MI. The first trial of sotalol, a class III antiarrhythmic agent with

β-blocking properties, showed an 18% reduction in overall mortality, which was similar to that seen in other β-blocking trials.128

The second trial, the Survival With Oral D-Sotalol (SWORD)

trial, evaluated the d-isomer of sotalol only. This isomer does

not have β-blocking properties, and this trial was stopped early

because the mortality rate was significantly increased.129 The

AHA/ACC recommend the routine use of oral β-blocker therapy

during the first 24 hours for patients who do not have contraindications (see Chapter 18, Acute Coronary Syndrome) to prevent

the early occurrence of VF. Furthermore, AHA/ACC assigned a

class I rating for the recommendation of long-term use of oral

β-blockers for secondary prevention in patients with low ejection

fraction, heart failure, or postshock.130 Hence, in A.S. a β-blocker

is an important first-line agent to try.

AMIODARONE

In high-risk patients with MI who are not candidates for

β-blockade, alternative antiarrhythmic therapy with amiodarone

can be considered. Amiodarone is a class III antiarrhythmic agent,

but also has antiadrenergic, class I, and class IV activity. In a

pivotal trial, treatment with amiodarone (800 mg/day for 7 days

followed by 400 mg/day for 6 days of the week for a year) was associated with a significant reduction in cardiac mortality and significant ventricular arrhythmias. Overall mortality showed a trend

toward benefit, but statistical significance was not achieved.130

An evaluation of amiodarone in post-MI patients with frequent

PVCs (∼10 per hour) or at least one run of VT was conducted

in the Canadian Amiodarone Myocardial Infarction Arrhythmia

Trial (CAMIAT).131 In this trial, amiodarone (10 mg/kg per day

for 14 days, then 300 to 400 mg/day for 16 months) significantly

reduced the incidence of VF or arrhythmic death by 48.5% compared with placebo. Arrhythmic death alone was reduced by

32.6%, and all-cause mortality was reduced by 21.2%, but statistical significance was not achieved for these end points. Patients

with heart failure or a previous MI had a majority of the benefit

from amiodarone therapy.

A complementary study, the European Myocardial Infarct

Amiodarone Trial (EMIAT), evaluated MI survivors with a

reduced ejection fraction (<40%).132 On the basis of the results

of this study, amiodarone (800 mg for 14 days, then 400 mg

for 14 weeks, and then 200 mg for the rest of the study) significantly reduced arrhythmic deaths by 35% compared with

placebo. However, this study did not demonstrate any trend

toward reduced mortality (mortality was 13.86% with amiodarone vs. 13.72% with placebo). This suggests that amiodarone

should not be used in all patients with a reduced ejection fraction

after an MI, but that it could benefit patients in whom antiarrhythmic therapy is indicated. Hence, if A.S. reports problematic

symptoms associated with the PVCs or develops additional risk

factors for arrhythmia while on β-blockade, the first-line treatment option, antiarrhythmic therapy with amiodarone can be

given without an increased risk of overall mortality.130–132

Nonsustained Ventricular Tachycardia

CASE 20-8

QUESTION 1: D.S., a 62-year-old man, was admitted

recently for an inferior wall MI. After the infarction, he has

been free of further pain and does not exhibit signs of HF.

An echocardiogram shows an ejection fraction of 48%, but

D.S. does experience runs of VT (Fig. 20-12) lasting from

three beats to 20 seconds in length. D.S. states that he feels

his heart racing during the longer episodes. Should D.S.’s

VT be treated? If so, what are the treatment options?

D.S. is experiencing NSVT, which can occur in patients with

underlying heart disease, both ischemic and nonischemic (idiopathic dilated cardiomyopathy, hypertrophic cardiomyopathy).

It is not clear which of these patients is at high risk for SCD.

The Multicenter Unsustained Tachycardia Trial (MUSTT) used

EP testing to see whether laboratory inducibility of sustained

monomorphic ventricular tachycardia could predict the duration

or frequency of NSVT in patients with NSVT, coronary artery

disease, and a reduced ejection fraction. No significant difference

in the frequency or duration of spontaneous NSVT was noted

and no clinically important differences were noted between the

groups with or without laboratory inducibility.133

At present, four patient subsets appear to be at higher risk

for adverse clinical outcomes (e.g., cardiovascular mortality,

increased risk of sudden death): (a) patients with no evidence

of cardiac disease but who experience two or more consecutive ventricular depolarizations during and after exercise; (b)

acute MI patients more than 24 hours after MI; (c) ischemic

patients with left ventricular ejection fraction (LVEF) less than

40%; and (d) young patients with hypertrophic obstructive

cardiomyopathy.134 If a patient has an ejection fraction greater

than 40% and no symptoms, therapy is not indicated. If symptoms

are present (e.g., palpitations, chest pain, syncope), a β-blocker is

preferred unless it is contraindicated by the presence of uncompensated HF, asthma, or chronic obstructive pulmonary disease (COPD).135 In addition to controlling symptoms,β-blockers

reduce the incidence of cardiac death in post-MI patients with and

without PVCs. β-Blockers have been shown to decrease mortality rates in patients with ischemic cardiomyopathy in conjunction

with impaired LVEF (<40%).136

Because D.S. is symptomatic, but has preserved ventricular

function, he should certainly be started on a β-blocker. Pindolol

or any β-blocker with intrinsic sympathomimetic activity should

be avoided because they have not been shown to be cardioprotective after an MI. The results from the CAMIAT study suggest

a role for amiodarone in this patient if β-blockers are contraindicated or inadequate.131 If D.S. fails to respond to a β-blocker,

the most appropriate alternative agents would be amiodarone

or sotalol.118

Sustained Ventricular Tachycardia

TREATMENT

CASE 20-9

QUESTION 1: S.L., a 64-year-old woman, presents to the

ED with a chief complaint of palpitations. Her medical history includes hypertension controlled with a diuretic, and an

510 Section 2 Cardiac and Vascular Disorders

inferior wall MI 6 months ago. She is pale and diaphoretic

but able to respond to commands. Her vital signs are BP,

95/70 mm Hg; pulse, 145 beats/minute; and respiratory

rate, 10 breaths/minute. When telemetry monitoring is

established, S.L. is found to be in SuVT (Fig. 20-14). S.L.’s

echocardiography (6 months earlier) revealed an LVEF of

35%. How should she be treated?

The acute treatment of patients with SuVT depends on their

hemodynamic stability. If unstable, patients should receive synchronous cardioversion, which will decrease the chance of triggering VF. If the patient is conscious, a short-acting benzodiazepine (e.g., midazolam) should be administered before the

procedure. The 2010 AHA guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care addressed the

potential efficacy of intravenous antiarrhythmic drugs in stable VT patients. A class IIa rating for the use of intravenous

procainamide was recommended by the AHA guidelines, with

amiodarone (class IIb) and sotalol (class IIb) representing alternative choices of antiarrhythmic therapy for wide-complex regular

tachycardias.137

ANTIARRHYTHMIC AGENTS

Data from three observational studies138–140 provided the basis

for AHA recommendations on using amiodarone in terminating shock-resistant or drug-refractory VT. Moreover, one randomized parallel-group study demonstrated the superiority of

amiodarone compared with lidocaine in the treatment of shockresistant VT.141 Amiodarone is primarily recommended for the

treatment of patients presenting with hemodynamically stable

VT, polymorphic VT with a normal QT interval, and widecomplex tachycardia of uncertain origin.137 Intravenous amiodarone should be administered as a 150-mg dose for 10 minutes,

followed by a 6-hour infusion at a rate of 1 mg/minute, and finally

a 0.5-mg/minute infusion for 18 hours. For recurrent or resistant

arrhythmias, supplemental infusions of 150 mg can be repeated

every 10 minutes, up to a maximal total daily IV dose of 2.25 g.

Commonly seen adverse effects associated with intravenous

amiodarone include hypotension and bradycardia, which can be

prevented by slowing the drug infusion rate.

Procainamide has been shown to be superior to lidocaine in

abolishing spontaneously occurring VT142 and may be considered for use in the treatment of patients with preserved ventricular function who present with stable monomorphic VT.

The beneficial effect of this agent is likely the result of slowing conduction in myocardial tissue. An initial infusion of 20 to

50 mg/minute for VT can be administered until arrhythmia suppression occurs, hypotension ensues, achievement of 50% prolongation from baseline duration of the QRS complex occurs,

or a cumulative dose of 17 mg/kg has been administered. The

AHA writing group discouraged the practice of giving bolus

doses of this drug to patients with VT because it increases

the occurrence of toxic drug concentrations and hypotension.

The maintenance infusion rate of procainamide hydrochloride

ranges from 1 mg/minute to 4 mg/minute in patients with normal renal function, but should be lowered in the presence of

renal dysfunction. The parent drug and the active metabolite,

N-acetylprocainamide (NAPA) can accumulate. NAPA itself has

class III antiarrhythmic activity and is eliminated entirely by the

kidneys, but the clinical significance of NAPA as an antiarrhythmic has not been fully established.143 Because of its potential to

prolong QT intervals, this agent should be used with caution in

patients receiving other QT-prolonging drugs. Continuous ECG

and blood pressure monitoring should take place during administration of procainamide.137

Sotalol, like procainamide, represents another alternative to

amiodarone therapy for termination of acute, monomorphic,

sustained VT.137 One randomized controlled trial demonstrated

the superior efficacy of this agent compared with lidocaine for terminating acute sustained VT.144 Similar to amiodarone, sotalol

prolongs the duration of action potentials and increases cardiac

tissue refractoriness. Per AHA 2010 recommendations, patients

with monomorphic VT who receive intravenous sotalol should

receive a 100-mg (1.5 mg/kg) dose infused for 5 minutes.137 Intravenous sotalol is approximately dose-equivalent to the oral formulation, because an intravenous dose of 75 mg equals an 80-mg

oral dose.145 The manufacturer suggests diluting sotalol in 100

to 250 mL of 5% dextrose, normal saline, or lactated Ringer’s

solution, and administering the drug using a volumetric infusion

pump for a 5-hour period. Common adverse effects associated

with sotalol include bradycardia and hypotension. The propensity of this agent to induce TdP is covered later in this chapter.

The mean elimination half-life of sotalol is 12 hours. Because it

is cleared by the kidneys, its clearance is reduced and its halflife prolonged in patients with renal dysfunction. Consequently,

patients receiving sotalol should receive continuous blood pressure, heart rate, and ECG monitoring. Patients who experience

excessive QT prolongation while on sotalol should receive lower

doses or the drug should be discontinued. Because S.L. appears

to be relatively stable and she has an ejection fraction less than

40%, amiodarone is a suitable intravenous antiarrhythmic agent

for terminating sustained VT.

Implantable Cardiac Defibrillators

CASE 20-9, QUESTION 2: On hospital day 2, S.L.

experiences a run of VT lasting about 2 minutes.

The cardiology consult service has recommended placement of an ICD. What is an ICD, and how does

it work?

ICDs are devices implanted under the skin with wires or

patches that are advanced or attached so they are in direct contact with the ventricular myocardium. The ICD is composed of

a pulse generator, sensing and pacing electrodes, and defibrillation coils. The pulse generator consists of a microprocessor, a

memory component capable of storing ECG data, a high-voltage

capacitor, and a battery. The microprocessor controls the analysis

of cardiac rhythm and delivery of therapy. An electrode is usually

placed at the endocardium of the right ventricular apex, but in

some rare cases, it is surgically placed on the epicardium. Patients

with dual-chamber ICDs have a second electrode placed in the

right atrial appendage. Biventricular ICDs have an additional electrode placed surgically on the epicardium of the left ventricle, or

more commonly, placed transcutaneously in a branch off of the

coronary sinus. Defibrillation coils are positioned on the right

ventricular electrode at the level of the right ventricle and the

superior vena cava. In most ICD systems, biphasic defibrillation

current flows from the distal defibrillation coil to the pulse generator and to the proximal defibrillation coil.146 ICDs can deliver

multitiered therapy when a ventricular arrhythmia is detected,

thereby reducing the need for high-energy defibrillation without

compromising ICD efficacy. A typical multitiered program set

for slow (160–180 beats/minute) ventricular tachycardia could

start with antitachycardia pacing, followed by low-energy cardioversion (e.g., 5 J) and higher-energy defibrillation (e.g., 35 J).

ICD programming for fast ventricular tachycardia (>180–

200 beats/minute) usually starts with antitachycardia pacing and

then proceeds directly to higher-energy defibrillation (e.g., 35 J).

Programming for VF (>200 beats/minute) is characterized by

multiple high-energy defibrillations (e.g., 35 J) delivered to the

511Cardiac Arrhythmias Chapter 20

patient experiencing this type of arrhythmia.146 Multiple clinical