When to try to restore sinus rhythm
When atrial fibrillation is first diagnosed, it may not be possible to determine if it is paroxysmal (ie, self-terminating) or persistent. If the episode does not quickly end on its own, consideration may be given to restoring sinus rhythm.
Although experts debate the merits of a rate control approach vs a rhythm control approach for managing atrial fibrillation in the long term, many, including ourselves, recommend trying to restore sinus rhythm at least once when atrial fibrillation is first discovered. It is not always clear if atrial fibrillation is truly asymptomatic. Symptoms such as fatigue or decreased exercise tolerance can be subtle. Additionally, these symptoms may be attributed to other factors such as deconditioning, obesity, or advancing age. Thus, in many cases, only restoring normal sinus rhythm for a time allows the patient and clinician to fully assess the symptoms attributable to atrial fibrillation.
Therefore, in patients with newly diagnosed atrial fibrillation, an attempt to restore sinus rhythm is often warranted. Exceptions are in select patients who have no apparent symptoms and who are very old or are deemed too frail to tolerate cardioversion.
Direct-current cardioversion is typically the treatment of choice when attempting to restore sinus rhythm. The procedure can be done without anticoagulation within 48 hours of the onset of atrial fibrillation, if the time of onset is clear.7 However, clinicians must be careful in defining the onset of atrial fibrillation for this purpose.
Symptoms such as fatigue or shortness of breath can be vague in terms of the exact time of onset and often cannot be relied upon for the purpose of deciding whether cardioversion can be done without anticoagulation. When in doubt, it is best to err on the side of safety and assume that the atrial fibrillation has been going on for more than 48 hours.
If the time of onset is unclear or if more than 48 hours have passed, there are two general strategies for proceeding to electrical cardioversion.
One is to order transesophageal echocardiography and begin anticoagulation therapy at the same time. If there is no thrombus in the left atrium, then cardioversion can be done.8 Therapeutic anticoagulation with heparin, low-molecular-weight heparin, or warfarin (Coumadin) should be achieved within 24 to 48 hours of transesophageal echocardiography and cardioversion to minimize the risk of thromboembolic events, which can occur even after sinus rhythm has been restored.
At our institution, we typically strive to achieve therapeutic anticoagulation with either heparin or low-molecular-weight heparin before cardioversion in this scenario so as to avoid situations in which a patient may undergo cardioversion but then fail to achieve therapeutic anticoagulation for some time due to unforeseen factors.
The other approach is to start warfarin and maintain a goal international normalized ratio (INR) of 2 to 3 for 3 weeks, at which time cardioversion can be performed safely without transesophageal echocardiography.8
Regardless of which strategy is used, anticoagulation should be continued for at least 4 weeks after cardioversion,8 as atrial dysfunction and the risk of stroke may persist for days to weeks after normal sinus rhythm is restored.9
Role of antiarrhythmic drugs
Antiarrhythmic drugs can be used for chemical cardioversion or, more often, to help maintain sinus rhythm after direct-current cardioversion.
Because most of these drugs have at least a small chance of restoring normal sinus rhythm, we need to follow the same rules when starting them as when performing direct-current cardioversion. Patients should not be started on an antiarrhythmic medication until they have had adequate anticoagulation for at least 3 weeks or adequate anticoagulation and a transesophageal echocardiogram confirming that there is no thrombus in the left atrium.
Antiarrhythmic drugs should be started in select patients with newly diagnosed atrial fibrillation in whom a rhythm control strategy will be pursued. For patients whose history suggests a single episode, or episodes that previously self-terminated, an antiarrhythmic may not be necessary. For those with frequent episodes or whose history suggests ongoing atrial fibrillation for a long period, an antiarrhythmic will likely be required to provide a reasonable chance of achieving freedom from atrial fibrillation.
The choice of antiarrhythmic drug should be tailored to the specific patient.
Propafenone (Rythmol) and flecainide (Tambocor) are first-line drugs7 but are contraindicated in patients with coronary artery disease and significant structural heart disease.10
Sotalol (Betapace) and dofetilide (Tikosyn) can be used in patients with coronary artery disease. However, sotalol is contraindicated in patients with congestive heart failure, and dofetilide carries a long list of drug interactions. Both must be used with extreme caution in patients with renal insufficiency, and hospital admission is required for initiation or upward titration of the dose.
Amiodarone (Cordarone) is effective, and in the short term it is typically very well tolerated. However, it has a long half-life, and its potential for long-term toxicity often makes it a poor choice for long-term treatment. The toxicity of amiodarone increases with the cumulative dose. Therefore, this drug should be avoided for long-term therapy of atrial fibrillation in younger patients.
The ‘pill-in-the-pocket’ strategy
The “pill-in-the-pocket” strategy, in which patients are instructed to take their medication only when they have a bout of atrial fibrillation, is a reasonable option for patients with symptomatic recurrences of paroxysmal atrial fibrillation. This strategy is mainly reserved for patients who have relatively infrequent recurrences. Those who have frequent recurrences are usually more effectively treated with daily dosing of an antiarrhythmic. Flecainide and propafenone are the agents of choice for this approach because of their safety profile and efficacy in chemical cardioversion.
While this strategy may be started on an outpatient basis in patients with lone, paroxysmal atrial fibrillation, those with structural heart disease or conduction abnormalities should be observed in the hospital during initiation of therapy to observe for excessive PR prolongation or development of dangerous or worrisome arrhythmias.11–13
Additionally, these agents can decrease the refractory period of the atrioventricular node, thereby increasing the ventricular rate. In the case of atrial flutter, patients may be converted from variable or 2:1 response to a 1:1 conduction. Thus, one should consider also using a beta-blocker with this strategy.
Since the goal of this approach is to convert the patient to sinus rhythm within a few hours of the onset of atrial fibrillation, it may be implemented without the use of warfarin. Patients are instructed that if they do not convert to normal sinus rhythm within a few hours, they should notify the physician so they can undergo electrical cardioversion within the 48-hour window from the onset of atrial fibrillation.
Dronedarone, a new antiarrhythmic drug
Dronedarone (Multaq) is now available and has been shown to be effective in treating atrial fibrillation.14 It has a long half-life and a mechanism of action similar to that of amiodarone. However, it may be inferior to amiodarone in terms of efficacy.15 It is metabolized by CYP3A4. No dosage adjustment is needed for patients with renal insufficiency.
Because dronedarone lacks the iodine moiety found in amiodarone, it should not carry the same toxicity profile. No pulmonary or thyroid toxicity was reported in early trials.16
Nevertheless, dronedarone has several important limitations. It carries a black box warning stating it is contraindicated in patients with severe or recently decompensated heart failure, as the mortality rate was twice as high when this drug was used in such patients in initial studies.17 Additionally, there have been reports of hepatotoxicity requiring liver transplantation in a small number of patients. The extent of this problem and strategies for avoiding it are not yet defined as of the writing of this paper. As with any new medication, patients who are started on dronedarone should be observed closely for any side effects, and these should be reported to assist in the development of the drug’s safety profile.