Atrial Fibrillation Part 2

Restoration and maintenance of sinus rhythm

Sinus rhythm can be restored with medication, electrical shocks, or a combination of both. Electrical shocks typically are more effective than medication for cardioversion and pose a lower risk of life-threatening ventricular arrhythmias. However, shocks require conscious sedation. In a proportion of patients refractory to medication or electrical shocks, the combination of both therapies results in return of sinus rhythm.

Pharmacologic Cardioversion

Antiarrhythmic medications typically alter the conduction properties of both diseased and normal atrial tissue, suppressing AF triggers or inhibiting the propagation of AF electrical wavelets. Although pharmacologic cardioversion might seem simpler than electrical cardioversion, it has a lower success rate and it poses a risk of life-threatening arrhythmias; the latter risk often precludes use of this strategy. The efficacy of medications for cardioversion of AF typically declines as the duration of AF increases.22

A number of medications can be used for cardioversion or for maintenance of sinus rhythm [see Tables 2 and 3]. Some medications can be used for both purposes, but others should be used for cardioversion only or for maintenance of sinus rhythm only.

Medication selection for pharmacologic cardioversion must be based on individual patient characteristics. Amiodarone, dofetilide, and ibutilide (agents with potassium channel blocking effects) can be given safely to patients with heart failure or reduced left ventricular systolic function. In contrast, flecainide and propafenone may exacerbate heart failure and should be avoided in such patients. Dofetilide and ibutilide have higher success rates for conversion of atrial flutter than of AF, whereas flecainide and propafenone have higher success rates with conversion of AF than of atrial flutter. Flecainide, propafenone, disopyramide, procainamide, and quinidine also may increase ventricular rate response, especially if patients convert from AF to atrial flutter. Before receiving one of these medications, the patient should be pretreated with an AV nodal blocking agent (typically, diltiazem or verapamil, or possibly digoxin).

Disopyramide, procainamide, and quinidine have either limited efficacy for cardioversion of AF or are associated with significant adverse effects that preclude their use except in rare circumstances. Sotalol effectively maintains sinus rhythm and controls ventricular rate in patients who have undergone cardioconversion from AF, but it has not been shown to effectively convert AF to sinus rhythm. Similarly, beta blockers, ver-apamil, diltiazem, and digoxin are effective for control of ventricular rate in patients with AF, but these medications have little role in AF cardioversion.

Figure 4 Antiarrhythmic drug therapy to maintain sinus rhythm in patients with recurrent paroxysmal or persistent atrial fibrillation.1 (AF—atrial fibrillation; LVH—left ventricular hypertrophy)

Electrical Cardioversion

DC cardioversion is the most effective mechanism for achieving sinus rhythm, with success rates of approximately 70% to 90%.23,24 DC cardioversion has an even greater rate of success with atrial flutter, approximating 95%.25 The efficacy of DC car-dioversion can be optimized by enhancing delivery of energy to the atrial myocardium. This is achieved through a number of maneuvers:

• Electrode paddle positioning. Anteroposterior positioning is more effective than anterolateral positioning.26 In addition, applying pressure to the paddles during conversion reduces transthoracic impedance, improving energy conduction.

• Timing of cardioversion. Application of the energy when the patient has fully exhaled reduces pulmonary resistance to the current.27

• Use of rectilinear biphasic energy. Traditional energy sources supply monophasic energy. Biphasic energy transfers more efficiently to atrial tissue, leading to higher cardioversion success rates and lower cumulative energy discharge.28

Although numerous protocols have been validated, a reasonable protocol that uses monophasic energy to convert AF is to start at 200 joules (J), followed by 300 J, then by 360 J or 400 J.29

For patients with atrial flutter, cardioversion is frequently achieved with 50 J of monophasic energy; therefore, the mono-phasic AF protocol can be modified for AF by starting with 50 J, followed by 100 J. If biphasic energy is utilized for AF, a protocol of 70 J or 100 J followed by 150 J and then by 200 J may be utilized.2830

Although success rates are high with DC cardioversion, a number of risk factors for cardioversion failure have been identified. These include longer duration of AF (notably, greater than 1 year), older age, left atrial enlargement, cardiomegaly, rheumatic heart disease, and transthoracic impedance.25,28 Pre-treatment with amiodarone, ibutilide, sotalol, flecainide, pro-pafenone, disopyramide, and quinidine have been shown to increase DC cardioversion success rates.1 Transvenous cardiover-sion also may be successfully used for cardioversion for patients in whom transthoracic cardioversion fails.

DC cardioversion of AF is extremely safe, typically resulting in no significant myocardial damage if cardioversion attempts are separated by at least 1 minute. Nevertheless, clinicians must give consideration to two types of adverse events33,34:

• Reprogramming or malfunction of permanent pacemakers or implantable cardioverter-defibrillators (ICDs). Electricity transmitted from endocardial wires to myocardium can lead to tissue scarring and an increased threshold for tissue cap-ture.35 In addition, cardioversion energy can erase or alter the programming of permanent pacemakers or ICDs. For that reason, all such devices should be interrogated before and after DC cardioversion.

Table 2 Drugs for Cardioversion of Atrial Fibrillation and Maintenance of Sinus Rhythm¹⁰

Medication	Route	Time to Conversion	Precautions	Drug Interactions	Side Effects	Comments
Amiodarone	Oral/ I.V.	Hours to weeks	—	Increases digoxin, procainamide, quinidine, and warfarin levels	Bradycardia, visual disturbances, nausea, constipation, phlebitis (I.V. form); hepatic, ocular, pulmonary, thyroid, neurologic toxicity	Safe for use in patients with left ventricular dysfunction; TdP/VT less common than with dofetilide, ibu-tilide, or sotalol
Dofetilide	Oral	Days to weeks	—	Levels increased by cimetidine and verapamil	—	Safe for use in patients with left ventricular dysfunction; associated with TdP
Ibutilide	I.V.	< 1 hr	Check serum potassium, magnesium levels; requires 4 hr of monitoring for TdP	—	—	Safe for use in patients with left ventricular dysfunction; associated with TdP; not used for maintenance of sinus rhythm
Sotalol	Oral	Incompletely studied; reduced efficacy or no proven efficacy for cardioversion of AF	May exacerbate CHF and/or COPD	—	Bradycardia	Use with caution in patients with reduced left ventricular function; associated with TdP
Flecainide	Oral	3 hr	Pretreat with AV nodal blocking agents* to avoid accelerated ventricular response; avoid in patients with heart failure, left ventricular dysfunction, or CAD	Levels increased by amiodarone	—
Propafenone	Oral/I.V.	< 6 hr	Pretreat with AV nodal blocking agents* to avoid accelerated ventricular response; avoid in patients with heart failure, left ventricular dysfunction, or CAD; may exacerbate COPD	Increases digoxin and warfarin levels	Blurred vision, hypotension	Efficacy reduced in patients with structural heart disease
Quinidine	Oral/I.V.	2-6 hr	Pretreat with AV nodal blocking agents* to avoid accelerated ventricular response; avoid in patients with heart failure or left ventricular dysfunction	Increases digoxin levels; levels increased by verapamil	Hypotension, nausea, diarrhea, fever, hepatic dysfunction, thrombocytopenia, hemolytic anemia	Safety limits use in cardioversion; side effects limit use; associated with TdP
Disopyramide	Oral/I.V.	< 12 hr	Incompletely studied, reduced efficacy or no proven efficacy for car-dioversion of AF; pretreat with AV nodal blocking agents* to avoid accelerated ventricular response; avoid in patients with heart failure or left ventricular dysfunction	—	Dry mucous membranes, constipation, urinary retention; significant reduction of left ventricular function	Side effects limit use; associated with TdP
Procainamide	I.V.	< 24 hr	Incompletely studied, reduced efficacy or no proven efficacy for car-dioversion of AF; pretreat with AV nodal blocking agents* to avoid accelerated ventricular response; avoid in patients with heart failure or left ventricular dysfunction	—	Drug-induced lupus, vasculitides, blood dyscrasias, central nervous system disturbances	Reduced efficacy, side effects limit use; associated with TdP

*AV nodal blocking agents typically used are verapamil or diltiazem, and possibly digoxin.

AF—atrial fibrillation

CAD—coronary artery disease

CHF—chronic heart failure

COPD—chronic obstructive pulmonary disease

TdP—torsade de pointes

VT—ventricular tachycardia

Table 3 Dosages of Drugs for Pharmacologic Cardioversion of Atrial Fibrillation and Maintenance of Sinus Rhythm¹⁰⁸⁰

Drug	Dosage for Cardioversion	Daily Dosage for Maintenance of Sinus Rhythm
Amiodarone	Oral, inpatient 1.2-1.8 g/day in divided doses until 10 g total, then 200-400 mg/day maintenance; or 30 mg/kg as single dose
	Oral, outpatient 600-800 mg/day in divided doses until 10 g total	100-400 mg
	Intravenous/oral 5-7 mg/kg over 30-60 min, then 1.2-1.8 g/day continuous I.V. or in divided oral doses until 10 g total
Dofetilide	Oral dosages for specified CCr values	500-1,000 \ig; dosage adjustment based on QTc
	500 |ig b.i.d. for Co- > 60 ml/min
	250 |ig b.i.d. for Cq- 40 to 60 ml/min
	125 |ig b.i.d. for CCr 20 to 40 ml/min
	Contraindicated for Cor < 20 ml/min
Ibutilide	I.V.: 1 mg over 10 min; repeat once, if necessary	Not available
Sotalol	Not effective for cardioversion	240-320 mg; dosage adjustment based on QTc; reduced dosing with renal insufficiency
Flecainide	Oral: 200-300 mg	200-300 mg; reduced dosing with renal insufficiency
Propafenone	Oral: 450-600 mg I.V.: 1.5-2.0 mg/kg over 10-20 min; reduced dosing with renal insufficiency	450-900 mg; reduced dosing with hepatic dysfunction
Quinidine	Oral: 0.75-1.5 g in divided doses over 6-12 hr I.V.: 1.5-2.0 mg/kg over 10-20 min	600-1,500 mg
Disopyramide	Oral: 200 mg q. 4 hr, up to 800 mg	400-750 mg; reduced dosing with renal insufficiency
Procainamide	I.V.: 100 mg q. 5 min, up to 1,000 mg	1,000-4,000 mg; reduced dosing with renal insufficiency or hepatic dysfunction

Note: Dosages given may differ from those recommended by the manufacturer; see Table 2 for guidance regarding medication selection and dosing adjustments. CCr—creatinine clearance QTc—corrected QT interval

Distancing of paddles from implanted devices may limit these adverse events. • Arrhythmias. Life-threatening arrhythmias are more common with pharmacologic conversion but can occur with DC cardioversion. Ventricular tachycardia and ventricular fibrillation can result from cardioversion in patients with hypo-kalemia or digoxin toxicity. Failure to synchronize DC energy with ventricular rhythm can lead to ventricular fibrillation if energy is applied during ventricular repolarization.

Finally, many patients with AF have underlying sinus node dysfunction that may require permanent pacing once car-dioversion is completed.