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      Antiarrhythmic Agents in Facilitating Electrical Cardioversion of Atrial Fibrillation and Promoting Maintenance of Sinus Rhythm

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          Atrial fibrillation (AF) is a prevalent arrhythmia associated with significant morbidity and mortality. Electrical cardioversion of AF is a potentially definitive treatment, but as little as 67% of patients may be successfully cardioverted and, after normal sinus rhythm (NSR) is achieved, AF often recurs. Class IA, IC, and III antiarrhytmic agents are used for both facilitation of electrical cardioversion and subsequent maintenance of NSR. The mechanisms of these agents may be related to suppressing automaticity, prolonging the wavelength of reentrant wavelets, and preventing electrical remodeling. The possibility of proarrhythmia and other adverse effects complicates use of these drugs, and no large trials have been completed to elucidate definite indications. Several factors may predict failure with electrical cardioversion alone (duration of AF, atrial size, age, underlying disease, and factors that affect transthoracic impedance), calling for empiric pharmacotherapy to facilitate cardioversion. For this purpose, class IA agents hold some promise, evidence for class IC agents is conflicting, and class III agents are the most effective. Adverse effects are rare given the short course before cardioversion, but ibutilide, the most efficacious in this regard, may be proarrhythmic after only a single dose. In promoting maintenance of sinus rhythm, antiarrhythmics across the different classes have similar efficacies: NSR may be maintained in ∼40–65% of patients compared to ∼30–35% with placebo at 1 year. Amiodarone is distinct in its success, with ∼60–80% of patients remaining in NSR. For all of these agents, long-term therapy may lead to proarrhythmia or other substantial adverse effects. Finally, a serial antiarrhythmic strategy may be effective, with maintenance of NSR and minimal adverse effects ultimately achieved by trial and error.

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          Most cited references 6

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          Amiodarone to prevent recurrence of atrial fibrillation. Canadian Trial of Atrial Fibrillation Investigators.

          The restoration and maintenance of sinus rhythm is a desirable goal in patients with atrial fibrillation, because the prevention of recurrences can improve cardiac function and relieve symptoms. Uncontrolled studies have suggested that amiodarone in low doses may be more effective and safer than other agents in preventing recurrence, but this agent has not been tested in a large, randomized trial. We undertook a prospective, multicenter trial to test the hypothesis that low doses of amiodarone would be more efficacious in preventing recurrent atrial fibrillation than therapy with sotalol or propafenone. We randomly assigned patients who had had at least one episode of atrial fibrillation within the previous six months to amiodarone or to sotalol or propafenone, given in an open-label fashion. The patients in the group assigned to sotalol or propafenone underwent a second randomization to determine whether they would receive sotalol or propafenone first; if the first drug was unsuccessful the second agent was prescribed. Loading doses of the drugs were administered and electrical cardioversion was performed (if necessary) within 21 days after randomization for all patients in both groups. The follow-up period began 21 days after randomization. The primary end point was the length of time to a first recurrence of atrial fibrillation. Of the 403 patients in the study, 201 were assigned to amiodarone and 202 to either sotalol (101 patients) or propafenone (101 patients). After a mean of 16 months of follow-up, 71 of the patients who were assigned to amiodarone (35 percent) and 127 of those who were assigned to sotalol or propafenone (63 percent) had a recurrence of atrial fibrillation (P<0.001). Adverse events requiring the discontinuation of drug therapy occurred in 18 percent of the patients receiving amiodarone, as compared with 11 percent of those treated with sotalol or propafenone (P=0.06). Amiodarone is more effective than sotalol or propafenone for the prevention of recurrences of atrial fibrillation.
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            Facilitating transthoracic cardioversion of atrial fibrillation with ibutilide pretreatment.

            Atrial fibrillation cannot always be converted to sinus rhythm by transthoracic electrical cardioversion. We examined the effect of ibutilide, a class III antiarrhythmic agent, on the energy requirement for atrial defibrillation and assessed the value of this agent in facilitating cardioversion in patients with atrial fibrillation that is resistant to conventional transthoracic cardioversion. One hundred patients who had had atrial fibrillation for a mean (+/-SD) of 117+/-201 days were randomly assigned to undergo transthoracic cardioversion with or without pretreatment with 1 mg of ibutilide. We designed a step-up protocol in which shocks at 50, 100, 200, 300, and 360 J were used for transthoracic cardioversion. If transthoracic cardioversion was unsuccessful in a patient who had not received ibutilide pretreatment, ibutilide was administered and transthoracic cardioversion attempted again. Conversion to sinus rhythm occurred in 36 of 50 patients who had not received ibutilide (72 percent) and in all 50 patients who had received ibutilide (100 percent, P<0.001). In all 14 patients in whom transthoracic cardioversion alone failed, sinus rhythm was restored when cardioversion was attempted again after the administration of ibutilide. Pretreatment with ibutilide was associated with a reduction in the mean energy required for defibrillation (166+/-80 J, as compared with 228+/-93 J without pretreatment; P<0.001). Sustained polymorphic ventricular tachycardia occurred in 2 of the 64 patients who received ibutilide (3 percent), both of whom had an ejection fraction of 0.20 or less. The rates of freedom from atrial fibrillation after six months of follow-up were similar in the two randomized groups. The efficacy of transthoracic cardioversion for converting atrial fibrillation to sinus rhythm was enhanced by pretreatment with ibutilide. However, use of this drug should be avoided in patients with very low ejection fractions.
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              Is there a place for the late cardioversion of atrial fibrillation? A long-term follow-up study of patients with post-thyrotoxic atrial fibrillation.

              As atrial fibrillation is associated with significant mortality and morbidity, restoration of sinus rhythm is desirable. However, previous data suggest that cardioversion should be restricted to patients in whom the fibrillation is of limited duration ( 12 months (median duration 28.5, interquartile range 15-47 months). Cardioversion was attempted using disopyramide and then electric shock. Ninety-eight patients were successfully cardioverted: at late follow-up, 80.6+/-37 months (mean+/-SD), 67% were in sinus rhythm. Although a relationship between the duration of fibrillation and maintenance of sinus rhythm was found, the high proportion remaining in sinus rhythm, compared with other series, suggests this influence may be less important than the presence or absence of structural heart disease. Copyright 2000 The European Society of Cardiology.

                Author and article information

                S. Karger AG
                May 2001
                25 May 2001
                : 95
                : 1
                : 1-8
                aDepartment of Internal Medicine and bCardiac Electrophysiology and Arrhythmia Service, Stanford University Hospital, Stanford, Calif., USA
                47335 Cardiology 2001;95:1–8
                © 2001 S. Karger AG, Basel

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                Page count
                Figures: 2, Tables: 2, References: 69, Pages: 8


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