Atrial Fibrillation
and Atrial Flutter |
The prevalence of atrial fibrillation (AF) sharply
increases after 65 years of age, and by 80 years,
roughly 10% of the population will have AF, regardless
of gender. Currently, about 2 million people in the
US have AF and this is projected to double by the
year 2025.
Major management strategies for AF are 1) relief
of symptoms, by effective rate control or restoration
and maintenance of normal sinus rhythm (NSR), 2) prevention
of thromboembolic complications, and 3) prevention
of tachycardia-induced cardiac myopathy.
The safety of the drugs used to control rate (calcium
channel blockers, beta-adrenergic blockers, digitalis)
and the non-pharmacologic strategies to control rate
are advantages for this strategy. However, disadvantages
include possible poor rate control throughout the
24-hour period and the substantial effort required
by the patient and physician to control rate effectively.
Rhythm control has a number of putative advantages
(few supporting data): better relief of symptoms,
reduction of stroke risk, hemodynamically better in
certain forms of structural heart disease (left ventricular
inflowing obstruction such as in mitral stenosis;
outflow obstruction such as hypertrophic cardiomyopathy
and aortic stenosis); and preventing tachycardia-induced
cardiomyopathy. The disadvantages of rhythm control
are low efficacy, possible hospitalization for initiating
antiarrhythmic drug therapy, and limited availability
of non-pharmacologic strategies.
The clinical dilemma has been whether to use rate
control or rhythm control. The usual clinical
practice has been to first try rhythm control, and
use rate control when rhythm control is unsuccessful.
Data from the Atrial Fibrillation Follow-up Investigation
of Rhythm Management (AFFIRM) and the Rate Control
Versus Electrical Cardioversion for Persistent Atrial
Fibrillation (RACE) trial, addresses this dilemma.
Rate control showed a small, but not statistically
significant, survival benefit over rhythm control
in the AFFIRM trial, conducted in the US and Canada;
the 2 strategies were shown to be at least equivalent.
No significant difference between rate control and
rhythm control was seen in the RACE trial, conducted
in Europe, at 2.3 years of follow-up, with 17% and
22% of each group, respectively, experiencing the
cumulative primary endpoint of death from cardiovascular
disease, thromboembolic complications, bleeding, the
need for pacemaker implantation, or adverse drug reaction.
At the end of the study, 10% of the rate control group
and 23% of the rhythm control group had NSR.
AFFIRM and RACE show that rate control is just as
good as rhythm control for managing AF. Therefore,
the rate control strategy should be used earlier in
the course of treating patients. Importantly, anticoagulation
should not be stopped despite the presence of NSR.
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Contemporary
Management of AF and Atrial Flutter |
For paroxysmal atrial flutter or AF, with minimal
or no symptoms, treatment comprises anticoagulation
and rate control as needed. Drugs are not needed to
prevent recurrence of AF. For AF with significant
or disabling symptoms, treatment is anticoagulation
and rate control. A trial period of antiarrhythmic
drug to try to maintain NSR may be needed for disabling
symptoms.
For lone AF (in the absence of structural heart disease),
the recommended sequence of drugs is flecainide (relatively
well tolerated, few non-cardiac side effects), propafenone
and sotalol. When these drugs fail, proceed to dofetilide
and amiodarone; treatment is more complicated with
these 2 drugs in general. When dofetilide or amiodarone
fail, resort to disopyramide, procainamide, or quinidine.
In a special subgroup of patients with vaguely mediated
AF, disopyramide may be particularly useful.
For underlying structural heart disease, drug selection
to maintain NSR must be done very carefully, to avoid
the increase in mortality seen in a number of studies
in this setting. For congestive heart failure,
use amiodarone and dofetilide. Prospective data from
the Diamond Congestive Heart Failure Study and the
CHF Stat Study show that amiodarone and dofetilide
do not increase mortality in patients with AF. For
coronary artery disease (CAD), the initial drug of
choice is sotalol and the second choice is amiodarone
and dofetilide.
For hypertension, drug selection is based on the
extent of left ventricular hypertrophy (LVH) by echocardiography.
For an LV wall greater than 1.4 cm, select amiodarone,
because of the significant risk of torsade de pointes
with many antiarrhythmic drugs. For an LV wall thickness
less than 1.4 cm, the initial drug choice is flecainide
with amiodarone, and secondary choice is dofetilide
and sotalol.
Azimilide, a new drug for treating AF, blocks the
rapid and slow component of the delayed rectified
potassium channel. No difference in overall mortality
was seen between the azimilide-treated and control
patients in the ALIVE trial (Azimilide Post-Infarct
Survival Evaluation). A 57% reduction in the incidence
of AF and atrial flutter was seen in the azimilide-treated
group, compared to control, in the approximately 3,000
post-MI patients (FF 15% to 25%, low heart rate variability)
followed for 1 year. Torsade de pointes and neutropenia
were observed in less than 1% of patients. More
trials of azimilide are underway to obtain regulatory
approval.
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Non-Pharmacologic
Strategies for AF |
One strategy is A-V junction ablation and pacemaker
implantation, which has a 95% success rate and a 2-3%
incidence of sudden death. The risk of sudden death
persists, even when the pacing rate is increased to
about 85 bpm in the 3 months following pacemaker implantation.
Other risks include persisting thromboembolic risk
and lifelong pacemaker-dependency. Focal catheter
ablation of AF is another strategy. The current approach
is segmental pulmonary vein isolation and linear atrial
ablation. The efficacy is 75%. The risks include pulmonary
vein stenosis and pulmonary thromboembolism. Surgical
ablation during concomitant mitral and coronary artery
surgery is a third approach.
Two significant studies, by Saksena and by Mirza,
have used multi-site pacing to prevent AF, in patients
with spontaneous or drug-induced bradyarrhythmia who
already require a pacemaker for their slow rhythms.
Dual-site pacing and biatrial pacing are the two strategies
used. In dual-site pacing, sites in the high and low
right atrium are selected. Biatrial pacing involves
the right atrium and the coronary sinus. Dual-site
pacing decreased the frequency of AF in both studies.
The studies suggest it is reasonable to consider dual-site
pacing in patients with AF who require a pacemaker.
The current strategy for pulmonary vein isolation,
refined since its introduction by Haissaguerre, uses
segmental pulmonary vein isolation; the area from
which the focus is arising is identified and then
ablated. Usually, only about 20% of the pulmonary
vein circumference must be ablated. An ablation within
the atrial floor is usually performed in this strategy.
Although this approach can cure about 75% of patients,
significant recurrence of AF remains.
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Prophylactic therapy to prevent sudden death is one
approach. The MADIT II trial compared conventional
therapy and ICD implantation for prophylactic therapy
in patients with documented MI and an EF of 30% or
less within three months of entry. The study was stopped
at 20 months, as recommended by the Data and Safety
Monitoring Board. A 25% mortality reduction with an
ICD in patients with a LVEF less than 30% or no associated
ventricular arrhythmia was found in MADIT II.
It was first estimated that roughly 300,000 patients
in the US would meet implantation criteria based on
the MADIT II study, for about a 10% increase in the
total national health care expenditure. Thus, a substantial
downward revision to10,000 patients was made. The
actualnumber of patients meeting the MADIT criteria
likely liessomewhere between these extremes. Zypes
stated in an editorial that the current challenge
is the need for a simpler device for primary and secondary
prevention in patients who do not have an arrhythmia
as their initial presenting symptom. In the
MADIT population, less than 5% of patients who received
an ICD had a device discharge. However, the current
trend is actually for more complex ICD devices, rather
than the simpler device that would be useful for primary
prevention.
The current devices are 1) dual-chamber ventricular
ICD, for coexisting atrial and ventricular arrhythmias,
2) dual-chamber atrioventricular ICD, for drug-refractory
AF, for both atrial and ventricular fibrillation,
and 3) multi-site pacing ICD, for class II or III
heart failure and QRS prolongation of no greater than
140 ms.
Presently, data supports an ICD for primary prevention
in: 1) non-sustained VT with coronary artery disease
and LV dysfunction, 2) CAD with LV dysfunction and
LVEF less than 31%, 3) familial syndromes with a high
risk of sudden death (LQT syndrome, Brugada syndrome,
hypertrophic cardiomyopathy, RV dysplasia), and 4)
refractory heart failure necessitating cardiac transplantation.
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Role of Antiarrhythmic
Drugs for Ventricular Arrhythmias |
The MADIT and AVID studies have fairly conclusively
settled the role of ventricular arrhythmias. The MADIT
trial showed that survival was clearly superior in
patients receiving an ICD, compared with patients
receiving conventional therapy (antiarrhythmic drugs).
Even when the MADIT trial data is corrected for the
higher use of beta blockers in the ICD patients, in
response to criticism, this trial, and at least two
others, firmly show ICD therapy to be superior to
antiarrhythmic drugs for ventricular arrhythmias.
The role of anti-arrhythmic drugs in patients with
an ICD is: 1) to reduce the number of VT episodes
and shocks required from the ICD, 2) to lengthen the
tachycardia cycle length to allow conversion of VT
by anti-tachycardia pacing, and 3) to prevent supraventricular
arrhythmias, for example, AF.
The use of anti-arrhythmic drugs to reduce the number
of episodes of VT and VF is supported by a few studies.
In a study of inducible VT by Kuhlkamp and colleagues,
patients who remained inducible on sotalol were randomized
to ICD plus sotalol or ICD only. The VT free interval
was higher in the sotalol-treated group compared to
ICD alone. Sotalol appears effective in reducing the
frequency of ICD discharges in patients with VT.
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Radiofrequency
Catheter Ablation for Ventricular Arrhythmias |
The role of radiofrequency (RF) catheter ablation
has been established for a subset of patients with
VT, and in some it is curative. One groups is patients
with idiopathic VT from the right ventricular outflow
tract and a similar tachycardia arising in the intraventricular
septum. The success rate is 90-95%. The other group
is bundle branch re-entrant VT, most frequently observed
in cardiomyopathy. For this VT, ablation is in the
region of the right bundle branch distal to the His
potential.
Structural heart disease, particularly CAD, presents
the greatest challenge for VT ablation, because of
1) the large size of the re-entrant circuit, 2) the
multiple morphologies of VT, with an average of 3
different morphologies in each patient, 3) hemodynamic
instability during VT, limiting the extent of catheter
mapping, 4) mid-myocardial and sub-epicardial location
of some arrhythmia circuits, and 5) the presence of
endocardial clots, particularly LV aneurysms, requiring
warfarin for a substantial period of time to show
that the clot is organized, before proceeding with
catheter ablation.
Saline-cooled RF catheters are used for large reentrant
circuits and for reentrant circuits located in the
mid-myocardium, or sub-epicardium. These catheters
can produce larger and deeper burns from the endocardium.
Epicardial mapping and ablation is useful in some
patients in whom the reentrant circuit location is
mid-myocardial or sub-epicardial.
RF energy can be delivered for longer periods of
time, from 60 to 180 seconds, because of the saline-cooled
catheter. For impedance greater than 250 ohms, automatic
shutdown occurs. RF catheter ablation can be applied
with electrode temperatures ranging from 40 to 50
degrees centigrade.
A multicenter study of catheter ablation for refractory
VT by Calkins and colleagues showed that at about
1 year, about 50% of patients had recurrent VT. Patient
survival was about 50%. Major procedure-related complications
of saline-cooled catheter ablation in this study were
stroke or TIAs, AV block, cardiac tamponade, injury
to the aortic valve, myocardial infarction, and damage
to the femoral artery access site. In total, 8% of
patients had complications. Four procedural deaths
occurred in the 146 study patients.
In a study by Delacretaz using a conventional RF
catheter, 33% of patients were non-inducible, VT was
modified in 45% patients, and there was no impact
on VT in 22% of patients. At 12 to 18 months, about
66% of patients were free of VT and 33% had VT recurrence.
Heart failure was found to be a more important cause
of death in these patients.
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Transthoracic
Epicardial Catheter Ablation of VT |
The rationale for transthoracic epicardial catheter
ablation of VT in studies by Sosa and colleagues was
the epicardial location of the reentrant circuit in
15% of VT patients. The routes to the epicardium include
surgery, direct visualization through the cardiac
veins, and pericardial puncture as introduced by Sosa
and colleagues. Pericardial access cannot be used
in patients with prior cardiovascular surgery.
The approach used by Sosa and colleagues involved
the sub-xiphoid insertion of an epidural needle. The
needle position is verified by injecting 1-2 ml of
contrast, and also is aided by positioning a catheter
in the coronary sinus and prior coronary angiography.
In 10% of patients, ventricular perforation occurred.
High-quality stable electrograms were obtained in
the patients in whom the procedure was successful.
Thermal mapping was used; RF pulses of 60 degrees
Fahrenheit for 10 seconds, or 30 seconds if VT was
interrupted. The major concern was the risk of damage
to coronary arteries. Preceding animal studies showed
that this risk was significant only when there was
less than 12 mm between the site of RF ablation and
the coronary artery. A success rate of 60% was
reported, in patients primarily with Chagats
disease.
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