ibutilide, and vernakalant [42-52]. Intravenous amiodarone may be more effective in converting AF after it has been given for hours and days. Oral amiodarone requires long- term loading and is effective in converting about 25 percent of patients with persistent AF to SR after six weeks of loading. Thus, we do not recommend it solely for the purpose of cardioversion. It is not approved by the US Food and Drug Administration for the treatment of AF. (See "Amiodarone: Clinical uses" and "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".) However, amiodarone may occasionally have value before cardioversion in patients who will receive the drug long term for maintenance and may be considered as adjunctive therapy to increase the likelihood of successful cardioversion in patients who are known to be refractory to electrical cardioversion or in those in whom there is a concern about early relapse. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations", section on 'Summary and recommendations'.) https://www.uptodate.com/contents/atrial-fibrillation-cardioversion/print 12/26 7/5/23, 9:05 AM Atrial fibrillation: Cardioversion - UpToDate Intravenous amiodarone is given at a dose of 150 mg over 10 minutes, with a subsequent infusion of 1 mg/minute for six hours, then 0.5 mg/minute for 18 hours or change to oral maintenance dosing (eg, 100 to 200 mg once daily) [53]. It should be kept in mind that the drug will likely have a significant rate-slowing effect, which may be beneficial in some patients [54]. A table on monitoring for adverse effects is available ( table 1). Vernakalant is available in Europe and Canada in intravenous forms for the rapid conversion (50 percent conversion within 10 minutes) of recent onset AF (less than eight days duration for patients not undergoing surgery, and less than four days duration for post-cardiac surgery patients) to SR. This drug is not available in the United States. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials", section on 'Vernakalant'.) In a 2019 systematic review and meta-analysis of nine trials (n = 1358) comparing vernakalant with placebo, amiodarone, or ibutilide [55], significant methodological bias was found in four trials. The following was also found: Vernakalant was superior to placebo for conversion within 90 minutes (50 percent conversion; risk ratio 5.15, 95% CI 2.24-11.84). No significant difference in the rate of conversion was found comparing vernakalant with active drug (56 versus 24 percent; risk ratio 2.40, 95% CI 0.76-7.58). Ibutilide, due to its propensity to prolong repolarization and the QT interval, has the potential to provoke torsades de pointes. Ibutilide is available only as an intravenous preparation (1 mg over 10 minutes and potentially repeated once after 20 minutes) and is useful for the acute reversion of AF [56-58]. It has been used in patients with structural heart disease (but without heart failure). We use ibutilide very rarely in this setting. (See "Therapeutic use of ibutilide".) In trials, the acute AF conversion rate is 28 to 51 percent. Ibutilide is more effective at converting atrial flutter to SR, with conversion rates of 50 to 75 percent. Ibutilide can work in acute situations of persistent AF and can be used (with caution) in patients with structural heart disease. However, while these rates seem low compared with flecainide or propafenone, ibutilide has never been directly compared with these other drugs. In addition, the average conversion times with ibutilide seem shorter than with flecainide and propafenone. Arrhythmia conversion occurred within a mean of 27 to 33 minutes after the start of the infusion [57,58]. In comparative studies, ibutilide has been more effective for AF reversion https://www.uptodate.com/contents/atrial-fibrillation-cardioversion/print 13/26 7/5/23, 9:05 AM Atrial fibrillation: Cardioversion - UpToDate than procainamide (51 versus 21 percent and 32 versus 5 percent) [59,60] or intravenous sotalol (44 versus 11 percent) [61]. In four large series, the rate of torsades de pointes with ibutilide ranged between 3.6 and 8.3 percent [56-58,60]. Sustained episodes of torsades de pointes, requiring cardioversion, were seen in 1.7 to 2.4 percent. In addition to polymorphic VT, nonsustained monomorphic VT occurred in an additional 3.2 to 3.6 percent of patients [57,58]. Because of the risk of ventricular proarrhythmia, patients treated with ibutilide should be observed with continuous rhythm monitoring for at least four hours after the infusion or until the QTc interval has returned to baseline. Pretreatment with intravenous magnesium appears to minimize the risk of ibutilide-induced torsades de pointes without affecting the efficacy of conversion [62]. Risk factors for the development of torsades de pointes with ibutilide are heart failure, baseline increase in QTc interval, and low potassium or magnesium. Electrolytes should be checked and normalized before cardioversion with ibutilide. We occasionally use ibutilide in patients resistant to electrical cardioversion and in patients for whom anesthesia, in conjunction with direct current cardioversion, is not readily available. The recommended dose varies with patient size. For patients weighing less than 60 kg, the recommended dose is 0.01 mg/kg infused over 10 minutes. If the arrhythmia does not terminate 10 minutes after the end of the infusion, a second bolus (same dose over 10 minutes) can be given. For patients weighing more than 60 kg, the recommended starting intravenous dose is 1 mg over 10 minutes. If AF does not terminate 10 minutes after the end of the infusion, a second bolus of 1 mg over 10 minutes can be given. Most patients studied have had arrhythmia for less than 90 days. Efficacy has not been proven with an AF duration exceeding 90 days. We do not use ibutilide in combination with other antiarrhythmic medications. Less effective or ineffective drugs Several medications such as quinidine and procainamide are no longer used for cardioversion as most of the agents presented above have greater efficacy or fewer side effects or both. The following antiarrhythmic drugs are not particularly effective for the restoration of SR: Sotalol Oral sotalol is less effective than quinidine [63] and equally effective to amiodarone for chemical cardioversion of AF (27 percent at 28 days) [64]. Intravenous sotalol is less effective than intravenous flecainide or ibutilide for reversion of AF [61,65]. Thus, we do not recommend either form for chemical cardioversion of AF. (See "Clinical uses of sotalol".) https://www.uptodate.com/contents/atrial-fibrillation-cardioversion/print 14/26 7/5/23, 9:05 AM Atrial fibrillation: Cardioversion - UpToDate Dronedarone We do not recommend dronedarone for the restoration of SR in patients with AF since conversion rates are very low [66]. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations".) Rate-control drugs such as digoxin, nondihydropyridine calcium channel blockers (eg, diltiazem or verapamil), and beta blockers have not been effective in restoring SR in placebo-controlled studies. Many clinicians overestimate the effectiveness (for cardioversion) of these agents [1,67-72]. Pill-in-the-pocket A "pill-in-the-pocket" approach with either flecainide (<70 kg: 200 mg; may not repeat in 24 hours; 70 kg: 300 mg; may not repeat in 24 hours) or propafenone can be used to terminate out-of-hospital paroxysmal AF of short duration after these drugs have been shown to be efficacious and safe in a monitored setting. In this approach, we have the patient take a diltiazem or a beta blocker 30 minutes or more (if they are not on chronic AV nodal blocker) before the oral antiarrhythmic drug to prevent a rapid ventricular rate should conversion to atrial flutter occur. Some of our contributors prefer the patient to be observed in the emergency department (or potentially during inpatient hospitalization) the first time the "pill-in-the-pocket" approach is taken so that monitoring of safety and efficacy occurs. Some authors also instruct their patients to begin a direct-acting oral anticoagulants (DOAC; also referred to as non-vitamin K oral anticoagulants [NOAC]) at the time of the beta blocker/diltiazem so as to decrease the risk of thrombus formation should the patient not convert to SR in the subsequent 48 hours and to prophylaxis for thrombus formation during the transient periconversion period of atrial appendage mechanical dysfunction. MAINTENANCE ANTIARRHYTHMIC DRUG THERAPY After successful electrical cardioversion, antiarrhythmic drugs increase the likelihood of long- term maintenance of SR [1]. The use of antiarrhythmic drugs to maintain SR is discussed elsewhere. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations".) We do not generally recommend maintenance antiarrhythmic drugs after electrical cardioversion in patients with their first episode of non-valvular AF, particularly those at low risk for recurrence (eg, short-duration AF, normal or only mildly increased left atrial size, normal left ventricular systolic function, absence of valvular dysfunction) or those with a transient cause (eg, pericarditis, pulmonary embolism, and corrected or treated hyperthyroidism) [73]. (See 'Recurrence of AF after cardioversion' above.) https://www.uptodate.com/contents/atrial-fibrillation-cardioversion/print 15/26 7/5/23, 9:05 AM Atrial fibrillation: Cardioversion - UpToDate RECOMMENDATIONS OF OTHERS Societal guidelines are available [53,74-76]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults".) SUMMARY AND RECOMMENDATIONS Unstable patients For the uncommon patient who is hemodynamically unstable or has angina due to AF and is at low risk for thromboembolism, we recommend urgent electrical cardioversion rather than no cardioversion (Grade 1C). (See 'Indications' above.) Stable patients Most patients with AF do not need emergency or even urgent cardioversion, as rate slowing will often improve symptoms. We also attempt to defer cardioversion to allow for initiation of heparin anticoagulation. For select, stable patients with nonvalvular AF, the restoration of sinus rhythm (SR) with either electrical or pharmacologic cardioversion is necessary or reasonable (see 'Ventricular rate control' above and 'Indications' above): Symptomatic, first episode of AF For most symptomatic patients with new onset/first episode of AF, we suggest an attempt at cardioversion, as opposed to no attempt (Grade 2C). In patients who do have factors that predict a high likelihood of success of electrical cardioversion, and in whom long-term maintenance antiarrhythmic drug therapy is not planned, we suggest electrical instead of pharmacologic cardioversion (Grade 2B). (See 'Reasons not to perform cardioversion' above and 'Electrical versus pharmacologic cardioversion' above.) In such patients who are older or have multiple medical comorbidities, it is reasonable to avoid cardioversion if the symptoms can be minimized and pharmacologic ventricular rate control is achieved; the approach needs to be individualized. https://www.uptodate.com/contents/atrial-fibrillation-cardioversion/print 16/26 7/5/23, 9:05 AM Atrial fibrillation: Cardioversion - UpToDate Patients who fail long-term rate control For patients in whom a long-term rate control strategy has failed due to persistent symptoms, a rhythm control strategy involving cardioversion is reasonable. Infrequent episodes of AF Periodic electrical cardioversion is an option for patients with infrequent episodes of AF that do not spontaneously convert, including those being managed with a rhythm control strategy. Roles of rate control and anticoagulation Most patients in whom cardioversion is chosen will need the ventricular rate controlled and the need for anticoagulation assessed prior to cardioversion. (See 'Ventricular rate control' above and 'Anticoagulation' above.) Antiarrhythmic drugs These may be initiated prior to electrical cardioversion to increase the likelihood of a successful electrical cardioversion, to increase the likelihood of maintaining SR in the hours after cardioversion, or as the first step in a plan for long-term antiarrhythmic therapy. (See 'Preprocedural antiarrhythmic drugs' above.) For patients with AF and no structural heart disease (including no evidence of coronary artery disease) for whom pharmacologic cardioversion is chosen, we suggest either flecainide or propafenone rather than other antiarrhythmic drugs (Grade 2B). The choice between these two drugs should be influenced by the practitioner s experience and the clinical situation. (See 'Pharmacologic cardioversion' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. 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Topic 1025 Version 66.0 https://www.uptodate.com/contents/atrial-fibrillation-cardioversion/print 23/26 7/5/23, 9:05 AM Atrial fibrillation: Cardioversion - UpToDate GRAPHICS Amiodarone baseline testing and monitoring for side effects Monitoring Area of interest for monitoring Possible adverse effect Baseline testing Follow-up testing Cardiac ECG (at baseline and Yearly QT prolongation; during loading dose) torsades de pointes After adding medications that interact with Symptomatic sinoatrial or conduction system amiodarone or prolong impairment the QT interval Implantable cardioverter- Defibrillation threshold testing (if clinically As needed for signs/symptoms Increased defibrillation threshold defibrillators indicated) Dermatologic Physical examination As needed for Photosensitivity to UV signs/symptoms light Blue-gray skin discoloration Endocrine TSH (with reflex testing 3 to 4 months after Hyperthyroidism, if abnormal) starting drug, then yearly hypothyroidism As needed for signs/symptoms Hepatic AST and ALT 6 months after starting drug, then yearly AST or ALT elevation 2 upper limit of reference range Ophthalmologic Eye examination Yearly Corneal microdeposits Optic neuropathy Pulmonary Chest radiograph, PFTs* Yearly for surveillance Pulmonary toxicity (cough, fever, dyspnea) Along with PFTs (including DLCO) and chest computed tomography for signs/symptoms Refer to UpToDate topics on pulmonary toxicity, thyroid toxicity, and clinical uses of amiodarone for additional information. https://www.uptodate.com/contents/atrial-fibrillation-cardioversion/print 24/26 7/5/23, 9:05 AM Atrial fibrillation: Cardioversion - UpToDate ECG: electrocardiogram; UV: ultraviolet; TSH: thyroid-stimulating hormone; AST: aspartate aminotransferase; ALT: alanine transaminase; PFTs: pulmonary function tests; DLCO: diffusing capacity of the lungs for carbon monoxide. There are differing opinions, and no concensus, of obtaining formal PFTs with assessment of diffusion capacity (ie, DLCO) as baseline testing in all patients. Some experts obtain baseline PFTs with DLCO prior to starting amiodarone, particularly among patients with underlying lung disease, while other experts rarely or never obtain baseline PFTs. Graphic 126072 Version 4.0 https://www.uptodate.com/contents/atrial-fibrillation-cardioversion/print 25/26 7/5/23, 9:05 AM Atrial fibrillation: Cardioversion - UpToDate Contributor Disclosures Gerald V Naccarelli, MD Consultant/Advisory Boards: Acesion [Antiarrhythmic drug development]; InCarda Therapeutics [Antiarrhythmic drug development]; Milestone [Antiarrhythmic drug development]; Sanofi [Antiarrhythmic agent]. All of the relevant financial relationships listed have been mitigated. Warren J Manning, MD Equity Ownership/Stock Options: Pfizer [Anticoagulants]. All of the relevant financial relationships listed have been mitigated. Bradley P Knight, MD, FACC Grant/Research/Clinical Trial Support: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; MDT [Electrophysiology]; Philips [Electrophysiology]. Consultant/Advisory Boards: Abbott [Electrophysiology]; Atricure [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Electrophysiology]; BSCI [Electrophysiology]; CVRx [Heart failure]; MDT [Electrophysiology]; Philips [Electrophysiology]; Sanofi [Arrhythmias]. Speaker's Bureau: Abbott [Electrophysiology]; Biosense Webster [Electrophysiology]; Biotronik [Electrophysiology]; Boston Scientific [Transeptal catheterization]; BSCI [Electrophysiology]; MDT [Electrophysiology]. All of the relevant financial relationships listed have been mitigated. Brian Olshansky, MD Other Financial Interest: AstraZeneca [Member of the DSMB for the DIALYZE trial]; Medtelligence [Cardiovascular disease]. All of the relevant financial relationships listed have been mitigated. James Hoekstra, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/atrial-fibrillation-cardioversion/print 26/26