Patients with nonvalvular and valvular AF have a 5- and 17-

fold increased risk for stroke compared with patients without AF,

respectively.4,5 Stroke can lead to death or significant neurologic

disability in up to 71% of patients, with an annual recurrence rate

as high as 10%.86 In three large, randomized trials, patients with

nonvalvular AF benefited from antithrombotic therapy.87–89 In

the Stroke Prevention in Atrial Fibrillation (SPAF) study, both

aspirin 325 mg/day and warfarin (titrated to an INR of 2.0 to 4.5)

reduced the risk of stroke significantly with an acceptable level

of hemorrhagic complications.89 The results of SPAF II, a direct

comparison of warfarin and aspirin, indicated that warfarin was

more effective than aspirin in preventing stroke.90 These results

were verified by the Copenhagen AFASAK study, which found

warfarin to be significantly better than aspirin and placebo at

preventing cerebral emboli and overall vascular deaths (cerebral

and cardiovascular).87 More recently, clopidogrel plus aspirin has

been studied for prevention of stroke in AF.91,92 When clopidogrel plus aspirin was compared with warfarin, warfarin was more

effective in stroke prevention and associated with a lower bleeding risk.92 However, when clopidogrel plus aspirin was compared

with aspirin alone in patients who were unable to take warfarin,

the clopidogrel plus aspirin regimen was superior in efficacy but

increased the risk of bleeding.91

Selection of an appropriate antithrombotic regimen for the

patient with AF must be based on assessment of the underlying

stroke and bleeding risk. Risk stratification in AF is performed

with the use of the CHADS2 scoring system. A CHADS2 score

is calculated by assigning one point each for the presence of

congestive heart failure, hypertension, age older than 75 years,

or diabetes and two points for a history of stroke. Points are

totaled, and the subsequent score correlates with stroke risk.42

Generally, patients with a CHADS2 score of 2 or greater should

receive warfarin (INR target 2–3) for stroke prophylaxis.42 Warfarin is selected over aspirin because stroke risk is relatively high

with a CHADS2 score of 2 or greater and warfarin is superior

to aspirin in prevention of stroke. Aspirin alone could be used

with a CHADS2 score of 0 or 1. The combination of clopidogrel

plus aspirin may be considered in the patient who is unable to

take warfarin because of practical issues (i.e., nonadherent with

medications or unable to comply with frequent monitoring of

INR). Although the combination of clopidogrel plus aspirin was

more efficacious than aspirin alone, it was also associated with

more bleeding.91 Therefore, the combination should not be used

in a patient who is unable to take warfarin as a result of perceived

high bleeding risk.

Dabigatran, a new orally available direct thrombin inhibitor,

was recently approved by the FDA to reduce the risk of stroke

and systemic embolism in patients with nonvalvular AF.93 In the

Re-Ly trial, dabigatran 110 mg twice daily and 150 mg twice

daily was compared with warfarin in patients with a CHADS2

score of 1 or more (average CHADS2 score of 2.1). The lower

dose of dabigatran was not inferior to warfarin for stroke prevention but was associated with less bleeding. High-dose dabigatran

was superior to warfarin for stroke prevention but comparable in bleeding.94 The dabigatran 150-mg twice-daily dose was

FDA-approved, as was a 75-mg twice-daily dose for those with

a CrCl of 15 to 30 mL/minute. Dabigatran offers an alternative

choice, does not require routine laboratory monitoring, does not

have food interactions, and is not a substrate or inhibitor of the

cytochrome P-450 system (see Chapter 16, Thrombosis, for more

information).93 Dabigatran is a P-glycoprotein substrate that

interacts with rifampin (use with rifampin is contraindicated),

but it does not appear to have clinically significant interactions

with other P-glycoprotein inhibitors used commonly in AF (verapamil, quinidine, dronedarone, flecainide, propafenone). The

capsules should not be chewed or opened. Dabigatran has no

specific dosing recommendation for patients with a CrCl less

than 15 mL/minute or those on dialysis. Numerous oral factor

Xa inhibitors are being investigated, and some will likely be available in the future.

Even though J.K. is in normal sinus rhythm at this time, in

the AFFIRM trial, only 73% and 63% of patients randomized

to rhythm control remained in sinus rhythm at 3 and 5 years,

respectively.41 As such, the use of an antiarrhythmic drug does

not eliminate the risk of stroke, and in fact, patients may return to

AF and not be aware they are no longer in normal sinus rhythm.

J.K. has a CHADS2 score of 3 and does not appear to have any

factors that would suggest a high bleeding risk (no recent history

502 Section 2 Cardiac and Vascular Disorders

of GI bleeding, etc.). Therefore, he should continue to receive

anticoagulation for stroke prophylaxis.

CASE 20-2

QUESTION 1: M.P. is a 38-year-old woman who has had

chronic atrial flutter for the past 2 years. She has no other

medical history and is taking metoprolol 50 mg twice daily.

She does not want to take the drug any more because it

reduces her exercise tolerance. Is there a nonpharmacologic

therapy for atrial flutter? Does the treatment of atrial flutter

differ from the treatment of AF? Is radiofrequency catheter

ablation an acceptable nonpharmacologic option for M.P.?

Atrial flutter is an unstable rhythm that often reverts to sinus

rhythm or progresses to AF. If atrial flutter is episodic, its underlying cause should be identified and treated if possible. If a patient

remains in atrial flutter, the treatment goals (control of ventricular rate, return to normal sinus rhythm) are the same as those

for AF. Similar agents and doses can be used to control the ventricular response. Chemical conversion, low-energy (<50 J) DC

cardioversion, or rapid atrial pacing may acutely convert atrial

flutter back to sinus rhythm, but the recurrence of atrial flutter

is high.

Radiofrequency catheter ablation therapy could be used as a

nonpharmacologic treatment for atrial flutter and, in some cases,

AF. With both atrial flutter and AF, an electrophysiologic study

is performed to identify whether ablation can be performed.

Various sections of the atria and pulmonary veins (where they

intersect with the atria) are probed with a catheter that delivers cardiac pacing. If an area is stimulated with pacing and an

atrial ectopic or re-entrant focus is recognized, that area could

be ablated. Ablation destroys tissue that is integral either to the

initiation or to the maintenance of the arrhythmia by delivering

electrical energy through electrodes on the catheter. If the focus

of the arrhythmia is in the atrial tissue (typically for atrial flutter), then the focus itself is ablated. This procedure is successful

in 75% to 90% of cases and can be recommended for patients

with atrial flutter who are drug-resistant or drug-intolerant, or

do not desire long-term therapy. In AF, an ectopic focus originating in the pulmonary veins can often initiate the arrhythmia.

In this case, circumferential ablation, in which a circle of ablated

tissue is made around the pulmonary veins, is performed. Circumferential ablation does not prevent the ectopic impulses from

the pulmonary veins from occurring; however, it does prevent

propagation of the impulse into the atria and may reduce the

recurrence of AF.

Radiofrequency ablation therapy may be suitable for M.P.

However, if exercise intolerance is her primary complaint, this

might be relieved by switching M.P. to another drug, such as

verapamil.95,96

ATRIAL FIBRILLATION AFTER BYPASS SURGERY

β-BLOCKERS AND AMIODARONE

CASE 20-3

QUESTION 1: H.L., a 55-year-old woman with triple-vessel

disease, is scheduled for coronary artery bypass graft

surgery (CABG) in 3 days. Her medical history includes

exercise-induced angina treated with nitrates, metoprolol,

and diltiazem. What is the incidence of AF after CABG

surgery? Should H.L. be treated with a drug to prevent the

postoperative occurrence of AF?

More than 750,000 CABG or heart valve surgeries (cardiothoracic surgery) are performed annually in the United States.97

Without prophylaxis, AF develops in up to 65% of patients, and

two-thirds of the cases occur on postoperative day 2 or 3.98 The

underlying mechanism is unknown, but may be related to sympathetic activation, pericarditis or inflammation, or atrial dilation

from volume overload.99–102 The arrhythmia usually converts

spontaneously, but can result in temporary symptomatology

(light-headedness), a higher risk of stroke, and a longer hospital stay.102

β-Blockers, amiodarone, sotalol, intravenous magnesium,

and statins are proven prophylactic strategies to reduce the

incidence of postcardiothoracic surgery AF.100–102 Of these,

β-blockers and amiodarone have been shown to reduce other

clinical events and shorten length of stay.97,100–102 In addition,

both β-blockers and amiodarone can be used together in the

same patient as a prophylactic strategy.100,101 If a patient is receiving a β-blocker before surgery and cannot receive it after surgery,

the risk of postcardiothoracic surgery AF is even higher than if

they were never on the β-blocker (β-blocker withdrawal). So it

is important to assure continuation of β-blockers after surgery if

possible.100,101

Although many studies evaluating the use of amiodarone prophylaxis have been conducted, the Atrial Fibrillation Suppression

Trial II (AFIST II) had a regimen that allowed for dosing patients

with elective and emergent surgery, and the beneficial results

were in addition to a high baseline utilization of β-blockers.101 In

AFIST II, a hybrid IV and oral amiodarone regimen was evaluated versus placebo. In this study, IV amiodarone (1,050 mg) was

given for 24 hours after surgery and then oral drug (400 mg three

times daily) was given for 4 postoperative days (equal to 7 g of

oral drug given for 5 days). In this study, amiodarone reduced the

30-day risk of AF by 43% and symptomatic AF by 68%. Amiodarone regimens using only oral dosing have also been studied

and showed similar benefits with similar delivered amiodarone

doses.100,102 H.L. is relatively young, does not have a history of

AF or heart failure, and is not undergoing valve repair or replacement, so the risk of developing postoperative AF is probably not

extremely high. Therefore, a prophylactic therapy may not be

necessary.

CASE 20-3, QUESTION 2: H.L.’s metoprolol therapy is discontinued, and she is not treated prophylactically. She

undergoes the surgery without complications. On postoperative day 2, she develops AF with a ventricular response

rate of 142 beats/minute and a BP of 126/75 mm Hg. How

should H.L. be managed?

The decision to treat H.L.’s AF depends on her heart rate and

how well she tolerates the arrhythmia; antiarrhythmic agents are

often not needed in the short-term management of this disorder.

For many years, digoxin has been used to control the ventricular

response. However, after surgery, patients have a high sympathetic tone, and digoxin often is ineffective. β-Blockers are effective and preferred if there are no contraindications.103 They are

especially preferred in patients like H.L. who have been taking

β-blockers preoperatively because withdrawal of β-blockers can

increase the occurrence of postoperative AF.103,104

H.L.’s rapid ventricular rate should be controlled. Propranolol

1 mg IV every 5 minutes (up to 0.1 mg/kg), metoprolol 5 mg IV

repeated at 2-minute intervals (up to a total dose of 15 mg), and

esmolol 0.5 mg/kg bolus followed by a continuous infusion at a

rate of 50 to 300 mcg/kg per minute are all options for H.L., who

appears to be hemodynamically stable. Verapamil 5 to 10 mg IV

every 1 to 4 hours could be an option for most patients; however,

this would be a therapeutic duplication because H.L. is already

taking diltiazem. If one of these therapy choices is ineffective,

503Cardiac Arrhythmias Chapter 20

a loading dose of digoxin can be administered IV as adjunctive

therapy with the β-blocker or verapamil.

CASE 20-3, QUESTION 3: Metoprolol is started, and ventricular rate control is achieved 4 minutes after administering the second 5-mg dose. The patient receives 50 mg oral

metoprolol therapy an hour later, converts to normal sinus

rhythm spontaneously the next day, and is preparing for discharge. The metoprolol therapy is discontinued. Should an

antiarrhythmic agent be initiated for H.L. to prevent recurrence of AF?

Using prophylactic antiarrhythmic agents after discharge in

patients with AF within a few days of CABG surgery does not

seem to protect against recurrent AF. In one trial, all patients

with AF after CABG surgery were given verapamil, quinidine,

amiodarone, or placebo at discharge and were then followed

with Holter monitoring for 90 days. There was no difference

in the occurrence of AF between the placebo group (3.3% incidence) and the other groups (6.7% incidence for each treatment

group).105 Because H.L. has coronary artery disease, it would be

reasonable to resume the metoprolol.

Paroxysmal Supraventricular Tachycardia

CLINICAL PRESENTATION

CASE 20-4

QUESTION 1: B.J., a 32-year-old woman, presents to the

emergency department (ED) complaining of fatigue and palpitations. She has had similar episodes approximately twice

a year for the past 2 years, but has not sought medical attention for them. She is in no apparent distress and has a temperature of 98.0◦F, heart rate of 185 beats/minute, BP of

95/60 mm Hg, and respiratory rate of 12 breaths/minute.

Her ECG (Fig. 20-6) shows regular rhythm with a heart rate

of 185. The P waves cannot be found, and the QRS complex is 110 ms (normal, <120 ms). The diagnosis is PSVT.

What is the clinical presentation of PSVT, and what are the

consequences of this arrhythmia?

PSVT often has a sudden onset and termination. At the time

of PSVT, the heart rate is usually 180 to 200 beats/minute. As

illustrated by B.J., patients experience palpitations and often nervousness and anxiety. In patients with a rapid ventricular rate,

dizziness and syncope (near-fainting) can occur, and the rhythm

may degenerate to other serious arrhythmias. Angina, HF, or

shock may be precipitated depending on the patient’s underlying

degree of coronary atherosclerosis and left ventricular function.

There is no evidence that patients with episodes of PSVT are at

an increased risk of stroke.

ARRHYTHMOGENESIS AND RE-ENTRY

CASE 20-4, QUESTION 2: What is the arrhythmogenic

mechanism of PSVT?

AV nodal re-entry is the most common mechanism of paroxysmal supraventricular arrhythmias (see Fig. 20-3). Under certain conditions, such as after an acute MI, atrial impulses will

be blocked in one of the two AV nodal pathways in a unidirectional manner (antegrade block). After the impulse reaches the

distal end of one pathway, it will conduct in a retrograde fashion through the other pathway, setting up a circular movement

causing tachycardia. When AV nodal re-entry is the mechanism

of the PSVT, it may be referred to as AV nodal re-entrant tachycardia or AVNRT. Reciprocating tachycardias occur when there

is an accessory pathway for conduction of impulses between

the atria and ventricles (also known as AVRT or atrioventricular re-entrant tachycardia). WPW syndrome is an example of a

situation in which an accessory pathway exists and can produce

PSVT (Fig. 20-7).

TREATMENT

CASE 20-4, QUESTION 3: B.J. tries the Valsalva maneuver,

and her ventricular rate is reduced to 150 beats/minute; the

other parameters are unchanged. She is given IV adenosine

6 mg, administered for 1 minute, with no effect on the PSVT

rate. Another dose of adenosine 12 mg has no effect. No

side effects are noted from therapy. What treatment options

can be used if B.J. is hemodynamically unstable? What is

the Valsalva maneuver? What is a probable reason for B.J.’s

unresponsiveness to adenosine? Are there any drug interactions that might diminish adenosine’s effect?

NONDRUG TREATMENT

Valsalva Maneuver

Although her BP is low at 95/60 mm Hg, B.J. is maintaining

an adequate perfusion pressure, so vagal maneuvers should be

attempted first. Two common vagal techniques are pressure over

the bifurcation of the internal and external carotid arteries and

the Valsalva maneuver (forcible exhalation against a closed glottis, similar to bearing down to have a bowel movement). The

increase in pressure induced by these maneuvers is sensed by the

baroreceptors, causing a reflex decrease in sympathetic tone and

an increase in vagal tone. The increase in vagal tone will increase

refractoriness and slow conduction in the AV node, thereby slowing the heart rate; the arrhythmia will terminate in 10% to 30%

of cases.96 If B.J. is hemodynamically unstable or becomes hemodynamically unstable, she should receive synchronized DC cardioversion.

FIGURE 20-6 Supraventricular tachycardia. (Reproduced with permission from Stein E. Rapid Analysis of

Arrhythmias: A Self-Study Program. 2nd ed. Philadelphia, PA: Lea & Febiger; 1992.)

504 Section 2 Cardiac and Vascular Disorders

S F-blocked

AV Node

Bundle of His

Left Bundle

Branch

S F

Blocked

Impulse

Retrograde

Conduction

up F

A B

Atrium

Atrium

Unidirectional

Block

Accessory

Pathway

SelfSustaining

Re-Entry

Conduction

C D

Right Bundle

Branch

FIGURE 20-7 The atrioventricular (AV) node in paroxysmal

supraventricular tachycardia and Wolff-Parkinson-White

syndrome. A: A bifurcation of an impulse, one propagated fast and

another slow. B: The slow impulse in (A) can send impulses in a

retrograde fashion. C: The re-entry from (A) to (B) can be selfsustaining. D: Normal impulse conduction through the AV node, but

abnormal retrograde conduction up an accessory pathway, as would

be seen in a patient with Wolff-Parkinson-White syndrome.

DRUG THERAPY

Adenosine

Drug therapy for PSVT involves blocking the AV node, because

most PSVT rhythms involve a re-entry circuit that includes this

area. Adenosine, a purine nucleoside that exerts a transient negative chronotropic and dromotropic effect on cardiac pacemaker

tissue,106 is considered the drug of choice for the acute treatment

of PSVT because of its rapid and brief effect. An initial 6-mg IV

bolus is given; if this is unsuccessful within 2 minutes, it can be

followed by one or two 12-mg IV boluses, up to a maximum

of 30 mg. Because of its short half-life (9 seconds), adenosine

should be administered as a rapid bolus (over 1 to 3 seconds),

followed immediately by a saline flush. Adenosine begins to be

metabolized immediately after entering the bloodstream; therefore, B.J.’s failure to respond is likely attributed to the prolonged

(1-minute) infusion time.

Theoretically, adenosine may be ineffective or higher doses

may be required in patients who are receiving theophylline

because theophylline is an effective adenosine receptor blocker.

Larger doses of other methylxanthines (caffeine, guarana) may

also theoretically interact like theophylline. Conversely, concomitant use of dipyridamole may accentuate adenosine’s effects

because dipyridamole blocks the adenosine uptake (and subsequent clearance).

CASE 20-4, QUESTION 4: B.J. is given 12 mg adenosine IV

during 2 seconds, followed by a 20-mL normal saline flush.

Thirty seconds later, she complains of chest tightness and

pressure. What is the explanation for these symptoms?

B.J. is experiencing a common side effect of adenosine.

Patients receiving adenosine should be warned that they may feel

transient chest heaviness, flushing, or a feeling of anxiety. Shortness of breath and wheezing may be observed in patients with

asthma. The denervated heart of the patient who has undergone