First Detected Episode Duration Known >48 Hours or Duration Unknown
Key Points:
- Antithrombotic with warfarin (international normalized ratio greater than or equal to 2.0 for three weeks) is recommended before electrical or pharmacologic cardioversion back to sinus rhythm.
- Transesophageal echocardiography-guided cardioversion without traditional pre-cardioversion anticoagulation cannot be routinely recommended.
- Amiodarone is the most effective antiarrhythmic drug for maintenance of normal sinus rhythm. However, it also is associated with the highest potential for non-cardiac toxicity, and requires regular scheduled medical follow-up.
- Angiotensin-converting enzyme (ACE)-inhibitors and angiotensin receptor blockers have a role as adjunctive medical therapies to antiarrhythmic drugs for maintenance of normal sinus rhythm.
General Recommendations
When the duration of atrial fibrillation or atrial flutter is unknown, the risk of thromboembolic complications is as high as 7% following cardioversion without anticoagulation. Thus, in this setting, anticoagulation with warfarin is required (international normalized ratio greater than or equal to 2.0 for three consecutive weeks). Though not a consistent clinical practice, the American College of Chest Physicians also recommends anticoagulation with warfarin (international normalized ratio greater than or equal to 2.0 for three consecutive weeks) prior to the initiation of antiarrhythmics.
Alternatively, the patient and/or physician may also opt for chronic anticoagulation (see Annotation #14, "Assess Patient for Chronic Anticoagulation") and chronic rate control (see Annotation #15, "Assess Patient for Rate Control Agents"). However, if this represents the first episode of persistent atrial fibrillation for the patient, there is general consensus that most patients deserve one trial of conversion back to normal sinus rhythm, given the high likelihood of initial success.
Short-Term Antithrombotic Issues Prior to and Following Cardioversion
Whenever possible, cardioversion should be undertaken with conventional anticoagulation prior to and following cardioversion.
When anticoagulation is temporarily contraindicated (refer to Table 1 in the original guideline document and "Contraindications" field in this summary), cardioversion should be delayed if possible until appropriate anticoagulation can be given prior to and following cardioversion.
When anticoagulation is contraindicated and cardioversion cannot be delayed, transesophageal echocardiography may identify high-risk patients but may not change therapeutic decisions.
However, if transesophageal echocardiography is used to guide anticoagulant therapy, the patient must be anticoagulated with therapeutic (not prophylactic) levels of heparin and warfarin. Heparin should be continued until the international normalized ratio is greater than or equal to 2.0 for two consecutive days. Warfarin should be continued a minimum of four weeks following successful cardioversion.
At this time, there is insufficient evidence to recommend routine transesophageal echocardiography to guide anticoagulant therapy prior to or following cardioversion [Conclusion Grade III: See Conclusion Grading Worksheet A - Annotation #9 (Transesophageal Echocardiography and Anticoagulation Therapy) in the original guideline document.] [A], [D], [M]
There is little experience reported on the use of low-molecular-weight heparins prior to or following cardioversion (with or without transesophageal echocardiography). A pilot study of transesophageal echocardiography-guided enoxaparin plus warfarin versus transesophageal echocardiography-guided unfractionated heparin plus warfarin (ACUTE II) is in progress. Unfortunately, this trial does not include a conventional therapy group, which is a significant omission in light of the ACUTE trial results.
For additional information on anticoagulation with warfarin, refer to the NGC summary of the ICSI Antithrombotic Therapy Supplement guideline.
As atrial fibrillation persists for longer periods of time, the efficacy of pharmacologic cardioversion decreases. Though direct current cardioversion requires conscious sedation, pharmacologic cardioversion is less effective and may cause serious arrhythmias, including torsades de pointes. Antiarrhythmics like ibutilide or propafenone may be administered prior to direct current cardioversion to increase the likelihood of its success [A], [D].
Direct Current Cardioversion
Direct current cardioversion has been used to treat a variety of rhythm disturbances including atrial fibrillation and atrial flutter since the early 1960s [D], [R]. The success of external direct current cardioversion depends on patient selection and cardioversion technique. Success rates range from 65% to 95%. Success of cardioversion is increased if the left atrium is less than 60 mm (3 cm/m2 body surface area and if the arrhythmia is of short duration.
Transthoracic cardioversion of atrial fibrillation may now be performed with biphasic waveform defibrillation. It typically requires less energy and may have greater efficacy than monophasic wave forms [A].
A recent study has shown that an anterior-posterior paddle position is superior to an anterior-lateral position in success of cardioversion. The anterior-posterior position also required lower energy levels for success [A]. If the first position is unsuccessful, paddle relocation should be considered.
Complications of direct current cardioversion are uncommon but include embolization, pulmonary edema, and arrhythmias including ventricular fibrillation and asystole [D]. Direct current cardioversion should be avoided in patients with known or suspected digoxin toxicity. It is unnecessary to interrupt digoxin therapy for cardioversion in patients without manifestations of toxicity.
See the original guideline document for specifics on direct current cardioversion technique and information on comparing electrical and chemical cardioversion.
Antiarrhythmic/Chemical Cardioversion [R]
All antiarrhythmics used to treat atrial fibrillation/atrial flutter can cause serious complications including the life-threatening arrhythmia torsades de pointes in up to 8% of patients [R]. Therefore, antiarrhythmics should be initiated in the presence of a physician or nurse with expertise in the administration of antiarrhythmics with telemetry monitoring for at least 4 hours, or longer if QT remains prolonged.
Risk factors for proarrhythmia include:
- Pre-existing bradycardia or atrioventricular block
- Underlying structural heart disease
- Active heart failure or ischemia- hypokalemia or hypomagnesemia, and
- Drug dosages (e.g., lower doses for quinidine and higher doses for sotalol)
Pharmacologic therapy aimed at restoring sinus rhythm is often helpful in patients with atrial fibrillation. As a general rule, regardless of the agent or route used, the conversion rate of atrial fibrillation of less than 48 hours duration is 60%-90%. Conversion rates drop to 15%-30% if present 48 hours or longer [R]. Successful conversion of atrial flutter is generally higher than for atrial fibrillation.
A summary of the agents with proven efficacy for pharmacologic cardioversion of atrial fibrillation of up to seven days duration or atrial fibrillation present for more than seven days is described in the tables below.
Table. Pharmacological Cardioversion Up to Seven Days
| Recommendations for Pharmacological Cardioversion of Atrial Fibrillation of Up to Seven Days |
| Agents with proven efficacy |
Dofetilide, flecainide, ibutilide, propafenone and amiodarone |
| Less effective or incompletely studied patients |
Disopyramide, flecainide, procainamide, propafenone and quinidine |
| Agents should not be administered |
Digoxin and sotalol |
Adapted from the American College of Cardiology (ACC)/American Heart Association (AHA) Atrial Fibrillation 2006 guideline (pages e299 and e300)
Table. Pharmacological Cardioversion for More Than Seven Days
| Recommendations for Pharmacological Cardioversion of Atrial Fibrillation Present for More Than Seven Days |
| Agents with proven efficacy |
Dofetilide, amiodarone, ibutilide |
| Less effective or incompletely studied patients |
Disopyramide, flecainide, procainamide, propafenone and quinidine |
| Agents should not be administered |
Digoxin and sotalol |
Adapted from the American College of cardiology (ACC)/American heart Association (AHA) Atrial Fibrillation 2006 guideline (pages e299 and e300)
Reported success rates vary in part because of the heterogeneity of patient populations– particularly with respect to the duration of atrial fibrillation in the published trials. Of the intravenous agents, only ibutilide is approved by the Food and Drug Administration for this indication.
Torsades de pointes is a potentially life-threatening arrhythmia and requires prompt evaluation and treatment. See Table 7 in the original guideline document for treatment of torsades de pointes.
Refer to Annotation #20, Table 13, "Antiarrhythmic Agents," in the original guideline document for more information on antiarrhythmic agents.
Ibutilide has been studied extensively for the conversion of recent onset atrial fibrillation and atrial flutter. Efficacy rates between 30% and 40% have been quoted in acute reversal of recent onset atrial fibrillation. Generally patients convert within 30 minutes. Significant adverse effect of torsades de pointes was noted in 4.3% of patients, 1.7% requiring electrical termination. There were no deaths or severe morbidities [A], [R].
Refer to Table 6 in the original guideline document for more information on use of ibutilide.
Proarrhythmia associated with initiation of membrane antiarrhythmic agents relates to the presence of underlying structural heart disease as well as the type of drug initiated. The drugs sotalol, dofetilide, and quinidine should be initiated in all patients under telemetry guidance. These drugs should not be allowed to prolong QTc (similar to sotalol and dofetilide) to longer than 500 milliseconds. The QTc prolongation maybe associated with torsades de points. Refer to Table 7 in the original guideline document for treatment of torsades de points.
Amiodarone, the other class III drug, is the subject of several articles regarding its efficacy in conversion of recent onset and permanent atrial fibrillation. Amiodarone is effective in converting atrial fibrillation both acutely and chronically. It has been studied by both the oral and intravenous routes. Amiodarone can be started at maintenance doses in the outpatient setting; when high-dose loading is required or the drug is initiated in patients with structural heart disease, hospitalization should be advised. The Class I-C drugs propafenone and flecainide can also be initiated in the outpatient setting with appropriate follow-up of QRS duration that should not lengthen more than 25%. For patients with structural heart disease, these agents should also be initiated in the inpatient setting [A].
Oral flecainide (300 mg single dose) has similar conversion rates compared to oral propafenone (600 mg single dose) when used in patients with atrial fibrillation of acute onset (approximately 72%-78% conversion rate at eight hours) [A].
Failed Cardioversion Treatment Options
If initial attempts to restore normal sinus rhythm for atrial fibrillation fail, cardioversion can be repeated following a parenteral or oral loading dose of an appropriate antiarrhythmic agent [A], [R]. However, this approach should be avoided in patients with ejection fractions less than 30% because of the increased risk of torsades de pointes.
Furthermore, it should be noted that this is not a strategy to maintain normal sinus rhythm but only a means to enhance conversion back to sinus rhythm. Appropriate anticoagulation practices are required prior to and following cardioversion if the duration of atrial fibrillation exceeds 48 hours. If atrial fibrillation continues despite these attempts, cardiology consultation is advised.
The patient and/or physician may also opt for chronic anticoagulation and chronic rate control at this point - though the general consensus is that most patients with a first episode of atrial fibrillation or atrial flutter have a high likelihood of successful conversion back to normal sinus rhythm.
Transthoracic cardioversion of atrial fibrillation may be achieved by applying biphasic waveform for defibrillation. It has been shown to be equally effective and to use less energy than monophasic waveforms.
Maintenance of Sinus Rhythm Following Conversion
Several antiarrhythmic drugs have been demonstrated to improve sinus rhythm maintenance following cardioversion, including amiodarone, propafenone, disopyramide, sotalol, flecainide, dofetilide, and quinidine [M].
It is essential to establish adequate rate control before administering antiarrhythmics. Class 1A drugs can accelerate ventricular rates via anticholinergic effects on the atrioventricular node. Class 1C drugs can also accelerate ventricular rates by organizing and slowing atrial activity allowing 1:1 conduction. Additional drugs to slow atrioventricular nodal conduction are recommended when using Class 1C drugs. Amiodarone has been shown to be the single most effective agent of the lot, although it also contributes the most to noncardiac drug-related toxicity [A]. When administered at 800 mg per day for 2 weeks prior to elective cardioversion, amiodarone chemically converts one-fifth of patients with persistent atrial fibrillation, and when continued for eight weeks at 200 mg per day, doubled the number of patients in normal sinus rhythm at that time [A].
Non-Antiarrhythmic Medical Therapies for Maintenance of Sinus Rhythm
Both the ACE inhibitor, enalapril, and angiotensin receptor blocker, irbesartan, have been demonstrated to enhance the maintenance of normal sinus rhythm after cardioversion when added to amiodarone [A]. A meta-analysis of studies using this class of compounds has added further credence to these initial observations [M].
There has been a demonstrated correlation between stroke risk and inflammatory marker (C-reactive peptide [CRP]) elevation in patients with non-valvular atrial fibrillation [B]. Retrospective and prospective studies of lipid lowering with statin therapies [A], [D] have demonstrated beneficial effects for the prevention of atrial fibrillation, both postcoronary artery bypass graft and de novo. Fish oil also has been demonstrated in small randomized control trials to have a significant beneficial effect [R].
Intravenous hydrocortisone has been revealed to have an antiarrhythmic effect for post-cardiac surgery [A], while dexamethasone demonstrated no such effect [A].
Further study of all these adjunctive medications will be required to assess their appropriate roles, post-coronary artery bypass graft, postdirect current cardioversion, postablation, and as primary prevention tools.
