More than 18 open-label and double-blind, randomized clinical
trials have been conducted of coenzyme Q in patients with HF
ranging from NYHA classes II to IV.361 Doses varied from 50 to
200 mg/day. In contrast to hawthorn, the patients in many of these
trials were also taking diuretics, ACE inhibitors, and digoxin.
Different trials used different end point measurements. Positive
effects on subjective symptoms, NYHA class improvement, EF,
quality of life, and hospitalization rates have all been observed.
Two trials, however, failed to demonstrate significant changes
in EF, vascular resistance, or exercise tolerance. None of the
trials had sufficiently large samples sizes or adequate duration of
heartburn, and appetite suppression. Mild increases in lactate
dehydrogenase and hepatic enzymes have been rarely reported
with coenzyme Q doses in excess of 300 mg/day.
It can be concluded that hawthorn and coenzyme Q are both
safe in the treatment of HF and might provide symptomatic
improvement, especially in patients with mild HF (NYHA class
II). Only coenzyme Q has been shown to be of benefit as an
adjunct to conventional therapies. It is unknown whether using
hawthorn and coenzyme Q together, as prescribed for W.L., will
have an additive effect. No conclusion can be drawn about their
W.L. has poorly controlled systolic HTN and HF that is
beginning to interfere with his activities of daily life. Although
evidence indicates that patients with NYHA class II HF obtain
symptomatic improvement with hawthorn and coenzyme Q,
this does not address W.L.’s HTN. (As reviewed by Tran et al.,361
conflicting data exist on the value of coenzyme Q in lowering
seen when combined with standard therapy. Even if W.L. and
his naturopath are both satisfied with his responses to hawthorn
and coenzyme Q, significant concern still exists about what will
happen when and if his disease progresses. Uncontrolled HTN in
patients with HF can further lead to cardiac remodeling, resulting
in worsening HF. Currently he is presenting with symptomatic
HF; therefore he should be started on a diuretic to alleviate his
symptoms. Starting with a 20-mg dose of furosemide and titrating
inhibitor to control his HTN. He should be counseled that the
urinary frequency he experienced previously should diminish
it is because of only one of the agents or the combination. With
this in mind, it might be more logical to continue hawthorn
alone at a dose of 450 mg BID. If no benefit is derived after
1 month, hawthorn should be stopped and coenzyme Q started
The use of natural supplements is not routinely recommended
ephedra (which contain catecholamines), ephedrine metabolites,
or imported Chinese herbs are contraindicated in HF because of
increased risk of mortality and morbidity. Also no regulatory
oversight, quality control, or regulations exist on the use of natural supplements.
488 Section 2 Cardiac and Vascular Disorders
A full list of references for this chapter can be found at
http://thepoint.lww.com/AT10e. Below are the key references
for this chapter, with the corresponding reference number in this
chapter found in parentheses after the reference.
appears in N Engl J Med. 2005;352:2146]. N Engl J Med. 2005;352:
Granger CB et al. Effects of candesartan in patients with chronic
Hunt SA et al. 2009 focused update incorporated into the
ACC/AHA 2005 Guidelines for the Diagnosis and Management
of Heart Failure in Adults: a report of the American College
of Cardiology Foundation/American Heart Association Task
Force on Practice Guidelines: developed in collaboration with
the International Society for Heart and Lung Transplantation
[published correction appears in Circulation. 2010;121:e258]. Circulation. 2009;119:e391. (1)
[No authors listed]. Effect of metoprolol CR/XL in chronic heart
failure: Metoprolol CR/XL Randomised Intervention Trial in
Congestive Heart Failure (MERIT-HF). Lancet. 1999;353:2001.
Packer M et al. Comparative effects of low and high doses of the
Circulation. 1999;100:2312. (165)
Failure Study Group. N Engl J Med. 1996;334:1349. (214)
Pitt B et al. Eplerenone, a selective aldosterone blocker, in
N Engl J Med. 2003;348:1309. (67)
Evaluation Study Investigators. N Engl J Med. 1999;341:709. (66)
Rathore SS et al. Association of serum digoxin concentration
and outcomes in patients with heart failure. JAMA. 2003;289:871.
Zannad F et al. Eplerenone in patients with systolic heart failure
and mild symptoms. N Engl J Med. 2011;364:11. (61)
C. Michael White, Jessica C. Song, and James S. Kalus
ATRIAL FIBRILLATION (AF)/FLUTTER
1 Chest palpitations, lightheadedness, and reduced exercise tolerance are the most
common symptoms of AF, but stroke is among the severe complications. The goals
of therapy are to control the ventricular rate and reduce the risk of stroke.
2 Digoxin, β-blockers, and nondihydropyridine calcium-channel blockers are
appropriate rate-controlling medications. Digoxin is usually adjunctive therapy.
Antiarrhythmic drugs are recommended in patients with symptoms but not needed
in asymptomatic patients (no symptoms other than palpitations).
3 Before converting AF to sinus rhythm, assurance of a lack of clot is important but not
required if someone is unconscious or cannot mentate. People with a CHADS2 score
of 2 or greater should receive chronic antithrombotic therapy with warfarin or
dabigatran. Those with a score of 0 can receive aspirin, and those with a score of 1
can receive aspirin or antithrombotic therapy.
4 Antiarrhythmic drugs convert patients out of AF 50% of the time, whereas electrical
shock is successful 90% of the time. To maintain sinus rhythm after conversion,
class Ib agents cannot be used, class Ic agents cannot be used in patients with
structural heart disease (left ventricular hypertrophy, myocardial infarction, or heart
failure), and class Ia and III agents can increase the risk of torsades de pointes.
Propafenone, sotalol, dronedarone, dofetilide, and amiodarone are commonly used
5 Atrial flutter is less common than AF, but similar rate control and antiarrhythmic
strategies can be tried. Radiofrequency ablation can be used to terminate atrial
6 A large percentage of patients exhibit AF after cardiac surgery. β-Blockers and
amiodarone have been shown to decrease clinical manifestations of AF and reduce
hospital length of stay. If AF occurs, it should be managed with rate control.
PAROXYSMAL SUPRAVENTRICULAR TACHYCARDIA (PSVT)
1 PSVT is caused by re-entry within the atrioventricular (AV) node. Palpitations and
hypotension can occur. The Valsalva maneuver, adenosine, or nondihydropyridine
calcium-channel blockers can be used to treat the arrhythmia.
2 In Wolff-Parkinson-White syndrome patients with PSVT, the use of AV nodal blocking
agents such as β-blockers, nondihydropyridine calcium-channel blockers, and
digoxin can increase the risk of cardiac arrest. Ablation can destroy the bypass tract
490 Section 2 Cardiac and Vascular Disorders
1 β-Blockers, digoxin, and nondihydropyridine calcium-channel blockers should be
withheld in patients with type 1 second- or third-degree AV block. Atropine can be
1 In patients with premature ventricular complexes (PVCs) and myocardial infarction,
β-blockers are the treatment of choice.
2 Patients with myocardial infarction and nonsustained ventricular tachycardia (VT)
should receive β-blockers and need to be risk stratified to determine whether they
should receive an implantable cardioverter-defibrillator.
3 Patients with sustained VT should be treated with intravenous antiarrhythmic agents
unless they are hemodynamically unstable, in which case they should be electrically
of painful shocks, both strategies are usually used simultaneously.
1 TdP occurs secondary to antiarrhythmic and nonantiarrhythmic medications that
prolong the QTc interval. Class Ia and III antiarrhythmic agents, antipsychotic
agents, fluoroquinolones, macrolides, azole antifungals, and methadone can
prolong the QTc interval. Magnesium is the treatment of choice for
2 Natural products such as omega-3 fatty acids, coenzyme Q10, and carnitine have
been studied to treat atrial and ventricular arrhythmias with the most compelling
evidence for omega-3 fatty acids in patients with coronary disease.
1 Cardiac arrest should be treated with 2-minute cycles of aggressive
cardiopulmonary resuscitation, electrical shock for VT or ventricular fibrillation (VF),
epinephrine or vasopressin, and amiodarone for refractory VT or VF according to
the advanced cardiac life support guidelines from the American Heart Association.
An electrical potential exists across the cell membrane, and the
electrical potential changes in a cyclic manner that is related to
the flux of ions across the cell membrane, principally K+, Na+,
and Ca2+. If the change in the membrane potential is plotted
against time in a given cycle of a His-Purkinje fiber, a typical
action potential results (Fig. 20-1).
The action potential can be described in five phases. Phase 0 is
related to ventricular depolarization resulting from sodium entry
Phase 1 is the overshoot phase in which calcium enters the cell and
contraction occurs. During phase 2, the plateau phase, inward
represented by the T wave. During phase 4, sodium moves out of
the cell and potassium moves into the cell via an active pumping
mechanism. During this phase, the action potential remains flat
in some cells (e.g., ventricular muscle) and does not change until
it receives an impulse from above. In other cells (e.g., sinoatrial
shape of the action potential depends on the location of the cell
(see Fig. 20-1). In both the SA and atrioventricular (AV) nodes, the
cells are more dependent on calcium influx than sodium influx,
resulting in a less negative resting membrane potential, a slow
rise of phase 0, and the capability of spontaneous (automatic)
phase 4 depolarization (Fig. 20-1).
The upward slope of phase 0, referred to as Vmax, is related to
the conduction velocity. The steeper the slope, the more rapid
the rate of depolarization. Another influence on Vmax is the point
at which depolarization occurs. The less negative the threshold
potential, the slower Vmax will be, and hence conduction velocity
491Cardiac Arrhythmias Chapter 20
potential less negative (e.g., class I agents).
The action potential duration (APD) is the length of time from
phase 0 to the end of phase 3. The effective refractory period is
the length of time that the cell is refractory and will not propagate
another impulse. Both of these measurements can be obtained
from intracardiac recordings of the action potential. Class Ia and
III agents prolong the refractoriness of the heart.
NORMAL CARDIAC ELECTROPHYSIOLOGY
Normal cardiac electrical activity begins with automatic impulse
generation (automaticity) at the SA node and then normal
impulse conduction through the heart.
in the SA and AV nodes and the His-Purkinje system. The SA
node is normally the dominant pacemaker because it reaches
node. If the normal conduction system is disrupted (e.g., after a
myocardial infarction [MI]), the AV node or Purkinje fibers may
temporarily become the dominant pacemaker.
An impulse normally originates in the SA node and travels down
before releasing it to the bundle of His. It then travels to the right
and left bundle branches and out to the ventricular myocardium
via the Purkinje fibers. The ECG tracing consists of a series of
have been labeled the P wave, QRS complex, and T wave. The
P wave represents depolarization of the atria, whereas the QRS
complex reflects ventricular depolarization. The T wave reflects
repolarization of the ventricles. To evaluate the intact conduction
system, conduction intervals at different sites can be obtained.
Calculation of the various intervals and widths is facilitated by
recording the ECG waveforms on graph paper consisting of large
squares defined by heavier lines, which in turn are composed
squares (5 mm in length) and represent 0.20 seconds (Fig. 20-2).
492 Section 2 Cardiac and Vascular Disorders
Normal Electrophysiological Intervals
Interval Indices (ms) Electrical Activity Measured By
PR 120–200 Atrial depolarization Surface ECG
QRS <140 Ventricular depolarization Surface ECG
QTca <400 Ventricular repolarization Surface ECG
J-Tb — Ventricular repolarization Surface ECG
aQTc interval is the QT interval corrected for heart rate. A common method for
ECG tracings are evaluated through a systematic review as
1. Is the rate fast or slow? A simple method to determine the
rate is to count the number of complexes occurring within 6
seconds and multiply by 10. Most ECG recording paper places
vertical lines at the top of the grid, 3 seconds apart. Therefore,
if eight complexes appear within a 6-second length of strip,
R wave intervals regular or irregular? If the rhythm is irregular,
is the pattern of irregularity consistent (regularly irregular)
or totally random (irregularly irregular)? P waves appearing
before the QRS complex usually indicate that the impulse
originated in the SA node and subsequently was conducted
to the ventricle. Abnormal-appearing P waves indicate that an
a site other than the SA node before the normal pacemaker
can fire (premature beat); they also may result from failure to
conduct impulses from the atria.
3. Are the P-R and QRS complexes within normal limits? Is the
ventricle give rise to wide, bizarre-appearing QRS complexes.
Pharmacologic Properties of Antiarrhythmic Agents
PR QRS QT Conduction Refractory
Type Interval Interval Interval Velocity Period
aConduction increases at low dosages and decreases at higher dosages.
b On atrial and atrioventricular nodal tissue.
c May cause PR prolongation independent of class III antiarrhythmic activity.
sinus bradycardia) or other sites (e.g., junctional or idioventricular
tachycardia). Causes of abnormal automaticity include hypoxia,
ischemia, or excess catecholamine activity.
by a pacemaker cell. These after-depolarizations may occur in
of membrane potential and may require a bradycardic state.
Torsades de pointes (TdP), a form of polymorphic ventricular
tachycardia (VT), is thought to be initiated by EAD. Delayed
after-depolarizations (DAD), often seen with digoxin toxicity,
are thought to be secondary to an overload of intracellular free
(e.g., AV node or left and right bundle branches). The impulse
impulse that passed through the unblocked pathway propagates
the first pathway again when it is not refractory. Supraventricular
and monomorphic VT are both examples of re-entrant arrhythmias (see Case 20-4, Question 3).
Another form of abnormal impulse conduction occurs when the
normal conducting pathway is blocked and the impulse is forced
to travel through nonpathway tissues to cause depolarization.
Common examples are left and right bundle branch blocks in
Typically, the nonpathway tissue conducts the electrical impulse
more slowly than conduction tissues do.
All arrhythmias originating above the bundle of His are
referred to as supraventricular arrhythmias. These may include
sinus bradycardia, sinus tachycardia, paroxysmal supraventricular
(PACs). All of these arrhythmias are characterized by normal
QRS complexes (i.e., normal ventricular depolarization) unless
there is a bundle branch block. Not all of these rhythm changes are
heart rates (sinus bradycardia). Vigorous exercise commonly is
accompanied by transient sinus tachycardia.
Arrhythmias originating below the bundle of His are referred
493Cardiac Arrhythmias Chapter 20
FIGURE 20-2 Electrocardiogram recording paper.
be a supraventricular site (e.g., first-, second-, or third-degree
AV block, see Case 20-6, Question 2) or in the ventricle (e.g.,
right or left bundle branch block). An alternative method of
classifying arrhythmias is based on the rate: bradyarrhythmia
(<60 beats/minute) or tachyarrhythmia (>100 beats/minute).
FIGURE 20-3 Re-entrant circuit in the pulmonary vein. In the
pulmonary vein there is a mixing of electrically active cells (shaded
circles) and electrically inactive cells (white circles). While the main
wave of depolarization goes homogenously down the atria a small
depolarization stimuli enters the pulmonary vein and meanders
through the electrically active tissue. In this case, there is a re-entrant
circuit formed where the impulse can continue to rotate through the
pulmonary vein and a route for it to stimulate the atria as well.
There is a website with useful rhythm evaluation tutorials at
On the basis of their electrophysiologic and pharmacologic
effects, there are four Vaughn-Williams antiarrhythmic drug
classes. Class I drugs, sodium-channel blockers, are subdivided
further depending on the duration of channel blockade (class Ia
is intermediate, Ib is quick, and Ic is long). Class II drugs are
β-adrenergic blockers, class III drugs are potassium-channel
blockers, and class IV drugs are calcium-channel blockers. The
classification, pharmacokinetics, and adverse effects of these
agents are summarized in Table 20-3.
IV antiarrhythmic agents can decrease the heart rate (may cause
bradycardia), decrease the force of ventricular contractility (may
decrease stroke volume), and prolong the PR interval (may cause
second- or third-degree AV block). Class Ib antiarrhythmic agents
work only in ventricular tissue, so they cannot be used in AF or
atrial flutter. Class Ic antiarrhythmic agents are useful, but should
never be used after an MI or with heart failure (HF) or severe left
ventricular hypertrophy (classified as structural heart diseases)
because increased mortality can result. These drugs are discussed
The specific arrhythmias include (a) those primarily atrial in
origin, such as AF, atrial flutter, paroxysmal sinus tachycardia,
ectopic atrial tachycardia, and multifocal atrial tachycardia; and
(b) AV nodal re-entrant tachycardia (AVNRT) and AV re-entrant
tachycardia (AVRT) involving accessory pathways within the
atria or ventricle. AVNRT and AVRT often self-terminate and
are paroxysmal (episodic) in nature; thus, they are commonly
referred to as paroxysmal supraventricular tachycardias (PSVT).
494 Section 2 Cardiac and Vascular Disorders
Vaughn-Williams Classification of Antiarrhythmic Agents
Drug and Classification Pharmacokinetics Indications Side Effects
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