Antiarrhythmic Agents
There are several groups of antiarrhythmic agents. One group
includes flecainide and propafenone. These two agents are sometimes
called Class I. These agents are often selected in patients with no
significant heart disease or heart abnormalities, including artery
narrowing of the heart, called the coronary arteries. Patients with a
prior history of heart attack or other abnormalities of pumping
function of the heart, called cardiomyopathy, are usually excluded
from treatment with flecainide or propafenone. The reason for this
exclusion is that some studies have shown that there may be an
increased risk of deaths with these agents and serious ventricular or
lower heart chamber rhythm abnormalities, such as ventricular tachycardia.
Flecainide and propafenone are generally well-tolerated, without
what we would call end-organ toxicity. The adverse effects are not
felt to accumulate over time. Flecainide and propafenone are
sometimes associated with mild central nervous system adverse effects,
including tingling around the mouth and sometimes mental slowing or a
sensation of being in a cloud. They also may cause some degree of
tremors. Most patients seem to tolerate these medications well.
Propafenone and flecainide may be increased in dose if at the initial
dose the desired effect is not obtained. Some physicians will check a
flecainide level, in order to assess in what part of the therapeutic
range the patient is at the current dose.
Flecainide and propafenone are particularly known to organize atrial
fibrillation into another rhythm called atrial flutter, which most
commonly has a single path or circuit. Atrial flutter has a different
electrocardiographic appearance and therefore the diagnosis may be
made by ECG. In uncommon situations, it is possible that patients may
develop faster heart rates in atrial flutter than in atrial
fibrillation. This is because with the organization the rate of the
atrium is slower than that in atrial fibrillation. Therefore, fewer
impulses try to get through the AV node to the lower heart chambers.
In atrial fibrillation, because there are so many impulses trying to
get down the AV node, the impulses tend to cause the conduction to be
slowed through the AV node. The analogy that may be used may be a
group of people trying to leave a room. If there are fewer people
trying to leave the room at the same time, they may be able to get
through more rapidly than if there are many people trying to get
through. Therefore, the slower atrial rate in atrial flutter can
sometimes lead to faster ventricular rate. In some cases this can
cause an extremely rapid heart rate that can cause the patient to be
dizzy or even pass out. This typically warrants discontinuation of the
medication or strategies to treat the atrial flutter. Sometimes an
extremely rapid rate can occur and can be often mistaken for
ventricular tachycardia.
Another category of medication includes that of sotalol and
dofetilide. Sotalol and dofetilide are also free of significant
end-organ toxicity. However, there are rare incidents of ventricular
arrhythmias that require that patient be hospitalized for initiation
of these medications. The purpose of hospitalization is to monitor the
patient's electrocardiogram or any changes that would likely increase
the risk of serious ventricular arrhythmias. Sotalol acts both to
treat the atrial fibrillation itself and try to maintain normal
rhythm, as well as controlling the overall ventricular rate in atrial
fibrillation. Sotalol's beta-blocking effect probably accounts for a
lot of its ability to control rate. Appropriate caution, however,
should be used if the patient's heart rate already is starting on the
slow side prior to initiation of sotalol. Dofetilide does not have a
beta blocker component and does not affect the heart rate in most
situations. It still however may be effective in treating atrial fibrillation.
Dofetilide has a number of drug interactions which must be
considered. Patients on these drugs cannot be started on dofetilide
because of concern that the level of dofetilide in the body will
significantly increase the risk of these serious ventricular
arrhythmias. Table 3 is a list of medications that have interactions
with dofetilide that are most prominent and serve as a
contraindication, as well as those that likely require intensive
monitoring or adjustment in dose. Hydrochlorothiazide, verapamil,
cimetidine and megestrol are a few of the c agents that should not be
used with dofetilide. Patients should not be taking sotalol or
dofetilide if they are on other medications that may prolong the QT
interval and may increase the risk of ventricular tachycardia.
Amiodarone is considered by most physicians to be the most potent
medication to control atrial fibrillation. It, however, has a large
number of side effects. These are largely dose related and therefore
patients at the lowest doses tend to have relatively few side effects.
However, they are significant and merit close follow-up. Thyroid
dysfunction is particularly common and increases with age for patients
on amiodarone. Most commonly underactive thyroid or hypothyroidism is
observed. However, not infrequently hyperthyroidism or overactive
thyroid may also result from amiodarone therapy. In the situation of
underactive thyroid, thyroid replacement may be necessary. In the case
of overactive thyroid, medication to block the effects of thyroid
hormone or surgery might be necessary. Observing for the development
of amiodarone related thyroid dysfunction can be performed by
obtaining thyroid function tests which are widely available blood
tests. TSH is the most commonly blood test, but other blood tests,
such as free T3 or free T4, may be used.
The most serious side effect of amiodarone is its potential for lung
toxicity. This effect is considered fairly specific and is called
pulmonary fibrosis or fibrosis of the lung. Only a small percentage
of patients develop this, but it is potentially life-threatening.
Patients with amiodarone related lung abnormalities can usually be
identified early prior to development of symptoms if testing such as
pulmonary function tests with diffusing capacity are used. A
pulmonary function test involves a machine in which one blows into a
tube. A specific test, called diffusing capacity, is generally thought
to be the most sensitive in terms of detecting early changes that
might represent pulmonary fibrosis. However, in many circumstances
these abnormalities are probably not related to amiodarone therapy and
fortunately reverse themselves.
There are a number of medications used to treat atrial
fibrillation. In this section, we will discuss medications,
specifically trying to keep the heart rhythm in normal rhythm, rather
than in atrial fibrillation. There are a variety of medications that
can be used to treat atrial fibrillation. The goal of these
treatments is to keep atrial fibrillation from recurring or in some
cases to convert atrial fibrillation.
Let us consider the first situation, in which we want to convert
atrial fibrillation with medications. First let us consider the
situation where we want to convert the rhythm rather urgently. This
may occur when the patient's blood pressure is particularly low. There
may be symptoms of chest pain, dizziness or shortness of breath.
Either intravenous or oral medication may be selected. Intravenous
medication would be delivered typically in the hospital or Emergency
Department setting and would include medications such as ibutilide or
other intravenous medications.
These medications are statistically more likely to convert the
rhythm if it has only been present for a relatively short time, such
as less than 24 or 48 hours. As the duration of the atrial
fibrillation increases, it still may be possible to stop the atrial
fibrillation with these intravenous medications, but the percent decreases.
The ibutilide may be given relatively rapidly, but has the potential
to result in possibly serious or life-threatening rhythm problems
called ventricular tachycardia, a fast heart rhythm of the lower
chambers. This is related to a specific property of ibutilide and is
related to its ability to prolong the interval recorded on the
electrocardiogram called the QT interval. Patients thus need to be
monitored even after they have received ibutilide for these
arrhythmias, typically for several hours.
Other intravenous medications include intravenous amiodarone or
intravenous procainamide. These medications typically involve an
initial dosage given, often called a bolus, and may be followed by a
continuous infusion, which is the medication being given intravenously
over a more extended period of time. Intravenous amiodarone is used in
a variety of in-hospital settings, as well as in the Emergency
Department. Intravenous amiodarone likely represents the most commonly
used of these intravenous agents, to control atrial fibrillation.
Oral medications may also be used to convert atrial fibrillation.
There are a number of studies that show the effectiveness of giving a
dose of medication in converting atrial fibrillation. As for
intravenous medications, oral medications are most likely to work if
they are given within 24 to 48 hours of the arrhythmia onset. A number
of studies have shown that a dose of oral medication that is higher
than what would be used if given on a regular basis is likely to
convert the rhythm of atrial fibrillation back to normal rhythm.
However, because the dose is considerably higher than that which has
been used on a regular basis, there is some caution regarding
potential serious side effects. As a result, many physicians require
at least the first time that the medication is given at this increased
dose to be performed while a physician monitors the patient, typically
in an Emergency Department situation. If the atrial fibrillation does
not convert with this initial dose of the medication, it is still
possible they will occur after the medication has been given for a
longer period of time.
In addition to converting atrial fibrillation, it can be used to
prevent its occurrence again. Even if the medication has not been
effective in converting the atrial fibrillation initially, it is still
possible that the medication may be effective in preventing it from
occurring. In many cases, atrial fibrillation may not be prevented
100% of the time, but may be decreased in its frequency. Therefore,
medications may improve the patient's quality of life significantly
without eliminating all episodes of atrial fibrillation. We therefore
consider frequently the goals of atrial fibrillation therapy to not be
100% elimination of atrial fibrillation, but to decrease its frequency
and often also its severity.
We are able to provide a list of various medications used to prevent
atrial fibrillation, decrease its recurrence or to convert atrial fibrillation.