion; 50 to 360 Joules is applied to achieve
the same. Following cardioversion, these patients may
be put on anti-arrythmics to maintain sinus rhythm.
Sotalol 13,14, amiodarone 15 , and dofetilide 16 all have
moderate efficacy in maintaining sinus rhythm, with
amiodarone appearing to be the most efficacious.
Although these agents have a common antiarrhythmic classification and similar cost, they have
different characteristics that are used in appropriate
drug selection for an individual patient.
216
All three agents have potential for pro-arrhythmia;
however, amiodarone has minimal risk of torsades de
pointes compared with sotalol and dofetilide. Thus, in
patients having their QTc in the upper ends of the
normal or are under a condition that prolongs QT (on
liquid protein diet, taking terfendrine or astemizole as
antiallergic medication); it would be safer to use
amiodarone. Amiodarone and dofetilide have been
proved safe in patients with left ventricular dysfunction
after myocardial infarction, and those with heart
failure. Whereas d-sotalol was found to increase
morbidity and mor tality in patients with a
compromised left ventricular ejection fraction after
myocardial infarction and those with symptomatic
heart failure. The safety of the commercially available
d, l-sotalol in this patient population is poorly
understood and is thus used with appropriate caution.
Another important mode of drug selection is based
on the adverse effect profile of the concerned
pharmaceutical agent. Sotalol and dofetilide have
minimal non-cardiac adverse effects; however, the risk
of torsades de pointes for both agents and the risk of
bradycardia with sotalol increase significantly with
renal insufficiency, and dosage adjustments are
needed in this setting. Also, sotalol and dofetilide
require hospitalisation during initiation of therapy,
thereby increasing associated costs. Dosage
adjustment of amiodarone is not required in renal
insufficiency. The main concern with amiodarone is its
various non-cardiac toxicities, including hepatotoxicity,
thyroid dysfunction, ophthalmologic, and gastrointestinal disturbances, and pulmonary fibrosis. These
adverse effects warrant diligent organ system
monitoring, thereby increasing associated costs and
complications in monitoring therapy. In this context it
is important to note that amiodarone when given at
the dose of 400 mg/day or less exhibits minimum
toxicity17. Selection of a particular class III agent should
thus be based not solely on the ability to suppress atrial
fibrillation. For each patient, concomitant cardiac
disease, age, and renal and hepatic function should be
balanced with safety, adverse effects, drug interactions,
and dosing and compliance issues of each drug. Table
II describes the drugs with their dosage schedules and
side effects.
Journal, Indian Academy of Clinical Medicine
Vol. 4, No. 3
July-September 2003
Table I : Drugs used for rate control.
Drugs commonly used to control ventricular rate in
patients with atrial fibrillation.
Drug
Initial dosing
Maintenance dosing
Comments
Calcium channel blockers
Diltiazem
15 to 20 mg IV over 2 minutes; may repeat in 15
minutes
5 to 15 mg per hour by continuous IV infusion
Convenient; easy to titrate to heart rate goal
Verapamil
5 to 10 mg IV over 2 minutes; may repeat in 30 minutes
Not standardised
More myocardial depression and hypotension than
with diltiazem
Beta blockers
Esmolol
Bolus of 500 mcg per kg IV over 1 minute; may repeat
in 5 minutes
50 to 300 mcg per kg per minute by continuous IV
infusion
Very short-acting; easy to titrate to heart rate goal
Propranolol
1 mg IV over 2 minutes; may repeat every 5 minutes
to maximum of 5 mg
1 to 3 mg IV every 4 hours
Short duration of action; hence, need for repeat
dosing
Digoxin
0.25 to 0.5 mg IV; then 0.25 mg IV every 4 to 6 hours
to maximum of 1 mg
0.125 to 0.25 mg per day IV or orally
Adjunctive therapy; less effective for rate control than
beta blockers or calcium channel blockers
Restoration of sinus rhythm for patients presenting to
the emergency with stable AF – either paroxysmal or
persistent – has been mired with a lot of uncertainty
and controversy. The results of the recently released
AFFIRM trial have helped us to determine the probable
algorithm to deal with such patients. In young patients
(age > 65 years) with a single episode of AF, but with
structurally normal heart, no other risk factors for
stroke, it is prudent to convert to sinus rhythm with
rhythm control in the hope of avoiding
anticoagulation. Though it is important to remember
at this juncture that if a patient having the profile
described above, comes back with a recurrence of AF,
he becomes a candidate for anticoagulation given the
SPAF 18 study data that the incidence of ischaemic
stroke is similar in recurrent and permanent AF. Factors
that significantly increase the risk for stroke include
previous stroke, previous transient ischaemic attack or
systemic embolus, hypertension, poor left ventricular
systolic function, age greater than 75 years, prosthetic
heart valve, and history of rheumatic mitral valve
disease. With persistent atrial fibrillation, patients
younger than 65 years and those with diabetes are also
at increased risk. The lowest risk for stroke is in patients
with atrial fibrillation who are less than 65 years of age
and have no history of cardiovascular disease, diabetes,
or hypertension.
The atrial fibrillation follow-up investigation of rhythm
management (AFFIRM) trial directly tested the 2 strategies
– rhythm vs. rate control – in patients with paroxysmal or
persistent AF who also had atleast 1 risk factor for stroke,
which justified anticoagulant treatment. As announced at
the American College of Cardiology meeting in March19,
neither strategy was found to be superior with respect to
the primary outcome, total mortality. There was also no
difference between the 2 strategies with regard to the
Table II : Drugs, dosage, and side effects of pharmaceuticals used in maintaining sinus rhythm in AF.
Drugs
Daily dose
Adverse effects
Amiodarone
100-400 mg/daily
Photosensitivity, thyrotoxicity, pulmonary toxicity, hepatic dysfunction,
GI upset, bradycardia, insomnia. torsade de pontes (rare).
Sotalol
240-320 mg/day
Torsade de pontes, CHF, bradycardia, exacerbation of COPD.
Dofetilide
500-1,000 microgms
Torsade de pontes.
Journal, Indian Academy of Clinical Medicine
Vol. 4, No. 3
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217
secondary composite end point of total mortality,
disabling stroke, or anoxic encephalopathy, major
bleeding, or cardiac arrest. However, it was noted that
patients in the rhythm control arm required
hospitalisation during follow-up significantly more often
than patients in the rate control arm. In addition, after an
adjustment for variables such as age and ejection fraction
in a multivariate Cox model, rate control had a significantly
lower risk of death than rhythm control. Such findings
indicate that there appears to be no advantage to the use
of anti-arrhythmic drugs, most of which are highly toxic,
for the maintenance of sinus rhythm in AF patients who
otherwise have to be anticoagulated. The only caveat is
that this is true as long as these patients are asymptomatic
with well controlled ventricular rates. Cardioversion with
rhythm control or interventional therapies are offered to
those who remain symptomatic with fast ventricular rates.
Restoration of sinus rhythm
In haemodynamically unstable patients or in stable
patients requiring cardioversion the choice is between
medical and electrical.
Medical (pharmacologic) cardioversion : Medical
cardioversion may be appropriate in certain situations,
especially when adequate facilities and support for
electrical cardioversion are not available, or when patients
have never been in atrial fibrillation before. It is also most
effective when initiated within 7 days after the onset of
AF. Pharmacologic agents are effective in converting atrial
fibrillation to sinus rhythm in about 40 percent of treated
patients7.
Physicians should use medical cardioversion only after
careful consideration of the possibility of pro-arrhythmic
Table III : Drugs, doses, and adverse effects of pharmaceuticals used in medical conversion of atrial flutter.
Drugs
Intravenous
Oral
Adverse effects
Amiodarone
5 to 7 mg/kg over
30 to 60 min, then
1.2 to 1.8 gm/day
continous i.v. upto
10 gms in divided
doses. Then a
maintenance dose of
200-400 mg/day.
In-patients: 1.2 to 1.8 gm/day upto
10 gms in divided doses. Then a
maintenance of 200-400 mg/day.
Out-patients: 600-800 mg/day upto
10 gms in divided dose. Then a
maintenance of 200-400 mg/day.
Hypotension and bradycardia, QT
prolongation, torsade de pointes,
phlebitis (while given i.v.)
Dofetilide
The dose is based on creatinine
clearance:
60 ml/min: 500 mcg BD.
40-60 ml/min: 250 mcg BD
20-40 ml/min:125mcgBD
> 20 ml/min: contraindicated
QT prolongation, torsade
de pointes.
Flecainide
200-300 mg
Hypotension, rapidly conducting
atrial flutter.
Ibutilide
Propafenone
Quinidine
218
QT prolongation, torsade
de pointes
1 mg given slow i.v.
over 10 min; repeat
1 mg if required.
1.5 to 2 mg/kg given
over 10 -20 min
450-600 mg
Hypotension, rapidly conducting
atrial flutter.
0.75 to 1.5 gm in divided doses
QT prolongation,
torsade de pointes.
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complications, particularly in patients with structural heart
disease or congestive heart failure11. The anticoagulation
protocol to be followed is identical to that followed during
electrical cardioversion and is discussed later on. A recent
review8 and a meta-analysis21 concluded that flecainide,
ibutilide, and dofetilide were the most efficacious agents
for medical conversion of atrial fibrillation, but that
propafenone and quinidine were also effective. In the
presence of Wolff-Parkinson-White syndrome, procainamide is the drug of choice for converting atrial fibrillation11.
However, some investigators consider amiodarone to be
the most effective agent for converting to sinus rhythm
in patients who do not respond to other agents11. Table III
compiles the drugs used for medical cardioversion.
Electrical cardioversion : When patients with atrial
fibrillation are haemodynamically unstable (e.g., angina,
hypotension) and not responding to resuscitative
measures, emergency electrical cardioversion is indicated.
However, i.v. heparin is given before the procedure. In
stable patients, elective cardioversion may be performed
after three weeks of warfarin therapy10, 11. To prevent
thrombus formation, warfarin is continued for four weeks
after cardioversion. Although the success rate for electrical
cardioversion is high (90 percent), proper equipment and
expertise are necessary for safe performance7. If there is
time, and patients are conscious, sedation should be
achieved before cardioversion is attempted. Synchronised
external direct-current cardioversion is performed with
the pads placed anteriorly and posteriorly22 (over the
sternum and between the scapulae) at 100 joules (J). If
no response occurs, the current is applied again at 200 J;
if there is still no response, the current is increased to 300
J, and then to a maximum of 360 J. A multinational,
multicentric study coordinated at our hospital showed
better results using biphasic, rather than uniphasic shocks.
Significantly less energy and cumulative energy was used
with the biphasic shocks, and significantly fewer shocks
were required for success in the biphasic group. In
addition, pain perception was significantly less at 1 and
24 hours after the procedure in the biphasic group (p <
.0001 for all parameters vs. monophasic group)23.
intracardiac clots. The clots, if present, have the propensity
to move into circulation, associated with cardioversion,
producing cerebrovascular insufficiency and ischaemic
stroke. Most atrial fibrillation-derived strokes occur within the
first 72 hours after medical (pharmacologic) or electrical
cardioversion.The risk of stroke is significant for both rhythm
conversion methods and is presumed to be due to the
presence of left atrial thrombi at the time of cardioversion,
rather than to the method used24. This usually calls for oral
anticoagulation for three to four weeks prior to elective
cardioversion. An alternative approach for achieving earlier
return to sinus rhythm is early electrical cardioversion and
the use of transoesophageal echocardiography 11.
Transoesophageal echocardiography is used to detect
thrombi in the right atrium. If no thrombi are present,
electrical cardioversion can be performed immediately; if
thrombi are detected, cardioversion can be delayed until
patients have undergone three weeks of oral anticoagulation
using warfarin25. One recent comparative study26 found no
differences in thromboembolic complications between
conventional treatment and early cardioversion following
transoesophageal echocardiography. Table IV profiles the
anticoagulation protocol to be followed in different situations
of cardioversion.
Table IV : Showing the anticoagulation protocol for
cardioversion.
Timing of cardioversion
Anticoagulation
Early cardioversion* in patients with atrial fibrillation
for less than 48 hours.
Heparin during cardioversion period to achieve PTT
of 1.5 to 2.5 times the baseline value.
Early cardioversion* in patients with atrial fibrillation
for more than 48 hours or an unknown duration, but
without documented atrial thrombi by TEE.
Heparin during cardioversion period to achieve PTT
of 1.5 to 2.5 times the baseline value. Warfarin for 4
weeks after cardioversion to achieve target INR of 2.5
(range: 2.0 to 3.0).
Elective cardioversion in patients with atrial fibrillation
for more than 48 hours or an unknown duration
Warfarin for 3 weeks before, and 4 weeks after
cardioversion to achieve target INR of 2.5 (range: 2.0
to 3.0).
Anticoagulation issues
Cardioversion, medical or electrical, mandates that it be
predated by adequate anticoagulation to rule out
Journal, Indian Academy of Clinical Medicine
PTT = partial thromboplastin time; INR = International normalised
ratio. * Electrical or medical (pharmacologic) cardioversion.
Vol. 4, No. 3
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219
Interventional strategies
Referral for interventional treatment is indicated in the
following circumstances: a) Symptomatic AF in patients
not adequately controlled, despite maximum tolerated
drug therapy; b) Patients not tolerating anticoagulants; c)
Patients with AF who are not tolerating/do not desire long
term anti-arrhythmics 27. The interventional options
available are :
Atrioventricular nodal ablation or modification
Linear ablations
Focal pulmonary vein ablation
Atrial pacing
Atrial defibrillation
Combination therapies
Atrioventricular nodal ablation versus
atrioventricular nodal modification
The therapeutic goal of AV nodal ablation and AV nodal
modification is to obtain adequate ventricular rate control
during paroxysmal or chronic atrial fibrillation refractory
to drugs. However, the end-point of the AV nodal ablation
is to induce complete AV block with subsequent
pacemaker implantation, while the end-point of the AV
nodal modification is to achieve an average ventricular
rate lower than 120 beats per minute during isoproterenol
or atropine infusion, with preserved AV conduction. In our
practice, we found that most patients offered this therapy
were those who either had a high basal or exercise
induced heart rate despite being on maximum tolerated
dose of rate controlling agents.
The target zone of AV nodal modification is the midseptal
or posteroseptal area of the right atrium, where the AV
nodal slow pathway would be expected. Figure 3 shows
the regional anatomy of the site of ablation. In patients
with atrial fibrillation, an analysis of the distribution of RR
intervals from Holter monitoring can be useful for the AV
nodal modification. A bimodal RR interval distribution
during atrial fibrillation is highly suggestive for the
presence of two anatomically distinctly separated
entrances to AV node, one from the interatrial septum, and
one from the terminal part of the crista terminalis between
the ostium of the coronary sinus and the tricuspid valve28.
Accordingly, patients with such finding are appropriate
220
candidates for AV nodal modification, targeting a
posteroseptal area of the right atrium. Recently, two
studies compared the benefits and limitations of AV nodal
ablation and AV nodal modification which are listed in
Table V29,30. The success rate of the AV nodal ablation is
almost 100%, but the patients have lifelong pacemaker
dependency 31 . The success rate of the AV nodal
modification is lower, about 70%, but the patients do not
need pacemaker implantation32,33. However, a complete
AV block, induced by this procedure was observed in
about 10–20% of patients.The AV nodal ablation has been
proven more effective than AV nodal modification in
ventricular rate control, in reducing symptoms, in
improving quality of life, and in improving the left
ventricular ejection fraction, when it was lower than 40%.
On the other hand, one-third of patients with AV nodal
modification continue to have palpitations, about 15 %
have recurrence of rapid atrial fibrillation, and some of
them, with reduced left ventricular function, have a
facilitation of polymorphic ventricular tachycardia30.
Because this type of ventricular arrhythmia may be
suppressed by an increase in rate, and facilitated by a
decrease in rate, it is likely that the relative bradycardia
that ensued after the radiofrequency modification
procedure is also a predisposing factor for polymorphic
ventricular tachycardia31. It must be noted that AV nodal
ablation and AV nodal modification are not curative
techniques for atrial fibrillation, since arrhythmia remains,
and the embolic risk may not be reduced. The ablate and
Fig. 3 : Showing the fast and the slow pathway.The cartoon clearly depicts
the anatomy of the site of ablation.
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Vol. 4, No. 3
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pace strategy has found wider clinical acceptance,
probably because it is easier to apply and is considered
to be safer and more effective in the long term. However,
the influence of these techniques on survival has yet to
be established.
Radiofrequency catheter ablation of atrial
fibrillation
Radiofrequency catheter ablation of atrial fibrillation is
primarily aimed either to divide the atrial anatomy in a
way that does not sustain this arrhythmia even though
the initiating potential exists, or to remove the focus that
generates the arrhythmia. These foci are generally in one
or multiple pulmonary veins which are structures that
enter the left atrium from the posterior aspect (figure 4).
The mode of therapy in an individual patient depends
essentially on the pathophysiology of the arrhythmia. The
different techniques used to ablate AF of different
mechanism is shown in Table VI. Therefore, the atrial
mapping during spontaneous or induced atrial fibrillation
is an important part of this therapeutic approach. The
reduction of atrial mass should be created by using linear
lesions in the right and left atrium, the purpose of which
is to make impossible the random re-entry of atrial
impulses through the atria. To achieve this, lesions need
to be continuous, transmural, and connected with other
lesions or anatomic structures that cause blockage of atrial
conduction. The area between the inferior vena cava and
the inferior part of the tricuspid annulus may be critical
Fig. 4 : The anatomical orientation of the pulmonary veins as they come in
from the posterior aspect of the left atrium – a three dimentional model.
Journal, Indian Academy of Clinical Medicine
for development and maintenance of atrial fibrillation34.
In these cases, the selected linear lesion should be done
between these anatomic structures. One of the catheter
orientation in the heart for creating linear ablation in the
left atrium is shown in figure 5. If an arrhythmogenic focus
is identified during electrophysiological study, it has to
be carefully mapped. The ablation should be performed
targeting the earliest bipolar atrial activity relative to the
P wave onset on a surface electrocardiogram. The results
of radiofrequency ablation of atrial fibrillation, imitating
the maze procedure, show that the success of this
therapeutic option depends on the number and site of
ablated lines. In the study by Haissguerre et al, the right
atrial ablation, performed with one, three, or four linear
lesions, organised local electrical activity and led to stable
sinus rhythm during the procedure in 18 (40%) of 45
patients, but non-inducibility of atrial fibrillation was
achieved only in 5 patients35. Final success rates with all
three types of lesions were similar, ranging from 13%
without drugs to 40% with drugs. When the linear lesions
Fig. 5 : Catheters inside the heart to do linear ablation. CS is the catheter
manoeuvered into the coronary sinus.The catheter marked with star is the
ablation catheter used to make linear ablation within the left atrium. The
ablation catheter was positioned guided by ICE.
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July-September 2003
221
were performed in the right (3 lesions), and in the left
atrium (3 lesions), the results were significantly better with
a success rate of 87 %. These results suggest that the left
atrium is more relevant for maintenance of atrial
fibrillation than the right atrium. Recent data from the
same group show that biatrial ablation (3 linear lesions in
the right, and 5 linear lesions in the left atrium) was
successful in 38 (84%) of 44 patients with multidrug
resistant atrial fibrillation, during a mean follow-up of 20
months36. However, the additional sessions were required
for focal ablation in 29 patients with atrial fibrillation, and
in 27 patients with newly created atrial flutter. The major
disadvantage of this procedure is a large number of
radiofrequency pulses necessary for compartmentalisation of the target chamber, and a long fluoroscopy
and procedure duration (> 10 hours). Although there is
increasing evidence about safety of this rather aggressive
approach, its efficacy in achieving the intended model,
and curing the clinical symptoms remains to be
determined.
Fig. 6 : Fluoroscopic image of typical mapping catheter positions during
radiofrequency ablation of focal ectopy arising from the pulmonary veins.
LSPV = left superior pulmonary vein; RSPV = right superior pulmonary vein;
CS = coronary sinus; HRA = high right atrium.
positioning of catheters to study the pulmonary veins. A
typical pulmonary foci as seen in intracardiac recording is
Table V : AV nodal ablation versus modification compared.
Ablation
Modification
1.
2.
3.
4.
5.
6.
1.
2.
3.
4.
5.
Success rate ~ 100%
Life-long pacemaker dependency
Better ventricular rate control
Better control of symptoms and quality of life
Greater improvement of LVEF, When < 40%
Facilitation of polymorphic VT in some
Success rate ~ 70%
No need for pacemaker implantation
Persistence of ventricular irregularity
Palpitations are not alleviated
Recurrence of rapid AF
LVEF = left ventricular ejection fraction; AF = atrial fibrillation; VT = ventricular tachycardia.
Table VI : Ablation strategy in atrial fibrillation depending on the mechanism.
Mechanism
Ablation strategy
1. Random re-entry – critical mass for AF
2. Spatio-temporal organisation, some zones are
more critical to maintain AF than others
3. Focal driving rotors, focal tachycardia
1. Restrict atrial mass available for contiguous conduction
2. Selected lines between anatomic barriers,
but ignore the mass
3. Targeting focal ablation
AF = atrial fibrillation
Discovery of the rapidly firing atrial foci mostly in the
pulmonary veins; as a possible trigger of atrial fibrillation,
has enabled the development of techniques for their
ablation37. Radiofrequency pulses can be successfully
delivered to discrete sites, presenting the earliest
activation during spontaneous extra beats or at the time
of onset of atrial fibrillation. Figure 6 shows the intracardiac
222
seen in Figure 7. In the study by Haissaguerre et al, 69
ectopic foci were identified as a trigger for atrial fibrillation,
and ablated in 45 patients with frequent paroxysmal atrial
fibrillation resistant to multiple drugs37. Sixty-five (94%)
foci originated from the pulmonary veins, and 4 foci from
the atrial tissue. The accuracy of mapping was confirmed
by abrupt disappearance of triggering atrial beats after
Journal, Indian Academy of Clinical Medicine
Vol. 4, No. 3
July-September 2003
Fig. 7 : Pulmonary vein as a source of ectopic beats producing A fib. Intracardiac and surface ecg recording showing ectopic generator in the right inferior
pulmonary vein (RIPV) and left superior pulmonary vein (LSPV) inducing atrial fibrillation. Source : Haissaguerre et al. NEJM 1998; 339 (10): 659, figure 3.
ablation with local radio-frequency energy. Figure 8 shows
the post-ablation intracardiac electrocardiogram. During
a mean follow-up period of nine months, atrial fibrillation
was eliminated completely in 28 (62%) patients without
the use of drug therapy. The patients with one or two foci
had a significantly higher success rate from the ablation
than patients with more foci. It is important to note that
significant pulmonary vein stenosis was induced in 10 %
of patients. The incidence of this complication tends to
be lower by decreasing radiofrequency power limit for
ablation from 50 to 30 watts38.
Fig. 8 : Ablating the pulmonary vein focus. The diagram on the left and
centre is before ablation. Surface ECG and intracardiac recording within left
inferior pulmonary vein is shown. The left panel shows that the
multicomponent spikes near the ostium whereas the center panel shows it
2 cm within the vein. The ostial spikes are earlier indicating the source of
pulmonary vien ectopy. The panel on the right is post ablation;
multicomponent spikes are no longer visible suggesting successful ablation
of the ectopic generator.
Journal, Indian Academy of Clinical Medicine
Recently, ablation limited to the right atrium (3-4 linear
lesions) was proposed as a therapeutic approach for
patients with idiopathic atrial fibrillation39,40. The rationale
for this approach is the probability that critical area
necessary for perpetuation of atrial fibrillation may be
located in the right atrium, and to avoid risk of left atrium
ablation in patients with this relatively benign arrhythmia.
The long-term results of this ablative approach were rather
modest with efficacy between 28% and 61% 39-41. In
Vol. 4, No. 3
July-September 2003
223
addition, Ernst et al observed 100% recurrence rate of
idiopathic atrial fibrillation after subsequent right atrial
ablation, using non-fluoroscopic mapping and 3
radiofrequency linear lesions42.
Although the above findings are encouraging,
radiofrequency ablation of atrial fibrillation is still
considered to be an experimental procedure. The
limitations of atrial ablation are related to the inability to
accurately assess the precise anatomical location and
extent of lesion formation.The risk/benefit ratio in the case
of extensive ablation of the left atrium is unfavourable.
With existing technology, map-guided ablation of a rapidly
firing atrial focus seems the most likely solution.
Pacing to prevent AF
Another therapy under study is the use of pacing to
prevent AF. Compared to patients who receive ventricular
pacing only, patients who require pacing for
bradyarrhythmias are less likely to develop AF if they are
paced atrially as well as ventricularly43-46. Studies have
shown that pacing may not only prevent the
arrhythmogenic effect of bradycardia, where there is
potential for ectopic beats to trigger AF47, but it may also
reduce variability in atrial refractory periods45-48. In turn,
pacing decreases ectopic beats, which increase the
potential for triggering AF and formation of re-entry
circuits49,50. Researchers believe that the longer a patient
can be kept in normal sinus rhythm (NSR), the more likely
the patient will stay in NSR, or “NSR begets NSR.”
ventricular tachyarrhythmias has stimulated the
investigators to create a similar device for atrial fibrillation.
At present, two devices are commercially available as
outlined in Table VII. The Metrix allows only defibrillation
of the atrium, while the Jewel AF is able to treat atrial
arrhythmias, including a shock to convert atrial fibrillation
to sinus rhythm, and has the capacity to terminate lifethreatening ventricular tachyarrhythmias. The Metrix uses
right atrial and coronary sinus lead configuration for atrial
defibrillation and sensing, and a bipolar right ventricular
pacing lead for R-wave synchronisation and pacing. The
Model 3020 is able to deliver shocks upto 6 Joules with
bifasic waveform of 6 ms/6 ms duration. To avoid the
potential ventricular proarrhythmic risk of atrial
defibrillation shocks, appropriate R-wave synchronisation
needs to be performed, and shocks should be delivered
only after RR intervals above 500 ms. The Jewel AF 7250
(Figure 9) is a dual chamber pacemaker, as well as a dual
cardioverter-defibrillator. The pacing and shock therapies
for termination of tachyarrhythmias can be delivered both
to atrial and ventricular electrode configurations.This dual
defibrillator consists of an active can with one atrial and
one ventricular lead, although an additional output may
be used to accommodate a coronary sinus lead for
lowering atrial defibrillation threshold. The primary goal
The above theories are applied to pacing treatments for
the purpose of reducing the number of AF episodes in
patients who do not require pacing for bradyarrhythmias.
Some small studies51,52 show that atrial pacing increases
the duration of AF-free periods and reduces the number
of cardioversions required for patients with persistent AF.
While pacing patients for the specific purpose of
preventing AF is promising for some patients, further
large-scale studies are needed to establish its
effectiveness53.
The implantable atrial defibrillator
The success of the implantable cardioverter-defibrillator
in the management of sudden cardiac death and recurring
224
Fig. 9 : The atrial defibrillator; the coiled lead is in the coronary sinus. The
right atrial and ventricular lead is also seen.The leads have been inserted
through the cephalic vein.The can is placed inside a subclavian pocket.
Journal, Indian Academy of Clinical Medicine
Vol. 4, No. 3
July-September 2003
of the Jewel AF is to treat promptly life-threatening
ventricular tachyarrhythmias. For the treatment of atrial
fibrillation, this device has an algorithm for prevention of
atrial arrhythmias, and it is designed for a tiered approach
to delivering atrial therapies, including anti-tachycardia
pacing, burst high frequency pacing, and shock therapy
with energy between 0.1 and 27 joules.
Table VII : The devices presently available for atrial
defibrillation.
Metrix
(1995)
Jewel AF
(1998)
Manufacturer
Weight/volume
Lead system
Pacing support
Prevention
ATP/50 Hz
Max. shock energy
VT/VF support
Guidant (in control)
82 g/53 cc
3
WI
–
–
6J
–
Medtronic
93 g/55 cc
2 or 3
DDD
+
+
27 J
+
Electrocardiogram
+
+
ATP = antitachycardia pacing; VT = ventricular tachycardia;
VF = ventricular fibrillation; J = Joules
The efficacy and safety of the Metrix were evaluated in a
prospective multicentre study including 51 patients with
recurrent symptomatic atrial fibrillation54. The patients
enrolled in this study had either failed, or had intolerable
side effects to a mean of 3.9 anti-arrhythmic drugs. Most
of these patients had no structural heart disease, and had
a normal left ventricular function. Forty-one of them used
an atrial defibrillator during the study. In those patients,
96% of 222 spontaneous episodes of atrial fibrillation were
converted to sinus rhythm by the atrial defibrillator. Shocks
did not induce ventricular arrhythmias or embolic events
in any patient. However, atrial fibrillation defibrillation
threshold increased from 1.5 to 2.5 during a mean followup of eight months. The initial clinical evaluation of the
Jewel AF was focused on patients with an accepted
indication for an implantable cardioverter-defibrillator,
who, in addition, suffered from atrial fibrillation and flutter,
or who had specific indication for dual chamber pacing.
At the present time, the Jewel AF has been implanted in
303 patients55. During a mean follow-up of eight months,
about 61% of spontaneous atrial tachycardia episodes
Journal, Indian Academy of Clinical Medicine
were terminated by painless therapy, with anti-tachycardia
pacing or high frequency burst pacing, and about 72% of
133 atrial fibrillation episodes were terminated by shock.
In the same time, therapy success rate for ventricular
tachycardia episodes, was 97%, and for ventricular
fibrillation episode was 100%. However, early recurrence
of atrial fibrillation after successful shock therapy was
observed in 22% of atrial fibrillation episodes56. From the
above, two different groups of patients with atrial
fibrillation may be selected for an implantable atrial
defibrillator. The patients at low risk for ventricular
tachyarrhythmias are candidates for the atrial defibrillator
only, while patients with atrial fibrillation, who have an
indication for cardioverter-defibrillator have an indication
for Jewel AF. There are several problems that must be
overcome before these devices can find wide clinical
acceptance. First is a pain perception during delivery of
atrial shock that is too strong, and has a negative influence
on the quality of life. Early re-initiation of atrial fibrillation
after successful shock therapy may cause premature
depletion of the device and reduce its long-term efficacy.
Thus, the most important issue is related to the selection
of the patients who really need the implantable atrial
defibrillator only.
Surgical Maze procedure
A surgical procedure to return or to maintain NSR may
be chosen for some patients. The surgical Maze
procedure is indicated for those who are young, resistant
to other therapies, and without high surgical risk, or those
who need to undergo cardiac surgery for another
purpose (mitral valve repair or replacement). This
procedure is performed to direct atrial conduction in an
orderly manner through to the AV node. Incisions that
produce scarring are created in the atrial tissue to block
undesired conduction paths and promote conduction
in the desired manner57. Recent modifications, such as
using cryoablation or radiofrequency ablation to make
the blocks in place of the incisions, shorten the operating
time. In addition, using minimally invasive techniques
and performing the surgery off of bypass reduces
surgical time and further limits risks58. While the Maze
procedure is very effective, with AF cure rates ranging
from 63-99%, it carries risks and costs of cardiothoracic
surgery57.
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July-September 2003
225
Conclusion
The spectrum of therapeutic approaches for atrial
fibrillation is large, but each approach has inherent
advantages and limitations, in part depending on the type
of atrial fibrillation being treated, and in part based on
the specific patient population. Given the complex
pathophysiology of underlying atrial fibrillation, it is
unlikely that one therapeutic modality will adequately
treat the majority of atrial fibrillation. Therefore, it is
reasonable to presume that therapy combining the
advantages of different approaches will offer optimal care
to patients. It is important that the physician treating this
disorder be cognizant of the different available
therapeutic modalities, and offer that which is best for a
particular patient.
References
1.
Fuster, Ryden et al . ACC/AHA/ESC guidelines for the
management of patients with atrial fibrillation. Executive
Summary JACC 2001; 38 (4): 1234.
2.
Wolf PA, Abott RD, Kannel WB. Atrial fibrillation as an
independent risk factor for stroke: the Framingham Study.
Stroke 1991; 22: 983-8.
3.
Ellenbogen KA, Wood MA, Stambler BS. Intravenous therapy
for atrial fibrillation: more choices, more questions, more
trials. Am Heart J 1999; 137: 992-5.
4.
Jung W, Schumacher B, Luderitz B. Catheter ablation and
implantable cardioverter defibrillator in supraventricular
cardiac arrhythmias. Med Klin 1997; 92: 202-7.
5.
Flaker GC, Blacksheat JL, McBride R et al. Antiarrhythmic
drug therapy and cardiac mortality in atrial fibrillation. J Am
Coll Cardiol 1992; 20: 527-32.
Group. Efficacy and safety of sotalol in digitalised
patients with chronic atrial fibrillation. Am J Cardiol
1991; 68: 1227-30.
14. Benditt DG, Williams JH, Jin J et al. Maintenance of sinus
rhythm with oral d,l-sotalol therapy in patients with
symptomatic atrial fibrillation and/or atrial flutter. Am J
Cardiol 1999; 84: 270-7.
15. Roy D, Talajic M, Dorian P et al. Amiodarone to prevent
recurrence of atrial fibrillation. N Engl J Med 2000; 342:
913-20.
16. Singh S, Zoble RG, Yellen L et al. Efficacy and safety of oral
dofetilide in converting to and maintaining sinus rhythm
in patients with chronic atrial fibrillation or flutter.
Circulation 2000; 102: 2385-90.
17. Vorperian VR, Havighurst TC, Miller S, January CT. Adverse
effects of low-dose amiodarone: a meta-analysis. J Am Coll
Cardiol 1997; 30: 791-8.
18. Stroke Prevention in Atrial Fibrillation Study. Final Results.
Circulation 1991; 84: 527-39.
19. Wyse DG. AFFIRM Investigators. Survival in patients
presenting with atrial fibrillation: the atrial fibrillation
follow-up investigation of rhythm management (AFFIRM)
study. Program and abstracts of the American College of
Cardiology 51st Annual Meeting; 2002; Atlanta, Georgia.
Abstract 405-1.
21. Miller MR, McNamara RL, Segal JB et al. Efficacy of agents
for pharmacologic conversion of atrial fibrillation and
subsequent maintenance of sinus rhythm: a meta-analysis
of clinical trials. J Fam Pract 2000; 49: 1033-46.
22. Kirchhof P, Eckardt L, Loh P et al. External cardioversion of
atrial fibrillation is more effective using anterior-posterior
electrode positions than using anterior-lateral electrode
positions: results of a randomised trial. Program and
abstracts of the XXIII Congress of the European Society of
Cardiology; 2001; Stockholm, Sweden. Abstract 739.
23. Dorian P, Koster RW, Chapman FW et al. A prospective,
randomised comparison of monophasic and biphasic
shocks for external cardioversion of atrial fibrillation: shock
efficacy and post-procedure pain. Program and abstracts
of the XXIII Congress of the European Society of Cardiology;
2001; Stockholm, Sweden. Abstract 740.
6.
Petraè D. Ventricular rate control in chronic atrial fibrillation.
G Ital Cardiol 1999; 29 (Suppl 5): 261-4.
7.
Li H, Easley A, Barrington W, Windle J. Evaluation and
management of atrial fibrillation in the emergency
department. Emerg Med Clin North Am 1998; 16: 389-403.
8.
Management of new onset atrial fibrillation. Evid Rep
Technol Assess (Summ) 2000; 12: 1-7.
24. Albers GW, Dalen JE, Laupacis A et al. Antithrombotic
therapy in atrial fibrillation. Chest 2001; 119 (suppl 1):
S194-206.
9.
Pritchett EL. Management of atrial fibrillation. N Engl J Med
1992; 326: 1264-71.
25. Camm AJ. Atrial fibrillation: is there a role for low-molecularweight heparin? Clin Cardiol 2001; 24 (suppl 3): I15-9.
10. Falk RH. Atrial fibrillation. N Engl J Med 2001; 344: 1067-78.
11. Prystowsky EN, Benson DW Jr, Fuster V et al. Management
of patients with atrial fibrillation. A statement for healthcare
professionals. From the Subcommittee on Electrocardiography and Electrophysiology, American Heart
Association. Circulation 1996; 93: 1262-77.
12. Falk RH, Leavitt JI. Digoxin for atrial fibrillation: a drug whose
time has gone? Ann Intern Med 1991; 114: 573-5.
13. Singh S, Saini RK, DiMarco J et al. And the Sotalol Study
226
26. Klein AL, Grimm RA, Murray RD et al. Use of transesophageal
echocardiography to guide cardioversion in patients with
atrial fibrillation. N Engl J Med 2001; 344: 1411-20.
27. Zipes DP, DiMarco JP, Gillette PC et al. Guidelines for clinical,
intracardiac, electrophysiological and catheter ablation
procedures. A report of the American College of Cardiology/
American Heart Association task force on practice
guidelines, developed in collaboration with the North
American Society of Pacing and Electrophysiology. JACC
Journal, Indian Academy of Clinical Medicine
Vol. 4, No. 3
July-September 2003
fibrillation: Efficacy of radifrequency ablation using
nonfluoroscopic catheter guidance. Circulation 1999; 100:
2085-92.
1995; 26: 555-73.
28. Olsson SB, Carlson J, Holm M, Nilsson AM. Atrioventriculae
nodal function in atrial fibrillation: What is the optimum
ventricular rate? In: Murgatroyd FD, Camm AJ (eds).
Nonpharmacological Management of Atrial Fibrillation.
Futura Publishing Co., Inc., Armonk, NY, 1997; 55-63.
29. Lee SH, Chen SA, Tai CT et al. Comparisons of quality of life
and cardiac performance after complete atrioventricular
junction ablation and atrioventricular junction modification
in patients with medically refractory atrial fibrillation. J Am
Coll Cardiol 1998; 31: 637-44.
30. Twidale N, McDonald T, Nave K, Seal A. Comparison of the
effects of AV nodal ablation versus AV nodal modification
in patients with congestive heart failure and uncontrolled
atrial fibrillation. PACE 1998; 21 (Part I): 641-51.
31. Petrac D, Radi´c B, Hamel D et al. The clinical outcome
of patients with atrial fibrillation after radiofrequency
ablation of the atrioventricular junction. G Ital Cardiol
1998; 28 (Suppl 1): 329-33.
32. Morady F, Hasse C, Strickberger A et al. Long-term followup after radiofrequency modification of the atrioventricular
node in patients with atrial fibrillation. J am Coll Cardiol 1997;
27: 113-21.
33. Carbucicchio C, Tondo C, Fassini G et al. Modulation of the
atrioventricular node conduction to achieve rate control
in patients with atrial fibrillation: Long-term results. PACE
1999; 22: 442-52.
43. Anderson HR, Nielson JC, Thomsen PE et al. Long-term
follow-up of patients from a randomised trial of atrial versus
ventricular pacing for sick-sinus syndrome. Lancet 1997; 350:
1210-6.
44. Rosenqvist M, Brandt J, Schuller H. Long-term pacing in
sinus node disease: effects of stimulation mode on
cardiovascular morbidity and mortality. Am Heart J 1988;
116 (1 pt 1): 16-22.
45. Sparks PB, Mond HG, Vohra JK et al. Electrical remodeling of
the atria following loss of atrioventricular synchrony.
Circulation 1999; 100: 1894-1900.
46. Skanes AC, Krahn AD, Yee R et al. Progression to chronic
atrial fibrillation after pacing: the Canadian Trial of
Physiologic Pacing. CTOPP Investigators. J Am Coll
Cardiol 2001; 38: 167-72.
47. Han J, Millet D, Chizzonitti B et al. Temporal dispersion of
recovery of excitability in atrium and ventricle as a function
of heart rate. Am Heart J 1966; 71: 481-7.
48. Capucci A, Biffi M, Boriani G et al . Dynamic
electrophysiological behavior of human atria during
paroxysmal atrial fibrillation. Circulation 1995; 92: 1193-1202.
49. Papageorgiou P, Anselme F, Kirchof CJ et al. Coronary sinus
pacing prevents induction of atrial fibrillation. Circulation
1997; 96: 1893-8.
34. Nabar A, Rodiguez LM, Timmermans C et al. Effect of right
atrial isthmus ablation on the occurrence of atrial
fibrillation. Circulation 1999; 99: 1441-5.
50. Garrigue S, Barold SS, Cazeau S et al. Prevention of atrial
arrhythmias during DDD pacing by atrial overdrive. Pacing
Clin Electrophysiol 1998; 21: 1751-9.
35. Haissaguerre M, Shah DC, Jais P, Clementy J. Role of
catheter ablation for atrial fibrillation. Curr Opin Cardiol
1997; 12: 18-32.
51. Delfaut P, Saksena S, Prakash A et al. Long-term outcome of
patients with drug-refractory atrial flutter and fibrillation
after single- and dual-site right atrial pacing for arrhythmia
prevention. J Am Coll Cardiol 1998; 32: 1900-8.
36. Jais P, Shah DC, Haissaguerre M et al. Long-term follow-up
of biatrial linear ablation of atrial fibrillation (abstract). PACE
1999; 22 (Part II): 738.
37. Haissaguerre M, Jais P, Shah DC et al. Spontaneous initiation
of atrial fibrillation by ectopic beats originating in the
pulmonary veins.N Engl J Med 1998; 339: 659-66.
38. Jais P, Haissaguerre M, Shah DC et al. Complications of
radiofrequency catheter ablation in the pulmonary
veins in 200 consecutive patients (abstract). PACE 2000;
23 (Part II): 627.
39. Gaita F, Riccardi R, Calo L et al . Atrial mapping and
radiofrequency catheter ablation in patients with idiopathic
atrial fibrillation. Circulation 1998; 97: 2136-45.
40. Natale A, Leonelli F, Beheiry S et al. Catheter ablation
approach on the right side only for paroxysmal atrial
fibrillation therapy: Long-term results. PACE 2000; 23:
224-33.
41. Tondo C, Riva S, Carbucicchio C et al. Long term clinical
outcome of right atrial ablation for paroxysmal atrial
fibrillation (abstract). PACE 2000; 23 (Part II): 672.
42. Ernst S, Schulter M, Ouyang F et al. Modification of the
substrate for maintenance of idiopathic human atrial
Journal, Indian Academy of Clinical Medicine
52. Lau CP, Tse HF, Yu CM et al. Dual site atrial pacing for atrial
fibrillation in patients without bradycardia. Am J Cardiol
2001; 88: 371-5.
53. Prakash A. Pacing for the prevention of atrial fibrillation. Curr
Opin Cardiol 2002; 17: 73-81.
54. Wellens HJJ, Lau CP, Luderitz B et al . For the METRIX
Investigators. Atrioverter: An implantable device for the
treatment of atrial fibrillation. Circulation 1998; 98: 1651-6.
55. Medtronic Tachyarrhythmia Management. AF-Bulletin
1999; 3.
56. Schwartzman D, Warman E, Musley S, Johnson J. Early
recurrence of atrial tachyarrhythmias following shock
cardioversion by an implanted atrial ICD (abstract). PACE
2000; 23 (Part II): 633.
57. Cox JL, Schuessler RB, Boineau JP. The development of the
Maze procedure for the treatment of atrial fibrillation. Semin
Thorac Cardiovasc Surg 2000; 12: 2-14.
58. Cox JL, Ad N, Palazzo T et al. Current status of the Maze
procedure for the treatment of atrial fibrillation. Semin
Thorac Cardiovasc Surg 2000; 12: 15-9.
Vol. 4, No. 3
July-September 2003
227