Atrial Fibrillation

(Fig. 226-4) AF is the most common sustained arrhythmia. It is marked by

disorganized, rapid, and irregular atrial activation. The ventricular response to the

rapid atrial activation is also irregular. In the untreated patient, the ventricular

rate also tends to be rapid and is entirely dependent on the conduction properties

of the AV junction. Although typically the rate will vary between 120 and 160

beats/min, in some patients it can be >200 beats/min. In other patients, because of

heightened vagal tone or intrinsic AV nodal conduction properties, the ventricular

response is <100 beats/min and occasionally even profoundly slow. The mechanism

for AF initiation and maintenance, although still debated, appears to represent a

complex interaction between drivers responsible for the initiation and the complex

anatomic atrial substrate that promotes the maintenance of multiple wavelets of

(micro)reentry. The drivers appears to originate predominantly from the atrialized

musculature that enters the pulmonary veins and either represent focal abnormal

automaticity or triggered firing that is somewhat modulated by autonomic

influences. Sustained forms of microreentry as drivers have also been documented

around the orifice of pulmonary veins; nonpulmonary vein drivers have also been

demonstrated. The role these drivers play in maintaining the tachycardias may also

be significant and may explain the success of pulmonary vein isolation procedures in

eliminating more chronic or persistent forms of AF.

 Although AF is common in the adult population, it is extremely unusual in

children unless structural heart disease is present or there is another arrhythmia

that precipitates the AF, such as paroxysmal SVT in patients with WPW syndrome.

The incidence of AF increases with age such that >5% of the adult population over

70 will experience the arrhythmia. As many patients are asymptomatic with AF, it
is anticipated that the overall incidence, particularly that noted in the elderly, may

be more than double previously reported rates. Occasionally AF appears to have a

well-defined etiology, such as acute hyperthyroidism, an acute vagotonic episode,

or acute alcohol intoxication. Acute AF is particularly common during the acute or

early recovery phase of major vascular, abdominal, and thoracic surgery where

autonomic fluxes and/or direct mechanical irritation potentiate the arrhythmia. AF

may also be triggered by other supraventricular tachycardias (see "AV Nodal

Tachycardias"), such as AV nodal reentrant tachycardia (AVNRT), and elimination

of these arrhythmias may prevent AF recurrence.

AF has clinical importance related to (1) the loss of atrial contractility, (2)

the inappropriate fast ventricular response, and (3) the loss of atrial appendage

contractility and emptying leading to the risk of clot formation and subsequent

thromboembolic events.

Symptoms from AF vary dramatically. Many patients are asymptomatic and

have no apparent hemodynamic consequences to the development of AF. Other

patients experience only minor palpitations or sense irregularity of their pulse.

Many patients, however, experience severe palpitations. The hemodynamic effect

in patients can be quite dramatic, depending on the need for normal atrial

contractility and the ventricular response. Hypotension, pulmonary congestion, and

anginal symptoms may be severe in some patients. In patients with the LV diastolic

dysfunction that occurs with hypertension, hypertrophic cardiomyopathy, or

obstructive aortic valvular disease, symptoms may be even more dramatic,

especially if the ventricular rate does not permit adequate ventricular filling.

Exercise intolerance and easy fatigability are the hallmarks of poor rate control

with exertion. Occasionally, the only manifestation of AF is severe dizziness or

syncope associated with the pause that occurs upon termination of AF before sinus

rhythm resumes (Fig. 226-1).

The ECG in AF is characterized by the lack of organized atrial activity and

the irregularly irregular ventricular response. Occasionally, one needs to record

from multiple ECG leads simultaneously to identify the chaotic continuous atrial

activation. Lead V1 may frequently show the appearance of organized atrial activity

that mimics AFL. This occurs because the crista terminalis serves as an effective

anatomic barrier to electrical conduction, and the activation of the lateral right

atrium may be represented by a more uniform activation wavefront that originates

over the roof of the right atrium. ECG assessment of the PP interval (<200 ms) and

the chaotic P wave morphology in the remaining ECG leads will confirm the presence

of AF.

Evaluation of the patient with AF should include a search for reversible

causes of the arrhythmia, such as hyperthyroidism or anemia. An echocardiogram

should be performed to determine if there is structural heart disease. Persistent

or labile hypertension should be identified and treated, and heart failure

treatment should be optimized.

Treatment for AF must take into account the clinical situation in which the

arrhythmia is encountered, the chronicity of the AF, the status of the patient's

level of anticoagulation, risk factors for stroke, the patient's symptoms, the

hemodynamic impact of the AF, and the ventricular rate.

Acute Rate Control

In the absence of hemodynamic compromise that might warrant emergent

cardioversion to terminate the AF, the initial goals of therapy are (1) to establish

control of the ventricular rate, and (2) to address anticoagulation status and begin

IV heparin treatment if the duration of AF is >12 h and risk factors for stroke

with AF are present (Table 226-1). Ventricular rate control for acute AF is best

established with beta blockers and/or calcium channel blocking agents, verapamil or

diltiazem. The route of administration and dose will be dictated by the ventricular

rate and clinical status. Digoxin may add to the rate-controlling benefit of the

other agents but is uncommonly used as a stand-alone agent, especially in acute AF.

Table 226-1 Risk Factors for Stroke in Atrial Fibrillation

History of stroke or transient ischemic Age > 75 years

attack
Congestive heart failure

Mitral stenosis
Left ventricular dysfunction

Hypertension
Marked left atrial enlargement (>5.0

Diabetes mellitus cm)

Spontaneous echo contrast

Anticoagulation is of particular importance in patients who have known risk

factors for stroke associated with AF. Factors associated with the highest risk of

stroke include a history of stroke, transient ischemic attack or systemic embolism,

or the presence of rheumatic mitral stenosis. Other identified risk factors include

age >65 years, history of congestive heart failure, diabetes mellitus, hypertension,

LV dysfunction, and evidence of marked left atrial enlargement (>5.0 cm). Chronic

anticoagulation with warfarin targeting an INR between 2.0 and 3.0 is

recommended in patients with persistent or frequent and long-lived paroxysmal AF

and risk factors. If patients have not been adequately anticoagulated and the AF is

more than 24–48 h in duration, a transesophageal echocardiogram (TEE) can be

performed to exclude the presence of a left atrial thrombus that might dislodge

with the attempted restoration of sinus rhythm using either nonpharmacologic or

pharmacologic therapy. Anticoagulation must be instituted coincident with the TEE

and maintained for at least 1 month following restoration of sinus rhythm if the

duration of AF has been prolonged or is unknown. Heparin is maintained routinely

until the INR is 1.8 with the administration of warfarin after the TEE. For patients

who do not warrant early cardioversion of AF, anticoagulation should be maintained

for at least 3 weeks with the INR confirmed to be >1.8 on at least two separate

occasions prior to attempts at cardioversion.

Termination of AF acutely may be warranted based on clinical parameters

and/or hemodynamic status. Confirmation of appropriate anticoagulation status as

described above must be documented unless symptoms and clinical status warrant

emergent intervention. Direct current transthoracic cardioversion during short-

acting anesthesia is a reliable way to terminate AF. Conversion rates using a 200-J

biphasic shock delivered synchronously with the QRS complex typically are >90%.

Pharmacologic therapy to terminate AF is less reliable. Oral and/or IV

administration of amiodarone or procainamide have only modest success. The acute

IV administration of ibutilide appears to be somewhat more effective and may be

used in selected patients to facilitate termination with direct current (DC)

cardioversion (Tables 226-2 and 226-3).

Table 226-2 Commonly Used Antiarrhythmic Agents—Intravenous Dose

Range/Primary Indication

Drug Loading Maintenance Primary Indication Classa

Adenosine 6–18 mg (rapid N/A Terminate reentrant SVT —

bolus) involving AV node

Amiodarone 15 mg/min for 10 0.5–1 mg/min AF, AFL, SVT, VT/VF III

min, 1 mg/min for

6h
Digoxin 0.25 mg q2h until 0.125–0.25 AF/AFL rate control —

1.0 mg total mg/d

Diltiazem 0.25 mg/kg over 5–15 mg/h SVT, AF/AFL rate control IV

3–5 min (max 20

mg)
Esmolol AF/AFL rate control II
500 g/kg 50 g/kg

over 1 min per min

Ibutilide 1 mg over 10 min N/A Terminate AF/AFL III

if over 60 kg
Lidocaine 1–3 mg/kg at 20– 1–4 mg/min VT IB

50 mg/min
Metoprolol 5 mg over 3–5 1.25–5 mg q6h SVT, AF rate control; II

min times 3 exercise-induced VT; long

doses QT
Drug Loading Maintenance Primary Indication Classa

Procainamide 15 mg/kg over 60 1–4 mg/min Convert/prevent AF/VT IA

min
Quinidine 6–10 mg/kg at N/A Convert/prevent AF/VT IA

0.3–0.5 mg/kg

per min
Verapamil 5–10 mg over 3–5 2.5–10 mg/h SVT, AF rate control IV

min

a
Classification of antiarrhythmic drugs: Class I—agents that primarily block inward

sodium current; class IA agents also prolong action potential duration; class II—

antisympathetic agents; class III—agents that primarily prolong action potential

duration; class IV—calcium channel-blocking agents.

Note: SVT, supraventricular tachycardia; AV, atrioventricular; AF, atrial

fibrillation; AFL, atrial flutter; VT, ventricular tachycardia; VF, ventricular

fibrillation.

Table 226-3 Commonly Used Antiarrhythmic Agents—Chronic Oral Dosing/Primary

Indications

Drug Dosing Oral, Half- Primary Route(s) of Most Common Classa

mg, Life, Metabolism/Elimination Indication

Drug Dosing Oral, Half- Primary Route(s) of Most Common Classa

mg, Life, Metabolism/Elimination Indication

Maintenance h
Long

QT/RVOT VT
Amiodarone 100–400 qd 40–55 Hepatic AF/VT III

d prevention
Atenolol 25–100 mg/d 6–9 Renal AF rate II

control/SVT
Long

QT/RVOT VT
Digoxin 0.125–0.5 qd 38–48 Renal AF rate —

control
Diltiazem 30–60 q6h 3–4.5 Hepatic AF rate IV

control/SVT
Disopyramide 100–300 q6– 4–10 Renal 50%/hepatic AF/SVT Ia

8h prevention
Dofetilide 0.125–0.5 10 Renal AF prevention III

q12h
Flecainide 50–200 q12h 7–22 Hepatic 75%/renal AF/SVT/VT Ic

prevention
Metoprolol 25–100 q6h 3–8 Hepatic AF rate II

control/SVT
Long

QT/RVOT VT
Mexiletine 150–300 q8– 10–14 Hepatic VT prevention Ib

12h
Drug Dosing Oral, Half- Primary Route(s) of Most Common Classa

mg, Life, Metabolism/Elimination Indication

Maintenance h
Moricizine 100–400 q8h 3–13 Hepatic 60%/renal AF prevention Ic
Nadolol 40–240 mg/d 10–24 Renal Same as II

metoprolol
Procainamide 250–500 q3– 3–5 Hepatic/renal AF/SVT/VT Ia

6h prevention
Propafenone 150–300 q8h 2–8 Hepatic AF/SVT/VT Ic

prevention
Quinidine 300–600 q6h 6–8 Hepatic 75%/renal AF/SVT/VT Ia

prevention
Sotalol 80–160 q12h 12 Renal AF/VT III

prevention
Verapamil 80–120 q6– 4.5– Hepatic/renal AF rate IV

8h 12 control/RVOT

VT
Idiopathic LV

VT

a
Classification of antiarrhythmic drugs: Class I—agents that primarily block inward

sodium current; class II—antisympathetic agents; class III—agents that primarily

prolong action potential duration; class IV—calcium channel-blocking agents.

Note: AF, atrial fibrillation; SVT, supraventricular tachycardia; RVOT, right

ventricular outflow tract; VT, ventricular tachycardia; LV, left ventriclar.

 Pharmacologic therapy to maintain sinus rhythm can be instituted once sinus

rhythm has been established or in anticipation of cardioversion to attempt to

maintain sinus rhythm (Table 226-3). A single episode of AF may not warrant any

intervention or only a short course of beta blocker therapy. To prevent recurrent

AF unresponsive to beta blockade, a trial of antiarrhythmic therapy may be

warranted, particularly if the AF is associated with rapid rates and/or significant

symptoms. The selection of antiarrhythmic agents should be dictated primarily by

the presence or absence of coronary artery disease, depressed LV function not

attributable to a reversible tachycardia-induced cardiomyopathy, and/or severe

hypertension with evidence of marked LV hypertrophy. The presence of any

significant structural heart disease typically narrows treatment to the use of

sotalol, amiodarone, or dofetilide. Severely depressed LV function may preclude

sotalol therapy or require only low-dose therapy be considered. Owing to the risk

of QT prolongation and polymorphic VT, sotalol and dofetilide need to be initiated

in hospital in most cases.

In patients without evidence of structural heart disease or hypertensive heart

disease without evidence of severe hypertrophy, the use of the class IC

antiarrhythmic agents flecainide or propafenone appears to be well tolerated and

does not have significant proarrhythmia risk. It is important to recognize that no

drug is uniformly effective, and arrhythmia recurrence should be anticipated in

over half the patients during long-term follow-up regardless of type and number of

agents tried. It is also important to recognize that although the maintenance of

sinus rhythm has been associated with improved long-term survival, the survival

outcome of patients randomized to the pharmacologic maintenance of sinus rhythm

was not superior to those treated with rate control and anticoagulation in the
AFFIRM and RACE trials. The AFFIRM and RACE trials compared outcome with

respect to survival and thromboembolic events in patients with AF and risk factors

for stroke using the two treatment strategies. It is believed that the poor

outcome related to pharmacologic therapy used to maintain sinus rhythm was

primarily due to frequent inefficacy of such drug therapy and an increased

incidence of asymptomatic AF. Many of the drugs used for rhythm control,

including sotalol, amiodarone, propafenone, and flecainide, enhance slowing of AV

nodal conduction. The absence of symptoms frequently leads to stopping

anticoagulant therapy, and asymptomatic AF without anticoagulation increases

stroke risk. Any consideration for stopping anticoagulation must, therefore, be

accompanied by a prolonged period of ECG monitoring to document asymptomatic

AF. It is also recommended that patients participate in monitoring by learning to

take their pulse on a twice-daily basis and to reliably identify its regularity if

discontinuing anticoagulant therapy is seriously contemplated.

It is clear that to reduce the risk of drug-induced complications when treating AF,

a thorough understanding of the drug planned to be used is critical—its dosing,

metabolism, and common side effects and important drug-drug interactions. This

information has been summarized in Tables 226-2, 226-3, 226-4, and 226-5 and

serves as a starting point for a more complete review. When using antiarrhythmic

agents that slow atrial conduction, strong consideration should be given to adding a

beta blocker or a calcium channel blocker (verapamil or diltiazem) to the treatment

regimen. This should help to avoid a rapid ventricular response if AF is converted

to "slow" AF with the drug therapy (Fig. 226-5).

Table 226-4 Common Nonarrhythmic Toxicity of Most Frequently Used

Antiarrhythmic Agents

Drug Common Nonarrhythmic Toxicity

Amiodarone Tremor, peripheral neuropathy, pulmonary inflammation,

hypothyroidism and hyperthyroidism, photosensitivity

Adenosine Cough, flushing
Digoxin Anorexia, nausea, vomiting, visual changes
Disopyramide Anticholinergic effects, decreased myocardial contractility
Dofetilide Nausea
Flecainide Dizziness, nausea, headache, decreased myocardial contractility
Ibutilide Nausea
Lidocaine Dizziness, confusion, delirium, seizures, coma
Mexiletine Ataxia, tremor, gait disturbances, rash, nausea
Moricizine Mood changes, tremor, loss of mental clarity, nausea,
Procainamide Lupus erythematosus–like syndrome (more common in slow

acetylators), anorexia, nausea, neutropenia

Propafenone Taste disturbance, dyspepsia, nausea, vomiting
Quinidine Diarrhea, nausea, vomiting, cinchonism, thrombocytopenia
Sotalol Hypotension, bronchospasm

Table 226-5 Proarrhythmic Manifestations of Most Frequently Used

Antiarrhythmic Agents

Drug Common Proarrhythmic Toxicity

Amiodarone Sinus bradycardia, AV block, increase in defibrillation threshold
Rare: long QT and torsades des pointes, 1:1 ventricular conduction

with atrial flutter

Adenosine All arrhythmias potentiated by profound pauses, atrial fibrillation
Digoxin High-grade AV block, fascicular tachycardia, accelerated junctional
Drug Common Proarrhythmic Toxicity
rhythm, atrial tachycardia
Disopyramide Long QT and torsades des pointes, 1:1 ventricular response to atrial

flutter; increased risk of some ventricular tachycardias in patients

with structural heart disease

Dofetilide Long QT and torsades des pointes
Flecainide 1:1 Ventricular response to atrial flutter; increased risk of some

ventricular tachycardias in patients with structural heart disease;

sinus bradycardia
Ibutilide Long QT and torsades des pointes
Procainamide Long QT and torsades des pointes, 1:1 ventricular response to atrial

flutter; increased risk of some ventricular tachycardias in patients

with structural heart disease

Propafenone 1:1 Ventricular response to atrial flutter; increased risk of some

ventricular tachycardias in patients with structural heart disease;

sinus bradycardia
Quinidine Long QT and torsades des pointes, 1:1 ventricular response to atrial

flutter; increased risk of some ventricular tachycardias in patients

with structural heart disease

Sotalol Long QT and torsades des pointes, sinus bradycardia

Note: AV, atrioventricular.

Chronic Rate Control

This is an option in patients who are asymptomatic or symptomatic due to

the resulting tachycardia. Rate control is frequently difficult to achieve in patients

who have paroxysmal AF. In patients with more persistent forms of AF, rate

control with beta blockers, calcium channel blockers, diltiazem or verapamil, and/or

digoxin can frequently be achieved. Using the drugs in combination may avoid some

of the common side effects seen with high-dose monotherapy. An effort should be

made to document the adequacy of rate control to reduce the risk of a

tachycardia-induced cardiomyopathy. Heart rates >80 beats/min at rest or 100

beats/min with very modest physical activity are indications that rate control is

inadequate in persistent AF. Extended periods of ECG monitoring and assessment

of heart rate with exercise should be considered.

In patients with symptoms resulting from inadequate rate control with

pharmacologic therapy or worsening LV function due to the persistent tachycardia,

a His bundle/AV junction ablation can be performed. The ablation must be coupled

with the implantation of an activity sensor pacemaker to maintain a physiologic

range of heart rates. Recent evidence that RV pacing can occasionally modestly

depress LV function should be taken into consideration in identifying which

patients are appropriate candidates for the "ablate and pace" treatment strategy.

Occasionally, biventricular pacing may be used to minimize the degree of

dyssynchronization that can occur with RV apical pacing alone. Rate control

treatment options must be coupled with chronic anticoagulation therapy in all

cases. Trials evaluating the elimination of embolic risk by surgical elimination or

isolation of the left atrial appendage or by endovascular insertion of a left atrial

appendage–occluding device are ongoing and may provide other treatment options

that can eliminate the need for chronic anticoagulation.

Catheter and Surgical Ablative Therapy to Prevent Recurrent AF

Although the optimum ablation strategy has not been defined, most ablation

strategies incorporate techniques that isolate the atrial muscle sleeves entering

the pulmonary veins; these muscle sleeves have been identified as the source of

the majority of triggers responsible for the initiation of AF. Ablation therapy is

currently considered an alternative to pharmacologic therapy in patients with

recurrent symptomatic AF. Elimination of AF in 50–80% of patients with a

catheter-based ablation procedure should be anticipated, depending on the

chronicity of the AF, with additional patients becoming responsive to previously

ineffective medications.

Catheter ablative therapy also holds promise in patients with more

persistent forms of AF and even those with severe atrial dilatation. If its efficacy

is confirmed with additional study, it may also afford an important alternative to

His bundle ablation and pacemaker insertion. Risks related to the left atrial

ablation procedure, albeit low (overall 2–4%), include pulmonary vein stenosis,

atrioesophageal fistula, systemic embolic events, and perforation/tamponade.

Surgical ablation of AF is typically performed at the time of other cardiac

valve or coronary artery surgery and, less commonly, as a stand-alone procedure.

The Cox surgical Maze procedure is designed to interrupt all macroreentrant

circuits that might potentially develop in the atria, thereby precluding the ability

of the atria to fibrillate. In an attempt to simplify the operation, the multiple

incisions of the traditional Cox-Maze procedure have been replaced with linear

lines of ablation and pulmonary vein isolation using a variety of energy sources.

Severity of AF symptoms and difficulties in rate and/or rhythm control with

pharmacologic therapy will frequently dictate the optimum AF treatment strategy.

Similar to the approach with pharmacologic rhythm control, a cautious approach to

eliminating anticoagulant therapy is recommended after catheter or surgical

ablation. Careful ECG monitoring for asymptomatic AF, particularly in patients with

multiple risk factors for stroke, should be considered until guidelines are firmly

established. If the left atrial appendage has been removed surgically, then the

threshold for stopping anticoagulation should be lowered. Antiarrhythmic therapy

typically can be discontinued after catheter or surgical ablation of AF. However, in

selected patients, satisfactory AF control may require maintenance of previously

ineffective drug therapy after the ablation intervention.