SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
VOLUME 7 NUMBER 2 • JUNE 2010
61
IfAFrequirescardioversion,thiscanbeachieved
pharmacologically
or
electrically
. Each has its merits: acute AF (
<
48 hours onset) can
be treated in hospital with a slowly administered bolus of flecainide
without the need for electrical cardioversion, avoiding the need for
general anaesthesia or sedation, but this becomes less effective as
the paroxysm continues past 24 hours.
If restoration of sinus rhythm is required on haemodynamic
grounds, acute electrical cardioversion can be offered under a brief
general anaesthetic. It must be emphasised that if a clear onset
of AF within 48 hours of presentation cannot be ascertained,
restoration of sinus rhythm should be deferred pending
therapeutic anticoagulation for at least three weeks, unless
haemodynamic symptoms warrant a strategy of transoesophageal
echocardiography to help exclude atrial thrombus followed by
direct current cardioversion.
The efficacy of pharmacological therapy when administered
>
48 hours after onset of AF is modest and because therapeutic
anticoagulation is required for at least three weeks before initiation
of such therapy the preferred strategy is that such anticoagulation
be followed by DC electrical cardioversion, usually as a day-case
hospital admission.
Maintenance of sinus rhythm,
ie
prevention of recurrent AF
(either paroxysmal or persistent), usually requires anti-arrhythmic
drug therapy. After a first AF episode, it is reasonable to await
a second episode before commencing anti-arrhythmic therapy,
because the time to recurrent AF is ‘unknown’.
Pharmacological therapy
The overall approach should be ‘stepwise,’ moving from lower-risk
interventions with some potential benefit to those that are more
effective but carry a greater risk of adverse effects. The first-line
agent, including after initial cardioversion, should generally be a
standard (non-sotalol)
beta-blocker
. If, despite maximum tolerable
dose-titration, this fails, the options are class I or III anti-arrhythmic
drugs. In most cases, it is appropriate for these to be initiated by a
cardiologist.
Class I anti-arrhythmic drugs
, which are sodium channel
blockers related to local anaesthetic agents, can be highly effective
at maintaining sinus rhythm. The main agents used in the UK are
flecainide (100–300 mg daily in divided doses), and propafenone.
They are negatively inotropic, have an association with poor
outcomes in patients with previous myocardial infarction, and also
increase the risk of electrical block in the His-Purkinje system, so
patients should be screened for:
structural heart disease including previous myocardial infarction,
•
symptomatic coronary artery disease, and cardiac failure
ECG abnormalities such as bundle branch block, 1st degree
•
heart block, prolonged QT.
However, in patients without structural heart disease, these drugs
can be regarded as an early second line of therapy, and are often
well tolerated. For infrequent symptomatic paroxysms, single-dose
‘pill-in-the-pocket’ therapy can be used. For daily use, even for
those with normal baseline ECG, repeat ECG and possibly exercise
testing should be considered after dose (particularly
≥
200 mg
daily) titration to establish there is not abnormal prolongation of
QRS width or QT interval, both of which may be associated with
pro-arrhythmia. This will usually be organised, or will need to be
reviewed by, the initiating cardiologist. Class I drugs may also
convert persistent AF to atrial flutter which may conduct rapidly
(1:1) to the ventricle, so AV-node blocking drugs (beta/calcium-
blocker) are often co-administered with maintenance flecainide
therapy to reduce this risk.
Sotalol, a class III anti-arrhythmic related to beta-blockers, can
also be effective in maintaining sinus rhythm. NICE guidelines
recommend it is up-titrated from 80 mg twice daily to 240 mg
twice daily. However, we would advise
extreme caution
when
doing this, especially in a primary care setting. There is a risk of
pro-arrhythmia due to QT prolongation and torsade de pointes
ventricular tachycardia, more likely to occur in women and when
the total daily dose of sotalol exceeds 160 mg.
54
An ECG should
be repeated 5–7 days after dose titration to check for excessive
QT prolongation (caution if
>
460 msec, and therapy should be
discontinued immediately if QTc
>
500 msec).
Amiodarone has less pro-arrhythmic risk, but is associated with
multiple extra-cardiac side effects, particularly thyroid dysfunction,
pulmonary inflammation/fibrosis, and skin problems such as
photosensitivity, corneal micro-deposits, and, less commonly,
liver and neurological problems. It interacts with warfarin very
significantly. Many effects are long term and dose dependent, so it
is not a favoured strategy in younger patients or when considered
for long-term use. The drug is, however, relatively safe in those
with heart failure – being ‘reassuringly’ mortality neutral in the
SCD-HeFT trial.
55
Amiodarone is the rhythm-control agent of choice in the short–
medium term for patients with structural heart disease, especially
those with LV dysfunction, but remains generally unsuitable for
long-term use. The elderly, in particular, are at risk of bradycardia
during initial loading therapy, both in AF and if sinus rhythm is
restored; thus caution should be exercised. However, it is probably
one of the safest anti-arrhythmic agents to be initiated out of
hospital.
Loading regimens for amiodarone vary, with
≥
1 g daily loading
under initial specialist care, but low-dose standard regimens are
advised in primary care (600 mg daily for one week in divided
doses, then 400 mg for one week, followed by 200 mg daily). The
patient must be counselled on the long-term side effects and will
need to have regular follow up to ensure early recognition of any
complications.
New oral anti-arrhythmics
Several new oral anti-arrhythmics are on the horizon, which offer
the potential for greater efficacy with fewer side effects. The first
available new drug,
dronedarone
, is a non-iodinated derivative
of amiodarone with less extra-cardiac toxicity but similar ‘broad-
spectrum’ anti-arrhythmic properties. Large clinical trial results
look promising
56
and, although its use may not extend to those
with heart failure,
57
it is likely to add to the armamentarium of AF
therapies, particularly given its apparently improved safety profile,
possibly at the expense of efficacy, compared with amiodarone.
58
A move to atrial-specific anti-arrhythmics and more ‘up-stream’
therapies in at-risk populations may lead to arrest or reversal of
the remodelling processes that encourage AF, and could offer new
promise in the pharmacological management of AF.
Repeat electrical cardioversion
Although routine repeat cardioversion for recurrent AF is no longer
recommended (given the availability of anti-arrhythmic therapy
and also data supporting rate control as an equivalent prognostic
