Acute Conversion to Sinus Rhythm

It is said that approx 50-60% of new onset (<72 h) episodes of AF terminate spontaneously. Excellent placebo-controlled studies have shown that when the episodes change from paroxysmal to persistent, AV-node-blocking agents such as digitalis, calcium-channel blockers, and beta-blockers do not improve the chances of cardioversion when compared to placebo. These drugs should therefore be used only to control heart rate, and to prepare for other means of cardioversion, either electrical (as discussed in the nonpharmacological therapy section) or pharmacological. It should be noted here that the likelihood of a successful cardioversion, electrical or pharmacological, generally decreases as the episode of AF becomes more prolonged. Thus, it is more difficult to cardiovert a patient with more than 12 mo of continuous AF than a patient who has had AF for only a few days or weeks. It should also be clear that any patient who is hemodynamically unstable because the rapid ventricular response precipitates an isch-emic event, pulmonary edema, or significant hypotension, should be cardioverted urgently with DC countershock. This method is successful in 80-90% of cases, as compared to drug cardioversion, which is successful in 40-80% of cases and may take much longer than electrical cardioversion.

Several antiarrhythmics have been used for the acute conversion of a persistent episode of AF to normal sinus rhythm. Class IA drugs such as quinidine and procainam-ide have been used for several decades with acute conversion rates of 40-60% for procainamide and up to 80% with quinidine, although many of the older studies were not randomized or placebo-controlled. These drugs have more recently been supplanted by the use of the class IC drugs flecainide and propafenone and the class III drug ibutilide, all approved by the FDA for use in patients with AF, with ibutilide indicated specifically for the acute conversion of AF to sinus rhythm. Although it has not been approved by the FDA for this use, procainamide continues to be used, especially as an iv drug in patients after cardiothoracic surgery (56). However, the efficacy and safety of procainamide in this setting should be scrutinized carefully by prospective studies, given the high incidence of ventricular arrhythmias and left ventricular dysfunction in this population. In fact, amiodarone may be a safer drug for the short term in this subset of patients.

Class IC drugs such as flecainide and propafenone, in oral or iv form, are very effective drugs for the acute cardioversion of AF because of their low side-effect profile compared to class III drugs, which have an inherent risk of QT prolongation and ventricular arrhythmias. They have been used extensively in Europe, with good results. The advantage of these drugs is that they can be given as a single oral dose (300

mg of flecainide or 600 mg of propafenone) with very little risk of hypotension and proarrhythmia, especially in patients with no significant structural heart disease. The rate of conversion with these drugs is reported to be as high as 80%. In one study comparing placebo vs amiodarone, flecainide, and propaferone, the placebo group converted 37% of the time, the amiodarone group converted 43% of the time, and the oral propafenone and flecainide groups converted 76% and 75% of the time respectively after eight hours (57). In another study by Capucci et al. (58) oral propafenone in combination with digoxin converted 50% of patients after 3 h and 80% of patients after 12 h. All of these patients had AF for less than 48 h. However, it seems clear that the effectiveness of these drugs, as well as others, decreases sharply depending on the duration of AF. In one study by Carr et al. (59), flecainide converted 95% of patients with onset < 72 h and only 11% of those with onset longer than 72 h but less than 1 mo.

For the purpose of acute conversion to normal sinus rhythm, class III drugs have also been used to convert patients to normal sinus rhythm. The FDA has recently approved iv ibutilide for this purpose. It has been shown to acutely convert 30-50% of AF and up to 60-80% of atrial flutter in a single iv dose or in two repeated doses given 10 min apart (60,61). The effects of ibutilide are short-term, but the most serious side effect is a 1-2% occurrence of sustained polymorphic ventricular tachycardia (VT) requiring countershock. This is caused by the QT prolongation observed with this drug and with other class III agents. Ibutilide has recently been shown to be superior to procainamide for acute cardioversion, and to significantly reduce the energy requirement for transthoracic electrical cardioversion, thus offering a new option to patients who fail transthoracic cardioversion alone and may have been referred for internal cardioversion. However, its efficacy has not been tested prospectively against class IC drugs, which may be at least as effective and free of the dangerous proarrhythmic effects related to QTc prolongation. The advantage of ibutilide over the IC drugs may be its more rapid time to cardioversion and a higher success rate in patients with atrial flutter. Intravenous sotalol is not available in the United States for acute conversion to normal sinus rhythm, but in a placebo-controlled trial in Europe, it was no more effective than placebo after 30 min (62).

Dofetilide is another class III antiarrhythmic recently approved for the acute termination of AF and atrial flutter. Conversion rates are similar to ibutilide (63), although the iv formulation is not available in the United States, and the long period to conversion with oral dofetilide makes this application impractical. One advantage of dofetilide is that it is available in oral form as a maintenance drug, and that it has recently been shown to be safe in patients with left ventricular dysfunction (64).

The experience with amiodarone has generally been disappointing. Both in the oral form and in the iv form, this drug has not yielded rates of cardioversion that significantly differ from placebo. The role of amiodarone seems most significant in the maintenance of sinus rhythm and in prophylaxis of AF occurrences and rate control in high-risk patients, especially in patients in the intensive care unit during the perioperative period after cardiothoracic surgery. In this setting, two studies have shown a significant decrease in AF postoperatively compared with placebo in patients loaded with the drug orally over the course of 1 wk preoperatively (43), or in those loaded with an iv infusion for 48 h postoperatively (44). Given its high cost, it remains to be determined whether this drug is superior in efficacy and is safer in the short term compared to other drugs traditionally used in the postoperative setting, such as beta-blockers or procainamide.

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Responses

  • jamie-leigh
    What antiarrhythmic drugs are used to convert to normal sinus rhythm?
    6 years ago
  • stefan
    Who can help convert atrial flutter to normal sinus ryhthym?
    3 months ago

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