topics

11/6/25

Paroxysmal Supraventricular Tachycardias

1895CHAPTER 249

cases, directly from the mitral valve annulus avoiding the coronary

sinus musculature altogether. In typical forms, the conduction time

from the compact AV node region to the atrium is similar to that from

the compact node to the His bundle and ventricles, such that atrial

activation occurs at about the same time as ventricular activation. The

P wave is therefore inscribed during, slightly before, or slightly after the

QRS and can be difficult to discern. Often the P wave is seen at the end

of the QRS complex as a pseudo-r′ in lead V1

and pseudo-S waves in

leads II, III, and aVF (Fig. 249-2).

More unusual forms of AVNRT have P waves falling later, anywhere

between QRS complexes, in which case, an inverted P wave is seen in

the inferior limb leads with the inverted P wave seen in the subsequent

T wave. The rate can vary with sympathetic tone through its effect

on the conduction time of AV nodal tissues. Simultaneous atrial and

ventricular contraction results in atrial contraction against a closed tricuspid valve, producing a cannon A wave visible in the jugular venous

pulse often perceived as a fluttering sensation in the neck. Elevated

venous pressures may also lead to release of natriuretic peptides that

cause posttachycardia diuresis. In contrast to ATs, maneuvers or medications that produce AV nodal block terminate the arrhythmia. Acute

treatment is the same as for other forms of PSVT (discussed below).

Whether ongoing therapy is warranted depends on the severity of

symptoms and frequency of episodes. Reassurance and instruction as

to how to perform the Valsalva maneuver or other vagal nerve stimulating maneuvers to terminate episodes are sufficient for many patients.

CS Tricuspid

valve

P waves

A B

Inferior AV node

extension:

Slow pathway

Compact AV node:

Fast pathway

FIGURE 249-1 Atrioventricular (AV) node reentry. A. Leads II and V1

are shown. P waves are visible at the end of the QRS complex and are negative in lead II and may give

the impression of S waves in the inferior limb leads II, III, and aVF and an R′ in lead V1

. B. Stylized version of the AV nodal reentry circuit within the triangle of Koch (see

Fig. 247-1) that involves AV node and its extensions along with perinodal atrial tissue. CS, coronary sinus.

ATRIOVENTRICULAR NODAL REENTRY

TACHYCARDIA

AVNRT is the most common form of paroxysmal supraventricular

tachycardia (PSVT), representing ~60% of cases referred for catheter

ablation. It most commonly manifests in the second to fourth decades

of life, often in women. It is often well tolerated, but rapid tachycardia, particularly in the elderly, may cause angina, pulmonary edema,

hypotension, or syncope. It is not usually associated with structural

heart disease. In patients without associated heart disease, AVNRT is

not a life-threatening arrhythmia; however, it may cause significant

symptoms.

The mechanism is reentry involving the AV node and the perinodal

atrium, made possible by the existence of multiple pathways for conduction from the atrium into the AV node that are capable of conduction in two directions (Fig. 249-1).

Most forms of AVNRT utilize a slowly conducting AV nodal pathway (right inferior extension) that extends from the compact AV node

near the His bundle, inferiorly along the tricuspid valve annulus to the

floor of the coronary sinus. The reentry wavefront propagates up this

slowly conducting pathway to the compact AV node and then exits

from the fast pathway at the top of the AV node. The path back to

the slow pathway probably involves the left atrial septum, which has

connections to the coronary sinus musculature. More unusual forms

of AVNRT utilize a left inferior extension that connects to the compact

AV node through the roof of the coronary sinus or, in extremely rare

III

aVR

aVL

aVF

III

aVR

aVL

aVF

FIGURE 249-2 Atrioventricular nodal reentry tachycardia with retrograde P waves before and after adenosine termination.

1896 PART 6 Disorders of the Cardiovascular System

Administration of an oral beta blocker, verapamil, or diltiazem at the

onset of an episode can be used to facilitate termination. Chronic therapy with these medications or flecainide is an option if prophylactic

therapy is needed. Catheter ablation of the slow AV nodal pathway is

recommended for patients with recurrent or severe episodes or when

drug therapy is ineffective, not tolerated, or not desired by the patient.

Catheter ablation is curative in >95% of patients. The major risk is AV

block requiring permanent pacemaker implantation, which occurs in

<1% of patients.

JUNCTIONAL TACHYCARDIA

Junctional ectopic tachycardia (JET) is due to automaticity within the

AV node. It is rare in adults and more frequently encountered as an

incessant tachycardia in children, often in the perioperative period

of surgery for congenital heart disease. It presents as a narrow QRS

tachycardia, often with ventriculoatrial (VA) block, such that AV

dissociation is present. JET can occur as a manifestation of increased

adrenergic tone and may be seen after administration of isoproterenol,

particularly after catheter ablation in the perinodal region. It may also

occur for a short period of time after ablation for AVNRT. Accelerated

junctional rhythm is a junctional automatic rhythm between 50 and

100 beats/min. Initiation may occur with gradual acceleration in rate,

suggesting an automatic focus, or after a premature ventricular contraction, suggesting a focus of triggered automaticity. VA conduction

is usually present, with P-wave morphology and timing such that it

resembles AVNRT at a slow rate. It can be related to increased sympathetic tone and may produce palpitations. It usually does not require

specific therapy.

ACCESSORY PATHWAYS AND THE

WOLFF-PARKINSON-WHITE SYNDROME

Accessory pathways (APs) occur in 1 in 1500–2000 people and are

associated with a variety of arrhythmias including narrow-complex

PSVT, wide-complex tachycardias, and, rarely, sudden death. Most

patients have structurally normal hearts, but APs are associated with

Ebstein’s anomaly of the tricuspid valve and forms of hypertrophic

cardiomyopathy including PRKAG2 mutations, Danon’s disease, and

Fabry’s disease (Fig. 249-3).

APs are abnormal connections that allow conduction between the

atrium and ventricles across the AV ring. They are present from birth

and are due to failure of complete partitioning of atrium and ventricle

by the fibrous AV rings. They occur across either an AV valve annulus

or the septum, most frequently between the left atrium and free wall

of the left ventricle, followed by posteroseptal, right free wall, and

anteroseptal locations. If the impulse from the sinus node conducts

through the AP to the ventricle (antegrade) before the impulse conducts through the AV node and His bundle, then the ventricles are

preexcited during sinus rhythm, and the electrocardiogram (ECG)

shows a short P-R interval (<0.12 s), slurred initial portion of the QRS

(delta wave), and prolonged QRS duration produced by slow conduction through direct activation of ventricular myocardium over the AP.

The morphology of the QRS and delta wave is determined by the AP

location and the degree of fusion between the excitation wavefronts

from conduction over the AV node and conduction over the AP

(Fig. 249-4).

Right-sided pathways preexcite the right ventricle, producing a left

bundle branch block–like configuration in lead V1

, and often create

marked preexcitation because of relatively close proximity of the AP

to the sinus node (Fig. 249-4). Left-sided pathways preexcite the left

ventricle and may produce a right bundle branch–like configuration in

lead V1

and a negative delta wave in aVL, indicating initial depolarization of the lateral portion of the left ventricle that can mimic Q waves

of lateral wall infarction (Fig. 249-4). Because of the relatively large

distance between the sinus node and left free wall APs, preexcitation

may be minimal or absent on 12-lead ECG. Preexcitation due to an AP

at the diaphragmatic surface of the heart, typically in the paraseptal

region, produces delta waves that are negative in leads III and aVF,

mimicking the Q waves of inferior wall infarction (Fig. 249-4). Preexcitation can be intermittent and disappear during exercise as conduction

over the AV node accelerates and may take over ventricular activation

completely.

Wolff-Parkinson-White (WPW) syndrome is defined as a preexcited

QRS during sinus rhythm and episodes of PSVT. There are a number of

variations of APs that may not cause preexcitation and/or arrhythmias.

Concealed APs allow only retrograde conduction, from ventricle to

atrium, so no preexcitation is present during sinus rhythm, but SVT

can occur. Other unusual forms of APs occur. Fasciculoventricular

Sinus rhythm—

antegrade

AP conduction

Orthodomic AV

reentry—retrograde

AP conduction

Antidromic AV

reentry—antegrade

AP conduction

Delta-wave p p

FIGURE 249-3 Wolff-Parkinson-White (WPW) syndrome. A. A 12-lead

electrocardiogram in sinus rhythm (SR) of a patient with WPW demonstrating short

P-R interval, delta waves, and widened QRS complex. This patient had an anteroseptal

location of the accessory pathway (AP). B. Orthodromic atrioventricular (AV) reentry in

a patient with WPW syndrome using a posteroseptal AP. Note the P waves in the ST

segment (arrows) seen in lead III and normal appearance of QRS complex. C. Three

most common rhythms associated with WPW syndrome: sinus rhythm demonstrating

antegrade conduction over the AP and AV node; orthodromic AV reentry tachycardia

(AVRT) using retrograde conduction over the AP and antegrade conduction over the

AV node; and antidromic AVRT using retrograde conduction over the AV node and

antegrade conduction over the AP.

Paroxysmal Supraventricular Tachycardias

1897CHAPTER 249

Left lateral Right free wall

aVL V1

Postero septal

II aVF III

Coronary

sinus (CS)

FIGURE 249-4 Potential locations for accessory pathways in patients with WolffParkinson-White syndrome and typical QRS appearance of delta waves that can

mimic underlying structural heart disease such as myocardial infraction of bundle

branch block. AV, aortic valve; MV, mitral valve; PV, pulmonary valve; TV, tricuspid

valve.

connections between the His bundle and ventricular septum produce

preexcitation but do not cause arrhythmia, probably because the circuit

is too short to promote reentry. Atriofascicular pathways, also known

as Mahaim fibers, probably represent a duplicate AV node and HisPurkinje system that connect the right atrium to fascicles of the right

bundle branch and produce a wide-complex tachycardia having a left

bundle branch block configuration.

ATRIOVENTRICULAR RECIPROCATING

TACHYCARDIA

The most common tachycardia caused by an AP is the PSVT designated orthodromic AV reciprocating tachycardia. The circulating reentry

wavefront propagates from the atrium anterogradely over the AV node

and His-Purkinje system to the ventricles and then reenters the atria

via retrograde conduction over the AP. The QRS is narrow or may

have typical right or left bundle branch block, but without preexcitation during tachycardia. Because excitation through the AV node and

AP are necessary, AV or VA block results in tachycardia termination.

During sinus rhythm, preexcitation is seen if the pathway also allows

anterograde conduction. Most commonly, during tachycardia, the R-P

interval is shorter than the P-R interval and can resemble AVNRT.

Unlike typical AVNRT, P waves always follow the QRS and are never

simultaneous with a narrow QRS complex because the ventricles must

be activated before the reentry wavefront reaches the AP and conducts

back to the atrium. The morphology of the P wave is determined by the

pathway location, but it can be difficult to assess because it is usually

inscribed during the ST segment. The P wave in posteroseptal APs is

negative in leads II, III, and aVF, similar to that of AV nodal reentry,

but P-wave morphology differs from AV nodal reentry for pathways

in other locations. Occasionally, an AP conducts extremely slowly

in the retrograde direction, resulting in tachycardia with a long R-P

interval, similar to most ATs. These pathways are usually located in the

septal region and have negative P waves in leads II, III, and aVF. Slow

AP conduction facilitates reentry, often leading to nearly incessant

tachycardia, known as permanent junctional reciprocating tachycardia

(PJRT). Tachycardia-induced cardiomyopathy can occur. Without

an invasive electrophysiology study, it may be difficult to distinguish

this form of orthodromic AV reentry from atypical AV nodal reentry

or AT.

PREEXCITED TACHYCARDIAS

Preexcited tachycardia occurs when the ventricles are activated by

antegrade conduction over the AP. The most common mechanism is

antidromic AV reciprocating tachycardia in which activation propagates

from atrium to ventricle via the AP and then conducts retrogradely to

the atria via the His-Purkinje system and the AV node (or rarely a second AP). The wide QRS complex is produced entirely via ventricular

excitation over the AP because there is no contribution of ventricular

activation over more rapidly conducting specialized His-Purkinje

fibers. This tachycardia is often indistinguishable from monomorphic

ventricular tachycardia. The presence of preexcitation in sinus rhythm

suggests the diagnosis.

Preexcited tachycardia also occurs if an AP allows antegrade conduction to the ventricles during AT, atrial flutter, atrial fibrillation

(AF), or AV nodal reentry, otherwise known as bystander AP conduction. AF and atrial flutter are potentially life-threatening if the AP

allows very rapid repetitive conduction (Fig. 249-5).

Approximately 25% of APs causing preexcitation allow minimum

R-to-R intervals of <250 ms during AF and are associated with a higher

risk of inducing ventricular fibrillation and sudden death. Preexcited

AF presents as a wide-complex, very irregular rhythm. During AF, the

ventricular rate is determined by the conduction properties of the AP

and AV node. The QRS complex can appear quite bizarre and change

on a beat-to-beat basis due to the variability in the degree of fusion

from activation over the AV node and AP, or all beats may be due

to conduction over the AP. Ventricular activation from the Purkinje

system may depolarize the ventricular aspect of the AP and prevent

atrial wavefront conduction over the AP. Slowing AV nodal conduction

without slowing AP conduction can thereby facilitate AP conduction

and dangerously accelerate the ventricular rate. Administration of

AV nodal–blocking agents, including oral or intravenous verapamil,

diltiazem, beta blockers, intravenous adenosine, and intravenous

amiodarone, is contraindicated during preexcited AF. Rapid preexcited

tachycardia should be treated with electrical cardioversion or intravenous procainamide or ibutilide, which may terminate the arrhythmia

or slow the ventricular rate.

MANAGEMENT OF PATIENTS WITH

ACCESSORY PATHWAYS

Acute management of orthodromic AV reentry is discussed below for

PSVT. Patients with WPW syndrome may have wide-complex tachycardia due to antidromic AV reentry, orthodromic AV with bundle

branch block, or a preexcited tachycardia, and treatment depends on

the underlying rhythm. Initial patient evaluation should include assessment for aggravating factors, including intercurrent illness and factors

that increase sympathetic tone. Examination should focus on excluding

underlying heart disease. An echocardiogram is reasonable to exclude

Ebstein’s anomaly and forms of hypertrophic cardiomyopathy that can

be associated with APs.

Patients with preexcitation who have symptoms of arrhythmia are

at risk for developing AF and sudden death if they have an AP that

allows rapid antegrade conduction. The risk of cardiac arrest is in the

range of 2 per 1000 patients in adults but is likely greater in children.

An invasive electrophysiology study is recommended to assess whether

the pathway can support dangerously rapid heart rates if AF were to

occur, and it is usually combined with potentially curative catheter

ablation. Catheter ablation is warranted for recurrent arrhythmias

1898 PART 6 Disorders of the Cardiovascular System

25mm/s 10mm/mV 150Hz 9.0.9 12SL 243 CID: 0

III

aVR

aVL

aVF

III

aVR

aVL

aVF

FIGURE 249-5 Preexcited atrial fibrillation (AF) due to conduction over a left free wall accessory pathway (AP). The electrocardiogram shows rapid irregular QRS

complexes that represent fusion between conduction over the atrioventricular node and left free wall AP. Shortest R-R intervals between preexcited QRS complexes of

<250 ms, as in this case, indicate a risk of sudden death with this arrhythmia.

when drugs are ineffective, not tolerated, or not desired by the patient.

Efficacy is in the range of 95% depending on the location of the AP.

Serious complications occur in <3% of patients but can include AV

block, cardiac tamponade, thromboembolism, coronary artery injury,

and vascular access complications. Procedure mortality is <1 in 1000

patients. Ambulatory monitoring or exercise testing is often used to

gain reassurance that the AP is not high risk, evaluating for abrupt loss

of conduction (preexcitation) at physiologic heart rates consistent with

a low-risk pathway, but this is not completely reliable. Gradual loss of

AP conduction with increased sympathetic tone does not reliably indicate low risk since this can occur as AV nodal conduction time shortens, and therefore, the possibility of rapid antegrade AP conduction is

not excluded definitively.

For patients with concealed APs or known low-risk APs causing

orthodromic AVRT, chronic therapy is guided by symptoms and frequency of events. Vagal maneuvers may terminate episodes, as may a

dose of beta blocker, verapamil, or diltiazem taken at the onset of an

episode. Chronic therapy with these agents or flecainide can reduce the

frequency of episodes in some patients.

Adults who have preexcitation but no arrhythmia symptoms have

a risk of sudden death estimated to be 1 per 1000 patient-years.

Electrophysiology study is usually advised for people in occupations

for which an arrhythmia occurrence would place them or others at

risk, such as police, military, and pilots, or for individuals who desire

evaluation for risk. Routine follow-up without therapy is reasonable

in others. Children are at greater risk of sudden death, ~2 per 1000

patient-years.

TREATMENT

Paroxysmal Supraventricular Tachycardia

Acute management of narrow QRS PSVT is guided by the clinical

presentation. Continuous ECG monitoring should be implemented,

and a 12-lead ECG should always be obtained when possible,

since this may be useful in determining the mechanism. In the

presence of hypotension with unconsciousness or respiratory distress, QRS-synchronous direct current cardioversion is warranted,

but this is rarely needed, because intravenous adenosine works

promptly in most situations (see below). For stable individuals, initial therapy takes advantage of the fact that most PSVTs are dependent on AV nodal conduction (AV nodal reentry or orthodromic

AV reentry) and, therefore, likely to respond to sympatholytic and

vagotonic maneuvers and drugs. As these are administered, the

ECG should be continuously recorded because the response can

establish the diagnosis. AV block with only transient slowing of

tachycardia may expose ongoing P waves, indicating AT or atrial

flutter as the mechanism (Fig. 249-6).

Common Atrial Flutter and Macroreentrant and Multifocal Atrial Tachycardias

1899CHAPTER 250

Regular narrow-complex

tachycardia

Hemodynamic instability

Cardioversion

Catheter

ablation

Antiarrhythmic

therapy

Non-DHP CCB

and/or Betablocker

Vagal reflex/

adenosine

Ineffective

Recurrent or

incessant

Recurrent

Yes

FIGURE 249-6 Treatment algorithm for patients presenting with hemodynamically

stable paroxysmal supraventricular tachycardia. CCB, calcium channel blocker;

DHP, dihydropyridine.

Carotid sinus massage is reasonable provided the risk of carotid

vascular disease is low, as indicated by absence of carotid bruits

and no prior history of stroke. A Valsalva maneuver should be

attempted in cooperative individuals, and if effective, the patient

can be taught to perform this maneuver as needed. If vagal maneuvers fail or cannot be performed, intravenous adenosine will terminate the vast majority of PSVT episodes by transiently blocking

conduction in the AV node. Adenosine may produce transient chest

pain, dyspnea, and anxiety. It is contraindicated in patients with

prior cardiac transplantation due to potential hypersensitivity due

to surgical sympathetic denervation. It can theoretically aggravate

bronchospasm. Adenosine precipitates AF, which is usually brief,

in up to 15% of patients, so it should be used cautiously in patients

with WPW syndrome in whom AF may produce hemodynamic

instability. Intravenous beta blockers and calcium channel blockers

(verapamil or diltiazem) are also effective but may cause hypotension before and after arrhythmia termination and have a longer

duration of action. These agents can also be given orally and can be

taken by the patient on an as-needed basis to slow ventricular rate

and facilitate termination by Valsalva maneuver.

The differential diagnosis of wide-complex tachycardia includes

ventricular tachycardia, PSVT with bundle branch block aberrancy,

and preexcited tachycardia (see above). In general, these should be

managed as ventricular tachycardia until proven otherwise. If the

tachycardia is regular and the patient is stable, a trial of intravenous

adenosine is reasonable. Very irregular wide-complex tachycardia is

most likely preexcited AF or flutter (see above) and should be managed with cardioversion, intravenous procainamide, or ibutilide. If

the diagnosis of PSVT with aberrancy is unequivocal, as may be the

case in patients with prior episodes, treatment for PSVT with vagal

maneuvers and adenosine is reasonable. In all cases, continuous

ECG monitoring should be implemented, and emergency cardioversion and defibrillation should be available.

Acknowledgment

Gregory F. Michaud and William G. Stevenson contributed to this chapter in the 20th edition, and some material from that chapter has been

retained here.

Macroreentrant atrial tachycardia is due to a large anatomic reentry circuit, often associated with areas of scar in the atria. Common or typical

right atrial flutter is due to a circuit pathway around the tricuspid valve

annulus, bounded anteriorly by the annulus and posteriorly by functional conduction block in the crista terminalis. The wavefront passes

between the inferior vena cava and the tricuspid valve annulus, known

as the sub-Eustachian or cavotricuspid isthmus, where it is susceptible

to interruption by catheter ablation. Thus, common atrial flutter is also

known as cavotricuspid isthmus-dependent atrial flutter. This circuit

most commonly revolves in a counterclockwise direction (as viewed

looking toward the tricuspid annulus from the ventricular apex), which

produces the characteristic negative sawtooth flutter waves in leads

II, III, and aVF and positive P waves in lead V1

. When the direction

is reversed, clockwise rotation produces the opposite P-wave vector

in those leads. The atrial rate is typically 240–300 beats/min but may

be slower in the presence of atrial disease or antiarrhythmic drugs. It

often conducts to the ventricles with 2:1 AV block, creating a regular

tachycardia at 130–150 beats/min, with P waves that may be difficult to

discern from the T wave. Maneuvers that increase AV nodal block will

typically expose flutter waves, allowing diagnosis. AV nodal disease or

AV nodal–blocking agents may render the conduction ratio between

atrium and ventricle higher, resulting in more obvious flutter waves

(Fig. 250-1).

Common right atrial flutter often occurs in association with atrial

fibrillation and often with atrial scar from senescence or prior cardiac

surgery. Right-sided cardiac or pulmonary vascular disease may also

predispose to common right atrial flutter. Some patients with atrial

fibrillation treated with an antiarrhythmic drug, particularly flecainide, propafenone, or amiodarone, will present with atrial flutter rather

than fibrillation, since these agents slow atrial conduction velocity

and can promote reentry, in addition to suppressing ectopic atrial

triggers.

Macroreentrant atrial tachycardias (ATs) that are not dependent

on conduction through the cavotricuspid isthmus are referred to as

atypical atrial flutters. They can occur in either atrium and are almost

universally associated with areas of atrial scar. Right atrial atypical flutter often occurs after cardiac surgery if an atriotomy is performed in

the right atrium as part of the surgery. Left atrial flutter and perimitral

left atrial flutter are commonly seen after extensive left atrial ablation

for atrial fibrillation or atrial surgery. The clinical presentation is similar to common atrial flutter but with different P-wave morphologies.

They can be difficult to distinguish from focal AT, and in most cases,

the mechanism can only be confirmed by an electrophysiology study

(Fig. 250-2).

250 Common Atrial Flutter

and Macroreentrant and

Multifocal Atrial Tachycardias

William H. Sauer, Paul C. Zei

■ FURTHER READING

Brugada J et al: 2019 ESC Guidelines for the management of patients

with supraventricular tachycardia. The task force for the management

of patients with supraventricular tachycardia of the European Society

of Cardiology (ESC) Developed in collaboration with the Association

for European Paediatric and Congenital Cardiology (AEPC). Eur

Heart J 41:655, 2020.

Callans DJ: Josephson’s Clinical Cardiac Electrophysiology: Techniques

and Interpretations, 6th ed. Philadelphia, Wolters Kluwer, 2021.

Jalife J, Stevenson W (eds): Zipes and Jalife’s Cardiac Electrophysiology: From Cell to Bedside, 8th ed. Philadelphia, Elsevier, 2022.

1900 PART 6 Disorders of the Cardiovascular System

III

aVR

aVL

aVF

Right atrium

Typical CTI-Dependent

Counterclockwise Atrial

Flutter

Tricuspid

Valve

Annulus

Tricuspid

Valve Annulus

CTI-Dependent

Counterclockwise

Atrial Flutter

FIGURE 250-1 Electrocardiogram (ECG) and electroanatomic map of typical flutter. In the upper panel, a 12-lead ECG of typical atrial flutter is shown. Note the sawtooth

pattern of atrial activation, with negative flutter (F) waves, as well as 4:1 atrioventricular (AV) conduction during flutter. In the lower panel, counterclockwise (more common,

left portion of the panel) and clockwise typical, cavotricuspid isthmus (CTI)–dependent atrial flutter is shown on electroanatomic maps. These maps of the electrical

activation pattern during flutter were obtained during electrophysiologic study and catheter ablation, viewed from the vantage point of the right ventricle through the

tricuspid valve. Colors refer to local activation time, demonstrating a complete timing of the electrical circuit around the peritricuspid RA.

ATRIAL FLUTTER

Initial management of atrial flutter is similar to that for atrial fibrillation, discussed in more detail in Chap. 251. Electrical cardioversion is warranted for hemodynamic instability or severe symptoms.

Otherwise, rate control can be achieved with administration of AV

nodal–blocking agents, but this is often more difficult than for atrial

fibrillation. The risk of thromboembolic events is thought to be similar

to that associated with atrial fibrillation, and hence, management of

stroke risk is similar to the approach for atrial fibrillation. Anticoagulation is warranted prior to conversion for episodes >48 h in duration

and chronically for patients at increased risk of thromboembolic

stroke based on the CHA2

DS2

-VASc scoring system (see Chap. 251

and Table 251-2).

For a first episode of atrial flutter, conversion to sinus rhythm

without subsequent chronic use of an antiarrhythmic drug therapy is

reasonable. For recurrent episodes, antiarrhythmic drug therapy with

sotalol, dofetilide, disopyramide, and amiodarone may be considered,

but >70% of patients experience recurrences. For recurrent episodes

of common atrial flutter, catheter ablation of the cavotricuspid isthmus abolishes the arrhythmia in >95% of patients with a low risk of

Common Atrial Flutter and Macroreentrant and Multifocal Atrial Tachycardias

1901CHAPTER 250

III

aVR

aVL

aVF

FIGURE 250-2 Electrocardiogram (ECG) and electroanatomic map of mitral annular flutter after pulmonary vein isolation. In the upper panel, a 12-lead surface ECG

demonstrates atypical atrial flutter. Note the flutter wave morphology with positively deflected flutter waves in the inferior leads (II, III, aVF), with 3:1 atrioventricular (AV)

conduction. In the lower panel, the corresponding electroanatomic map obtained during electrophysiologic study and catheter ablation is shown. This panel shows the left

atrium (LA) from the vantage point of the left ventricle, through the mitral valve. Colors refer to local activation time, demonstrating a complete timing of the electrical circuit

around the peri-mitral valve LA tissues. (Adapted from Fig. 245-1 in the 20th edition of Harrison’s Principles of Internal Medicine.)

complications that are largely related to vascular access and rarely heart

block. Therefore, catheter ablation for atrial flutter can be considered as

first-line therapy. Approximately 50% of patients presenting with atrial

flutter develop atrial fibrillation within 5 years after diagnosis, which

is an important consideration in patients with a high-risk profile for

thromboembolism. In general, patients with atrial flutter are treated

identically to those with atrial fibrillation in terms of recommendations

for anticoagulation for stroke prevention (Fig. 250-3).

MULTIFOCAL ATRIAL TACHYCARDIA

Multifocal AT (MAT) is characterized by a rhythm with at least three

distinct P-wave morphologies with rates typically between 100 and

150 beats/min. Unlike atrial fibrillation, there are clear isoelectric

intervals between P waves and the atrial rate is slower. The mechanism

is likely triggered automaticity from multiple atrial foci. It is usually

encountered in patients with chronic pulmonary disease and acute

illness (Fig. 250-4).

Therapy for MAT is directed at treating the underlying disease and

correcting any metabolic abnormalities. Electrical cardioversion is

ineffective. The calcium channel blockers verapamil or diltiazem may

slow the atrial and ventricular rate. Patients with severe pulmonary

disease often do not tolerate beta blocker therapy. MAT may respond to

amiodarone, but long-term therapy with this agent is usually avoided

due to its toxicities, particularly pulmonary fibrosis. The associated risk

of thromboembolism in MAT remains unclear but is not considered to

be the same as atrial fibrillation or atrial flutter.

1902 PART 6 Disorders of the Cardiovascular System

Atrial flutter/MRAT

Hemodynamic

instability

No Yes

Yes

If not available

or contraindicated

IV ibutilide

or dofetilide IV or

oral (in-hospital)

(I B)

PPM/ICD

present?

Electrical

cardioversion

preferred

Low-energy

synchronized

cardioversion (I B)

IV beta blocker

IV diltiazem or

verapamil

(IIa B)

Rhythm control

strategy

Synchronized

cardioversion

(I B)

High-rate

atrial pacing

(I B)

IV amiodarone

(IIb C)

Invasive or noninvasive

high-rate atrial pacing

(IIb B)

FIGURE 250-3 Approach to the patient with atrial flutter or macroreentrant atrial tachycardia (MRAT). ICD, implantable cardioverter-defibrillator; PPM, permanent

pacemaker. (Adapted from FM Kusumoto et al: Heart Rhythm 16:e128, 2019.)

FIGURE 250-4 Multifocal atrial tachycardia. Rhythm strip obtained from a patient with severe pulmonary disease during an acute illness. Arrows note three distinct P-wave

morphologies.

Atrial Fibrillation

1903CHAPTER 251

Acknowledgment

Gregory F. Michaud and William G. Stevenson contributed to this chapter in the 20th edition and some material from that chapter has been

retained here.

■ FURTHER READING

Brugada J et al: 2019 ESC Guidelines for the management of patients

with supraventricular tachycardia. The task force for the management

of patients with supraventricular tachycardia of the European Society

of Cardiology (ESC) developed in collaboration with the Association

for European Paediatric and Congenital Cardiology (AEPC). Eur

Heart J 41:655,2020.

Callans DJ: Josephson’s Clinical Cardiac Electrophysiology: Techniques

and Interpretations, 6th ed. Philadelphia, Wolters Kluwer, 2021.

Jalife J, Stevenson W (eds): Zipes and Jalife’s Cardiac Electrophysiology: From Cell to Bedside, 8th ed. Philadelphia, Elsevier, 2022.

PATHOPHYSIOLOGY AND EPIDEMIOLOGY

Atrial fibrillation (AF) is a cardiac arrhythmia characterized by seemingly disorganized, rapid, and irregular atrial electrical activation,

resulting in loss of organized atrial mechanical contraction. These

rapid and irregular electrical signals input into the atrioventricular

(AV) node, which determines ventricular activation and rate. The

conducted ventricular rate is variable, resulting in an irregular, usually

rapid ventricular rate, ranging typically between 110 and 160 beats/

min in most. In some patients, the sustained ventricular rate can

exceed 200 beats/min, whereas in others with either high vagal tone or

AV nodal conduction disease, the ventricular rate may be excessively

slow (Fig. 251-1).

251 Atrial Fibrillation

William H. Sauer, Paul C. Zei

III

aVR

aVL

aVF

III

aVR

aVL

aVF

FIGURE 251-1 Electrocardiogram of an irregularly irregular heart rhythm without discernable P waves. The disorganized atrial activation is best appreciated in lead V1

for this patient.

AF is the most common sustained arrhythmia; as a result, it is a

major public health issue. Prevalence increases with age, with >95%

of AF patients >60 years of age. The prevalence in humans over age

80 is ~10%. The lifetime risk of developing AF for men aged 40 years

old is ~25%. AF is slightly more common in men than women and

more common in whites than blacks. Risk factors for developing AF in

addition to age and underlying cardiac disease include hypertension,

diabetes mellitus, cardiac disease, family history of AF, obesity, and

sleep-disordered breathing. AF is not a benign condition, with a 1.5-

to 1.9-fold increased risk of mortality after controlling for underlying

cardiac disease. Perhaps the most important consequence of AF is a

significantly increased risk of stroke compared to the general population, causing ~25% of all strokes. The risk of dementia is increased in

patients with AF, as is the risk of MRI-detected asymptomatic embolic

infarct. AF, most often when ventricular rate remains uncontrolled for

prolonged periods, increases the risk of developing congestive heart

failure and cardiomyopathy. Moreover, as a corollary, patients with

underlying heart disease, in particular cardiomyopathy and congestive heart failure, are at higher risk for developing AF. AF is a marker

for worsened morbidity and mortality in patients with existing heart

disease, although the precise extent of the independent risk increase

associated with AF in heart disease is unclear. AF may, on occasion, be

associated with an identifiable precipitating factor, such as hyperthyroidism, acute alcohol intoxication, myocardial infarction, pulmonary

embolism, pericarditis, and cardiac surgery, where AF occurs in up to

30% of patients postoperatively.

AF is clinically most typically defined by the pattern of episodes.

Paroxysmal AF is defined as a pattern of AF episodes that occur

spontaneously and terminate with a relatively short duration, most

commonly defined as 7 days or less. Persistent AF refers to AF that

occurs continuously for >7 days but <1 year, whereas long-standing

persistent AF refers to AF that has been persistent for >1 year. These

descriptors for AF correlate with the underlying pathophysiology of

AF. AF tends to be a progressive condition, with, at this point, no definitive “cure” that will completely eliminate AF durably in a predictable

fashion. The pathophysiology of AF, however, remains incompletely

understood. Most data support a multifactorial process that leads to

the development of manifest AF. Clinical and epidemiologic studies

have demonstrated that, in addition to cardiovascular disease, obesity,

1904 PART 6 Disorders of the Cardiovascular System

hypertension, diabetes mellitus, and sleep-disordered breathing are

associated with higher risk of developing AF. The proposed pathophysiology suggests a “final common pathway” of these risk factors leading

to electrophysiologic changes in atrial tissues. Alterations in regulation

of membrane channels and other proteins result in abnormal electrical

excitability. Atrial tissues, in particular pulmonary vein musculature,

exhibit enhanced automaticity, resulting in ectopic beats (premature

atrial contractions), as shown in Fig. 251-2. Bouts of rapid atrial ectopy

may then initiate either atrial tachycardia or frank AF. Additional cellular and, eventually, tissue remodeling results in abnormal conduction

properties throughout the atria, including, in particular, shortening of

atrial tissue refractory periods. This enables sustained AF through a

combination of rapid automaticity-based “drivers” and areas of functional reentry. Further remodeling leads to the development of fibrosis

and left atrial enlargement (Table 251-1).

These functional and anatomic changes in atrial tissues appear to

correlate with the progression of clinical AF. AF tends to be a progressive disease in most, although exceptions occur. Typically, for a period

of time, patients experience sporadic ectopic beats, likely originating

from the pulmonary veins, preceding the onset of frank AF.

Other regions of the atria have been demonstrated to produce

ectopic depolarizations that may trigger AF; these include the muscular tissue sleeves within the superior vena cava, coronary sinus, or

the remnant of the vein of Marshall. When enough frequent bursts

of ectopic beats/tachycardia and/or changes in underlying substrate

support the maintenance of AF for short periods, the patient develops

episodes of paroxysmal AF. In the untreated patient, over time, as

electrical and remodeling continues to progress, episodes of paroxysmal AF may be prolonged to the point of not terminating spontaneously, the hallmark of persistent AF. After further remodeling,

not only do patients continue on to long-standing persistent AF but

Sinus

P wave

Blocked PAC PAC initiates AF

Sinus

P wave

25 mm/sec 10 mm/mV 0.5–40 Hz

FIGURE 251-2 Surface electrocardiogram (ECG) of atrial ectopy initiating atrial fibrillation (AF). In this single-lead surface ECG recording, the tracing begins with two

conducted sinus beats. A nonconducted premature atrial contraction (PAC) (labeled “blocked PAC”) is shown after the second QRS complex. After the next sinus P wave

and QRS, an ectopic beat (PAC) initiates atrial fibrillation, as demonstrated by (somewhat organized) erratic atrial activity and an irregular ventricular response.

TABLE 251-1 Categorization of Atrial Fibrillation (AF) by Clinical Temporal Characteristics and Associated Features

PAROXYSMAL AF PERSISTENT AF LONG-STANDING PERSISTENT AF

Definition Episodes self-terminate or via CV in <7 d Episodes do not self-terminate in <7 d Persistent AF >1 year

LA size Normal to mildly enlarged Mild to severely enlarged Typically, severely enlarged

LA scar burden Low Moderate High

Efficacy of AAD Often effective Not as effective Usually refractory

When to offer ablation? First-line therapy reasonable First-line appropriate but usually offered after

AAD failure

After AAD failure, not always a good

option

Ablation technique PV isolation alone usually effective PV isolation and any identified non-PV AF

source

PV isolation; additional ablation for

substrate modification likely needed

Note: With paroxysmal, persistent, and long-standing persistent AF, definitions are based on duration of events and diagnosis overall. These categorizations correlate with

LA size, LA scar burden, and resultant efficacy of medical and ablative therapies.

Abbreviations: AAD, antiarrhythmic drugs; CV, cardioversion; LA, left atrium; PV, pulmonary vein.

also the efficacy of therapeutic interventions to restore sinus rhythm

diminishes.

CLINICAL PRESENTATION AND

MANIFESTATIONS

The clinical manifestations of AF result from (1) symptoms related

to the irregular, often rapid but sometimes slow ventricular rates that

result; (2) the hemodynamic consequences of altered cardiac function;

(3) the consequences of cardioembolic phenomena; and/or (4) the

impact of AF on cardiovascular function over time. AF is diagnosed by

electrocardiogram (ECG), either by 12-lead standard ECG or limited

lead ambulatory monitor ECG, with findings of lack of organized atrial

activity (no P wave), with an irregular ventricular response. The role

of screening populations for AF is evolving with the use of wearable

monitors and home ECG capabilities.

With irregular, rapid ventricular rates, there is variable cardiac displacement and contraction, resulting in the sensation of palpitations

and awareness of the heartbeat, when of course, in a normal rhythm,

most humans do not sense each and every heartbeat. Interestingly,

many patients are, for the most part, unaware of the irregular ventricular beating for unknown reasons.

During AF, there is loss of the contribution of atrial systole to overall

cardiac output and, with irregular ventricular rates, variable ventricular

filling and, as a consequence, variable stroke volume. The resultant

impact on overall cardiac output may result in exercise intolerance,

fatigue, weakness, presyncope, or dyspnea. In patients with underlying

cardiac disease, the additional hemodynamic compromise resulting

from AF may result in exacerbation of the disease and/or symptoms.

Patients with hypertrophic cardiomyopathy, coronary artery disease,

heart failure with either depressed or preserved ejection fraction, or

amyloidosis are particularly susceptible. In patients with concomitant

Atrial Fibrillation

1905CHAPTER 251

AV nodal conduction disease, bradycardia during AF may result in

presyncope or syncope. Pauses at the time of spontaneous conversion

from AF to sinus rhythm, a manifestation of sinus node dysfunction

that commonly occurs in patients with AF, may result in presyncope

or syncope as well.

With the loss of atrial mechanical contraction, blood stasis may promote in situ thrombosis, which, when embolized, may result in a range

of clinical consequences, most importantly, ischemic stroke. Thrombus

formation occurs primarily in the left atrial appendage. Over time,

recurrent thromboembolism to the brain, even if asymptomatic, may

result in debilitating neurologic sequelae. An increased risk of dementia in patients with AF may be the consequence of this phenomenon.

In patients with prolonged periods of rapid ventricular rates

resulting from AF, there is risk of developing a tachycardia-induced

cardiomyopathy, with associated depressed left ventricular function.

Tachycardia-induced myopathy appears generally to be reversible once

ventricular rates are controlled. In patients with long-standing persistent AF, the atria, especially the left atrium, tend to be more dilated and

to contain a higher burden of fibrotic, noncontractile atrial tissue. More

recently, the hemodynamic consequences of a noncompliant, fibrotic

left atrium, including elevated left atrial filling pressures, volume

overload, and congestive heart failure, have been described as “stiff left

atrial syndrome.”

TREATMENT

Atrial Fibrillation

The treatment and management of the patient with AF centers on

three aims: (1) control of patient symptoms through a strategy of

rate control and/or rhythm control; (2) appropriate mitigation of

thromboembolism risk; and (3) addressing modifiable risk factors

for progression of AF. In the acute onset of AF, if significant hemodynamic compromise, pulmonary edema, or evidence of coronary ischemia is present, emergent cardioversion is recommended.

Electrical cardioversion can be achieved with a QRS synchronous

shock, preferably in a sedated patient, or via pharmacologic cardioversion, most typically with the intravenous administration of

the class III antiarrhythmic ibutilide. Ibutilide should be avoided

in patients with baseline prolonged QT interval or severe left ventricular dysfunction, given the risk of torsades des pointes. In the

hemodynamically stable patient with new-onset AF, therapy should

focus on control of ventricular rate to prevent hemodynamic sequelae, consideration of anticoagulation to mitigate thromboembolic

risk, and consideration of restoration and maintenance of sinus

rhythm—a so-called rhythm control strategy. If restoration of sinus

rhythm is being considered, a more immediate risk of thromboembolism must be factored into the management strategy. Although

there is a lack of definitive data, it is presumed that if the presenting

episode of AF is >48 h or if the episode duration is unknown, there

is risk for precipitating a thromboembolic complication through

cardioversion, whether electrical or pharmacologically achieved.

Therefore, in this circumstance, the patient should be either initiated on anticoagulation, with cardioversion deferred for at least

4 weeks after uninterrupted anticoagulation, or evaluated to exclude

the presence of left atrial appendage thrombus. Most commonly,

transesophageal echocardiography (TEE) is used to evaluate for left

atrial appendage thrombus, although computed tomography (CT)

angiography has been demonstrated to have excellent sensitivity

and specificity as well.

CARDIOVERSION AND ANTICOAGULATION

The major source of thromboembolism and stroke in AF is formation of thrombus in the left atrial appendage where flow is relatively

stagnant, although thrombus occasionally forms in other locations

as well. Following conversion from prolonged AF to sinus rhythm,

atrial mechanical function can be delayed for weeks, such that

thrombi can form even during sinus rhythm. When AF has been

present for >48 h and in patients at high risk for thromboembolism,

such as those with mitral stenosis or hypertrophic cardiomyopathy,

conversion to sinus rhythm is associated with an increased risk of

thromboembolism. Thromboembolism can occur soon or several

days after restoration of sinus rhythm if appropriate anticoagulation

measures are not taken.

Cardioversion within 48 h of the onset of AF is common practice

in patients who have not been anticoagulated, provided that they

are not at high risk for stroke due to a prior history of embolic

events, rheumatic mitral stenosis, or hypertrophic cardiomyopathy with marked left atrial enlargement. These low-risk patients

with occasional episodes of AF can be instructed to notify their

physician when AF occurs to arrange for cardioversion to be done

within 48 h.

If the duration of AF exceeds 48 h or is unknown, there is greater

concern for thromboembolism after cardioversion, even in patients

considered low risk (CHA2

DS2

-VASc of 0 or 1 [see below]) for

stroke. There are two approaches to mitigate the risk related to

cardioversion. One option is to anticoagulate continuously for

3 weeks before and a minimum of 4 weeks after cardioversion. A

second approach is to start anticoagulation and perform a TEE or

high-resolution cardiac CT scan to detect the presence of thrombus

in the left atrial appendage. If thrombus is absent, cardioversion

can be performed and anticoagulation continued for a minimum

of 4 weeks to allow time for recovery of atrial mechanical function.

In either case, cardioversion of AF is associated with a substantial

risk of recurrence, which may not be symptomatic. Longer-term

maintenance of anticoagulation is considered based on the patient’s

individual risk for stroke, commonly assessed using the CHA2

DS2

VASc score.

ACUTE RATE CONTROL

The goal of rate control in AF is to allow more diastolic filling

time, improving cardiac output and reducing patient symptoms.

In the longer term, adequate rate control will minimize the risk of

congestive heart failure and tachycardia-induced cardiomyopathy.

Acute rate control can be achieved with beta blockers and/or the

calcium channel blockers verapamil and diltiazem administered

either intravenously or orally, as warranted by the urgency of the

clinical situation. Digoxin has been used for many years for rate

control, particularly in patients susceptible to congestive heart

failure, because it lacks the negative inotropic effect seen in calcium

channel blockers and beta blockers. It acts synergistically with

beta blockers and calcium channel blockers and, therefore, may be

useful as an added agent when rate control is inadequate. However,

recent evidence suggests increased mortality with its use, and so its

utilization has declined.

CHRONIC RATE CONTROL

For patients who remain in AF chronically, the goal of rate control is to

both alleviate symptoms and prevent deterioration of ventricular function from excessive rates. β-Adrenergic blockers and calcium channel

blockers are often used either alone or in combination. Exertionrelated symptoms are often an indication of inadequate rate control.

Rate should be assessed with exertion and medications adjusted

accordingly. Adequate rate control is defined as a resting heart rate

of <80 beats/min that increases to <100 beats/min with light exertion, such as walking. If it is difficult to slow the ventricular rate to

that degree, allowing a resting rate of up to 110 beats/min is acceptable provided it does not cause symptoms and ventricular function

is normal; however, periodic assessment of ventricular function

is warranted because some patients develop tachycardia-induced

cardiomyopathy.

If adequate rate control in AF is difficult to achieve, further consideration should be given to restoring sinus rhythm (see below).

Catheter ablation of the AV junction to create permanent AV block

and implantation of a permanent pacemaker reliably achieve rate

control without the need for AV nodal–blocking agents, a so-called

“ablate and pace” strategy. These patients not only remain in AF but

also become dependent on the pacemaker to support ventricular

1906 PART 6 Disorders of the Cardiovascular System

rate. The typical pacing configuration with placement of a ventricular lead in the right ventricular apex may induce dyssynchronous

ventricular activation that can depress ventricular function in some

patients. Biventricular pacing or direct pacing of the His bundle or

left bundle branch may be used to minimize the degree of ventricular dyssynchrony.

STROKE PREVENTION IN ATRIAL FIBRILLATION

Thromboembolic complications, in particular, stroke, are the most

significant and potentially life-threatening sequelae of AF. Therefore, appropriate stroke prevention strategies are a key aspect of

AF management. The mainstay of stroke prevention is continuous

anticoagulation therapy, most commonly using an oral medication.

Specific patient populations have a high risk of stroke, including patients with hypertrophic cardiomyopathy, mitral stenosis,

and prior stroke history, and therefore, anticoagulation is recommended, barring contraindications. AF in patients without mitral

stenosis is commonly referred to as nonvalvular AF. In the majority

of patients with AF, the decision about whether a stroke prevention

regimen is indicated is largely based on an assessment of stroke

risk, balanced by the risk of the preventative therapy. The risk of

stroke appears to be most accurately predicted by the presence

of underlying risk factors known in increase stroke risk. The

CHA2

DS2

-VASc scoring system (Fig. 251-3) is a widely used tool

to estimate stroke risk. Anticoagulation is currently recommended

in the United States for patients with a score of ≥1, unless the lone

risk factor is female gender. Stroke risk increases with increasing

CHA2

DS2

-VASc score, such that annual stroke risk may be as high

as nearly 20% without anticoagulation. On the other hand, anticoagulation carries a risk of serious and potentially life-threatening

bleeding complications, in particular, intracranial hemorrhage and

gastrointestinal bleed. Bleeding risk is often assessed using the

HAS-BLED scoring system (Fig. 251-3). If bleeding risk is deemed

to be outweighed by stroke risk, anticoagulation is recommended.

It is important to note that the perceived burden of AF has not been

shown to predict stroke risk. The approach to patients with paroxysmal AF is therefore the same as for persistent AF. It is recognized

that many patients who appear to have infrequent AF episodes

based on office visits often have asymptomatic episodes that put

them at risk. Absence of AF during periodic monitoring is not sufficient to indicate low risk. The role of continuous monitoring with

implanted recorders or pacemakers as a guide for anticoagulation in

patients with a borderline risk profile is not clear.

The options for anticoagulation are the oral factor Xa inhibitors

apixaban, edoxaban, or rivaroxaban; the oral antithrombin inhibitor

dabigatran; and the vitamin K antagonist warfarin.

Antiplatelet agents alone are generally not sufficient. In nonvalvular AF, warfarin reduces the annual risk of stroke by 64%

compared to placebo and by 37% compared to antiplatelet therapy.

Patients with AF with an increased risk of stroke also have an

increased risk of venous thromboembolism, which appears to be

lower with oral anticoagulation. The direct-acting anticoagulants

dabigatran, rivaroxaban, apixaban, and edoxaban were noninferior

to warfarin in individual trials of nonvalvular AF patients, and

intent-to-treat analysis of pooled data suggests superiority to warfarin by small absolute margins of 0.4–0.7% in reduction of mortality,

stroke, major bleeding, and intracranial hemorrhage. Warfarin is

required for patients with rheumatic mitral stenosis or mechanical

heart valves. The newer, direct-acting anticoagulants have not been

tested in rheumatic heart disease, and a direct thrombin inhibitor

did not prevent thromboembolism in patients with mechanical heart

valves. Warfarin can be an inconvenient agent that requires several

days to achieve a therapeutic effect (prothrombin time [PT]/international normalized ratio [INR] >2), requires monitoring of PT/INR to

adjust dose, and has many drug and food interactions that can hinder patient compliance and render maintaining a therapeutic effect

challenging. The direct-acting agents are easier to use and achieve

reliable anticoagulation promptly without requiring dosage adjustment based on blood tests. Dabigatran, rivaroxaban, and apixaban

have renal excretion, cannot be used with severe renal insufficiency

(creatinine clearance <15 mL/min), and require dose adjustment

for modest renal impairment, which is of particular concern in the

elderly, who are at increased bleeding risk. Limited experience with

apixaban demonstrates safety and efficacy in patients undergoing

chronic hemodialysis for end-stage kidney disease. Excretion can

also be influenced by P-glycoprotein inducers and inhibitors. Warfarin anticoagulation can be reversed by administration of fresh frozen

plasma, prothrombin complex concentrate, and vitamin K. Reversal

agents are available for dabigatran (idarucizumab), and Xa inhibitors

are available (andexanet alfa), and both are administered intravenously. These agents may be pro-thrombotic and administration

must be judicious. The antiplatelet agents aspirin and clopidogrel are

inferior to warfarin for stroke prevention in AF and do not have less

risk of bleeding. Clopidogrel combined with aspirin is better than

aspirin alone for stroke prevention, but this combination is inferior

to warfarin and has a greater bleeding risk than aspirin alone.

Bleeding is the major risk of anticoagulation. Major bleeding

requiring transfusion and intracranial bleeding occur in ~1% of

patients per year with warfarin. Direct-acting anticoagulants appear

to have a lower risk of intracranial bleeding compared with warfarin

without sacrificing protective effects against thromboembolism.

Risk factors for bleeding include age >65–75 years, heart failure,

renal insufficiency, prior bleeding, and excessive alcohol or nonsteroidal anti-inflammatory drug use. In patients who require dual

antiplatelet therapy (e.g., aspirin and clopidogrel) after coronary

or peripheral arterial stenting, there is a substantially increased

bleeding risk when standard oral anticoagulation with warfarin or

a direct-acting anticoagulant is added. The optimal combination

of agents for patients with AF who also require antiplatelet therapy

remains unclear.

Chronic anticoagulation is contraindicated in some patients

due to bleeding risks. Because most atrial thrombi likely originate

CHA2DS2-VASc HAS-BLED

Risk Criteria

Congestive heart

failure

1 Hypertension 1

Age >75 2 Abnormal renal or liver

function

1 each

Hypertension 1 Bleeding diasthesis 1

Diabetes mellitus 1 Labile INR (on warfarin) 1

Prior stroke or TIA 2 Age >65 1

Vascular disease 1 Drugs or alcohol 1 each

Age >65 1

Sex category (F) 1

1 2 3 4 5 6

Annual Stroke or Major Bleeding Rate (%)

as a Function of Score

CHA2DS2-VASc HAS-BLED

FIGURE 251-3 CHA2

DS2

-VASc and HAS-BLED Systems. The CHA2

DS2

-VASc scoring

system gives a point for each outlined stroke risk factor, whereas the HAS-BLED

scoring system gives a point for each bleeding risk factor, as outlined in the table. In

the chart below the table, the corresponding risk of stroke (CHA2

DS2

-VASC) or major

bleed event (HAS-BLED) is plotted as a percent risk per annum as a function of

score. F, female; INR, international normalized ratio; TIA, transient ischemic attack.

Atrial Fibrillation

1907CHAPTER 251

in the left atrial appendage, surgical removal of the appendage,

combined with atrial maze surgery, may be considered for patients

undergoing surgery, although removal of the appendage has not

been unequivocally shown to reduce the risk of thromboembolism.

Percutaneously deployed devices that occlude or ligate the left atrial

appendage are also available, appear to be noninferior to warfarin in

reducing stroke risk, and are considered in patients who have a high

risk of thromboembolism but serious bleeding risk from chronic

oral anticoagulation (Table 251-2).

RHYTHM CONTROL

The decision to administer antiarrhythmic drugs or perform catheter ablation to attempt maintenance of sinus rhythm (commonly

referred to as the rhythm control strategy) is mainly guided by

patient symptoms and preferences regarding the benefits and risks

of therapies. In general, patients who maintain sinus rhythm have

better survival than those who continue to have AF. This may

be because continued AF is a marker of disease severity. In older

randomized trials, administration of antiarrhythmic medications

to maintain sinus rhythm did not improve survival or symptoms

compared to a rate control strategy, and the drug therapy group

had more hospitalizations. Disappointing efficacy and toxicities of

available antiarrhythmic drugs and patient selection bias may be

factors that influenced the results of these trials. Recently, a randomized trial evaluating an early rhythm control strategy (within

1 year of initial presentation) compared to standard rate control

demonstrated a reduction in cardiovascular events, including death

from cardiovascular causes and stroke. Differences between this

study and earlier randomized trials that failed to show a significant

difference in outcomes in rate versus rhythm control included the

use of catheter ablation and a high adherence rate to anticoagulation despite apparent rhythm control. In patients with heart failure

due to depressed left ventricular function, a catheter ablation–based

strategy to maintain sinus rhythm appears to provide mortality benefit compared with a medical rhythm control strategy. In a broader

population of patients with AF, a large, randomized, prospective

study comparing catheter ablation rhythm control medications

demonstrated a nonsignificant trend toward reduced hospitalizations and improved mortality, mostly driven by patients with heart

failure.

A rhythm control strategy is usually selected for patients with

symptomatic paroxysmal AF, recurrent episodes of symptomatic

persistent AF, AF with difficult rate control, and AF that has

resulted in depressed ventricular function or that aggravates heart

failure. A rhythm control strategy is more likely to be favored in

younger patients than in sedentary or elderly patients in whom rate

control is more easily achieved. Even if sinus rhythm is apparently

maintained, anticoagulation is recommended according to the

CHA2

DS2

-VASc stroke risk profile because asymptomatic episodes

of AF are common. Following a first episode of persistent AF, a

strategy using AV nodal–blocking agents, cardioversion, and anticoagulation is reasonable, in addition to addressing possible aggravating factors. If recurrences are infrequent, periodic cardioversion

is reasonable. However, if a patient has frequent symptomatic AF

despite rate control, then a rhythm control strategy incorporating

catheter ablation and/or antiarrhythmic medications is indicated.

Based on recent randomized trial data demonstrating superiority

of ablation over medications for maintenance of sinus rhythm and

benefits of an early rhythm control strategy, there is a trend toward

offering ablation earlier in the course of treatment, especially for

individuals with paroxysmal AF.

Pharmacologic Therapy for Maintaining Sinus Rhythm The goal

of pharmacologic therapy is to maintain sinus rhythm or reduce

episodes of AF. Risks and side effects of antiarrhythmic drugs are

a major consideration in selecting therapy. Drug therapy can be

instituted once sinus rhythm has been established or in anticipation of cardioversion. However, antiarrhythmic medications may

in some instances pharmacologically cardiovert the patient into

sinus rhythm. Therefore, an appropriate anticoagulation strategy

approach similar to electrical cardioversion is recommended, particularly at the time of initiation of therapy. β-Adrenergic blockers

and calcium channel blockers help control ventricular rate, improve

symptoms, and possess a low-risk profile, but have low efficacy for

preventing or terminating AF episodes. Class I sodium channel–

blocking agents (e.g., flecainide, propafenone, disopyramide) are

options for patients without significant structural heart disease, but

negative inotropic and proarrhythmic effects warrant avoidance

in patients with coronary artery disease or heart failure. The class

III agents sotalol and dofetilide can be administered to patients

with coronary artery disease or structural heart disease but have

~3% risk of inducing excessive QT prolongation and torsades des

pointes. Dofetilide should be initiated only in a hospital with ECG

monitoring, and many physicians take this approach with sotalol as

well. Dronedarone increases mortality in patients with heart failure

or long-standing persistent AF. All of these agents have modest

efficacy in patients with paroxysmal AF, of whom ~30–50% will

benefit. Amiodarone is more effective, maintaining sinus rhythm

in approximately two-thirds of patients. It can be administered to

patients with heart failure and coronary artery disease. However,

>40% of patients experience amiodarone-related toxicities during

long-term therapy, and thus, careful monitoring of potential toxicities, including liver, lung, and thyroid abnormalities, must be

accompanied with this therapy.

Catheter And Surgical Ablation for Maintaining Sinus Rhythm

Successful catheter ablation avoids antiarrhythmic drug toxicities,

but procedural risks and efficacy depend on operator experience.

For patients with previously untreated but recurrent paroxysmal

AF, catheter ablation has superior efficacy compared to antiarrhythmic drug therapy, and ablation is even more clearly superior to antiarrhythmic drugs for patients who have recurrent AF despite drug

treatment. Long-term control of AF is more difficult to achieve in

patients with persistent AF, likely because of more extensive atrial

abnormalities and associated greater comorbidities in these patients

(Fig. 251-4).

Catheter ablation involves percutaneous venous access (typically

via the femoral veins), trans(atrial) septal puncture, and radiofrequency ablation or cryoablation to electrically isolate the left atrial

regions around the pulmonary vein antra, abolishing the ability

of triggering foci in these regions to initiate AF and also likely

impacting the substrate for reentry in the left atrium. Extensive

areas of ablation are required, and gaps in healed ablation areas

TABLE 251-2 Novel Oral Anticoagulant Dosing

DABIGATRAN RIVAROXABAN APIXABAN EDOXABAN

Standard dose 150 mg bid 20 mg qd 5 mg bid 60 mg qd

Reduced dose 110 mg bid 15 mg qd 2.5 mg bid 30 mg qd

Dose reduction criteria Dabigatran 110 mg bid in patients

with: age ≥80 years, concomitant

use of verapamil, or increased

bleeding risk

Creatine clearance

15–49 mL/min

At least 2 of 3 criteria: age

≥80 years, body weight ≤60 kg,

or serum creatinine ≥1.5 mg/dL

(133 mol/L)

If any of the following: creatinine clearance

30–50 mL/min, body weight

≤60 kg, or concomitant use of dronedarone,

cyclosporine, erythromycin, or ketoconazole

Note: As of publication, four novel or direct oral anticoagulants are available and indicated for stroke prevention for atrial fibrillation. The standard dosing, reduced dosing,

and criteria for reduced dosing are shown for each agent.

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