1908 PART 6 Disorders of the Cardiovascular System

or emergence of new trigger sites outside the pulmonary veins

necessitate a repeat procedure in 10–30% of patients. Several alternative energy sources to create ablative lesions are being evaluated

for ablation of AF and other arrhythmias, including laser, external

beam radiation, and pulsed field electroporation.

In patients with paroxysmal AF, sinus rhythm is maintained for

>1 year after a single ablation procedure in ~70% of patients and

is achieved in >90% of patients after multiple procedures in some

studies. Many patients become more responsive to antiarrhythmic

drugs or become less symptomatic with a reduced AF burden after

a pulmonary vein isolation procedure, and thus, repeat ablation

may not be required for symptom control in some. Ablation is less

effective in patients with persistent AF, particularly long-standing

persistent AF, especially when associated with more extensive cardiac disease, comorbidities, and evidence of left atrial enlargement.

More extensive ablation is often required, targeting areas that likely

support reentry and/or AF maintenance and regions outside but

adjacent to the pulmonary venous antra. There is no proven strategy for selecting ablation targets outside the pulmonary vein antral

regions, and a variety of approaches have been pursued. Ablation

of areas of rapid activity during AF and creation of ablation lines to

block conduction across regions of the atria have not been proven

to improve outcomes in unselected patients. Other ablation targets

include non–pulmonary vein foci that fire in response to high-dose

isoproterenol, areas of atrial fibrosis, and regions with repetitive

rotational or focal activation during AF. More than one ablation

PV ectopy and fibrillation

isolated from the atrium

B

A

II

aVF

V1

Ls 10,1

Ls 8,9

Ls 7,8

Ls 6,7

Ls 5,6

Ls 4,5

Ls 3,4

Ls 2,3

Ls 1,2

FIGURE 251-4 A. Electroanatomic map superimposed on an MRI reconstruction of a left atrium with mapping catheter in the left common pulmonary vein and ablation

catheter at the pulmonary vein–left atrium junction. B. Spontaneous pulmonary vein (PV) ectopy initiating fibrillatory conduction contained within the isolated vein.

Atrial Fibrillation

1909CHAPTER 251

procedure is often required to maintain sinus rhythm in patients

with persistent and long-standing persistent AF because of lack of

lesion durability and complex atrial substrate with non–pulmonary

vein sources that may be incompletely treated at the initial ablation

session (Fig. 251-5).

Catheter ablation has a 2–7% risk of major procedure-related

complications, with the long-term trend suggesting steady improvement in complication rates. Complication rates are clearly lowest

with high-volume operators and centers. Complications including

stroke (0.5–1%), cardiac tamponade (1%), phrenic nerve paralysis, bleeding from femoral access sites, and fluid overload with

heart failure, which can emerge 1–3 days after the procedure. It

is important to recognize the potential for delayed presentation

of some complications. Ablation within the PV can lead to PV

stenosis, presenting weeks to months after the procedure with

dyspnea or hemoptysis. The esophagus abuts the posterior wall

of the left atrium where it is subject to injury, and esophageal

ulcers can form immediately after the procedure and may rarely

lead to a fistula between the left atrium and esophagus (estimated incidence of <0.1%) that presents as endocarditis and stroke

10 days to 3 weeks after the procedure. Early diagnosis of atrioesophageal fistula is important because delayed diagnosis leads to

likely death. Diagnosis is made by chest CT scan with water-soluble

oral and IV contrast. Endoscopy should be avoided in patients

with a suspected fistula because of the risk of air/esophageal fluid

embolus. Definitive repair of the atrioesophageal fistula with emergent surgery is required.

Surgical ablation of AF is most frequently performed concomitant with cardiac valve or coronary artery surgery and less

commonly as a stand-alone procedure. However, for patients with

persistent AF, surgical or hybrid procedures (a combination of a

surgical and catheter-based approach, most often in separate procedures) appear to have comparable efficacy to catheter ablation.

Risks include sinus node injury requiring pacemaker implantation

and higher morbidity with surgical ablation. Surgical removal of

the left atrial appendage may reduce stroke risk, although thrombus can form in the remnant of the appendage or if the appendage

is not completely ligated.

RISK FACTORS FOR AND LIFESTYLE

IMPACT ON ATRIAL FIBRILLATION

There is strong evidence that AF is associated with obesity, hypertension, alcohol use, and sleep apnea. Aggressive treatment of these risk

factors can substantially reduce AF episodes in some patients and is

warranted in all patients, as additional benefits to the patient are likely

beyond AF improvement. The amount of exercise appears to have a

complex relationship with the risk of AF development. In males, a

U-shaped curve exists, where AF risk is high among those with sedentary lifestyles and those who participate extensively in endurance

athletics such as long-distance running or cycling. Moderate exercise

appears to confer a lower risk of AF. On the other hand, in females, a

linear relationship exists between exercise and AF risk, with risk of AF

decreasing continuously with increasing exercise activity. Although

caffeine intake is often invoked as a risk for AF development or as a

trigger for AF episodes in patients with a known AF diagnosis, large

cohort studies have demonstrated, in contrast, a modest decrease in AF

risk with modest caffeine intake. Other proposed risk factors are being

evaluated, including psychological stress. Genetic predisposition to AF

is seen in those with first-degree relatives with AF, and a small subset of

AF patients can be determined have a familial form of AF.

There is emerging emphasis on an integrated approach to management of AF patients, with coordinated management of risk factor

modification, stroke prevention, rate control, rhythm control, and

management of associated comorbidities of critical importance.

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

Blum S et al: Incidence and predictors of atrial fibrillation progression:

A systematic review and meta-analysis. Heart Rhythm 16:502, 2019.

Hindricks G et al: 2020 ESC guidelines for the diagnosis and management

of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J 42:373, 2021.

January CT et al: 2019 AHA/ACC/HRS focused update of the 2014

AHA/ACC/HRS guideline for the management of patients with

Symptomatic AF

Paroxysmal AF

Consider patient choice

Antiarrhythmic

drugs

Catheter

ablation

Catheter

ablation

Catheter

ablation

Catheter

ablation

Antiarrhythmic

drugs

Antiarrhythmic

drugs

Antiarrhythmic

drugs

Failed drug therapy

Continue antiarrhythmic

drugs

No Yes No Yes

Continue antiarrhythmic

drugs

Perform catheter ablation Perform catheter ablation

(I) (IIa)

Perform

catheter

ablation

Perform

catheter

ablation

Perform

catheter

ablation

Perform

catheter

ablation

Failed drug therapy

Consider patient choice Consider patient choice Consider patient choice

(IIa) (IIb) (I)

Persistent AF without major

risk factors for AF recurrence

Persistent AF with major risk

factors for AF recurrence

Paroxysmal or persistent AF

and heart failure with

reduced EF

FIGURE 251-5 Rhythm control strategy for symptomatic atrial fibrillation (AF). This chart outlines the guideline-based management of patients with symptomatic atrial

fibrillation. As outlined in Table 251-1, the first step is determination of the temporal nature of the patient’s AF (paroxysmal vs persistent) and any associated risk factors for AF

recurrence, such as left atrial anatomic dimensions. A decision is then made regarding medical versus catheter ablation–based rhythm control, with recommendations for

when to consider catheter ablation based on guideline recommendations (class IIa for paroxysmal, IIb for persistent without major risks for recurrence, or AF of any sort in

patients with heart failure with reduced ejection fraction [EF], class I). Note the importance of patient choice, as well as the subsequent decisions to consider catheter ablation

if drugs have failed. (G Hindricks et al: 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of

Cardio-Thoracic Surgery (EACTS). Eur Heart J 42:17, 2020. (Translated and) Reprinted by permission of Oxford University Press on behalf of the European Society of Cardiology.)

1910 PART 6 Disorders of the Cardiovascular System

There are myriad types of ventricular arrhythmias (VAs), affecting patients

with normal hearts and those with structural heart disease ranging from

benign to life-threatening. An understanding of an approach to these

arrhythmias is critical to being appropriately parsimonious with benign

forms, while understanding an approach to the malignant forms.

252 Approach to Ventricular

Arrhythmias

William H. Sauer, Usha B. Tedrow

B

A

C

Art. Pr.

1000 ms

I

FIGURE 252-1 A. Unifocal premature ventricular contractions (PVCs) at bigeminal frequency. Trace shows electrocardiogram lead 1 and arterial pressure (Art. Pr.). Sinus

rhythm beats are followed by normal arterial waveform. The arterial pressure following premature beats is attenuated (arrows) and imperceptible to palpation. The pulse

in this patient is registered at half the heart rate. B. Multifocal PVCs. The two PVCs shown have different morphologies. C. Example of accelerated idioventricular rhythm.

(See text for details.)

atrial fibrillation: A report of the American College of Cardiology/

American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration with the Society

of Thoracic Surgeons. Circulation 140:e125, 2019.

Kirchhof P et al: Early rhythm-control therapy in patients with atrial

fibrillation. N Engl J Med 383:1305, 2020.

Packer DL et al: Effect of catheter ablation vs antiarrhythmic drug

therapy on mortality, stroke, bleeding, and cardiac arrest among

patients with atrial fibrillation: The CABANA randomized clinical

trial. JAMA 321:1261, 2019.

Valembois L et al: Antiarrhythmics for maintaining sinus rhythm

after cardioversion of atrial fibrillation. Cochrane Database Syst Rev

9:CD005049, 2019.

TYPES OF VAs

VAs can arise from focal sites of origin or from reentrant circuits.

Focal VAs can originate from myocardial or Purkinje cells capable

of automaticity or triggered activity. Reentrant VAs often involve

areas of scar such as old myocardial infarction or a cardiomyopathic

process. Less commonly, diseased Purkinje conduction pathways

can also result in reentrant circuits. VAs are characterized by their

electrocardiographic appearance and duration. Conduction away

from the ventricular focus or reentrant circuit exit, propagating

through the ventricular myocardium, is slower than activation of

the ventricles over the normal Purkinje system. For this reason, the

QRS complex duration during VAs will be wide, typically >0.12 s,

though there are unusual situations that can arise with narrow QRS

duration as well.

Premature ventricular beats (also referred to as a premature ventricular contractions [PVCs]) are single ventricular beats that fall earlier

than the next anticipated supraventricular beat (Fig. 252-1). PVCs that

originate from the same focus will have the same QRS morphology

and are referred to as unifocal (Fig. 252-1A). PVCs that originate from

different ventricular sites have different QRS morphologies and are

referred to as multifocal (Fig. 252-1B). Two consecutive ventricular

beats are ventricular couplets.

Ventricular tachycardia (VT) is three or more consecutive beats at

a rate faster than 100 beats/min. Three or more consecutive beats at

slower rates are designated an idioventricular rhythm. VT that terminates spontaneously within 30 s is designated nonsustained, whereas

sustained VT persists for >30 s or is terminated by an active intervention, such as administration of an intravenous medication, external

cardioversion, antitachycardia pacing, or a shock from an implanted

cardioverter defibrillator (Fig. 252-2).

Approach to Ventricular Arrhythmias

1911CHAPTER 252

I

II aVR V1 V4

V5 V2

V3 V6

aVL

aVF

II

III

V1

FIGURE 252-2 Repetitive monomorphic nonsustained ventricular tachycardia (VT) of right ventricular outflow tract origin. The VT has a left bundle branch block pattern

with inferior axis with tall QRS complexes in the inferior leads.

Monomorphic VT has the same QRS complex from beat to beat,

indicating that the activation sequence is the same from beat to beat

and that each beat likely originates from the same source (Fig. 252-3A).

The initial site of ventricular activation largely determines the sequence

of ventricular activation. Therefore, the QRS morphology of PVCs and

monomorphic VT provides an indication of the site of origin within

the ventricles (Fig. 252-4). The likely origin often suggests whether an

arrhythmia is idiopathic or associated with structural disease. Arrhythmias that originate from the right ventricle or septum result in late

activation of much of the left ventricle, thereby producing a prominent

S wave in V1

 referred to as a left bundle branch block–like configuration. Arrhythmias that originate from the free wall of the left ventricle

have a prominent positive deflection in V1

, thereby producing a right

bundle branch block–like morphology in V1

. The frontal plane axis of

the QRS is also useful. An axis that is directed inferiorly, as indicated

by dominant R waves in lead II, III, and AVF, suggests initial activation

of the cranial portion of the ventricle, whereas a frontal plane axis that

is directed superiorly (dominant S waves in II, III, and AVF) suggests

initial activation at the inferior wall.

Very rapid monomorphic VT has a sinusoidal appearance, also

called ventricular flutter, because it is not possible to distinguish the

QRS complex from the T wave (Fig. 252-3B). Relatively slow sinusoidal

VTs have a wide QRS indicative of slowed ventricular conduction

(Fig. 252-3C). Hyperkalemia, toxicity from excessive effects of drugs

that block sodium channels (e.g., flecainide, propafenone, or tricyclic

antidepressants), and severe global myocardial ischemia are possible

causes.

Polymorphic VT has a continually changing QRS morphology indicating a changing ventricular activation sequence. Polymorphic VT

that occurs in the context of congenital or acquired prolongation of the

QT interval often has a waxing and waning QRS amplitude, creating a

characteristic shifting axis referred to as torsades des pointes after the

classic ballet sequence (Fig. 252-3D).

Ventricular fibrillation (VF) has continuous irregular activation with

no discrete QRS complexes. Monomorphic or polymorphic VT may

transition to VF in susceptible patients. Cardiac ischemia is the most

common cause of VF (Fig. 252-3E).

The term idiopathic ventricular arrhythmia generally refers to PVCs

or VT that occurs in patients with a normal electrocardiogram (ECG),

without structural heart disease, and not associated with an underlying

genetic syndrome or risk of sudden death.

CLINICAL MANIFESTATIONS

Common symptoms of VAs include palpitations, dizziness, exercise

intolerance, episodes of lightheadedness, syncope, or sudden cardiac

arrest leading to sudden death if not resuscitated. VAs can also be

asymptomatic and encountered unexpectedly as an irregular pulse

or heart sounds on examination or may be seen on a routine ECG,

exercise test, or cardiac ECG monitoring. Occasionally when every

other beat is a PVC (bigeminy), pulse measurements for heart rate can

be erroneously low (pseudobradycardia) because the PVCs may not

generate a separate pulse wave.

Syncope is a concerning symptom, particularly when occurring

without prodrome, during exercise, or in the setting of abnormal ECG

or structural heart disease. Such episodes can be due to VT that produces severe hypotension, warranting concern for risk of cardiac arrest

and sudden death with arrhythmia recurrence. Although benign processes such as reflex-mediated neurocardiogenic (vasovagal) episodes

and orthostatic hypotension are the most common causes of syncope,

it is important to consider the possibility of underlying heart disease

or a genetic syndrome causing VT. When these are suspected, hospitalization for further evaluation and monitoring is often appropriate.

Sustained VT may present as a wide QRS complex tachycardia

that must be distinguished from supraventricular tachycardia with

aberrancy (Chap. 246). Symptoms can be minor but more commonly

include hypotension with syncope and even imminent cardiac arrest.

Sustained VT may degenerate to VF, particularly if it is rapid and polymorphic. Many patients who are at risk for VT have known heart disease, and many have an implantable cardioverter defibrillator (ICD). In

patients with an ICD, VT episodes may cause transient lightheadedness,

palpitations, or syncope followed by a shock from the ICD (see below).

EVALUATION OF PATIENTS WITH

DOCUMENTED OR SUSPECTED

VENTRICULAR ARRHYTHMIAS

There are several important considerations that guide evaluation of

patients with documented or suspected cardiac arrhythmias. First,

establish whether a VA is the cause of the symptoms or clinical

1912 PART 6 Disorders of the Cardiovascular System

A

B

C

D

E

FIGURE 252-3 A. Monomorphic ventricular tachycardia (VT) with dissociated

P waves (short arrows). B. Ventricular flutter. C. Sinusoidal VT due to electrolyte

disturbance or drug effects. D. Polymorphic VT resulting from prolongation of QT

interval (torsade de pointe VT). E. Ventricular fibrillation. (See text for details.)

presentation. Second, determine whether the arrhythmia is associated

with a cardiac disease, and establish the prognostic significance of that

disease and, in particular, whether it is associated with a risk of sudden

cardiac death. Finally, define the likelihood of arrhythmia recurrence

and the symptoms and risk imposed by the recurrence. The risks of

cardiac arrest and sudden cardiac death are largely determined by the

cause of the arrhythmia and the associated underlying heart disease.

The diagnosis of VAs can be established by recording the arrhythmia

on an ECG, by an ambulatory or implanted cardiac monitor, by an

implanted rhythm management device such as a pacemaker or ICD, or

in some cases, initiation of the arrhythmia during an electrophysiologic

study. A 12-lead ECG of the arrhythmia should be obtained when possible and often provides clues to the potential site of origin and possible

presence of underlying heart disease (see above) (Fig. 252-4).

For patients with sustained wide-complex tachycardia, initial management is guided by the patient’s hemodynamic stability. The approach

to sustained wide-complex tachycardia is discussed in Chap. 254. The

management of VT that causes cardiac arrest is discussed in Chap.

306. Once hemodynamic stability is restored, further management is

guided by the possibility of a recurrence and the risk imposed by a

recurrence.

■ EVALUATION OF THE PATIENT WITH

ARRHYTHMIA SYMPTOMS

When symptoms are intermittent, initial evaluation aims to establish

symptom severity, provocative factors, and presence of underlying

heart disease. Syncope or near syncope raises concern that an arrhythmia is causing episodes of hypotension and that there may be a risk of

cardiac arrest. Symptoms that occur with exertion suggest arrhythmias

that are provoked by sympathetic stimulation but can also be related to

exertional ischemia in patients with coronary artery disease, although

non-arrhythmia causes must also be considered. A past history of any

cardiac disease is important. A review of all medications is relevant.

Medications that prolong the QT interval predispose to polymorphic

VT (Chap. 255). Adrenergic stimulants can provoke PVCs.

Family history should determine the presence of premature coronary artery disease, cardiomyopathy, or cardiac arrhythmias, particularly a history of sudden death. Family history may also suggest that a

possibility of a genetic cause of an arrhythmia warrants careful consideration. Details of premature deaths are relevant. Sudden death victims

are often said to have died of a “massive heart attack” despite absence

of definite confirmation of thrombotic myocardial infarction and when

other causes such as arrhythmia may have been possible.

The physical examination focuses on evidence of structural heart

disease with assessment of pulse, jugular venous pressure lung fields,

and cardiac auscultation. Stigmata of neuromuscular disease or dysmorphic features may suggest a genetic arrhythmia syndrome.

A 12-lead ECG should be obtained even if the patient is not having

symptoms at the time of evaluation. Occasionally, premature ventricular beats will be detected. Patients with benign idiopathic arrhythmias

usually have a completely normal ECG during sinus rhythm. Any

ECG abnormality warrants further evaluation. Particularly relevant

findings include Q waves that indicate prior myocardial infarction,

which may have been silent, and ventricular hypertrophy, which may

indicate hypertrophic cardiomyopathy or other ventricular disease. An

ECG finding is the major diagnostic manifestation of several genetic

arrhythmia syndromes in patients without structural heart disease,

including the long QT syndrome, Brugada syndrome, and short QT

syndrome.

If there is suspicion for structural heart disease, cardiac imaging is

warranted to assess ventricular function and structure. Transthoracic

echocardiography is most frequently employed for initial evaluation.

Depressed ventricular function increases concern for a risk of sudden

death and warrants further evaluation to establish the cause, which

may be cardiomyopathy, coronary artery disease, or valvular heart

disease. Ventricular thickening may indicate hypertrophic cardiomyopathy or infiltrative diseases such as amyloidosis. Cardiac MRI with

gadolinium contrast imaging provides similar assessment but also can

detect areas of ventricular scar, evident as regions of delayed hyperenhancement, which are usually present in patients who have sustained

monomorphic VT (Fig. 252-5). The nature and location of abnormalities are helpful in assessing the type of heart disease. Evaluation to

exclude atherosclerotic coronary artery disease should be performed

in patients at risk, guided by age and other risk factors.

■ TREATMENT OPTIONS FOR

VENTRICULAR ARRHYTHMIAS

Treatment of VAs is guided by the severity and frequency of symptoms.

For some, reassurance and removal of aggravating factors (e.g., caffeine) are all that is needed. For arrhythmias associated with a sudden

death risk, ICD implantation is usually indicated and will provide a

“safety net” to terminate life-threatening VT or VF, preventing sudden

death but without preventing the arrhythmia. When suppression of

the arrhythmia is required, antiarrhythmic drug therapy or catheter

ablation is a major consideration.

Approach to Ventricular Arrhythmias

1913CHAPTER 252

II

III

III

II

RV LV

V1 = LBBB

Septal or RV origin

V1 = RBBB

LV origin

V1

II, III AVF = Inferior axis

superior origin

II, III AVF = Superior axis

inferior origin

FIGURE 252-4 Site of ventricular tachycardia origin based on QRS morphology. (See text for details.)

LBBB, left bundle branch block; LV, left ventricle; RBBB, right bundle branch block; RV, right ventricle.

FIGURE 252-5 Imaging studies of the left ventricle (LV) used to assist ablation for ventricular tachycardia (VT). Left panel is an MRI image of a longitudinal section

demonstrating thinning of the anterior wall and late gadolinium enhancement in a subendocardial scar (white arrows). The middle panel shows a two-dimensional image

of the LV in long axis corresponding to the sector through the mid-LV (arrow in figure on right panel) obtained by an intracardiac echocardiography probe positioned in

the right ventricle. An electroanatomic three-dimensional map of the LV in the left anterior oblique projection is displayed in the right panel. The purple areas depict areas

of normal voltage (>1.5 mV). Blue, green, and yellow represent progressively lower voltages, with the red areas indicating scar (<0.5 mV). Channels of viable myocardium

with slow conduction within the scar are identified with the light blue dots. Areas of ablation delivered to regions involved in reentrant VT are indicated by maroon dots.

■ ANTIARRHYTHMIC DRUGS

Use of antiarrhythmic drugs is based on consideration of the risks and

potential benefit for the individual patient. Efficacy and side effects for

the individual patient are not predictable and are assessed by individual therapeutic trial. Adverse effects are mostly noncardiac and minor

but can sometimes be severe enough to limit their use. Cardiac side

effects, however, include the potential for “proarrhythmia,” whereby a

drug can increase the frequency of arrhythmia or cause a new arrhythmia. Aggravation of bradyarrhythmias is also a common concern.

Although antiarrhythmic drugs are classified based on their actions on

receptors or ion channels, most have multiple effects, affecting more

than one channel.

■ β-ADRENERGIC BLOCKERS

Many VAs are sensitive to sympathetic stimulation,

and β-adrenergic stimulation also diminishes the

electrophysiologic effects of many membrane-active

antiarrhythmic drugs. The safety of β-blocking agents

makes them the first choice of therapy for most VAs.

They are particularly useful for exercise-induced

arrhythmias and idiopathic arrhythmias but have

limited efficacy for most arrhythmias associated with

heart disease. Bradyarrhythmias and negative inotrophic effects are the major cardiac adverse effects.

■ CALCIUM CHANNEL BLOCKERS

The nondihydropyridine calcium channel blockers

diltiazem and verapamil can be effective for some

idiopathic VTs. The risk of proarrhythmia is low, but

they have negative inotropic and vasodilatory effects

that can aggravate hypotension.

■ SODIUM CHANNEL–BLOCKING

AGENTS

Drugs whose major effect is mediated through

sodium channel blockade include mexiletine, quinidine, disopyramide, flecainide, and propafenone,

which are available for chronic oral therapy. Blockade

of the fast inward sodium current has been referred

to as a class I antiarrhythmic drug effect. Antiarrhythmic actions are the result of depressing cardiac

conduction and membrane excitability. Conduction

slowing can be manifest as a prolongation of QRS

duration. Lidocaine, quinidine, and procainamide

are available as intravenous formulations. Quinidine,

disopyramide, and procainamide also have potassium

channel–blocking effects that prolong the QT interval

(class III antiarrhythmic drug action), contributing to

their antiarrhythmic effect. These agents have potential proarrhythmic

effects and, with the possible exception of quinidine, also have negative

inotropic effects that may have contributed to the increased mortality

observed when some were administered chronically to patients with

prior myocardial infarction. Long-term therapy is generally avoided in

patients with structural heart disease but may be used to reduce symptomatic arrhythmias in patients with ICDs.

■ POTASSIUM CHANNEL BLOCKING AGENTS

Sotalol and dofetilide block the delayed rectifier potassium channel IKr,

thereby prolonging action potential duration (QT interval) and the cardiac refractory period, known as the class III antiarrhythmic drug effect.

Sotalol also has nonselective β-adrenergic–blocking activity. It has been

1914 PART 6 Disorders of the Cardiovascular System

shown to have a modest effect on reducing ICD shocks due to ventricular

and atrial arrhythmias. Proarrhythmia due to the polymorphic VT torsade de pointe that is associated with QT prolongation occurs in 3–5% of

patients. Both sotalol and dofetilide are excreted via the kidneys, necessitating dose adjustment or avoidance in renal insufficiency. These drugs

must be avoided in patients with other risk factors for torsade de pointe,

including QT prolongation, hypokalemia, and significant bradycardia.

■ AMIODARONE

Amiodarone blocks multiple cardiac ionic currents and has sympatholytic activity. It is the most effective antiarrhythmic drug for

suppressing VAs. It is administered intravenously for life-threatening

arrhythmias. During chronic oral therapy, electrophysiologic effects

develop over several days. It is more effective than sotalol in reducing

ICD shocks and is often used for VAs in patients with heart disease.

Bradyarrhythmias are the major cardiac adverse effect. Ventricular

proarrhythmia can occur, but torsade de pointe VT is rare. Noncardiac toxicities are a major problem and contribute to drug discontinuation in at least a third of patients during long-term therapy.

Hyper- and hypothyroidism are related to the iodine content of the

drug. Pneumonitis or pulmonary fibrosis occurs in ~1% of patients.

Photosensitivity is common, and neuropathy and ocular toxicity can

occur. Systematic monitoring is recommended during chronic therapy

including assessment for thyroid, liver, and pulmonary toxicity. Intravenous administration of amiodarone via a peripheral vein for >24 h

can cause severe peripheral thrombophlebitis. Dronedarone has structural similarities to amiodarone but without the iodine moiety. Efficacy

for VAs is poor, and dronedarone increases mortality in patients with

heart failure, so dronedarone is not typically used for treatment of VAs.

■ IMPLANTABLE CARDIOVERTER DEFIBRILLATORS

ICDs detect sustained VT, largely based on heart rate, and then terminate the arrhythmia. In transvenous devices, VF is terminated by a

shock applied between a lead in the right ventricle and the ICD pulse

generator. The lead can provide pacing for bradycardia if needed. This

transvenous form of ICD has the disadvantages of vascular occlusion,

risk of lead fracture, endocarditis in the event of infection, and difficulty with removal. Monomorphic VT can also be terminated by a

burst of rapid pacing faster than the VT, known as antitachycardia

pacing (ATP) (Fig. 252-6A). If ATP fails or is not a programmed

treatment, as is often the case for rapid VT or VF, a shock is delivered

(Fig. 252-6B). ICDs can also be subcutaneous, without a transvenous

lead. The rhythm is also sensed by this lead, in a manner similar to a

surface ECG. The lead is placed overlying the left chest with a coil parallel to the sternum. Only shocks can be delivered from a subcutaneous

ICD, and pacing is not possible. No matter the type of ICD, shocks are

painful if the patient is conscious. ICDs are highly effective for termination of VT. The most common ICD complication is the delivery of

unnecessary therapy (either ATP or shocks) in response to an inappropriately detected rapid supraventricular tachycardia or electrical noise

as a result of an ICD lead fracture or electromagnetic interference from

an external source. ICDs record and store electrograms from arrhythmia episodes that can be retrieved by interrogation of the ICD, which

can be performed remotely and communicated via Internet. This

assessment is critical after an ICD shock to determine the arrhythmia

diagnosis and exclude an unnecessary therapy. Device infection is an

important problem long term and occurs in ~1% of patients. This risk

may be less for subcutaneous implants.

ICDs decrease mortality in patients at risk for sudden death due to

structural heart diseases. In all cases, ICDs are recommended only if

there is also expectation for survival of at least a year with acceptable

functional capacity. The exception is in cases of patients with endstage heart disease who are awaiting cardiac transplantation outside

the hospital or who have left bundle branch block QRS prolongation

such that they are likely to have improvement in ventricular function

with cardiac resynchronization therapy from a biventricular ICD

(Fig. 252-6C). In these cases, an ICD may be warranted despite guarded

prognosis. A wearable ICD system with electrodes incorporated into a

vest and an external battery pack is also available for short-term use in

patients pending decision regarding a permanent implanted system.

ICD shock

LV

lead

RV

lead

Atrial

lead

ICD

B C

Anti-tachycardia pacing

A

FIGURE 252-6 Implantable cardioverter defibrillator (ICD) and therapies for ventricular arrhythmias. A. A monomorphic ventricular tachycardia (VT) is terminated by a

burst of pacing impulses at a rate faster than VT (anti-tachycardia pacing). B. A rapid VT is converted with a high-voltage shock (arrow). The chest x-ray in the panel C

shows the components of an ICD capable of biventricular pacing. ICD generator in the subcutaneous tissue of the left upper chest, pacing leads in the right atrium and the

left ventricular (LV) branch of the coronary sinus (LV lead) and a pacing/defibrillating lead in the right ventricle (RV lead) are shown.

Premature Ventricular Contractions, Nonsustained Ventricular Tachycardia, and Accelerated Idioventricular Rhythm

1915CHAPTER 253

Despite prompt termination of VT or VF by an ICD, the occurrence of these arrhythmias predicts subsequent increased mortality

and risk of heart failure. Occurrence of VT or VF should therefore

prompt assessment for potential causes including worsening heart

failure, electrolyte abnormalities, and ischemia. Repeated shocks, even

if appropriate, often induce posttraumatic stress disorder. Antiarrhythmic drug therapy, most commonly amiodarone, or catheter ablation is

often required for suppression of recurrent arrhythmias. Antiarrhythmic drug therapy can alter the VT rate and the energy required for

defibrillation, thereby necessitating programming changes in the ICD’s

algorithms for detection and therapy.

■ CATHETER ABLATION FOR VT

Catheter ablation is usually performed by applying radiofrequency

(RF) current to cause thermal injury by resistive heating of cardiac

tissue responsible for the arrhythmia. An electrode catheter with an

electroanatomic mapping system is used to map local electrical activity

to identify the ventricular myocardium that is causing the arrhythmia,

referred to as the arrhythmia substrate. The size and location of the

arrhythmia substrate determine the ease and likely effectiveness of the

procedure, as well as the potential complications. When the arrhythmia

originates from the endocardium, as is most commonly the case, it

can be reached from an endovascular approach via a femoral vein or

artery. Less commonly, arrhythmias originate from the subepicardium,

and percutaneous pericardial puncture, similar to pericardiocentesis,

is required to insert a catheter into the pericardial space for mapping

and ablation. In patients with scar-related VT due to prior infarction or

cardiomyopathy, ablation targets abnormal regions in the scar. Because

these scars often contain multiple reentry circuits over relatively large

regions, extensive areas of ablation are required, and these areas are

often identified as regions of low voltage displayed on anatomic reconstructions of the ventricle (Fig. 252-5).

Catheter ablation is often performed in patients with recurrent

VAs associated with poor cardiac function, and the procedure-related

mortality in this situation is 0.5–3%. Outcomes are better for patients

with prior infarction and VT than for patients with nonischemic cardiomyopathies in which the scar locations are more variable and often

intramural or subepicardial. Ablation can be lifesaving for patients with

very frequent or incessant VT. Methods of delivering ablative energy to

intramural areas or areas requiring very extensive ablation are under

development. These include needle catheters capable of delivering

ablative energy into intramural sources. Stereotactic body radiation

therapy (SBRT), classically used for treating thoracic tumors, has been

used to direct radiation therapy to a specific portion of the scar substrate to noninvasively ablate VT with encouraging early studies.

Idiopathic VTs and PVCs that occur in the absence of structural

heart disease usually originate from a small focus, for which catheter

ablation typically has a higher success rate for preventing recurrent

arrhythmia. Long-term arrhythmia-free survival in these patients is

excellent.

ARRHYTHMIA SURGERY

When antiarrhythmic drug therapy and catheter ablation fail or are not

an option, surgical cryoablation, often combined with aneurysmectomy, can be effective therapy for recurrent VT due to prior myocardial

infarction and has also been used successfully in a few patients with

nonischemic heart disease. Few centers now maintain the expertise for

this therapy, though some use this therapy as an adjunct to ventricular

assist device implantation.

Acknowledgment

Roy M. John and William G. Stevenson contributed to this chapter in

the 20th edition, and some material from that chapter has been retained

here.

■ FURTHER READING

Al-Khatib SM et al: 2017 AHA/ACC/HRS guideline for management

of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/

American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. Heart Rhythm 15:e73,2018.

Callans DJ: Josephson’s Clinical Cardiac Electrophysiology: Techniques

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

Cronin EM et al: 2019 HRS/EHRA/APHRS/LAHRS expert consensus statement on catheter ablation of ventricular arrhythmias. EP

Europace 21:1143, 2019.

Jalife J, Stevenson W (eds): Zipes and Jalife’s Cardiac Electrophysiology: From Cell to Bedside, 8th ed. Philadelphia, Elsevier, 2021.

Ventricular ectopic beats are very common and may be identified

during outpatient or inpatient telemetry monitoring either due to

symptoms of palpitations or as an incidental finding. In most cases,

ventricular ectopy, presenting as premature ventricular contractions

(PVCs), nonsustained ventricular tachycardia (NSVT), and accelerated

idioventricular rhythm (AIVR), is asymptomatic and does not require

specific treatment. While most commonly benign when presenting

in patients with structurally normal hearts and normal ECGs, these

ventricular arrhythmias can rarely be associated with structural heart

disease and a risk of sudden death.

PREMATURE VENTRICULAR

CONTRACTIONS AND NON-SUSTAINED VT

PVCs are very common and can be due to enhanced automaticity,

triggered automaticity, or reentry. PVCs are often sensitive to sympathetic stimulation and can be a sign of increased sympathetic tone,

myocardial ischemia, hypoxia, electrolyte abnormalities, or underlying

heart disease. During myocardial ischemia or in association with other

structural heart disease, PVCs can be a harbinger of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).

The electrocardiogram (ECG) characteristics of the arrhythmia are

often suggestive of whether structural heart disease is present. PVCs

with smooth uninterrupted contours and sharp QRS deflections may

suggest an ectopic focus in relatively normal myocardium, whereas

broad notching and slurred QRS deflections may suggest a diseased

myocardial substrate. The QRS morphology also suggests the likely site

of origin within the ventricle. PVCs that have a dominant S wave in V1

,

referred to as a left bundle branch block–like configuration, originate

from the right ventricle or interventricular septum. Those with a dominant R wave in V1

 originate from the left ventricle. A superior frontal

plane axis (negative in II, III, aVF) indicates initial depolarization of

the inferior wall (diaphragmatic aspect of the heart), whereas an inferior frontal plane axis (positive in II, III, aVF) indicates an origin in the

cranial aspect of the heart. The location of arrhythmia origin often suggests the nature of underlying heart disease. Most common ventricular

arrhythmias that are not associated with structural heart disease have a

left bundle branch block–like configuration. PVCs with a right bundle

branch block configuration are more likely to be associated with structural heart disease. Multiple morphologies of PVCs (multifocal PVCs)

are also more likely to indicate structural heart disease or a myopathic

253 Premature Ventricular

Contractions, Nonsustained

Ventricular Tachycardia, and

Accelerated Idioventricular

Rhythm

William H. Sauer, Usha B. Tedrow

1916 PART 6 Disorders of the Cardiovascular System

disease process. In patients with heart disease, greater frequency and

complexity (couplets and NSVT) of these arrhythmias are associated

with more severe disease.

PVCs AND NSVT DURING ACUTE ILLNESS

These arrhythmias are often encountered in patients who are being

evaluated in the emergency department or who have been hospitalized

and are on a cardiac monitor. When encountered during acute illness

or as a new finding, evaluation should focus on detection and correction of potential aggravating factors and causes, specifically myocardial

ischemia, ventricular dysfunction, and electrolyte abnormalities, most

commonly hypokalemia. If there is a suspicion of underlying heart

disease, then this should be evaluated. Otherwise, asymptomatic PVCs

and NSVT in the hospitalized patient do not indicate any specific treatment outside the patient’s presenting illness.

PVCs AND NSVT IN PATIENTS WITHOUT

HEART DISEASE

Idiopathic ventricular arrhythmias frequently originate from the left

or right ventricular outflow tracts near the valve annuli, giving rise to

PVCs or VT that have a left bundle branch block–like configuration,

with an inferiorly directed frontal plane axis, as discussed below. Other

regions that give rise to PVCs in normal hearts include the papillary

muscles and fascicular tissue. NSVT from a benign idiopathic source

is usually monomorphic, with rates <200 beats/min. NSVT that is very

rapid, polymorphic, or with a first beat that occurs prior to the peak

of the T wave (“short-coupled”) is uncommon and should prompt

concern and careful evaluation for underlying disease or genetic syndromes associated with sudden death.

A family history of sudden death should prompt evaluation for

genetic syndromes associated with sudden death, including cardiomyopathy, long QT syndrome, and arrhythmogenic right ventricular

cardiomyopathy (ARVC) (see below). Any abnormality on the 12-lead

ECG warrants further evaluation. Repolarization abnormalities are

seen in a number of genetically determined syndromes associated with

sudden death, including the long QT syndrome, Brugada syndrome,

ARVC, and hypertrophic cardiomyopathy (Fig. 253-1). Structural

abnormalities such as mitral valve prolapse and mitral annular disjunction can be associated with papillary muscle PVCs and sudden death.

An echocardiogram is often necessary to assess ventricular function,

B

V3

V2

V1

A

V3

V2

V1

FIGURE 253-1 Electrocardiogram leads depicting Brugada syndrome. Precordial chest leads V1

–V3

 showing

typical abnormalities of arrhythmogenic right ventricular cardiomyopathy (ARVC) (A) and Brugada syndrome

(B). In ARVC, there is T inversion and delayed ventricular activation manifest as epsilon waves (arrows). Panel

B shows ST elevation in V1

 and V2

 typical of the Brugada syndrome.

wall motion abnormalities, and valvular heart disease. Contrastenhanced cardiac magnetic resonance imaging (MRI) is also useful for

this purpose and for the detection of ventricular scarring that is the

substrate for sustained VT. Exercise stress testing should be performed

in patients with effort-related symptoms and for those at risk for coronary artery disease.

TREATMENT OF IDIOPATHIC

ARRHYTHMIAS

For PVCs and NSVT in the absence of structural heart disease or a

genetic sudden death syndrome, no specific therapy is needed unless

the patient has significant symptoms or evidence that frequent PVCs

are depressing ventricular function (see below). Reassurance that the

arrhythmia is benign is often sufficient to allow the patient to cope

with the symptoms, which will often wax and wane in frequency over

years. Avoiding stimulants, such as caffeine and alcohol, is helpful in

some patients. If symptoms require treatment, β-adrenergic blockers

and nondihydropyridine calcium channel blockers (verapamil and

diltiazem) are sometimes helpful. If these fail, more membrane active

antiarrhythmic drugs and catheter ablation are options. The antiarrhythmic agents flecainide, propafenone, mexiletine, and amiodarone

can be effective, but the potential for side effects warrants careful consideration prior to prescribing these agents for long-term use. Catheter

ablation is effective at suppressing this arrhythmia in ~90% of patients.

Failure of ablation is usually due to inability to provoke the arrhythmia

for mapping in the electrophysiology laboratory or if the site of origin

is near a vital structure, such as the coronary arteries or His-Purkinje

system, or is not accessible due to a site of origin deep within the

myocardium.

PVCs AND NSVT ASSOCIATED WITH ACUTE

CORONARY SYNDROMES

In the peri-infarct period, PVCs and NSVT are common and can be

an early manifestation of ischemia and a harbinger of subsequent VF.

Treatment with β-adrenergic blockers and correction of hypokalemia

and hypomagnesemia reduce the risk of VF. Routine administration of

antiarrhythmic drugs such as lidocaine or amiodarone does not reduce

mortality and is not indicated for suppression of PVCs or asymptomatic NSVT but may be implemented transiently if an episode of

sustained VT or VF occurs, with the goal of reducing the likelihood of

a subsequent episode.

Following recovery from acute myocardial

infarction (MI), frequent PVCs (typically >10

PVCs/h), repetitive PVCs with couplets, and

NSVT are markers for depressed ventricular

function and increased mortality, but routine

antiarrhythmic drug therapy to suppress these

arrhythmias has not been shown to improve

mortality. Therefore, amiodarone is an option

for treatment of symptomatic arrhythmias in

this population when the potential benefit outweighs its potential toxicities. β-Adrenergic

blockers reduce sudden death but have limited

effect on spontaneous arrhythmias.

For survivors of an acute MI, an implantable

cardioverter defibrillator (ICD) reduces mortality in certain high-risk groups: patients who

have survived >40 days after the acute MI and

have a left ventricular ejection fraction of <30%,

or who have an ejection fraction <35% and have

symptomatic heart failure (functional class II or

III); and patients >5 days after MI who have a

reduced left ventricular ejection fraction, NSVT,

and inducible sustained VT or VF on electrophysiologic testing. ICDs do not reduce total

mortality when routinely implanted early after

MI and have not been demonstrated to improve

mortality when implanted early after coronary

artery revascularization.

Premature Ventricular Contractions, Nonsustained Ventricular Tachycardia, and Accelerated Idioventricular Rhythm

1917CHAPTER 253

PVCs AND NSVT ASSOCIATED WITH

DEPRESSED VENTRICULAR FUNCTION

AND HEART FAILURE

PVCs and NSVT are common in patients with depressed ventricular

function and heart failure and are markers for disease severity and

increased mortality, but antiarrhythmic drug therapy to suppress these

arrhythmias has not been shown to improve survival. The use of antiarrhythmic drugs whose major action is blockade of the cardiac sodium

channel (flecainide, propafenone, mexiletine, quinidine, and disopyramide) is avoided in patients with structural heart disease because of

a risk of proarrhythmia and negative inotropic effects. Amiodarone

suppresses ventricular ectopy and reduces sudden death but does not

improve overall survival. ICDs are the major therapy to protect against

sudden death in patients at high risk and are recommended for those

with a left ventricular ejection fraction <35% and New York Heart

Association class II or III heart failure, in whom they reduce mortality

from 36 to 29% over 5 years.

PVC AND NSVT ASSOCIATED WITH OTHER

CARDIAC DISEASES

Ventricular ectopy is associated with increased mortality in patients

with hypertrophic cardiomyopathy or with congenital heart disease

associated with right or left ventricular dysfunction. In these patients,

management is similar to that for patients with ventricular dysfunction. Pharmacologic suppression of the arrhythmia has not been shown

to improve mortality. ICDs are indicated for patients considered at high

risk for sudden cardiac death.

PVC-INDUCED VENTRICULAR

DYSFUNCTION

Very frequent ventricular ectopy and repetitive NSVT can depress

ventricular function, possibly through an effect similar to chronic

tachycardia or by inducing ventricular dyssynchrony. Depression of

ventricular function rarely occurs unless PVCs account for at least

10–20% of total beats over a 24-h period, and only a minority of

patients with PVCs will have a reversible cardiomyopathy. Often the

PVCs are idiopathic and unifocal, most commonly originating from the

outflow tract regions or left ventricular papillary muscles (Fig. 253-2),

where they can be targeted for ablation.

Other sites of origin such as the mitral and tricuspid valve annuli,

right ventricular moderator band, and even the epicardial surface

of the heart also occur (Fig. 253-3). The factors that can potentially

predict development of heart failure and increased risk of adverse outcomes include PVC frequency, characteristics of the PVC morphology,

and timing of the PVC coupling interval. In addition, the presence of

late gadolinium enhancement on cardiac MRI may suggest the presence of an additional underlying cardiomyopathic process. The degree

of expected recovery of ventricular function with PVC suppression is

difficult to predict. Even in the setting of known underlying cardiomyopathy, controlling frequent ventricular ectopy can be helpful to

improve ejection fraction and improve other factors such as delivery of

resynchronization pacing.

ACCELERATED IDIOVENTRICULAR

RHYTHMS

Three or more ventricular beats at a rate slower than 100 beats/min are

termed an AIVR (Fig. 253-4). Automaticity is the likely mechanism,

although in some rare cases, a reentrant circuit utilizing diseased myocardium can cause AIVR. Idioventricular rhythms are common during

acute MI and may emerge during sinus bradycardia. Often, they are

not symptomatic, but hemodynamic compromise may occur with the

loss of atrioventricular synchrony in susceptible patients. Atropine may

be administered to increase the sinus rates if this is a concern. This

rhythm is also common in patients with cardiomyopathies or sleep

apnea. It can also be idiopathic, often emerging when the sinus rate

slows during sleep. Therapy should target any underlying cause and

correction of bradycardia. Specific antiarrhythmic therapy for asymptomatic idioventricular rhythm is not necessary.

FUTURE DIRECTIONS

Recently, it has been appreciated that inflammation plays a role in

the genesis of PVCs in specific patients with inflammatory cardiomyopathies and even in inherited cardiomyopathies. The roles of early

identification of this process and targeted treatment are areas of active

research.

GE

III

II

I

aVF

aVL

aVR

V3

V2

V1

V6

V5

V4

FIGURE 253-2 Ventricular bigeminy with premature ventricular contractions (PVCs) originating from the posteromedial papillary muscle. Twelve-lead electrocardiogram

showing normal sinus rhythm with ventricular bigeminy. The PVCs have a right bundle branch block configuration in V1

 with superiorly directed axis. The leads V4

–V6

 are

negative. The configuration is consistent with a PVC origin in the posteromedial papillary muscle of the left ventricle.

1918 PART 6 Disorders of the Cardiovascular System

FIGURE 253-3 Catheter ablation of premature ventricular contractions (PVCs) from the left ventricular outflow tract. Shown is an electroanatomic map on the left and PVC

morphology with superimposed pacing morphology on the right. The left ventricle is seen from the atrial side (posteriorly), and an ablation catheter is seen passing through

the aortic valve at the top of the electroanatomic map and contacting the anterolateral portion of the left ventricular outflow tract. Maroon dots are ablation lesions that have

been delivered at the site of interest. Pacing from the site of interest generates a QRS complex very similar to the clinical PVC as seen on the right.

V1

V1

V2

V3

aVR

aVL

aVF

I

II

III

V4

V5

V6

FIGURE 253-4 Accelerated idioventricular rhythm. Shown is an example of a slow regular wide-complex rhythm. Fusion beats are seen on complexes 4 and 10, which are

more positive in lead V1

 and narrower than the rest of the beats. These features are consistent with an accelerated idioventricular rhythm.